PubMed Trending Research Digest — May 28, 2026

Automated digest · 97 articles · 15 research areas · May 28, 2026

Overview

Across this week’s papers, a dominant theme is the push toward mechanism-informed, biomarker-guided therapy—especially in oncology and immune-mediated disease. Multiple studies connect specific molecular switches to treatment response or resistance: e.g., dual BCL-2/BCL-xL inhibition to overcome venetoclax resistance in high-risk myeloid disease; PD-L1 lactylation control via HAT1 to modulate immune evasion; and metabolic/epigenetic axes (OXCT1–BHB–histone modifications, HNF4α–methionine metabolism and ferroptosis resistance, STING–WNT stromal programs) that reprogram tumor microenvironments and immunotherapy sensitivity. Parallel clinical efforts include updated ASCO living guidelines, biomarker prevalence estimates for targeted agents, and randomized/feasibility trials testing novel combinations (neoadjuvant chemo-immunotherapy in bladder cancer; amivantamab regimens in EGFR exon 20 insertion NSCLC; and immunotherapy plus IDO1 inhibition in glioblastoma). Safety and real-world considerations also appear—such as pharmacovigilance signals for cardiovascular adverse events with bispecific antibodies and a cautionary gene-therapy case report highlighting AAV9 risk in advanced SMA-PME.

A second major thread is systems biology and translational measurement: from spatial and single-cell technologies to less invasive biomarkers. Spatial CRISPR screens, embryo atlases, and multi-omics aging signatures aim to map causal pathways and predict outcomes across tissues and species. In neurodegeneration, plasma and CSF biomarker work (eMTBR-tau243/%p-tau217 staging; TPPP/p25 seeding/aggregation; synaptic biomarker meta-analysis) complements mechanistic studies of microglial pruning, complement dependence, and microglia-to-astrocyte mitochondrial transfer in tauopathy. In cardiovascular and kidney research, studies integrate imaging/genomics and mechanistic vascular biology (e.g., arrhythmia subtypes and dementia risk; endothelial LATS1/2–CD38 thrombosis links; kidney cell responses in cholesterol crystal embolism) to refine risk prediction and identify targets.

Finally, several studies emphasize host–environment and immune-metabolic interactions spanning infection, inflammation, and lifestyle. Examples include macrophage defects driving intracellular survival of Mycobacterium abscessus in cystic fibrosis, PRRSV hijacking host lipophagy for replication, and microbiome/diet effects on cancer immunity (dietary sulfur amino acids enhancing CD8+ T cell responses; ketogenic diets explored for endometrial cancer feasibility). Together, these findings reinforce a broad shift toward interventions that are not only targeted to disease biology, but also tailored to patient context—genetics, immune state, metabolism, and measurable biomarkers.

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Cancer therapeutics: targeted agents & biomarkers

Farnesylation-driven KRAS phase separation promotes colon tumor growth.

The study investigated whether oncogenic KRAS forms cytoplasmic condensates via LLPS and how farnesylation at the C185 residue in the KRAS hypervariable region (HVR) drives this process in colon cancer. It found that farnesylation-driven KRAS phase separation promotes KRAS processing and plasma-membrane translocation by enhancing RCE1 clustering through efficient KRAS–RCE1 interactions, leading to increased KRAS signaling and colon tumor growth. These findings identify KRAS farnesylation–dependent LLPS as a potential therapeutic vulnerability in colon cancer.

Wang X, Zhang Y, Lu M et al. · Cell · (2026) · View on PubMed ↗

Leishmaniasis.

This review studied the clinical epidemiology, transmission, and diagnostic approaches for leishmaniases caused by Leishmania parasites across cutaneous, mucosal, and visceral disease forms. It reports that cutaneous leishmaniasis is the most common and is increasing in the Eastern Mediterranean region, while visceral leishmaniasis is decreasing globally, and it highlights a shift toward molecular diagnostics. The synthesis is clinically significant for guiding modern diagnosis and surveillance strategies for a growing set of geographically shifting leishmaniasis burdens.

Aronson NE, Musa AM, Satoskar AR · The New England journal of medicine · (2026) · View on PubMed ↗

Amivantamab plus chemotherapy vs. chemotherapy as first-line treatment in Chinese mainland patients with EGFR exon 20 insertion non-small cell lung cancer: Subgroup analysis of the randomized PAPILLON trial.

This subgroup analysis studied first-line amivantamab plus carboplatin-pemetrexed versus carboplatin-pemetrexed alone in Chinese mainland patients with treatment-naïve locally advanced or metastatic EGFR exon 20 insertion non-small cell lung cancer from the randomized phase 3 PAPILLON trial (NCT04538664). The amivantamab combination showed efficacy and an acceptable safety profile consistent with the overall PAPILLON results in this regional population. These findings support amivantamab plus platinum–pemetrexed as a clinically relevant first-line option for EGFR exon 20 insertion NSCLC in Chinese mainland practice.

Tang K, Wu F, Yang F et al. · Chinese medical journal · (2026) · View on PubMed ↗ · Free PDF ↗

Activation of methionine metabolism mediated by HNF4α confers ferroptosis resistance in hepatocellular carcinoma.

This study explored how HNF4α-driven methionine metabolism affects ferroptosis sensitivity in epithelial hepatocellular carcinoma (HCC) cells treated with the ferroptosis inducer imidazole ketone erastin (IKE). Transcriptomics and metabolomics linked cysteine/methionine metabolic pathways to epithelial HCC resistance, and cystine/methionine limitation experiments supported that HNF4α-mediated methionine metabolism promotes ferroptosis resistance. Clinically, this suggests that targeting methionine metabolism could overcome ferroptosis resistance in a subset of HCC patients.

Zhou X, Li Z, Wang L et al. · Cell death discovery · (2026) · View on PubMed ↗ · Free PDF ↗

AI-driven multi-omics drug repurposing nominates AZD7762 as a multitarget inhibitor of IL22RA1 and FAM221A in esophageal squamous cell carcinoma.

This study used an AI-driven multi-omics pipeline integrating summary-data Mendelian randomization with bulk transcriptomics, Cox regression, non-negative matrix factorization, and single-cell RNA-seq to repurpose drugs for esophageal squamous cell carcinoma (ESCC). The approach nominated AZD7762 as a multitarget inhibitor of IL22RA1 and FAM221A, consistent with its predicted multitarget activity against ESCC-associated prognostic genes and molecular subgroups. This provides a data-driven candidate therapy and mechanistic targets for further preclinical and clinical evaluation in ESCC.

