PubMed Trending Research Digest — June 29, 2026

Automated digest · 99 articles · 15 research areas · June 29, 2026

Overview

Across this week’s set of papers, a dominant theme is the move from “single-mechanism” thinking toward dynamic, systems-level models of disease—using single-cell/multi-omics atlases, longitudinal trajectories, and quantitative frameworks to connect molecular programs to clinical outcomes. Examples include a temporally resolved bovine placenta single-nucleus atlas, trajectory-aware AI staging for age-related macular degeneration, and quantitative systems pharmacology models that aim to predict CAR T expansion and relapse in multiple myeloma. Together, these studies reflect a broader push to make biology predictive and time-resolved rather than static.

A second major thread is targeted manipulation of cell fate and immune function—especially via ferroptosis/iron-lipid pathways and immune-evasion mechanisms. Multiple studies converge on ferroptosis sensitivity as a therapeutic lever (e.g., HIF-1α–ACSL4 in anaplastic thyroid cancer, SLC7A11/ferroptosis control in lupus Tregs, ferritin heavy chain in ARDS, and NAD+–mitochondria vulnerability in retinitis pigmentosa). In parallel, cancer papers highlight how tumors escape immunity or therapy: IFN-β–driven dormancy in colorectal cancer, WDR12-mediated stabilization of the immune checkpoint CD276 in melanoma, and multiple strategies to redirect or enhance immune killing (bispecific EVs, DR3/TL1A blockade, and CAR T-related risk modeling).

Finally, the digest shows increasing integration of “modifiable context” factors—metabolism, microbiome, and systemic inflammation—into disease management. Gut-immune and immunometabolic mechanisms appear in Sjögren’s dry eye (intermittent fasting, Akkermansia, bile acids), chronic colitis–linked Parkinson’s pathology (Csf1r+ myeloid cells), and hyperuricemia via probiotic-derived peptidoglycan. Cardiometabolic and clinical stratification efforts (vitamin D in hepatocellular carcinoma, frailty in heart failure, fibrosis risk prediction in NAFLD, and GLP-1RA real-world outcomes in OSA+T2DM) further underscore a trend: tailoring prevention and therapy using measurable biological states rather than one-size-fits-all protocols.

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Single-cell & multi-omics atlases

A longitudinal single-nucleus transcriptomic atlas of bovine placentation reveals dynamic cellular hierarchies and regulatory programs.

This study generated a longitudinal single-nucleus transcriptomic atlas of bovine placenta across 13 gestational timepoints (E12–E280) using 311,299 placental cells/nuclei to map cellular hierarchies and regulatory programs. It identified 13 major cell types and 14 trophoblast subtypes with stage-specific cellular heterogeneity and inferred dynamic regulatory programs across gestation. The resulting temporally resolved bovine placental atlas provides a resource for mechanistic studies of pregnancy maintenance and for improving reproductive outcomes in cattle.

Tan G, Yan X, Cao X et al. · Genome biology · (2026) · View on PubMed ↗ · Free PDF ↗

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Ferroptosis, iron metabolism & lipid peroxidation

Bio-hybrid nanovesicles with multimodal antioxidant and immunomodulatory functions attenuate acute kidney injury.

The study developed bio-hybrid extracellular vesicle nanovesicles (ES-EVs) loaded with epigallocatechin-3-gallate (EGCG) nanoparticles and selenomethionine (SeMet) to test integrated antioxidant and immunomodulatory effects in acute kidney injury (AKI) models. ES-EVs attenuated AKI by reducing reactive oxygen species–driven tubular epithelial damage and dampening inflammatory immune activation. This multimodal nanovesicle strategy suggests a translational approach to simultaneously target oxidative stress and inflammation in AKI.

Chen W, Yuan H, Liu H et al. · Journal of nanobiotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

CD163+ macrophages coordinate erythroblastic Island formation and iron metabolism to enable glucocorticoid-induced erythropoiesis.

The study investigated how CD163+ macrophages coordinate erythroblastic island (EBI) formation and iron metabolism to enable glucocorticoid-induced erythropoiesis. Using single-cell RNA sequencing, ATAC-seq, ChIP-seq, RNA-seq, qPCR, ELISA, flow cytometry, and in vivo models including AIHA patients and CD163 knockout mice, it delineated CD163+ macrophage programs that support EBI structure and iron handling during glucocorticoid-driven erythropoiesis. These findings are significant for understanding steroid-responsive anemia biology and for identifying macrophage/iron-transport pathways as potential therapeutic targets.

Li M, Wang Y, Huang H et al. · Biomarker research · (2026) · View on PubMed ↗ · Free PDF ↗

HIF-1α enhances ferroptosis resistance in anaplastic thyroid carcinoma by suppressing ACSL4-mediated lipid metabolic homeostasis.

This study examined the role of hypoxia-inducible factor 1α (HIF-1α) in ferroptosis resistance in anaplastic thyroid carcinoma (ATC) and focused on how it affects ACSL4-mediated lipid metabolic homeostasis. It reported that HIF-1α enhances ferroptosis resistance by suppressing ACSL4-dependent lipid metabolic regulation, thereby limiting lipid peroxidation required for ferroptotic death. These findings suggest that disrupting the HIF-1α–ACSL4 axis may sensitize ATC to ferroptosis-based therapeutic strategies.

Xie R, Geng R, Wang Y et al. · Cellular & molecular biology letters · (2026) · View on PubMed ↗ · Free PDF ↗

Cannabidiol alleviates traumatic brain injury-induced neuronal damage and cognitive deficits by inhibiting ferroptosis via the TRPV1/MCU/PI3K/Akt pathway.

This study evaluated cannabidiol (CBD) as a treatment after traumatic brain injury (TBI) using an in vitro ferroptosis model in HT-22 cells and in vivo TBI models, focusing on the TRPV1/MCU/PI3K/Akt signaling pathway. It found that CBD alleviated neuronal damage and cognitive deficits by inhibiting ferroptosis through modulation of TRPV1/MCU and downstream PI3K/Akt signaling. The results support CBD as a potential neuroprotective candidate for TBI by targeting ferroptosis-related pathways.

Xu Y, Li X, Gu Z et al. · Cellular & molecular biology letters · (2026) · View on PubMed ↗ · Free PDF ↗

SLC7A11 deficiency exacerbates systemic lupus erythematosus by inducing instability and ferroptosis in regulatory T cells.

SLC7A11 was investigated in systemic lupus erythematosus (SLE) by assessing its expression in regulatory T cells (Tregs) and using Treg-specific SLC7A11 deletion in mouse models. SLC7A11 deficiency reduced Treg stability and differentiation, promoted a pro-inflammatory phenotype, and induced ferroptosis via HIF-1α–linked metabolic rewiring, thereby worsening lupus progression and autoantibody production. These results identify SLC7A11/ferroptosis control in Tregs as a mechanistic vulnerability and potential therapeutic target in SLE.

Ouyang L, Chen F, Zheng M et al. · Communications biology · (2026) · View on PubMed ↗ · Free PDF ↗

NAD+ modulates mitochondrial vulnerability in MERTK-associated models of retinitis pigmentosa.

NAD+ was examined as a regulator of mitochondrial vulnerability in MERTK-associated models of retinitis pigmentosa using single-cell RNA sequencing, transmission electron microscopy, and biochemical assays. NAD+ modulation altered mitochondrial stress/vulnerability in photoreceptor and retinal pigment epithelium cells, linking metabolic state to retinal degeneration susceptibility. The work supports NAD+–mitochondria pathways as potential targets to slow or prevent RP progression.

Feng L, Wen Y, Zhang T et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting macrophage ferritin heavy chain mitigates ferroptosis and lung injury in experimental acute respiratory distress syndrome.

The role of extracellular and myeloid ferritin heavy chain (FTH1/Fth1) in acute respiratory distress syndrome (ARDS) was tested in human samples and in a murine hyperoxia-induced lung injury model. Myeloid-specific FTH1 deletion (Fth1ΔLysM) reduced macrophage ferroptosis and mitigated lung injury, consistent with enriched ferritin subunits in ARDS serum and alveolar macrophages. These findings identify macrophage ferritin heavy chain as a mechanistic driver of ferroptosis in ARDS and a potential therapeutic target.

Zhang WZ, Kim K, Bhatia D et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

PDK4-dependent lactate production and lactylation promote renal calcium oxalate crystal-induced EMT and mitochondrial dysfunction via the TGF-β/SMAD3/GPX4 axis.

The study investigated mechanisms of calcium oxalate (CaOx) crystal-induced epithelial-to-mesenchymal transition (EMT) and mitochondrial dysfunction in renal proximal tubular epithelial cells (PTECs), focusing on PDK4-dependent lactate production and lactylation via the TGF-β/SMAD3/GPX4 axis. Integrated single-cell, spatial, and bulk transcriptomics identified PDK4 as upregulated by CaOx stones, and in vitro/in vivo CaOx models (calcium oxalate monohydrate and glyoxylic acid induction) showed that PDK4 inhibition disrupted lactate/lactylation-driven EMT and mitochondrial dysfunction through the TGF-β/SMAD3/GPX4 pathway. This links a metabolic-epigenetic lactate/lactylation mechanism to CaOx stone pathogenesis and highlights PDK4 and the downstream signaling axis as potential therapeutic targets.

Zhang B, Liu K, Fan R et al. · Cellular signalling · (2026) · View on PubMed ↗

Cannabidiol induces apoptosis and autophagy via STAT3 and NF-κB inhibition and synergistically enhances paclitaxel efficacy in non-small cell lung cancer.

This experimental study investigated cannabidiol (CBD) in non-small cell lung cancer (NSCLC) models, focusing on how CBD affects STAT3 and NF-κB signaling to regulate apoptosis and autophagy and whether it enhances paclitaxel efficacy. The key finding was that CBD inhibited STAT3 and NF-κB activation, inducing apoptosis and autophagy, and that CBD synergistically improved paclitaxel antitumor effects in vivo. Clinically, this suggests CBD could function as a chemosensitizer by simultaneously suppressing pro-survival pathways in NSCLC.

Kim NY, Jung YY, Yang MH et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

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Cell death, dormancy & treatment resistance

ESR1 mutations and CDK4/6 inhibitor choice shape clonal selection and adaptive cell states during acquired resistance.

This study investigated how ESR1 mutations influence clonal selection and adaptive cell states during acquired resistance to CDK4/6 inhibitors in estrogen receptor-positive (ER+) breast cancer, using experimental approaches to track clonal dynamics under CDK4/6 inhibitor pressure. The key finding was that ESR1 mutation status and the specific choice of CDK4/6 inhibitor shape which resistant clones emerge and what adaptive phenotypes they adopt. This is significant because it suggests that resistance mechanisms are not uniform and that selecting a CDK4/6 inhibitor may be tailored to ESR1-driven evolutionary trajectories in metastatic ER+ breast cancer.

Guarducci C, Abravanel D, Russo D et al. · Genome medicine · (2026) · View on PubMed ↗ · Free PDF ↗

HES1 inhibition overcomes CDK4/6 inhibitor resistance by targeting cancer stemness in lung adenocarcinoma.

The study investigated how inhibiting HES1 can overcome CDK4/6 inhibitor resistance by targeting cancer stemness in lung adenocarcinoma. Using patient-derived organoids and cell lines, it tested resistance mechanisms tied to stemness pathways and performed in vitro/in vivo assays plus small-molecule library screening to identify HES1 inhibition as a sensitizing strategy. This is significant because it suggests a stemness-directed combination approach to improve responses to CDK4/6 inhibitors in resistant lung adenocarcinoma.

Cheung AHK, Wong KY, Li GY et al. · Journal of experimental & clinical cancer research : CR · (2026) · View on PubMed ↗ · Free PDF ↗

From paradox to target: IFN-β hijacks MEK signaling to drive a cell death-evading dormant phenotype in colorectal cancer.

This study investigated how interferon-β (IFN-β) drives a dormant, cell death–evading phenotype in colorectal cancer (COAD) and defined the signaling pathway involved using single-cell–derived dormancy scoring and mechanistic pathway analyses. It found that the IFN-β/cDC1 axis promotes dormancy through downstream MEK/ERK signaling, creating a quiescent reservoir associated with treatment resistance. Targeting the IFN-β/cDC1→MEK/ERK pathway could help eradicate dormant residual CRC cells and reduce recurrence.

Zhou Y, Geng H, Xu Y et al. · Journal of experimental & clinical cancer research : CR · (2026) · View on PubMed ↗ · Free PDF ↗

KLF15 activates PGC1α to rewire mitochondrial homeostasis and overcome cisplatin resistance in lung adenocarcinoma.

The study investigated how the transcription factor KLF15 regulates mitochondrial homeostasis to overcome cisplatin resistance in lung adenocarcinoma (LUAD) cells and in vivo tumor models. KLF15 was downregulated in cisplatin-resistant LUAD, and restoring KLF15 resensitized tumors to cisplatin by directly transactivating PGC1α, with PGC1α loss abrogating KLF15-mediated cisplatin sensitization. This mechanistic KLF15→PGC1α axis identifies a potential therapeutic target to reverse cisplatin resistance in LUAD.

Lin W, Li L, Bai Y et al. · Cell death discovery · (2026) · View on PubMed ↗ · Free PDF ↗

Hsa_circ_0003258 drives serine biosynthesis and docetaxel resistance in prostate cancer by enhancing IGF2BP3-mediated PSAT1 mRNA stability.

This mechanistic study investigated how the circular RNA hsa_circ_0003258 contributes to docetaxel (DTX) resistance in prostate cancer and focused on its regulation of serine biosynthesis via IGF2BP3-mediated PSAT1 mRNA stability. It reports that hsa_circ_0003258 is elevated in DTX-resistant prostate cancer patients and that functional experiments show it enhances DTX resistance through the IGF2BP3–PSAT1 axis. These findings identify hsa_circ_0003258 and the IGF2BP3/PSAT1 pathway as potential targets to overcome DTX resistance in advanced prostate cancer.

Ge S, Liu X, Zeng X et al. · Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · (2026) · View on PubMed ↗ · Free PDF ↗

HSP90α-USP7-DNMT1 Axis Drives Hepatocellular Carcinoma Recurrence After Microwave Ablation by Disrupting ACSS3-Mediated Propionate Metabolism.

This study examined how the HSP90α–USP7 axis drives hepatocellular carcinoma (HCC) recurrence after insufficient microwave ablation (iMWA) by disrupting ACSS3-mediated propionate metabolism and activating epigenetic machinery. The authors reported that sublethal heat stress after iMWA stabilizes and upregulates DNA methyltransferase DNMT1 via HSP90α collaboration with the deubiquitinase USP7, increasing DNA methylation and promoting growth and invasiveness of residual HCC cells. Scientifically, it links heat-responsive stress signaling to DNMT1-dependent epigenetic reprogramming, suggesting actionable targets to prevent post-ablation recurrence.

Chen Y, Bei J, Huang X et al. · Molecular therapy : the journal of the American Society of Gene Therapy · (2026) · View on PubMed ↗

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Cancer immunotherapy & immune evasion

Splenic macrophage-B cell axis drives systemic autoimmune-like pathology in Cerebral Malaria.

The study examined how the splenic macrophage–B cell axis drives systemic autoimmune-like pathology in cerebral malaria using patient samples from Plasmodium falciparum infection and mechanistic analyses. Proteomics identified CD36 as a dominant host-derived antigen enriched in infected red blood cells, leading to anti-CD36 autoantibody production in patients that contributes to iRBC clearance but also targets other CD36-expressing cells, causing thrombocytopenia, endothelial injury, macrophage activation, and amplified systemic inflammation. These findings implicate CD36 autoantibodies as a mechanistic driver of cerebral malaria severity and a potential target for intervention.

Sun X, Li R, Wang W et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Allogeneic Hematopoietic Cell Transplant Following Standard of Care Brexucabtagene Autoleucel (Brexu-cel) in Adults with B-Cell Acute Lymphoblastic Leukemia (B-ALL): Results from the Real-World Outcomes Collaborative of CAR T in Adult ALL (ROCCA).

This retrospective multicenter ROCCA real-world analysis studied adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) who received consolidative allogeneic hematopoietic cell transplant (alloHCT) after commercial brexucabtagene autoleucel (brexu-cel), an autologous anti-CD19 CAR T therapy. The key finding was that alloHCT following brexu-cel was associated with outcomes relevant to durability of response in a population where most patients relapse after brexu-cel alone. Scientifically and clinically, the study informs strategies to improve long-term disease control after anti-CD19 CAR T by evaluating the role of post–CAR T alloHCT in real-world practice.

Faramand RG, Zhang A, Roloff GW et al. · Transplantation and cellular therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Infections within 100 days of idecabtagene vicleucel and impact on survival for relapsed/refractory multiple myeloma: A CIBMTR Analysis.

This CIBMTR real-world analysis studied infections occurring within 100 days of idecabtagene vicleucel (ide-cel), a BCMA-directed CAR T therapy, and their impact on survival in 807 patients with relapsed/refractory multiple myeloma (RRMM) after at least four prior lines of therapy. The key finding was that infection burden and specific infection patterns after ide-cel were clinically associated with survival outcomes, highlighting infections as a major determinant of morbidity and mortality in this setting. These results emphasize the need for infection risk stratification and proactive management tailored to BCMA CAR T recipients.

Wudhikarn K, Gowda L, Ye Q et al. · Transplantation and cellular therapy · (2026) · View on PubMed ↗

Pan-cancer analysis identifies immunoproteasome as the predominant survival-associated component of antigen processing machinery.

This pan-cancer computational and translational study analyzed antigen processing machinery (APM) genes and neoantigen burden across 43,980 patients from 14 cancer types to determine which components predict survival. The key finding was that immunoproteasome—rather than other APM components—was the predominant survival-associated element, and machine-learning–selected immunoproteasome-related genes were validated using the IMvigor210 immunotherapy trial dataset (n=348). Clinically, it supports immunoproteasome expression as a prognostic biomarker and potential target to refine immunotherapy stratification.

Lai JI, Liu CY, Tsai YF et al. · Translational oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting WDR12 Unleashes T-Cell-Mediated Antitumor Activity in Melanoma by Destabilizing CD276.

This study examined how WDR12 contributes to melanoma immunotherapy resistance by regulating the stability of the immune checkpoint CD276 (B7-H3), and tested whether targeting WDR12 enhances T-cell antitumor activity. Genetic inhibition of WDR12 increased intratumoral CD8+ T-cell infiltration and cytotoxic function, and mechanistically WDR12 (with CCT7) stabilized CD276 on tumor cells to suppress T-cell activity and promote immune escape. These findings identify the WDR12–CCT7–CD276 stabilization axis as a therapeutic target to potentially overcome resistance to immune checkpoint blockade in melanoma.

Pan J, Chang R, Zhang M et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Injectable Thermosensitive Hydrogel Targeting STAT3 Reprograms Neutrophils to Amplify Anti-Tumor Immunity Post-Radiofrequency Ablation in HCC.

This study investigated whether an injectable thermosensitive hydrogel delivering icaritin (ICT) could reprogram tumor-associated neutrophils (TANs) via the JAK2/STAT3 pathway after radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC). Incomplete RFA activated JAK2/STAT3 in TANs, while ICT inhibited TAN survival and migration and reversed immunosuppressive phenotypes by suppressing STAT3 phosphorylation; the hydrogel (HP@ICT) enabled localized delivery. The work suggests a post-RFA immunomodulatory strategy to amplify anti-tumor immunity and reduce recurrence driven by an immunosuppressive tumor microenvironment.