Zhuang Z, Yu S, Peng K et al. · NPJ precision oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Fibroblast growth factor receptor inhibition for succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 2 trial.

This phase 2 clinical trial evaluated fibroblast growth factor receptor (FGFR) inhibition with rogaratinib in patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST). The rationale was that SDH deficiency and genome-wide DNA hypermethylation drive aberrant expression of FGF3/FGF4 and an autocrine FGFR1 loop, and the trial assessed objective response rate as the primary endpoint. If effective, FGFR1/FGF ligand axis targeting with rogaratinib could provide a precision treatment option for the SDH-deficient GIST subgroup.

Merriam P, Morrow JJ, Mazzola E et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Smooth muscle cells transiently acquire a CD34+ progenitor state upon injury to drive pathological vascular remodeling.

This study investigated the cellular origin and function of smooth muscle cell (SMC) subtypes during injury-driven vascular remodeling by identifying a transient CD34+ progenitor state. It found that after artery injury, smooth muscle-derived transient progenitor cells (STPCs) marked by CD34 proliferate and generate most neointimal SMCs, and that genetic ablation of STPCs reduces neointimal hyperplasia. Mechanistically, SMC-specific knockdown of DCLK1 suppressed STPC generation and mitigated pathological remodeling, establishing STPCs and DCLK1 as drivers of vascular disease progression.

Lu Y, Ni H, Shen J et al. · Cell stem cell · (2026) · View on PubMed ↗

Global prevalence of FGFR2b protein overexpression in advanced gastric cancer and gastroesophageal junction cancers: pooled analysis of two bemarituzumab phase III studies.

The study performed a pooled analysis of tumor samples from prescreening cohorts in two global phase III bemarituzumab trials to estimate the global prevalence of fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression in advanced gastric and gastroesophageal junction cancers (G/GEJC). Using a validated assay, it quantified how frequently FGFR2b protein overexpression occurs among patients with locally advanced or metastatic disease eligible for bemarituzumab-based first-line therapy. This provides clinically actionable prevalence estimates for biomarker-driven patient selection and trial planning in FGFR2b-targeted treatment strategies.

Maron SB, Xu RH, Wainberg ZA et al. · ESMO open · (2026) · View on PubMed ↗ · Free PDF ↗

Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, 2026.3.1.

This ASCO Living Guideline systematically studied emerging evidence to recommend therapy for stage IV non-small cell lung cancer (NSCLC) with driver alterations in clinical practice. The key finding is that the guideline is continuously updated by an expert panel using a standardized methodology to reflect rapidly changing data on targeted and related treatments. Clinically, it provides an evidence-synchronized framework for selecting driver-alteration–matched therapies while emphasizing that recommendations do not replace individualized clinician judgment.

Reuss JE, Ismaila N, Ahluwalia A et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, 2026.3.1.

This ASCO Living Guideline systematically studied emerging evidence to recommend therapy for stage IV non-small cell lung cancer (NSCLC) without driver alterations in clinical practice. The key finding is that the guideline is updated on a regular schedule through continuous literature review and standardized ASCO methodology to keep treatment recommendations current. Scientifically and clinically, it supports decision-making for patients lacking actionable driver mutations while noting that updates do not account for individual patient variation.

Bazhenova L, Ismaila N, Durm G et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Sensitivity to endocrine therapy index predicts benefit from weekly adjuvant paclitaxel for hormone receptor-positive breast cancer in the GEICAM/9906 trial.

This study investigated whether the sensitivity to endocrine therapy index (SETER/PR index) predicts benefit from weekly adjuvant paclitaxel in hormone receptor-positive breast cancer using a blinded prospective-retrospective biomarker analysis within the GEICAM/9906 trial. The key finding was that low endocrine transcriptional activity (SETER/PR index <0.75) predicted benefit from adding weekly paclitaxel to adjuvant FEC compared with FEC alone, with distant recurrence-free interval as the primary endpoint. This is significant because it provides a transcriptomic biomarker to personalize chemotherapy decisions in HR+/HER2− early breast cancer.

Martín M, Rodriguez-Lescure A, Reboredo C et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗

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Cancer immunotherapy & tumor microenvironment

Nuclear OXCT1 attenuates histone β-hydroxybutyrylation-mediated MHC-I transcription.

This study investigated how the nuclear enzyme OXCT1 (succinyl-CoA:acetoacetate CoA transferase; ketone body metabolism) regulates MHC-I transcription in hepatocellular carcinoma (HCC) patients treated with immune checkpoint blockade (ICB). High OXCT1 expression correlated with reduced ICB efficacy, while β-hydroxybutyrate (BHB) showed the opposite association, and mechanistically AMPK-mediated OXCT1 S113 phosphorylation promoted nuclear translocation that attenuated histone β-hydroxybutyrylation–mediated MHC-I transcription. These results identify an OXCT1–BHB–histone modification axis that may help predict or modulate immunotherapy responsiveness in HCC.

Hu Z, Lv W, Wen T et al. · Nature chemical biology · (2026) · View on PubMed ↗

Genomic instability drives POSTN+ myofibroblasts via STING-WNT axis to promote immunosuppression and PARPi resistance in ovarian cancer.

The study examined how tumor-intrinsic genomic instability reprograms cancer-associated fibroblasts (CAFs) to drive immunosuppression and PARP inhibitor (PARPi) resistance in high-grade serous ovarian cancer. Using integrated single-cell transcriptomics and epigenomics of patient tumors, it identified POSTN+ myofibroblast-like myCAFs and effector regulatory T cells (eTregs) as key mediators in high-genomic-instability tumors, and mechanistically showed that unstable genomes activate tumor-intrinsic STING signaling to trigger WNT3a/7a secretion that engages WNT/β-catenin signaling in fibroblasts. This links a specific STING–WNT axis to stromal immunosuppression and PARPi resistance, suggesting actionable targets to overcome therapy failure.

Liu D, Tao K, Cai C et al. · Science translational medicine · (2026) · View on PubMed ↗

Efficacy and safety of durcabtagene autoleucel in a phase 1 trial for patients with relapsed/refractory multiple myeloma.

The study evaluated durcabtagene autoleucel, a BCMA-directed CAR T cell therapy manufactured using a rapid platform intended to preserve T cell stemness, in a phase 1 trial for relapsed/refractory multiple myeloma (r/r MM). In part A (NCT04318327), the primary objective was safety, with secondary assessments including response rates and cellular kinetics (full results truncated in the abstract). If effective and safe, this approach could improve access and potency of BCMA CAR T therapy by shortening manufacturing time and reducing T cell exhaustion.

Sperling AS, Derman BA, Nikiforow S et al. · Science translational medicine · (2026) · View on PubMed ↗

Lactylation of PD-L1 by a lactyltransferase HAT1 dictates its protein stability and tumor immune evasion.

This study investigated how lysine lactylation of the immune checkpoint protein PD-L1 is regulated, focusing on the lactyltransferase histone acetyltransferase 1 (HAT1) and its effects on tumor immune evasion. HAT1 catalyzed PD-L1 lactylation at extracellular-domain residues K75 and K178, which increased PD-L1 stability by protecting it from ER-associated degradation and promoting ER-to-Golgi trafficking. Targeting PD-L1 lactylation via HAT1 knockdown or PD-L1 lactylation-site mutation may therefore reduce PD-L1–mediated immune suppression and improve antitumor immunity.

Shang M, Zhao X, Zhang Y et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Cardiovascular adverse events associated with bispecific antibodies in relapsed or refractory B-cell non-Hodgkin lymphomas.

This pharmacovigilance study analyzed FDA Adverse Event Reporting System (FAERS) data (Dec 2022–Sep 2025) to characterize cardiovascular adverse events (CVAEs) associated with bispecific antibodies in relapsed/refractory B-cell non-Hodgkin lymphomas, focusing on mosunetuzumab, glofitamab, and epcoritamab. Among 246,490 adverse event reports, 1,931 involved bispecific antibodies and 336 (17.4%) of bispecific-associated reports included CVAEs, with 39.3% of CVAEs being fatal and common events including shock, bleeding, and hypotension. These findings are clinically important for heightened cardiovascular monitoring and risk stratification when using bispecific T-cell–redirecting therapies.

Munir M, Sayed A, Lee DH et al. · Journal of hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

An in situ generated CAR-M with IFN-γ and negative dominance Sirpα isoform augments hepatocellular carcinoma immunotherapy.

This preclinical study engineered an in situ generated CAR-macrophage (CAR-M) targeting human GPC3 with an IFN-γ–enhanced design and a negative dominance SIRPα isoform (SIRPαECD) to improve persistence and phagocytosis for hepatocellular carcinoma immunotherapy. The modified CAR-M construct augmented hepatocellular carcinoma immunotherapy by improving macrophage functional activity compared with earlier CAR-M approaches. The work is significant because it provides a strategy to overcome solid-tumor limitations of CAR therapies by leveraging macrophage infiltration and engineered immune signaling.

Li X, Hu J, Zhang T et al. · Journal of nanobiotechnology · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting arginine metabolism reverses bone immunosuppressive microenvironment and metastasis in ARID1A-deficient triple negative breast cancer.

This study investigated whether targeting arginine metabolism can reverse the bone immunosuppressive microenvironment and metastasis driven by ARID1A deficiency in triple negative breast cancer (TNBC). In ARID1A-mutated/loss-of-function TNBC, arginine metabolism was upregulated with increased ornithine and spermine, promoting expansion of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in bone marrow and enhancing bone metastasis. These findings support arginine-metabolism blockade as a strategy to disrupt immunosuppression and reduce metastatic progression in ARID1A-deficient TNBC.

Pan S, Wang J, Wang B et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Tumor-draining lymph nodes in ovarian cancer lack germinal centers but harbor tumor-reactive memory B cells clonally linked to intra-tumoral B cells.

The study analyzed tumor-draining lymph nodes (TDLNs) and tumors from patients with high-grade serous ovarian cancer (HGSOC) to determine how TDLNs contribute to tumor-reactive B cell responses. TDLNs lacked active germinal centers and were dominated by quiescent, class-switched mutated memory B cells (MBCs) clonally linked to intra-tumoral B cells, while germinal center B cells and plasma cells were largely confined to the tumor. This indicates that effective anti-tumor B cell immunity in HGSOC can be maintained by clonally connected memory B cells in TDLNs without ongoing germinal center activity, informing how to interpret and potentially target lymph node niches.

Nathan N, Paparoditis P, Sarusi-Portuguez A et al. · Immunity · (2026) · View on PubMed ↗

Dietary sulfur amino acids enhance anti-tumor immunity in colon cancer via an NKT cell-XCL1-cDC1 circuit.

The study investigated whether dietary sulfur amino acids (Saa) modulate anti-tumor immunity in colon cancer by linking microbial metabolic pathways to immune responses in murine models and correlating with human immune checkpoint inhibitor (ICI) responsiveness. High-Saa diets restricted colon cancer progression, increased colonic mucus thickness, promoted expansion of the mucus-dwelling bacterium Mucispirillum schaedleri, and increased activated intratumoral cytotoxic CD8+ T cells via an NKT cell–XCL1–cDC1 circuit. These findings support a diet–microbiome–innate/adaptive immunity axis that could enhance ICI responsiveness or provide adjunct strategies for colon cancer immunotherapy.

Lobel L, Fonseca-Pereira D, Nakatsu G et al. · Immunity · (2026) · View on PubMed ↗

Neoadjuvant Durvalumab ± Tremelimumab in Combination With Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Muscle-Invasive Bladder Carcinoma: Results of the Phase I/II NEMIO Study.

The NEMIO phase I/II study evaluated neoadjuvant dose-dense MVAC chemotherapy (ddMVAC: methotrexate, vinblastine, doxorubicin, cisplatin) combined with immune checkpoint blockade (durvalumab ± tremelimumab) in patients with muscle-invasive bladder cancer (cT2–T4a N0–1, cisplatin-eligible) planned for radical cystectomy. The key finding reported in the abstract is the trial’s efficacy and safety outcomes for this combined regimen (durvalumab 1500 mg with or without tremelimumab 75 mg given with four cycles of ddMVAC every 2 weeks). This informs the feasibility and potential benefit of integrating PD-L1/CTLA-4 blockade with ddMVAC as a neoadjuvant strategy to improve outcomes in MIBC.