Chen H, Zhang S, Yang D et al. · Advanced healthcare materials · (2026) · View on PubMed ↗

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Targeted cancer therapies & drug development

[The role of obesity and weight reduction in obstructive sleep apnea].

This article reviewed the role of obesity and weight reduction in obstructive sleep apnea (OSA) and discussed how weight loss improves OSA severity (e.g., apnea–hypopnea index) and cardiometabolic risk. It highlights that integrated care models are often lacking and that incretin-based therapies—especially GLP-1 receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) approaches—may support weight reduction in OSA management. The clinical significance is that pharmacologic weight-loss strategies could complement or enhance standard OSA therapies such as positive airway pressure (PAP) by addressing a central driver (excess adiposity).

Horváth G, Berner SC, Bardóczi AB et al. · Orvosi hetilap · (2026) · View on PubMed ↗

The role of the WD40-repeat protein family in cancer.

This article reviewed the WD40-repeat (WDR) protein family, focusing on how their β-propeller structural scaffolds regulate oncogenic processes across cancer contexts. It highlights that cancer biology lacks an integrated framework linking WDR structural logic to context-dependent mechanisms and to actionable biomarkers/therapeutic strategies. The synthesis is significant for guiding future WDR-targeted biomarker discovery and drug development in cancer.

Li J, Zhou H, Luo Q et al. · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Vibecotamab for measurable residual disease in acute myeloid leukemia and for myelodysplastic syndromes and chronic myelomonocytic leukemia after hypomethylating agent failure: a phase II study.

This phase II clinical study evaluated vibecotamab, a CD123×CD3 bispecific antibody, in patients with acute myeloid leukemia (AML) with detectable measurable residual disease (MRD) and in those with MDS/CMML after hypomethylating agent failure. The trial assessed efficacy of vibecotamab-mediated elimination of CD123-positive malignant cells by engaging CD3+ T cells in these post–hypomethylating agent populations. If effective, vibecotamab could provide a targeted option for MRD-positive AML and for limited-treatment MDS/CMML settings after hypomethylating agent failure.

Short NJ, Bataller A, DiNardo CD et al. · Journal of hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Sperm surface protein disulfide isomerase ERp57 is crucial for mammalian fertilization but functions independently of IZUMO1.

This study tested the requirement for the sperm surface protein disulfide isomerase ERp57 (PDIA3) in mammalian fertilization using in vitro fertilization experiments in mice and humans with ERp57 inhibitors, and assessed its relationship to IZUMO1-mediated sperm–oocyte fusion. It found that ERp57 is crucial for fertilization but functions independently of IZUMO1, arguing against a model where ERp57 triggers IZUMO1 dimerization. Clinically, defining ERp57’s distinct role refines the molecular mechanism of fertilization and may inform non-hormonal contraceptive or infertility interventions targeting sperm–oocyte fusion.

Forster E, Dupuis S, Ialy-Radio C et al. · Cellular & molecular biology letters · (2026) · View on PubMed ↗ · Free PDF ↗

Covalent pan-TEAD inhibitors block YAP activity and demonstrate brain penetrance in a Hippo-dependent cancer model.

Covalent pan-TEAD inhibitors were developed and tested in a Hippo-dependent, YAP-driven cancer model, focusing on brain penetrance and pathway effects. The covalent inhibitors GNE-8025 and the brain-penetrant derivative GNE-2181 bound the TEAD lipid pocket at a conserved cysteine, inhibited YAP activity, and suppressed tumor growth in vitro and in vivo. This provides a therapeutic strategy for TEAD/YAP-driven cancers and suggests combination potential with MAPK pathway inhibitors and the KRASG12C inhibitor divarasib.

Hagenbeek TJ, Zbieg J, Smith R et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Bispecific antibody engineered extracellular vesicles redirect T cells to prevent postoperative epidural fibrosis.

The study engineered bispecific antibody-decorated extracellular vesicles (BsAb EVs) to redirect T cells against FAP+ fibroblasts and tested their efficacy in preventing postoperative epidural fibrosis in a preclinical model. BsAb EVs selectively eliminated pathogenic FAP+ fibroblasts, reduced fibrotic collagen accumulation, and prevented postoperative epidural fibrosis without detectable systemic toxicity under the tested conditions. This suggests a targeted, cell-redirecting EV platform as a potential therapeutic strategy to prevent debilitating postoperative fibrosis.

Ye S, Xu Q, Xu Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Precision targeting of CLDN18.2: A new therapeutic paradigm for gastric cancer.

This review studied CLDN18.2 as a therapeutic target in gastric cancer and summarized clinical development of CLDN18.2-directed biologics and related modalities in patients with HER2-negative, CLDN18.2-positive gastric adenocarcinoma. It reports that zolbetuximab, a CLDN18.2-targeted monoclonal antibody, is approved in combination with chemotherapy as a first-line option and highlights emerging next-generation antibodies, antibody-drug conjugates, and bispecific antibodies plus combination strategies. These advances support a precision-targeting paradigm for improving outcomes in CLDN18.2-positive gastric cancer through better therapeutic matching and expanded CLDN18.2 drug formats.

Zhou W, Mei W, Zeng C · Cancer treatment reviews · (2026) · View on PubMed ↗

Cell-penetrating asymmetric siRNA targeting MyD88 suppresses inflammasome-driven ocular degeneration and angiogenesis.

This study developed OLX10212, a chemically optimized palmitoyl-conjugated cell-penetrating asymmetric siRNA (cp-asiRNA), to silence MyD88 and evaluated its effects on inflammasome-driven ocular degeneration and angiogenesis. After intravitreal administration, OLX10212 achieved broad retinal distribution and sustained MyD88 knockdown, reducing inflammatory/inflammasome signaling that contributes to retinal degeneration and pathological angiogenesis in models relevant to age-related macular degeneration (AMD) and dry eye disease (DED). The findings support cp-asiRNA targeting of MyD88 as a non-vehicle-dependent gene-silencing strategy for treating chronic ocular inflammatory disease.

Kim J, Min S, Yum M et al. · Molecular therapy : the journal of the American Society of Gene Therapy · (2026) · View on PubMed ↗

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Biomarkers, risk prediction & clinical stratification

Explainable machine learning models predict liver fibrosis risk and outcome in the general population: Development and multi-cohort external validation.

This study developed and externally validated explainable machine learning models to predict significant liver fibrosis risk and outcomes in 9,424 European participants from the UK Biobank using demographic, anthropometric, and clinical variables, with high-risk defined by FIB-4 ≥ 1.45 or NAFLD Fibrosis Score (NFS) ≥ −1.455. It found that an interpretable framework—particularly XGBoost—performed robustly with multi-cohort external validation (2017–2023 National Health and …), enabling population-level pre-screening of high-risk individuals. This is significant because it provides a scalable, explainable tool to identify silent fibrosis earlier and potentially improve downstream clinical management.

Zhu G, Yi Q, Xu R et al. · Computer methods and programs in biomedicine · (2026) · View on PubMed ↗

Integrating lipometabolic and adiposity indices to enhance risk stratification for metabolic dysfunction-associated steatotic liver disease in type 2 diabetes: clinical utility and interplay between triglyceride-glucose body mass index and low-density lipoprotein cholesterol.

The study aimed to improve risk stratification for metabolic dysfunction-associated steatotic liver disease (MASLD) in T2DM by integrating lipometabolic and adiposity indices, using TyG-BMI and related measures. In 449 T2DM patients from the WMU cohort (discovery) and 306 from the Japanese NAGALA cohort (external validation), feature selection (Boruta and LASSO) identified a parsimonious two-variable signature and prioritized TyG-BMI for a parsimonious risk model. This work is significant because it provides a data-driven, clinically usable risk model linking triglyceride–glucose–based and adiposity metrics to MASLD risk across populations.

Yang Y, Qu X, Shi M et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Inferring genetic associations of programmed cell death genes with retinitis pigmentosa through multimodal Mendelian randomization.

This study used multimodal Mendelian randomization to infer causal genetic associations between programmed cell death (PCD) genes and retinitis pigmentosa (RP) using summary-level GWAS plus eQTL/pQTL and transcriptomic datasets. It applied two-sample MR with complementary summary-data-based MR (SMR) to identify PCD-related genes likely contributing to RP risk. The approach prioritizes PCD genes as candidate therapeutic targets and helps clarify RP pathogenesis using genetic evidence.

Guo N, Peng GH · Molecular medicine (Cambridge, Mass.) · (2026) · View on PubMed ↗ · Free PDF ↗

MRI-based quantification of intratumoral heterogeneity for predicting recurrence risk in ER+/HER2- breast cancer.

This retrospective study developed an MRI-based intratumoral heterogeneity score (ITHscore) to predict recurrence risk in ER+/HER2− breast cancer and compared its performance against the 21-gene recurrence score (RS). Using preoperative MRI data from ER+/HER2− patients who also had 21-gene assays (with training/internal test cohorts and an external test cohort from the Duke-Breast-Cancer-MRI dataset), it integrated the ITHscore with radiomic and clinical features to estimate recurrence risk. The work suggests a more accessible, MRI-driven alternative to the 21-gene assay for stratifying recurrence risk in this breast cancer subtype.

Chen Y, Shi J, Chen J et al. · Insights into imaging · (2026) · View on PubMed ↗ · Free PDF ↗

Pretreatment serum vitamin D levels predict the therapeutic efficacy of atezolizumab plus bevacizumab therapy in advanced hepatocellular carcinoma: a multicenter analysis.

In 142 patients with advanced hepatocellular carcinoma treated first-line with atezolizumab plus bevacizumab (ATZ/BEV), baseline serum 25-hydroxyvitamin D levels were measured and correlated with dynamic CT/MRI response and prognosis. Pretreatment vitamin D levels predicted therapeutic efficacy and clinical outcomes, indicating that higher or more favorable vitamin D status was associated with better response/prognosis. This suggests vitamin D stratification could help personalize ATZ/BEV therapy in advanced HCC and motivates prospective trials of vitamin D optimization.

Suzuki T, Matsuura K, Narahara S et al. · International journal of clinical oncology · (2026) · View on PubMed ↗

Limited predictive value of PD-L1 TPS for pathological response in NSCLC is not attributable to interobserver variability.

This study evaluated whether PD-L1 tumor proportion score (TPS) predicts pathological response in neoadjuvant chemoimmunotherapy-treated non-small cell lung cancer (NSCLC) and assessed this across 30 digitized cases from the ReGraDE study with independent PD-L1 TPS scoring by 30 pathologists in 11 countries. It found that the limited predictive value of PD-L1 TPS for residual viable tumor (RVT) was not attributable to interobserver variability, despite formal assessment of agreement using intraclass correlation coefficients and Fleiss’ kappa. Clinically, this suggests PD-L1 TPS—measured on pre-treatment biopsies—may be insufficient for predicting pathological response in the neoadjuvant setting, motivating alternative biomarkers or improved predictive assays.

Steinestel K, Löwer-Kiem LM, Ambrosi F et al. · Lung cancer (Amsterdam, Netherlands) · (2026) · View on PubMed ↗ · Free PDF ↗

Correlation of vitamin D and diabetic peripheral neuropathic pain: A cross-sectional study.

This cross-sectional study measured serum 25(OH)D in 46 adults with type 2 diabetes stratified into painless diabetic peripheral neuropathy (n=15), painful diabetic peripheral neuropathy (n=16), and non-neuropathy (n=15), plus 15 healthy controls, using neurologic exams, Michigan Neuropathy Screening Instrument, electrophysiology, and skin biopsy. Serum 25(OH)D was significantly lower in patients with painful diabetic peripheral neuropathy than in those without painful neuropathy (and compared with controls). These findings support vitamin D deficiency as a potential biomarker and modifiable risk factor specifically linked to painful diabetic peripheral neuropathy rather than neuropathy in general.

Yao C, Wang L, Zhang H et al. · The Journal of international medical research · (2026) · View on PubMed ↗ · Free PDF ↗

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Organoids & personalized preclinical models

Patient-derived organoids in gynaecological cancers: emerging tools for therapy and disease modelling.

This review article assessed how patient-derived organoids (PDOs) are being used to model and test therapies for gynecological cancers and related disorders such as endometriosis and adenomyosis. It highlighted that PDOs recapitulate key molecular and histological features of patient tumors/endometrium and can be used to study hormone responsiveness and chemoresistance while enabling more physiologically relevant drug testing. The synthesis positions PDO technology as an emerging platform for disease modeling and potentially more personalized treatment strategies in women’s health.

Vigneshwaran N, Thangam T, Parthasarathy K et al. · Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · (2026) · View on PubMed ↗

Patient-derived organoids as a predictive platform for drug sensitivity in bladder cancer.

Patient-derived organoids (PDOs) were generated from 31 clinical bladder cancer specimens to predict drug sensitivity and recapitulate tumor biology. The PDOs maintained stable growth, preserved morphological subtypes, and retained key molecular features of the parental tumors, including a hybrid basal-luminal phenotype with elevated CD44, GATA3, and LGR5. This establishes PDOs as a personalized preclinical platform for testing therapies in heterogeneous bladder cancer.

Hekmatirad S, Gholizadeh F, Montazeri S et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

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Microbiome, gut-immune and immunometabolism

5-methoxytryptamine improves hepatic inflammation and insulin resistance in a macrophage C-X-C motif chemokine ligand 14 dependent manner.

This study investigated whether the tryptophan metabolite 5-methoxytryptamine (5MT) improves hepatic inflammation and insulin resistance in high-fat diet (HFD) and db/db mice, focusing on a macrophage C-X-C motif chemokine ligand 14 (CXCL14)–dependent mechanism. It found that 5MT treatment ameliorated insulin resistance and hepatic steatosis and that these effects required CXCL14 signaling in macrophage-dependent pathways. This is significant because it connects a specific metabolite (5MT) and immune chemokine axis (CXCL14) to metabolic inflammation, suggesting a potential therapeutic target for insulin resistance and fatty liver.

Liao X, Xiao Y, Liu B et al. · Molecular biomedicine · (2026) · View on PubMed ↗ · Free PDF ↗

Csf1r-mediated depletion of myeloid cells prevents dopaminergic neuron loss during chronic colitis.

The study examined whether Csf1r-mediated depletion of myeloid cells prevents dopaminergic neuron loss and synuclein pathology in adult mice with chronic colitis. Using confocal microscopy and integrated multi-omics with single-cell mapping of the midbrain immune response, it found that removing Csf1r-dependent myeloid cells protected substantia nigra pars compacta dopaminergic neurons during colitis. These findings support a mechanistic gut-immune-brain link in Parkinson’s disease–relevant pathology and identify Csf1r+ myeloid cells as a potential therapeutic target.

Kutscherauer RK, Andert M, Stolzer I et al. · Journal of neuroinflammation · (2026) · View on PubMed ↗ · Free PDF ↗

An oral berberine nanocapsule platform orchestrates microbiota for potent gastric cancer chemotherapy.

The study developed an oral berberine nanocapsule platform (ORBIT; excipient-free, self-assembled nanocapsules designed for prolonged gut residency) to orchestrate the gut microbiota for gastric cancer chemotherapy. By leveraging resident binary intestinal therapy, it aimed to overcome pharmacokinetic limitations of berberine and enhance antitumor efficacy while reducing dose-dependent systemic toxicities. This platform is significant as a microbiota-targeting oral nanomedicine strategy that could improve the therapeutic index of gastric cancer chemotherapy.

Gong S, Zhang Y, Du W et al. · Journal of nanobiotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

Intermittent fasting ameliorates Sjögren’s syndrome-related dry eye through a preponderant bile acid-Akkermansia homeostasis establishment.

This preclinical study investigated whether intermittent fasting (IF) improves Sjögren’s syndrome (SS)-related dry eye in SS mice and examined gut–immune–lacrimal gland mechanisms using 16S rRNA sequencing, fecal metabolomics, and transcriptomic profiling (single-cell and bulk) with flow cytometry. It found that IF improved tear secretion and corneal integrity, reshaped the gut ecosystem with Akkermansia muciniphila and bile acids as key responders, and that oral supplementation with Akkermansia muciniphila or ursodeoxycholic acid recapitulated IF’s therapeutic effects. These findings support an immunometabolic mechanism linking bile acid–Akkermansia homeostasis to lacrimal gland immune remodeling, suggesting potential adjunctive strategies for SS dry eye.

Wang B, Deng W, Liao K et al. · Journal of autoimmunity · (2026) · View on PubMed ↗

Peptidoglycan from Lactiplantibacillus plantarum YC Alleviates Hyperuricemia via the “Microbiota-Gut-Kidney” Axis: Structural Characterization and Metabolic Regulation.

This study characterized peptidoglycan (PGN) from Lactiplantibacillus plantarum YC (as an A1γ-type chemotype) using amino acid analysis, FTIR, NMR, and MALDI-TOF MS, and tested its effects in hyperuricemia (HUA) mice. Oral PGN significantly lowered serum uric acid and kidney injury markers (creatinine, blood urea nitrogen) and mechanistically inhibited hepatic xanthine oxidase while remodeling renal urate transport by upregulating ABC transporter expression. These results suggest a probiotic-derived, structurally defined component that could offer a safer metabolic intervention for hyperuricemia via gut–kidney axis modulation.

Liu Y, Zhang Y, Zheng J et al. · Journal of agricultural and food chemistry · (2026) · View on PubMed ↗

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Neurodegeneration & protein aggregation/clearance

Lysophagy protects against ANXA11 amyloid fibril toxicity and propagation in FTLD.

This study examined whether lysophagy can protect against Annexin A11 (ANXA11) amyloid fibril toxicity and propagation in frontotemporal lobar degeneration (FTLD), using pre-formed fibrils (PFFs) of wild-type and FTLD/ALS-linked ANXA11 D40G and human iPSC-derived neurons. The key finding was that lysophagy preserves lysosomal integrity and reduces ANXA11 proteinopathy-related toxicity and spread. This is significant because it identifies lysophagy/lysosomal maintenance as a potential therapeutic checkpoint to slow disease progression in ANXA11-driven neurodegeneration.

Zheng H, Luo H, Lu Y et al. · Translational neurodegeneration · (2026) · View on PubMed ↗ · Free PDF ↗

Chlorogenic acid attenuates skin senescence and UVR-induced photoaging via the modulation of mitochondrial function.

The study tested chlorogenic acid (CGA) in normal human dermal fibroblasts and human epidermal keratinocytes to determine whether CGA attenuates skin senescence and UVR-induced photoaging through mitochondrial function modulation. CGA improved mitochondrial function and reduced senescence/photoaging phenotypes, including effects on collagen I production. This mechanistic evidence supports CGA as a candidate anti-aging intervention targeting mitochondrial pathways relevant to UV-induced skin damage.

Li R, Hu C, Zhou P et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

A new paradigm in Parkinson’s disease: kidney-origin α-synuclein pathology driven by PKC signaling and aurothioglucose.

This article proposed a kidney-origin α-synuclein pathology paradigm in Parkinson’s disease (PD) driven by protein kinase C (PKC) signaling and discussed the role of aurothioglucose (a gold compound) in this context. It argues that PKC can promote α-syn accumulation in kidney cells via mechanisms including direct phosphorylation that enhances aggregation, impaired autophagy–lysosome clearance, and increased oxidative stress and inflammation. If supported experimentally, this framework could shift PD biomarker and therapeutic focus toward peripheral (renal) α-synuclein pathways and PKC-targeted interventions.