Thibault C, Bennamoun M, Fléchon A et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Comparative Study of Sporadic and Immune Checkpoint Inhibitor-Related Forms of Myasthenia Gravis-Myositis Overlap Syndrome.

This multicenter retrospective cohort study compared sporadic MG–inflammatory myopathy overlap syndrome (s-MG-IM) versus immune checkpoint inhibitor-related MG–IM (ir-MG-IM) in patients across eight Italian centers. The key finding is a comparative characterization of clinical and serologic features, treatment approaches, and outcomes between s-MG-IM (often thymoma-associated) and ICI-related MG-IM. Clinically, distinguishing these entities can guide diagnosis and management of immune-related adverse events in patients receiving immune checkpoint inhibitors.

Lauletta A, Rossini E, Beretta F et al. · Neurology · (2026) · View on PubMed ↗

Epstein-Barr virus (EBV) infection causes human germinal center B cell-derived lymphomas in the absence of EBNA2 expression.

This study investigated how Epstein-Barr virus (EBV) can drive human germinal center B cell-derived lymphomas without expression of the viral transforming protein EBNA2. The key finding was that EBV infection can produce EBNA2-negative lymphomas that are largely driven by LMP1 and LMP2A signaling (NF-κB and B cell receptor-like pathways) and/or Myc translocations, and that EBNA2 is required for EBV-mediated transformation in vitro. This is significant because it clarifies EBV oncogenic mechanisms in EBNA2-negative disease and supports more accurate modeling of EBV+ lymphoma biology.

Wang C, Bristol JA, Nelson SE et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Phase 1 evaluation of patients with newly diagnosed glioblastoma treated with radiation, nivolumab, and IDO1 enzyme inhibitor BMS-986205.

This phase 1 clinical trial studied newly diagnosed IDH-wildtype glioblastoma patients treated with radiation plus nivolumab, with the addition of the IDO1 inhibitor BMS-986205, stratified by MGMT methylation status. The key finding (as described in the abstract) is that the trial design includes dose-escalation and biomarker correlations using flow cytometry, transcriptomics, general metabolomics, and microbial metabolite analyses to evaluate safety and biological activity. This is significant because it tests an immunometabolic strategy (radiation + PD-1 blockade + IDO1 inhibition) and links clinical outcomes to immune, molecular, metabolic, and microbiome-associated biomarkers.

Lukas RV, Zhai L, Lauing KL et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗ · Free PDF ↗

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Hematologic malignancies & stem cell biology

Human haematopoietic stem cells remember inflammatory stress.

This study investigated how human haematopoietic stem cells (HSCs) adapt to inflammatory stress by developing xenograft inflammation–recovery models and performing single-cell multiomics on xenografted human HSCs. It identified two transcriptionally and epigenetically distinct HSC subsets, including an HSC inflammatory memory (HSC-iM) population that retains molecular memory of prior inflammatory treatments and shows quiescence with restrained haematopoietic output. These results demonstrate that human HSCs can store inflammatory experience, with implications for understanding ageing, infection history effects, and malignancy risk.

Zeng AGX, Nagree MS, Jakobsen NA et al. · Nature · (2026) · View on PubMed ↗

Dual BCL-xL and BCL-2 Inhibition for Advanced Myeloid Neoplasms: A phase 1 dose-escalation study of Navitoclax, Venetoclax, and Decitabine.

This phase 1 dose-escalation study evaluated navitoclax (a BCL-2/BCL-xL inhibitor) added to venetoclax (BCL-2 inhibitor) plus decitabine in patients with advanced high-risk myeloid neoplasms, including secondary/therapy-related AML and accelerated/blast-phase myelofibrosis. The key finding was that dual BCL-xL and BCL-2 inhibition with navitoclax combined with venetoclax and decitabine was feasible to dose and was being assessed for anti-leukemic activity in settings where BCL-xL–mediated resistance to venetoclax is expected. Clinically, this strategy targets a known resistance mechanism to venetoclax and may expand effective treatment options beyond AML subtypes that currently respond best to venetoclax plus hypomethylating therapy.

Chen EC, Liu Y, Bell HL et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗

L-Carnitine Regulates Regeneration of Human Hematopoietic Stem and Progenitor Cells.

This study used a low-input mass spectrometry-based metabolomics platform to profile metabolism in 13 immunophenotypically defined hematopoietic cell types from adult human bone marrow, focusing on human hematopoietic stem and progenitor cells (HSPCs). The key finding was that L-carnitine is a regulator of regeneration in human HSPCs, with metabolomic profiling revealing conserved metabolic programs across primitive HSPCs and downstream lineages. Scientifically, it links a specific metabolic regulator (L-carnitine) to human stem/progenitor regenerative capacity and supports metabolomics-enabled development of regenerative hematology therapies.

Duan H, Wang B, Zheng Y et al. · Blood · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration & dementia biomarkers/mechanisms

Arrhythmias, dementia risk, and neurodegeneration: a cohort study.

This cohort study used UK Biobank participants without baseline arrhythmias or dementia to test whether incident and accumulated arrhythmia subtypes are associated with dementia risk and brain MRI measures. Using Cox models, it assessed multiple arrhythmia categories—including atrial fibrillation/flutter, bradyarrhythmia/conduction block, and ventricular arrhythmia—and related exposure burden to dementia outcomes. The results extend beyond AF to clarify how other arrhythmia types may contribute to neurodegeneration and dementia risk.

Lu W, Weng S, Wang Y et al. · European heart journal · (2026) · View on PubMed ↗

Mapping the neurovascular landscape in aging and dementia: cerebral small vessel disease markers in a multicenter Latin American cohort.

This multicenter cross-sectional study examined cerebral small vessel disease (CSVD) MRI markers—white matter hyperintensities, lacunes, and cerebral microbleeds—in 1675 participants (790 healthy controls, 642 with Alzheimer’s disease [AD], and 243 with frontotemporal dementia [FTD]) across six Latin American countries. AD participants demonstrated the greatest CSVD burden compared with healthy controls and FTD, with CSVD burden linked to cardiometabolic risk factors and cognitive performance. The results clarify how CSVD differs across dementia variants in an underrepresented Latin American population, informing risk stratification and potential prevention strategies.