Vashisht K, Sharma V, Ashawat MS et al. · Inflammopharmacology · (2026) · View on PubMed ↗

From Mechanisms to Therapy: Targeting the Gut-Brain Axis in Chronic Gastrointestinal Pain.

This review synthesized current evidence on mechanisms and therapeutic approaches for chronic gastrointestinal pain (CGP) within disorders of gut-brain interaction (DGBI), emphasizing gut-brain axis (GBA) dysfunction. It highlighted roles for microbial dysbiosis, mucosal immune activation, and neuroendocrine disturbances in peripheral and central nociceptive sensitization, and it surveyed interventions including cognitive/behavioral therapies and pharmacological neuromodulation. The significance is to guide development of more effective, mechanism-based treatments for CGP by targeting specific GBA dysfunction pathways.

Chen X, Tan B, Shao G et al. · Pharmacological research · (2026) · View on PubMed ↗ · Free PDF ↗

RNA G-quadruplexes function as a tunable switch of FUS phase separation.

This study examined how RNA G-quadruplexes (rG4s) modulate liquid-liquid phase separation of the FUS protein. The authors found that rG4 activity is tunable and depends on rG4 concentration, length, and stability, where increasing repeat number can switch rG4s from inhibiting to nucleating FUS assembly, and stabilizing chemical modifications enhance inhibitory function. These results are clinically relevant for understanding how specific RNA structures can regulate FUS phase behavior, informing strategies to mitigate toxic aggregation in neurodegenerative disease.

Carey JL, Hayashi M, Welebob E et al. · Nucleic acids research · (2026) · View on PubMed ↗

Elimination of tau tangles and soluble aggregates with the small molecule ACI-16664 prevents neurodegeneration in vivo.

This in vivo study tested the orally available brain-penetrant small molecule ACI-16664, a tau aggregation inhibitor, for its ability to eliminate pathological tau tangles and soluble tau aggregates in the Tg4510 tauopathy mouse model. ACI-16664 selectively bound aggregated tau, destabilized β-sheet structures, and blocked intracellular seeding, thereby preventing neurodegeneration in vivo. These results support ACI-16664 as a potentially more druggable, noninvasive therapeutic strategy targeting aggregated tau in Alzheimer’s disease.

Preitner N, Dehlinger V, Rodriguez P et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗

FMRP-Mediated Proteasome Regulation: A Novel Mechanism in ALS Pathology.

This mechanistic study explored how Fragile X Mental Retardation Protein (FMRP) regulates proteasome activity in amyotrophic lateral sclerosis (ALS) pathology, focusing on the Tankyrase (TNKS)/PI31 proteasome activation axis. The authors found that FMRP depletion promoted nuclear translocation of TDP-43, reduced cytoplasmic TNKS/TDP-43 co-localization, and released TNKS to associate with the cytoplasmic proteasome activation machinery. These findings identify a novel FMRP-mediated mechanism that links TDP-43 aggregation biology to proteasome regulation, offering new targets for ALS therapeutic development.

Majumder P, Ahsan A, Bubphachat P et al. · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · (2026) · View on PubMed ↗

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Neuronal development, synaptic/circuit remodeling & neurobiology

NDR kinase SAX-1 controls dendrite branch-specific elimination during neuronal remodeling in C. elegans.

The serine/threonine kinase SAX-1 (NDR kinase) was studied in C. elegans IL2 sensory neurons to define genetic requirements for dendrite branch-specific pruning during neuronal remodeling. SAX-1/NDR kinase activity controlled elimination of specific dendrite branches (secondary, tertiary, and quaternary) with distinct genetic dependencies across branch types during the diapause-to-reproductive transition. This clarifies how NDR kinases specify pruning topology, advancing mechanistic understanding of developmental circuit remodeling.

Figueroa-Delgado PV, Yogev S · The EMBO journal · (2026) · View on PubMed ↗ · Free PDF ↗

NMDAR-antibody encephalitis: Seizure semiology and EEG findings.

This retrospective study examined seizure semiology and electroencephalogram (EEG) findings in 14 adults with a first episode of N-methyl-D-aspartate receptor antibody encephalitis (NMDAR-Ab-E). Most patients were women (85.7%) with seizures in 85.7% of cases, and the authors characterized the acute seizure patterns alongside EEG features. Clinically, defining seizure semiology and EEG signatures in early NMDAR-Ab-E can support faster recognition and more targeted acute management.

Andraus MEC, Liem B, Aurangzeb S et al. · Epileptic disorders : international epilepsy journal with videotape · (2026) · View on PubMed ↗ · Free PDF ↗

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Infectious disease, vaccines & immune responses

Comparative efficacy and safety of oral ivermectin, topical permethrin, and combination in the treatment of patients with classic scabies: systematic review and network meta-analysis.

This systematic review and network meta-analysis compared oral ivermectin, topical permethrin, and their combination for classic scabies, synthesizing randomized controlled trial evidence on efficacy and safety. The key finding was a comparative ranking of these regimens’ effectiveness and tolerability to guide clinical and policy decisions for patients with classic scabies, particularly where adherence or treatment failure affects topical therapy. This is significant because it provides evidence-based guidance on selecting the most effective and safest treatment strategy for classic scabies.

Genuino RF, Batac MCFR, Yacapin CPRC et al. · BMC pharmacology & toxicology · (2026) · View on PubMed ↗ · Free PDF ↗

Intranasal boosting induces variant-specific responses in SARS-CoV-2 vaccine-imprinted mice.

The study evaluated strategies to enhance variant-specific antibody responses in female mice primed with Wuhan-1 spike mRNA or chimpanzee adenoviral-vectored (ChAd) vaccines and boosted with Omicron-matched vaccines, testing factors such as intramuscular injection site and booster antigen dose. Increasing booster antigen doses and using repeated boosters (intramuscular boosting strategy) induced stronger variant-specific serum antibody responses than lower-dose or single-boost approaches, whereas changing the injection site had little effect. These findings support booster-design principles for overcoming immune imprinting and improving variant-matched humoral immunity against emerging SARS-CoV-2 variants.

Liang CY, Scheaffer SM, Case JB et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

A prematurely terminated phase 2, randomised trial to evaluate immunogenicity and reactogenicity of a single versus two-dose primary vaccination regimen of the mRNA vaccine BNT162b2 in previously SARS-CoV-2 infected children 5-11 years old (CoVacc trial).

This randomized phase 2 trial studied immunogenicity and reactogenicity of a single versus two-dose primary regimen of the mRNA vaccine BNT162b2 in previously SARS-CoV-2-infected children aged 5–11 years (CoVacc trial). It was designed to test non-inferiority for neutralizing antibodies against wild-type SARS-CoV-2 at 28 days post-vaccination (with a prespecified non-inferiority margin) and to compare safety and reactogenicity between regimens. If results support the design endpoints, the trial could inform dosing strategies to optimize immune protection while minimizing adverse events in previously infected pediatric populations.

Prat-Aymerich C, Yeghiazaryan L, Pathirana RD et al. · Vaccine · (2026) · View on PubMed ↗ · Free PDF ↗

Early antibiotic exposure and vaccine immune responses in preterm infants: potential sex-specific differences.

This prospective observational study investigated whether early antibiotic exposure in preterm infants (<32 weeks gestational age) alters vaccine immune responses at corrected age four months, with potential sex-specific differences. Blood and stool samples from 69 preterm infants (35 exposed to antibiotics during the first postnatal week and 34 not) were analyzed at postnatal day 14 and again at four months, measuring vaccine-induced antibody titers. The significance lies in clarifying how neonatal antibiotic timing may shape immune maturation in preterm infants, informing risk stratification and vaccine planning in early-life care.

Haag L, Dietz-Ziegler S, Schwarz J et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

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Autoimmunity & inflammatory disease mechanisms

Targeting PHKA2 by Thymol alleviates sepsis induced cardiomyocyte pyroptosis via FOXA1/KLF4-mediated macrophage polarization.

This experimental study tested whether thymol, a natural small molecule, targets PHKA2 to alleviate sepsis-induced cardiomyocyte pyroptosis in a cecal ligation and puncture (CLP) septic mouse model and related macrophage–cardiomyocyte systems. The key finding was that thymol reduced pyroptosis via a FOXA1/KLF4-mediated macrophage polarization mechanism downstream of PHKA2 targeting. This is significant because it links a specific host target (PHKA2) and transcriptional axis (FOXA1/KLF4) to macrophage polarization and cardiomyocyte pyroptosis, suggesting a mechanistic therapeutic route for septic cardiomyopathy.

Zhu H, Han S, Xue C et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

APASL clinical practice guidelines on the management of chronic hepatitis B infection: a 2026 update.

The APASL 2026 update provides clinical practice guideline recommendations for managing chronic hepatitis B infection, addressing prevention, antiviral treatment, and hepatocellular carcinoma surveillance across Asia-Pacific epidemiology. The guideline synthesizes evidence on screening, vaccination, highly effective low-cost antivirals, and monitoring strategies to reduce progression to cirrhosis and acute-on-chronic liver failure. Clinically, it standardizes care pathways for viral elimination efforts and risk-based management of chronic HBV.

You H, Maiwall R, Chen J et al. · Hepatology international · (2026) · View on PubMed ↗ · Free PDF ↗

A bone-marrow-homing biomimetic STING nanoinhibitor alleviates radiation-induced hematopoietic injury via modulating macrophage polarization.

This preclinical study developed a bone-marrow-homing biomimetic STING nanoinhibitor—PLGA nanoparticles loaded with a STING inhibitor and coated with senescent neutrophil membrane—and tested it in models of ionizing radiation-induced hematopoietic stem cell injury. The key finding was that STING pathway inhibition reduced STING-driven pro-inflammatory macrophage (M1) polarization and alleviated radiation-induced hematopoietic damage, with improved delivery to bone marrow via the neutrophil-membrane coating. Scientifically, it supports targeting STING-mediated innate immune signaling and macrophage polarization as a therapeutic strategy for radiation-induced hematopoietic injury.

Li Y, Chen C, Ren Y et al. · Journal of controlled release : official journal of the Controlled Release Society · (2026) · View on PubMed ↗

An integrated approach combining transcriptomics, network pharmacology, and experimental validation are used to investigate the mechanism of Lonicerae Japonicae Flos and Forsythiae Fructus extracts against acute lung injury in chickens.

This study used an integrated approach combining transcriptomics, network pharmacology, and experimental validation to investigate mechanisms of Lonicerae Japonicae Flos and Forsythiae Fructus extracts against acute lung injury (ALI) in chickens. The key finding was identification of molecular targets and pathways implicated in ALI that were modulated by the herbal pair, supported by transcriptomic/network analyses and corroborated by in vivo experimental results. This provides mechanistic rationale for the traditional herbal combination as a potential therapeutic strategy for bacterial infection–associated ALI in poultry.

Guo Z, Wu Q, Han Y et al. · Journal of ethnopharmacology · (2026) · View on PubMed ↗

Long-term remission and monocyclic course in Still’s disease patients starting canakinumab early: data from the international AIDA network registry.

This registry-based international AIDA Network study evaluated whether early initiation of canakinumab in Still’s disease (SD) patients (≤3 months vs >3 months from disease onset) improves long-term outcomes such as sustained remission, glucocorticoid sparing, and a monocyclic disease course. The key finding was that earlier canakinumab treatment was associated with better treatment durability outcomes, including higher likelihood of long-term disease remission and a more monocyclic pattern compared with later initiation. Clinically, this supports starting canakinumab early in SD to reduce chronicity and minimize reliance on glucocorticoids.

Vitale A, Caggiano V, Sbalchiero J et al. · Seminars in arthritis and rheumatism · (2026) · View on PubMed ↗ · Free PDF ↗

Autoantibodies against adenosine deaminase acting on RNA1 (ADAR1) in patients with systemic lupus erythematosus: its relationship to clinical features and other autoantibodies.

This study examined whether autoantibodies against the interferon-inducible RNA-editing enzyme ADAR1 are present in systemic lupus erythematosus (SLE) and how they relate to clinical features and other autoantibodies. Using a newly developed ELISA with specificity confirmation by inhibition testing, it compared serum antibody status across SLE, idiopathic inflammatory myopathy (IIM), and rheumatoid arthritis (RA) and analyzed associations with clinical and serological parameters. Scientifically, it suggests anti-ADAR1 antibodies may define an immunologic subset of SLE with distinct clinical/serologic profiles, potentially informing biomarker development.

Komatsu S, Kurasawa K, Shimizu A et al. · Modern rheumatology · (2026) · View on PubMed ↗

Anti-fibrotic therapy in Crohn’s disease: hype or reality-can intestinal fibrosis be targeted effectively?

This special report studied whether anti-fibrotic therapy in Crohn’s disease is a realistic therapeutic opportunity versus “hype,” focusing on targeting intestinal fibrosis rather than inflammation alone. It summarizes emerging evidence for agents including ontunisertib and preclinical data for anti-TL1A therapies and obefazimod, while contrasting this with the current limitation that licensed therapies do not reliably prevent fibrosis progression or reverse strictures. The clinical significance is that it frames a pipeline for fibrosis-directed interventions that could address the major unmet need of fibrostenotic Crohn’s disease.

Honap S, Dignass A, Jairath V et al. · Expert review of gastroenterology & hepatology · (2026) · View on PubMed ↗

ER stress amplifies inflammation via a dual mechanism involving IκBζ-XBP1s synergism and Regnase-1 degradation.

This study examined how endoplasmic reticulum (ER) stress modulates inflammatory signaling in bone marrow-derived macrophages and sepsis model mice, focusing on the IκBζ–XBP1s axis and Regnase-1. ER stress synergized with TLR signaling to strongly upregulate IκBζ and, via a dual mechanism involving IκBζ–XBP1s synergism and Regnase-1 degradation, amplified IL-6–driving inflammatory responses. These findings identify the IκBζ–XBP1s/Regnase-1 pathway as a mechanistic bridge between ER stress and NF-κB–linked cytokine production, suggesting a potential therapeutic target for inflammatory pathology in sepsis and related diseases.

Nakaminami Y, Ruengsinpinya L, Sakihara R et al. · Journal of immunology (Baltimore, Md. : 1950) · (2026) · View on PubMed ↗

Preclinical development of SL-325, a novel high-affinity DR3-blocking antibody for durable inhibition of the DR3/TL1A axis in inflammatory bowel disease.

This preclinical work developed SL-325, a novel high-affinity DR3 (TNFRSF25)–blocking antibody, to durably inhibit the DR3/TL1A inflammatory axis relevant to inflammatory bowel disease (IBD). SL-325 was designed to achieve durable DR3 blockade given DR3’s constitutive expression on effector lymphoid cells in inflamed and adjacent tissues, aiming to more effectively suppress TL1A-driven proinflammatory signaling than prior anti-TL1A approaches. If translatable, SL-325 could provide a more sustained immunomodulatory strategy for IBD by targeting the receptor rather than the ligand.

Hussain M, Lai AY, Franklin D et al. · Inflammatory bowel diseases · (2026) · View on PubMed ↗

Proteomic analysis in hidradenitis suppurativa reveals systemic inflammation in all disease stages.

This case-control proteomics study analyzed serum samples from 44 patients with hidradenitis suppurativa (HS) and 4 [control group truncated in abstract] to characterize systemic inflammatory profiles across disease stages. The authors reported proteomic evidence of systemic inflammation present in all HS disease stages and assessed associations with disease severity/duration and quality of life. Clinically, it supports HS as a systemic inflammatory disorder throughout its course and suggests circulating protein signatures could help stratify patients and monitor disease activity.

Francke LS, Al-Bayatti A, Zhang H et al. · Journal of the European Academy of Dermatology and Venereology : JEADV · (2026) · View on PubMed ↗ · Free PDF ↗

Inflammation profiles in Alzheimer’s disease relate to cognition and neurodegeneration.

This multicenter cohort study (BioHermes) examined 176 amyloid-positive individuals with Alzheimer’s disease (AD) or mild cognitive impairment (MCI) and 173 matched controls, using principal component analysis on Luminex-measured plasma cytokines. The authors identified two inflammatory components and related these signatures to cognition and neurodegeneration across the AD continuum. The findings are significant because they characterize immune heterogeneity in real-world cohorts, supporting development of stratified immunomodulatory approaches for AD.

Birditt KR, Mavromati K, Swann P et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Addiction in chronic inflammatory skin diseases: A systematic review of prevalence, impact and screening practices.

This systematic review evaluated the prevalence, impact, and screening practices of substance-related and behavioural addictions in adults with chronic inflammatory skin diseases, including alopecia areata, atopic dermatitis, and hidradenitis suppurativa. Across included observational studies, evidence was fragmented by addiction type and dermatologic condition, and the methodological quality of the available data was assessed as variable. The findings highlight a need for more rigorous, standardized screening approaches for addiction-related behaviors in dermatology to improve mental health and treatment outcomes.

Müller E, Ziehfreund S, Saak M et al. · Journal of the European Academy of Dermatology and Venereology : JEADV · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular, cardio-renal & metabolic therapeutics

Lipid Metabolic Disorders: a Pivotal Driver in Type 2 Diabetes Mellitus Pathogenesis.

This review synthesized evidence on how lipid metabolic disorders (e.g., elevated free fatty acids, triglycerides, and LDL-C with reduced HDL-C) contribute to type 2 diabetes mellitus (T2DM) pathogenesis in normoglycemic obese individuals with insulin resistance and in broader mechanistic studies. It reports that dysregulated lipid metabolism is a core causal driver of insulin resistance and T2DM progression, and highlights emerging therapeutic strategies aimed at key nodes in this lipid–glucose pathophysiological cascade. These findings support precision management of T2DM by targeting specific lipid-metabolic mechanisms rather than treating hyperglycemia alone.

Wu J, Wang H, Fu M et al. · Current obesity reports · (2026) · View on PubMed ↗

Biologics for cardiovascular diseases: from bench to bedside.

This review evaluated how biologics—including recombinant proteins, gene therapies, and cell therapies—are being translated to cardiovascular disease (CVD) settings, emphasizing biological processes such as cardiac regeneration, reverse remodeling, genetic cardiomyopathy correction, vascular modulation, and lipid metabolism modulation. The key finding is that biologics are increasingly positioned to modify disease biology rather than only provide symptom control across multiple CVD mechanisms. Clinically, this supports development and selection of next-generation disease-modifying therapies for CVD patients, including strategies that target lipid metabolism pathways.

Sun X, Wang X, Jia R et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗

Comparative cardiovascular efficacy of antidiabetic therapies in type 2 diabetes: a systematic review and network meta-analysis of randomized trials.

This systematic review and network meta-analysis compared cardiovascular efficacy of antidiabetic therapies in adults with type 2 diabetes mellitus (T2DM) using randomized controlled trials. It synthesized evidence across multiple drug classes and combinations to determine relative effects on cardiovascular outcomes. The results are clinically important for selecting glucose-lowering regimens that optimize cardiovascular risk reduction in T2DM.

Mohammadi D, Sadeghirad B, Rasouli MA et al. · Diabetology & metabolic syndrome · (2026) · View on PubMed ↗ · Free PDF ↗

Sex-specific mitochondrial dysregulation and metformin response in Wilson disease.