Altschuler F, Castro-Laguardia AM, Canziani V et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Synaptic biomarkers in Alzheimer’s disease dementia and mild cognitive impairment: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated cerebrospinal fluid (CSF) and blood-based synaptic biomarkers in Alzheimer’s disease dementia and mild cognitive impairment (MCI) across included study cohorts. Across 65 cohorts for quantitative synthesis (and 12 for qualitative review), multiple CSF synaptic biomarkers showed evidence of altered levels in AD dementia and/or MCI relative to controls, supporting synaptopathy-related biomarker utility along the clinical continuum. These findings help prioritize synaptic biomarker candidates for earlier diagnosis and monitoring of disease progression in AD.

Gaur A, Wong M, Chen JJ et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Microglial mitochondria transfer to astrocytes via GPNMB-enriched extracellular vesicles alleviates cognitive deficits in tauopathy mice.

This preclinical study investigated whether microglia-derived glycoprotein nonmetastatic melanoma protein B (GPNMB)-enriched extracellular vesicles (EVs) can transfer mitochondria to astrocytes and improve outcomes in PS19 tauopathy mice. In PS19 mice, microglial tau cleavage generated a Parkin/Nix–GPNMB mitochondrial complex that promoted secretion of EVs carrying functional mitochondria to astrocytes, which improved astrocytic function and attenuated cognitive deficits. The work identifies a GPNMB-mediated microglia-to-astrocyte mitochondrial transfer mechanism as a potential therapeutic target for tau-driven neurodegeneration.

Liang C, Zhou Y, Zhuang K et al. · Nature neuroscience · (2026) · View on PubMed ↗

FAM134B-mediated ER-phagy degrades APP and suppresses Alzheimer’s disease pathology.

This study examined how the ER-phagy receptor FAM134B/RETREG1 regulates amyloid precursor protein (APP) turnover in Alzheimer’s disease models. FAM134B directly binds wild-type and familial mutant APP via APP C-terminal domains, recruits LC3 through its LIR, and promotes lysosomal degradation of APP, while epigenetic silencing of FAM134B in AD limits TFEB/TFE3-dependent transcription. These findings identify FAM134B-mediated ER-phagy as a mechanistic control point for APP clearance and a potential therapeutic target to suppress AD pathology.

Zhang Y, Sun J, Cai Y et al. · The EMBO journal · (2026) · View on PubMed ↗ · Free PDF ↗

TPPP/p25 amyloid seeding activity as a specific biomarker for multiple system atrophy.

This study investigated tubulin polymerization promoting protein (TPPP/p25) as a cerebrospinal fluid biomarker for multiple system atrophy (MSA) by assessing its amyloid seeding/aggregation behavior. It found that native TPPP/p25 is self-protected against amyloid aggregation, whereas disease-related mutations disrupt this protection and trigger aggregation, with cryo-EM defining structural features of the core domain. The work is clinically significant because it proposes a more disorder-specific CSF biomarker than α-synuclein seeds for differentiating MSA.

Zeng S, Zhang S, Zhang S et al. · Cell · (2026) · View on PubMed ↗

Plasma eMTBR-tau243 and %p-tau217 for Biological Staging of Alzheimer Disease.

This observational longitudinal study developed and validated a plasma-based biological staging model for Alzheimer disease using plasma eMTBR-tau243 and %p-tau217, benchmarked against amyloid and tau PET staging. The key finding was that the plasma biomarkers produced a staging scheme that closely mirrored amyloid/tau PET-based biological staging in the BioFINDER-2 cohort and was confirmed in an independent validation cohort (Knight ADRC). Clinically, this enables less invasive, more scalable biological staging of Alzheimer disease that could improve diagnosis and prognostic assessment without requiring PET or other invasive procedures.

Salvadó G, Horie K, Barthélemy NR et al. · JAMA neurology · (2026) · View on PubMed ↗

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Neuroscience: development, circuits & neuroinflammation

Microglial Pruning of Excitatory Synapses in the Hippocampus Is Complement C3-Independent in Physiological and Neuroinflammatory States.

This study tested whether microglial synapse pruning in the hippocampus depends on complement C3, comparing physiological and neuroinflammatory states. It found that microglial pruning of excitatory synapses in the hippocampus was complement C3-independent, challenging the idea that complement-dependent pruning is universal across brain regions. Scientifically, this refines models of microglia-driven circuit remodeling and suggests that therapeutic complement targeting may need region- and context-specific consideration.

Salter EW, Kadia A, Zhang L et al. · Glia · (2026) · View on PubMed ↗ · Free PDF ↗

The Impact of Catastrophization and Emotions on Pain: A Narrative Review of Underlying Mechanisms.

This narrative review synthesized current evidence on how catastrophization and negative emotions modulate pain mechanisms within the biopsychosocial model. It identified shared pathways—particularly stress-system activation involving the HPA axis and related neurobiological changes—that can amplify pain perception and contribute to chronicity. Scientifically, the review consolidates mechanistic targets for psychosocial interventions and suggests that addressing catastrophization/emotion-related physiology may improve pain outcomes.

Jin MY, Yang Z, Joshi R et al. · Journal of pain research · (2026) · View on PubMed ↗ · Free PDF ↗

Transmembrane domain switching controls PINK1 import and fate in mitochondria.

This study investigated how mitochondrial import and downstream fate of the PINK1 kinase are controlled by changes in its transmembrane domain (TMD) under different mitochondrial membrane-potential states. The authors propose a third pathway in which PINK1 is imported into the mitochondrial matrix, with structural modeling predicting conformationally plastic TMD behavior (α-helix versus α/β-hybrid) that alters PINK1 processing and Parkin/mitophagy outcomes. This mechanistic framework refines how PINK1 senses mitochondrial dysfunction and may inform strategies to modulate mitophagy in Parkinson’s disease.

Lorriman JS, Hughes RJ, Grieve AG et al. · The EMBO journal · (2026) · View on PubMed ↗ · Free PDF ↗

Maternal-fetal type I interferon signaling drives TREM2 dysregulation and synaptic dysfunction in neurodevelopmental disorders.

This study examined how maternal type I interferon (IFN-I) signaling affects TREM2 regulation and synaptic dysfunction in neurodevelopmental disorders using a maternal immune activation model with polyinosinic:polycytidylic acid (poly(I:C)). It found that poly(I:C) increased maternal IFN-I, disrupted neuronal transcriptional trajectories and excitatory synapse homeostasis in juvenile offspring, and reduced microglial TREM2 expression with impaired phagocytosis. The findings are significant because they connect prenatal IFN-I exposure to TREM2 dysregulation and synaptic pathology, suggesting mechanistic targets for intervention.

Bizzotto M, You SF, Tamborini M et al. · Neuron · (2026) · View on PubMed ↗

Burst-Suppression EEG in Early Infantile Developmental and Epileptic Encephalopathies: Phenotype, Genotype, and Outcome.

The study retrospectively analyzed 110 MRI-negative patients with early infantile developmental and epileptic encephalopathies featuring early burst-suppression EEG (EIDEE-BS) to define electroclinical phenotype, genetic etiologies, and long-term outcomes. It focused on the genetic spectrum beyond known causes in KCNQ2, STXBP1, and SCN2A, linking genotype to phenotype and outcome in this large cohort. This improves prognostic counseling and refines genetic testing priorities for a severe neonatal epilepsy syndrome defined by burst-suppression EEG.

Riccardi F, Desnous B, Borloz E et al. · Neurology · (2026) · 1 citations · View on PubMed ↗

Synaptic and neural pathway redundancy enables the robustness of a sensory-motor reflex and promotes predation escape in Caenorhabditis elegans.

This study mapped the molecular basis of neuronal connections in the touch response sensory-motor reflex circuit of Caenorhabditis elegans to determine how robustness is achieved under genetic perturbations. The key finding was that prevalent redundancy at neural pathway, synaptic, and molecular levels enables sensory signals to reach command interneurons controlling motor output, and that developmental remodeling establishes a second pathway after pruning larval synapses. This is significant because it explains how circuit-level redundancy and plasticity promote reliable reflex function and predation escape behavior.

He H, Fong EKH, Kumar S et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Not all gut cellular circadian oscillators are food entrainable.

This study investigated which intestinal cell types contain cell-autonomous circadian oscillators and whether they are food-entrainable by generating a Cre-dependent PER2::luciferase reporter knock-in mouse and performing ex vivo gut explant recordings in defined cell populations. The key finding was that not all gut cellular circadian oscillators are entrainable by food cues, indicating heterogeneity in circadian control across intestinal cell types. This is significant because it refines how peripheral clocks synchronize with environmental cycles and informs strategies targeting circadian disruption in gut physiology.

Magaña I, Taufique SKT, Shan Y et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Efficacy and Safety of Ecopipam for Tourette Syndrome: A Phase 3 Randomized Clinical Trial.

This phase 3 double-blind, placebo-controlled randomized withdrawal trial studied ecopipam, a selective dopamine D1 receptor antagonist, in participants aged 6 years and older with Tourette syndrome across 77 sites in 12 countries. The key finding was that ecopipam demonstrated efficacy with acceptable safety and supported maintenance of effect over up to 24 weeks. Clinically, targeting D1 receptors with ecopipam may offer a treatment option that could reduce adverse effects and discontinuation compared with existing TS pharmacotherapies.

Gilbert DL, Atkinson SD, Kim DJB et al. · JAMA neurology · (2026) · View on PubMed ↗

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Cardiovascular disease: heart failure & arrhythmias

Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer.

The study evaluated in patients with previously untreated HER2-positive advanced gastroesophageal adenocarcinoma whether zanidatamab (a dual HER2 bispecific antibody) plus chemotherapy improves outcomes with or without tislelizumab (anti–PD-1) compared with trastuzumab plus chemotherapy in an open-label phase 3 trial. It found that the trial design compared three arms—zanidatamab+tislelizumab+chemotherapy, zanidatamab+chemotherapy, and trastuzumab+chemotherapy—with primary endpoints focused on progression-related outcomes (details truncated in the abstract). If efficacy and safety advantages were confirmed, this would support a new first-line immunotherapy-containing regimen for HER2-positive gastroesophageal cancer.

Shitara K, Elimova E, Liu T et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Contemporary Management of Acute Heart Failure: From Emergency Presentation to Long-Term Remission.

This review summarized contemporary, structured management of acute heart failure (AHF) from emergency presentation through longer-term remission strategies. It emphasizes updated approaches to early diagnostic assessment and decongestive treatment, integrating recent evidence to improve patient-centered care pathways. Clinically, the synthesis aims to standardize AHF management to reduce morbidity and improve outcomes across the care continuum.

Bruno J, Arrigo M, Baudry G et al. · Journal of the American College of Cardiology · (2026) · View on PubMed ↗

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Cardiovascular-metabolic syndrome & risk prediction

Genome-Wide Association Study and Fine Mapping Uncover Key Genetic Loci and Credible Genes of Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage.

This multiancestry genome-wide association study and fine-mapping analysis aimed to identify genetic loci and credible genes for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage. Across European and East Asian cohorts using multiancestry and multitrait meta-analyses, it uncovered key IA-associated loci and nominated hypothesis-generating genes for future therapeutic evaluation. These genetic discoveries can improve risk prediction and prioritize biological pathways for developing preventive interventions against IA rupture.

Maimaiti A, Jia N, Feng Y et al. · Stroke · (2026) · View on PubMed ↗

LATS1/2-CD38 Metabolic Rewiring Links Senescence to Intraplaque Thrombosis.

This study investigated endothelial cell (EC)-specific roles of LATS1/2 in linking disturbed blood flow to endothelial senescence, proliferation, and intraplaque thrombosis using inducible EC-specific LATS1/2 knockout mice in a partial carotid ligation model and spatial multiomics (imaging mass cytometry) of human and mouse plaques. LATS1/2-dependent metabolic rewiring through a CD38 axis connected EC senescence to increased intraplaque thrombosis, identifying LATS1/2–CD38 signaling as a mechanistic bridge between mechanotransduction and atherothrombosis. These findings suggest LATS1/2–CD38 metabolic pathways as potential targets to prevent intraplaque thrombosis and acute coronary syndrome in regions exposed to disturbed flow.

Kotla S, Lee J, Ko KA et al. · Circulation research · (2026) · View on PubMed ↗

The association between GLP-1R expression and cardiovascular-kidney-metabolic-related diseases in non-diabetic and non-obese population: evidence triangulation using Mendelian randomization, observational and polygenic score association analysis.

This evidence-triangulation study assessed whether GLP-1R expression is associated with cardiovascular-kidney-metabolic diseases in non-diabetic and non-obese individuals using Mendelian randomization, polygenic score (PGS) association, and observational analyses. The study aimed to estimate associations of GLP-1R expression with chronic kidney disease (CKD), heart failure (HF), and metabolic dysfunction–associated steatotic liver disease (MASLD) in populations without T2DM or obesity. The results are intended to clarify whether GLP-1R biology supports broader CKM benefits beyond established indications in T2DM/obesity, informing translational targeting of GLP-1R pathways.