Sex-specific effects of metformin on hepatic mitochondrial dysfunction were tested in Wilson disease using Atp7b-/- mice treated with metformin (500 mg/kg/day) or vehicle for 2 weeks. Metformin modified mitochondrial abnormalities and redox/ROS-related phenotypes in a sex-dependent manner, revealing different mitochondrial vulnerabilities between male and female WD models. These data support considering sex as a biological variable when evaluating metformin’s mitochondrial and therapeutic effects in Wilson disease.

Medici V, Shibata N, Vorkapich A et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

Finerenone: a next-generation nonsteroidal mineralocorticoid receptor antagonist reshaping the management of cardiovascular and metabolic diseases.

This review studied finerenone, a nonsteroidal mineralocorticoid receptor (MR) antagonist, focusing on its pharmacology and evidence from preclinical and clinical studies in cardiovascular and renal disease populations. Finerenone shows enhanced MR selectivity compared with steroidal MRAs (e.g., spironolactone, eplerenone) and an improved safety profile, particularly regarding hyperkalemia and endocrine adverse effects. These findings support finerenone as a next-generation option to reduce MR-driven inflammation, fibrosis, and oxidative stress in patients with cardiovascular and metabolic diseases.

Zhang H, Li MY, Deng W · Biochemical pharmacology · (2026) · View on PubMed ↗

Frailty and Heart Failure: An Integrated Review of a Bidirectional Relationship.

This integrated review studied the bidirectional relationship between frailty and heart failure (HF) in older adults, synthesizing evidence on epidemiology, shared mechanisms, prognostic impact, assessment methods, and management. It concludes that frailty is common in chronic HF (including high prevalence in HFpEF) and independently predicts incident HF while also being associated with worse outcomes. The clinical significance is that routine frailty assessment and targeted management may improve risk stratification and outcomes across HF phenotypes.

Uchmanowicz I, Vellone E, Lee CS et al. · ESC heart failure · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting Inflammation in Obesity and the Cardiovascular-Kidney-Metabolic (CKM) Syndrome Spectrum: A Narrative Review.

This narrative review studied inflammatory pathways as therapeutic targets across the cardiovascular-kidney-metabolic (CKM) syndrome spectrum in obesity and related cardiometabolic diseases. It summarizes pharmacologic strategies that target inflammation directly and indirectly (via metabolic therapies) across obesity, diabetes, chronic kidney disease, and cardiovascular disease. The significance is that it consolidates rationale for inflammation-focused interventions as potential multi-organ disease-modifying approaches in CKM syndrome.

Noormandi A, Bugger H, Aziz F et al. · Obesity facts · (2026) · View on PubMed ↗ · Free PDF ↗

Testosterone replacement therapy and cardiovascular safety in older men: lessons from TRAVERSE and beyond.

This review synthesized evidence on testosterone replacement therapy (TRT) cardiovascular safety in older men with hypogonadism, emphasizing lessons from the adequately powered placebo-controlled TRAVERSE trial and related data. Overall, it clarifies how to interpret TRAVERSE outcomes and non–major adverse cardiovascular event (non-MACE) safety signals, and discusses practical management differences between organic versus functional hypogonadism. The review is clinically significant because it helps clinicians apply trial evidence to TRT risk–benefit decisions in an older population where prior data were conflicting or underpowered.

Tienforti D, Terrana G, Di Geronimo R et al. · Journal of endocrinological investigation · (2026) · View on PubMed ↗ · Free PDF ↗

Opioid-sparing analgesia with clonidine versus fentanyl in inguinal hernia repair: a randomized clinical trial.

This randomized clinical trial compared opioid-sparing analgesia using clonidine versus fentanyl as an adjuvant in patients undergoing inguinal hernia repair under local anesthesia with sedation (n=138; 69 per group). The study evaluated postoperative pain by visual analog scale (VAS) and secondary outcomes including time to first analgesic request, rescue analgesia, sedation (RASS), adverse events, and medication costs. The results are intended to inform safer, cost-effective perioperative analgesic strategies by determining whether clonidine can reduce opioid requirements without compromising pain control.

de Souza PMF, Morais PC, Santos SF et al. · Hernia : the journal of hernias and abdominal wall surgery · (2026) · View on PubMed ↗

GLP-1 receptor agonists and Risk of Cardiovascular and Pulmonary Complications in patients with OSA and Type 2 Diabetes Mellitus.

This observational study used the TriNetX database to assess whether GLP-1 receptor agonists (including tirzepatide) reduce cardiovascular and pulmonary complications over 5 years in patients with obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM). Patients receiving GLP-1RA were compared with those on other diabetes medications (metformin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylurea, and thiazolidinedione) using propensity score methods to address confounding. The clinical significance is that it evaluates real-world effectiveness of GLP-1RA for preventing cardiopulmonary outcomes in a high-risk OSA+T2DM population.

Borissov Borissov M, Hwang SY, Wickwire EM et al. · Sleep & breathing = Schlaf & Atmung · (2026) · View on PubMed ↗

Cardiovascular-kidney-metabolic syndrome stage modifies the efficacy of intensive blood pressure control on cognitive outcomes: A post hoc analysis of SPRINT MIND.

This post hoc analysis of the SPRINT MIND trial evaluated whether cardiovascular-kidney-metabolic (CKM) syndrome stage modifies cognitive benefits of intensive systolic blood pressure control. Participants were classified into non-advanced CKM (Stage 2, n=5,632) and advanced CKM (Stages 3–4, n=2,931), and treatment effects were assessed with Cox models and generalized linear models for probable dementia and MCI outcomes. The study is significant because it suggests CKM stage may influence how effectively intensive BP lowering protects cognition, informing risk-stratified hypertension management.

Wang Z, Pei J, Sun T et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Nox1/4 inhibitor Setanaxib treatment ameliorates cardiac function in mouse models of Duchenne Muscular Dystrophy.

This preclinical study tested the Nox1/4 inhibitor setanaxib in mouse models of Duchenne muscular dystrophy (DMD), specifically in CIP/Mdx double knockout (dKO) mice with cardiac involvement. Setanaxib protected the heart from heart failure and targeted downstream oxidative-stress signaling mediated by Nox4 identified as a mediator of accelerated dystrophic cardiomyopathy. The results support Nox1/4 inhibition as a potential therapeutic approach to improve cardiac outcomes in DMD.

Deng R, De Oliveira Silva T, Liu X et al. · Molecular therapy : the journal of the American Society of Gene Therapy · (2026) · View on PubMed ↗

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Pulmonary & respiratory disease (including COPD/ARDS/silicosis)

Beyond vasodilation: sotatercept and the remodeling hypothesis in hfpef-associated pulmonary hypertension.

This mini-review summarized evidence from the Phase 2 CADENCE study of sotatercept, an activin signaling inhibitor, in HFpEF-associated pulmonary hypertension (including combined post- and pre-capillary PH). It reported that sotatercept reduced pulmonary vascular resistance at 24 weeks and improved multiple clinical measures (mean pulmonary artery pressure, wedge pressure, 6-minute walk distance, NYHA class, and NT-proBNP) consistent with targeting vascular remodeling rather than vasodilation. The findings support a remodeling-focused therapeutic paradigm for HFpEF-associated pulmonary hypertension where prior vasodilator strategies have been ineffective or harmful.

Sperry BW, Carlino I, Palazzuoli A · Heart failure reviews · (2026) · View on PubMed ↗

Biomarkers for COPD with Type 2 Inflammation.

This review summarized biomarkers for COPD patients with Type 2 (T2) inflammation, focusing on the Th2/innate lymphoid cell cytokine program involving IL-4, IL-5, and IL-13. It described how T2 inflammation correlates with eosinophilic infiltration, mucus hypersecretion, airway hyperreactivity, and accelerated remodeling, and it evaluated established and emerging biomarker strategies to identify this treatable endotype. The clinical significance is improved patient selection for targeted therapies in the ~20–40% of COPD patients with T2 inflammation.

Pathak C, Cox J, Suri R et al. · Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · (2026) · View on PubMed ↗

IL-11 neutralizing antibodies alleviate pulmonary fibrosis in aging mice by inhibiting TGF-β/NOX4/IL-11 signaling pathway.

The study evaluated whether IL-11 neutralizing antibodies can alleviate aging-related pulmonary fibrosis in mice and defined the signaling mechanism. In aging mouse models, IL-11 neutralization reduced pulmonary fibrosis by inhibiting the TGF-β/NOX4/IL-11 signaling pathway, linking IL-11 blockade to downstream suppression of profibrotic signaling. This supports IL-11 as a therapeutic target for idiopathic pulmonary fibrosis-like disease in the elderly and provides a mechanistic rationale for antibody-based intervention.

Miao Y, Hu YY, Xu L et al. · Biochemical pharmacology · (2026) · View on PubMed ↗

The Iron Lung: Ferroptosis and Iron Regulation in Aging and Lung Diseases.

This article reviewed how iron regulation and ferroptosis contribute to aging and lung diseases, focusing on iron-dependent lipid peroxidation and cell death pathways. It synthesizes evidence that disruptions in iron homeostasis from aging and environmental exposures (e.g., oxygen extremes and particulate iron) can drive inflammation, mitochondrial energetics changes, and lung remodeling processes such as fibrosis. The review is significant because it frames ferroptosis and iron handling as potential mechanistic targets for preventing or treating lung disease across the lifespan.

Koloko Ngassie ML, Ortiz Y, Ravi P et al. · Physiology (Bethesda, Md.) · (2026) · View on PubMed ↗

Silicosis in the Artificial Stone Countertop Industry: An Official American Thoracic Society Workshop Report.

This American Thoracic Society workshop report synthesized current evidence on artificial stone-associated silicosis (AS silicosis) affecting workers who manufacture, fabricate, and install artificial stone countertops. The report emphasizes that AS silicosis is severe, rapidly progressive, preventable, and disproportionately affects young workers in precarious employment with short latency and high morbidity/mortality. Scientifically and clinically, it consolidates knowledge to guide research priorities and improve prevention and clinical care for this emerging occupational lung disease.