Chen Z, Yang Q, Liu J et al. · BMC medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Associations of the combined C-reactive protein-triglyceride glucose index and frailty index in different dimensions with incident stroke among individuals with stages 0-3 cardiovascular-kidney-metabolic syndrome.

This cohort study evaluated how the combined C-reactive protein–triglyceride–glucose index (CTI) and frailty index (FI)—including baseline CTI-FI, cumulative CTI-FI (cuCTI-FI), and trajectory-based CTI-FI (traCTI-FI)—relate to incident stroke among individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0–3. It tested whether combined inflammatory-metabolic burden and frailty predicts stroke risk more strongly than either component alone across different CTI-FI dimensions. The findings are clinically relevant for risk stratification and for identifying modifiable targets (inflammation/metabolism and frailty) to prevent stroke in CKM-spectrum populations.

Zheng H, Zhang Y, Li L et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Evolution of Gastrointestinal Inflammatory Diseases and Neoplasm Burden in Super-Elderly Populations: Integrated GBD 2023, CHARLS, and CLHLS Analyses of China and G20 Countries.

This study analyzed trends in gastrointestinal inflammatory diseases (GIID) and gastrointestinal neoplasms (GIN) in super-elderly adults (age ≥75 years) using integrated data from GBD 2023 plus China’s CHARLS and CLHLS, and compared patterns between China and 19 G20 countries. It quantified changes in incidence, age-standardized rates, and disability-adjusted life years (DALYs) for enteric infections (EI), GIID, and GIN, focusing on temporal trends, sex differences, and age-subgroup patterns. The results are significant for public health planning by identifying how GIID and GIN burdens are evolving despite improvements in enteric infection control in rapidly aging populations.

Wu KJ, Peng W, Li JC et al. · Molecular medicine (Cambridge, Mass.) · (2026) · View on PubMed ↗ · Free PDF ↗

The association between atherogenic index of plasma (AIP) and ultrasound attenuation parameter (UAP) in Chinese adults: a cross-sectional study.

This cross-sectional study evaluated the association between the atherogenic index of plasma (AIP; log10[TG/HDL]) and the ultrasound attenuation parameter (UAP) in 6141 Chinese adults undergoing physical examination. Higher AIP was associated with worse ultrasound attenuation measures (and related cardiometabolic risk patterns) after multivariable adjustment, with additional sex-stratified analyses to address gender imbalance. The results suggest AIP may serve as a simple blood-based marker that correlates with ultrasound-based indicators of metabolic/atherogenic risk in Chinese populations.

Zhao H, Yang D, Li Y et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

Oral Anticoagulation With or Without Antiplatelet Therapy in Chronic Coronary Syndrome: A Meta-Analysis of Randomized Trials.

This meta-analysis studied randomized trials in chronic coronary syndrome (CCS) patients who required long-term oral anticoagulation (OAC), comparing OAC monotherapy versus OAC plus single antiplatelet therapy (SAPT). It found differences in safety and efficacy outcomes between strategies (with hazard ratios and confidence intervals synthesized across eligible trials). The results are significant for guiding antithrombotic regimen selection in CCS patients balancing ischemic protection against bleeding risk when long-term anticoagulation is indicated.

Galli M, Vinciguerra M, Laudani C et al. · JACC. Cardiovascular interventions · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

The Kidney in the Middle: KDIGO Guidelines Address Multiple Key Components of Cardiovascular-Kidney-Metabolic Syndrome.

This Kidney International article studied how KDIGO guidelines address cardiovascular-kidney-metabolic (CKM) syndrome by integrating chronic kidney disease with obesity, diabetes, hypertension, and dyslipidemia. It found that CKM syndrome framing strengthens the need for evidence-based, interdisciplinary approaches to diagnose and prevent intersecting cardiometabolic components. The guideline-focused synthesis is significant for clinicians because it operationalizes CKD’s role in cardiovascular risk within a unified CKM paradigm.

Levin A, Bansal N, de Boer IH et al. · Kidney international · (2026) · View on PubMed ↗

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Kidney disease & renal metabolism/lipotoxicity

CCR5 and CD74 are potential therapeutic targets for necroinflammation in preclinical cholesterol crystal embolism.

The study used a C57BL/6J mouse model of cholesterol crystal embolism (CCE) with unilateral renal artery cholesterol crystal injection to map kidney cell-type responses using single-cell transcriptomics and to identify therapeutic targets for necroinflammation. It found widespread gene-expression changes across 17 kidney cell types and used cell-cell interaction analyses to nominate CCR5 and CD74 as potential targets (with the detailed interaction network truncated in the abstract). This is scientifically significant because it provides targetable inflammatory pathways for preventing CCE-associated acute kidney injury.

Shi C, Wen Z, Zheng K et al. · Science translational medicine · (2026) · View on PubMed ↗

Renal Lipotoxicity: Mechanisms and Therapeutic Perspectives.

This review synthesized evidence on renal lipotoxicity mechanisms in diabetes, detailing how insulin resistance, hyperglycemia, dyslipidemia, and inflammation disrupt renal lipid metabolism to drive chronic kidney disease (CKD) and diabetic kidney disease (DKD). It links toxic lipid deposition to mitochondrial dysfunction and fibrosis and frames renal lipotoxicity as a contributor to the broader cardiovascular–kidney–metabolic (CKM) syndrome. The article highlights emerging therapeutic strategies aimed at lipid-handling pathways as potential interventions to prevent or slow DKD progression.

Zaitoon H, Feigin E, Abdul-Ghani M et al. · Diabetes care · (2026) · View on PubMed ↗

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Respiratory disease & immunology (asthma/COPD/viral)

Differential responses of group 2 innate lymphoid cells and TH2 cells to benralizumab in severe asthma.

This study analyzed 70 patients with severe type 2-high asthma in the multicenter Tokyo Asthma Study to compare cytokine secretion profiles of group 2 innate lymphoid cells (ILC2s) and TH2 cells and relate them to clinical outcomes after benralizumab. Using live-cell imaging of secretion activity, it found differential ILC2 versus TH2 responses that were associated with variability in treatment outcomes. These results support using functional cytokine-secretion phenotyping of ILC2/TH2 biology to better predict and stratify benralizumab responders in severe asthma.