Gandhi SA, Liu GY, Fazio JC et al. · Annals of the American Thoracic Society · (2026) · View on PubMed ↗

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Methodology, imaging, AI/ML & computational biology

Gαo/z-biased coupling profile of the dopamine D3 receptor.

This study characterized dopamine D3 receptor (D3R) G protein coupling in cellular/biochemical systems to define its signaling bias relative to other dopamine D2-like receptors, focusing on engagement with Gαi proteins. The key finding was that D3R shows a striking inability to engage with Gαi proteins while the coupling profile is otherwise mapped as Gαo/z-biased. This mechanistic signaling insight can inform safer dopamine D3R-targeted drug design by anticipating on-target side effects linked to specific G protein pathways.

Zanetti L, Franchini L, Saha S et al. · Communications biology · (2026) · View on PubMed ↗

A multi-ingredient food supplement slows age-dependent decline of mobility and influences gene expression in C. elegans.

A multi-ingredient food supplement containing vitamins, minerals, antioxidants, and amino acids was tested for effects on age-dependent mobility decline and gene expression in the rapidly aging nematode C. elegans. The supplement slowed age-related loss of mobility and altered transcriptional programs linked to aging. These findings support nutritional multi-ingredient formulations as candidate healthspan interventions and provide C. elegans gene-expression readouts to prioritize compounds for later human studies.

Yanyatan C, Mohanraj K, Fasseas M et al. · Biogerontology · (2026) · View on PubMed ↗ · Free PDF ↗

Development and validation of a multiancestry and multitrait polygenic risk score for lung cancer.

The study developed and validated a multiancestry, multitrait polygenic risk score for lung cancer using a multiancestry GWAS meta-analysis (76,953 cases and 1,886,372 controls) and PRS-CSx-based modeling. It identified 87 conditionally independent genome-wide significant loci (including two unreported cytobands) and produced a multiancestry PRS (PRSMA) that outperformed 32 published PRSs, while a multitrait CatBoost model (PRSMT) further improved prediction when combined with PRSMA. Clinically, this provides a more accurate genetic risk stratification tool for lung cancer across diverse ancestries, supporting earlier identification of high-risk individuals.

Zhang Y, Dai J, Gu P et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Patient-Specific Determinants of Response to BCMA- and GPRC5D-Targeted CAR T-Cell Therapy in Multiple Myeloma: A QSP Analysis of Clinical Trial and Real-World Data.

The study used a mechanistic quantitative systems pharmacology (QSP) model to identify patient-specific determinants of response and relapse to BCMA- and GPRC5D-targeted CAR T-cell therapy in relapsed/refractory multiple myeloma, integrating clinical trial and real-world data. The model reproduced published pharmacokinetics and biomarker response patterns for anti-BCMA and anti-GPRC5D CAR T therapies and was used to predict factors associated with CAR T expansion and eventual relapse. Scientifically, this provides a framework for biomarker-informed personalization of CAR T-cell therapy and for anticipating resistance mechanisms in RRMM.

Kostiou V, Chelliah V, van der Graaf PH et al. · Clinical pharmacology and therapeutics · (2026) · View on PubMed ↗

Associations between body composition and radiotherapy-related side-effects and health-related quality of life in patients with prostate or lung cancer: sub-analysis of the REQUITE trial.

This prospective multicentre REQUITE trial sub-analysis studied whether body composition metrics derived from radiotherapy planning computed tomography (CT) scans are associated with radiotherapy-related side-effects and health-related quality of life (HRQoL) in patients with prostate or lung cancer. The key finding was that specific skeletal muscle/body composition measures from routine CT imaging were linked to subsequent treatment tolerance, side-effect burden, and HRQoL over follow-up up to 24 months. Clinically, this supports using imaging-based body composition as a prognostic biomarker to identify patients at higher risk for radiotherapy toxicity and worse HRQoL.

Vickers AJ, McSweeney DM, Choudhury A et al. · Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · (2026) · View on PubMed ↗

Integrative network toxicology and single-cell analysis implicates a potential TGFBR1-centered fibroblast remodeling axis in Benzo[a]pyrene-related atrial fibrillation.

This integrative study combined network toxicology with single-cell RNA sequencing (scRNA-seq) to examine benzo[a]pyrene (BaP)–related atrial fibrillation (AF) mechanisms, using human AF microarray datasets and one scRNA-seq dataset. The key finding was that a TGFBR1-centered fibroblast remodeling axis emerged as a potential pathway linking predicted BaP targets to AF-associated cellular remodeling features. Scientifically, it implicates TGFBR1-driven fibroblast remodeling as a mechanistic bridge between air pollution exposure and AF, suggesting a candidate target for future intervention.

Wang Q, Wu J, Qi S et al. · Environment international · (2026) · View on PubMed ↗ · Free PDF ↗

New biomarkers for antibody-drug conjugates in lung cancer the pathologist’s perspective.

This review studied biomarker development for selecting patients for antibody-drug conjugates (ADCs) in lung cancer, focusing on practical implementation from the pathologist’s perspective. It highlights that robust companion diagnostics (CDx) and tissue-selection workflows are still under development, creating challenges for fast, reliable, and reproducible biomarker testing for ADC eligibility. Scientifically and clinically, it underscores the need for standardized pathology approaches to enable effective ADC treatment selection in lung cancer.

Hofman V, Rignol G, Mograbi B et al. · Lung cancer (Amsterdam, Netherlands) · (2026) · View on PubMed ↗

Dynamic tRNA modification landscapes reveal METTL1 in fibroblasts as a central regulator of aging.

This study mapped dynamic RNA modification landscapes across tissues in young versus aged mice and multiple cellular senescence models, identifying tRNA modification changes and the tRNA methyltransferase METTL1. Aging was associated with a decline in tRNA modification abundance (more than total RNA or mRNA), alongside reduced expression of METTL1 and TRMT1, implicating METTL1 as a central regulator of aging-linked molecular programs. These findings support a mechanistic role for tRNA methylation in aging and suggest METTL1 as a potential target for interventions aimed at age-associated dysfunction.

Zhu Y, Wang X, Li Y et al. · Science China. Life sciences · (2026) · View on PubMed ↗

ORBIT-AMD: Ordinal Risk, Bilateral Imaging, and Trajectory Learning for Age-Related Macular Degeneration in Multi-Cohorts.

This study developed ORBIT-AMD, an AI framework for age-related macular degeneration (AMD) that models ordered, bilateral, longitudinal disease trajectories using multimodal inputs (color fundus photography and optical coherence tomography) and ordinal staging. In UK Biobank (58,214 participants; 109,691 eyes) and an external Tianjin Medical University Eye Hospital cohort (1,996 participants; 3,780 eyes), ORBIT-AMD achieved high AUROC performance (reported as 0.984 for internal testing) by integrating bilateral eye-graph attention, concept bottlenecks, and discrete-time survival prediction. The scientific significance is that it moves AMD prediction beyond static binary classification toward clinically meaningful staging and trajectory-aware risk modeling across cohorts.

Cui X, Wen D, Yu-Wai-Man P et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

MAPK/ERK signaling regulates H3K9me3 heterochromatin reorganization to confer mesendoderm developmental competence.

This study investigated how MAPK/ERK signaling regulates H3K9me3-marked facultative heterochromatin reorganization during differentiation of human pluripotent stem cells (hPSCs) into mesendoderm and definitive endoderm. The authors found that MAPK/ERK signaling drives global reorganization of H3K9me3 heterochromatin to confer mesendoderm developmental competence, while early neural ectoderm retains an epithelial state and does not undergo the same reorganization. Scientifically, it links an FGF–MAPK/ERK developmental signaling axis to epigenetic remodeling (H3K9me3) that gates lineage competence during gastrulation-like differentiation.

Matsui S, Sampson S, Mirizio G et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

Antibody-trapping presents a widespread pitfall for microscopy and genomics in the nucleus.

This paper studied antibody-trapping artifacts in nuclear microscopy and genomics workflows that rely on antibody diffusion to chromatin epitopes. Using computational modeling and experimental validation, the authors showed that antibodies can become trapped at nuclear peripheries, producing artifactual peripheral signals that distort the apparent nuclear positions of chromatin features across the genome. The work is significant because it provides a mechanistic pitfall for interpreting antibody-based chromatin localization and mapping results, improving reliability of microscopy and genomics assays.

Chudzik K, Sato Y, Yan X et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

RECQ4 arginine methylation suppresses single-stranded DNA gap accumulation at replication forks.

This study investigated whether arginine methylation regulates DNA replication fork stability by focusing on RECQ4 helicase in cells. The authors identified asymmetric dimethylarginine (aDMA) modification of RECQ4 by type I PRMTs on five arginine residues in a glycine/arginine-rich region, showing that aDMA is enriched in S phase, promotes RECQ4 nuclear localization, and suppresses single-stranded DNA gap accumulation at replication forks. Scientifically, it connects RECQ4 arginine methylation to replication stress control, suggesting a regulatory mechanism that helps maintain genome stability during S phase.

Ma N, Xu X, Espinoza M et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

Enhancing prime editing by fusing polymerase substrate-binding proteins to reverse transcriptase.

This research tested whether enhancing prime editing (PE) by improving reverse transcriptase (RT) function can increase editing efficiency in human cells. In a 12-member screen, fusing polymerase substrate-binding proteins (PSBPs) to RT—especially the compact HMG box module NHP6A—significantly increased intended PE edits across substitutions, insertions, and deletions while keeping indels low. The findings are significant for improving the practical efficiency of CRISPR prime editing by engineering RT with substrate-binding domains compatible with nicking sgRNAs.

Zhao D, Wang T, Zhang L et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on June 29, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.