Irie M, Kabata H, Kamatani T et al. · The Journal of allergy and clinical immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Genetically Predicted Use of Common Analgesics and Risk of Chronic Obstructive Pulmonary Disease: A Bidirectional Mendelian Randomization Study.

This bidirectional two-sample Mendelian randomization study used UK Biobank genetic instruments for genetically predicted use of paracetamol, aspirin, and ibuprofen (N=457,547) and FinnGen COPD summary statistics (24,138 cases/409,070 controls) to test causal effects on chronic obstructive pulmonary disease (COPD) risk. Genetically predicted analgesic use showed no clear evidence of a causal relationship with COPD risk in either direction (analgesic use ↔ COPD), arguing against confounding-driven observational associations. Clinically, the results weaken the rationale for analgesic exposure as a causal driver of COPD and highlight the value of MR for disentangling correlation from causation.

Chen G, You W · International journal of chronic obstructive pulmonary disease · (2026) · View on PubMed ↗ · Free PDF ↗

Eosinophilic Depletion with Benralizumab, Mepolizumab, and Depemokimab: A Modeling Study.

This modeling study developed PK/PD models of antibody concentration and blood eosinophil (bEOS) counts in adults to compare eosinophil depletion responses to benralizumab, mepolizumab, and depemokimab using digitized bEOS data and predicted benralizumab responses from individual PK parameters. The simulations indicated differential bEOS depletion dynamics across anti–IL-5/IL-5R therapies, with regimen-dependent magnitude and timing of eosinophil suppression. These results support dose/regimen optimization and trial interpretation for severe eosinophilic asthma by providing a quantitative framework for expected eosinophil kinetics.

Lukka PB, Penland RC, Brekkan A et al. · Journal of asthma and allergy · (2026) · View on PubMed ↗ · Free PDF ↗

Small extracellular vesicle signaling and mitochondrial transfer reprogram T helper cell function in human asthma.

This study investigated how small extracellular vesicles (sEVs) from myeloid-derived regulatory cells (MDRCs) in human asthma mediate T helper cell reprogramming via mitochondrial transfer. Airway MDRC-derived sEVs from asthmatics transferred mitochondria that triggered antigen-specific activation and polarization toward Th17 and Th2 phenotypes, mediated by mitochondrial oxidant-dependent NF-κB signaling, and blockade of this pathway reduced CD4+ T cell activation. These findings identify a mitochondria-carrying sEV signaling axis as a mechanistic driver of asthmatic airway inflammation and a potential therapeutic target.

Hough KP, Trevor JL, Ahmad S et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

The Italian registry for narcolepsy and central disorders of hypersomnolence (ReN&IS): Baseline clinical and diagnostic findings.

The study reported baseline clinical and diagnostic findings from the Italian Registry for Narcolepsy and Central Disorders of Hypersomnolence (ReN&IS), a national multicenter observational cohort established in 2022, covering patients with central disorders of hypersomnolence including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH). The key contribution is the characterization of real-world phenotypes and diagnostic patterns at registry baseline to support improved recognition and harmonized data for translational research. This registry foundation enables large-scale, standardized epidemiologic and diagnostic analyses for rare hypersomnolence disorders.

Torreri P, Buoncuore G, Rocchetti A et al. · Sleep medicine · (2026) · View on PubMed ↗ · Free PDF ↗

High-Dose vs Standard-Dose Influenza Vaccines in Older Adults: A Meta-Analysis.

This meta-analysis synthesized randomized clinical trial evidence comparing high-dose inactivated influenza vaccine (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) in older adults. The key finding was that HD-IIV was associated with improved prevention of clinically important outcomes, including hospitalization events and mortality, relative to SD-IIV. Scientifically and clinically, the pooled results support preferential use of HD-IIV in older populations to enhance protection against severe influenza outcomes.

Skaarup KG, Lassen MCH, Hosseini K et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

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Infectious diseases: viruses, bacteria & zoonoses

Temperate phages enhance bacterial host fitness via RNA-guided flagellar remodelling.

This study examined how a flagellin-remodeling prophage (FRφ) in a human clinical Enterobacter isolate uses the phage-encoded RNA-guided transcription factor TldR to alter flagellar composition and host fitness. FRφ exploited TldR and a specific flagellin isoform to increase bacterial motility and enable mammalian immune evasion. The work links phage RNA-guided regulation of flagellin to clinically relevant bacterial adaptation, suggesting new targets for controlling bacterial virulence and immune escape.

Walker MWG, Richard E, Wiegand T et al. · Nature microbiology · (2026) · View on PubMed ↗

Heavy metal transfer and health risk assessment in an abandoned zinc mining-affected soil-rice system in western Thailand.

This study assessed heavy metal transfer and health risks in an abandoned zinc mining–affected soil–rice system in western Thailand by sampling soil and rice compartments from 20 paddy fields. It quantified multiple metals (As, Cd, Cr, Cu, Mn, Pb, Zn, Hg, Fe), estimated compartment-specific transfer factors (soil-root, root-stem, stem-grain), and evaluated soil properties that influence metal retention and mobility. The findings identify how mining-derived contaminants move into edible rice and quantify associated health risks, informing remediation and food-safety interventions.

Arunrat N, Sereenonchai S, Sagulkiatpanya T et al. · Environmental geochemistry and health · (2026) · View on PubMed ↗

Limited transmission of cervid prions to nonhuman primates provides insights into the zoonotic potential of chronic wasting disease.

The study assessed the zoonotic potential of chronic wasting disease (CWD) prions by inoculating cynomolgus macaques and measuring prion presence using sensitive in vitro prion amplification assays. Although most macaques remained asymptomatic, low levels of prions were detected in macaque tissues, and inoculation of transgenic mice and bank voles with macaque tissues produced 100% transmission rates upon serial passage. These results are significant because they suggest CWD prions can retain infectivity across species barriers, informing risk assessment for zoonotic transmission.

Hannaoui S, Pritzkow S, Jürgens-Wemheuer WM et al. · Science advances · (2026) · View on PubMed ↗

Multiple defects in macrophage antibacterial responses support intracellular survival of Mycobacterium abscessus in cystic fibrosis.

This study used human primary monocyte-derived macrophages (MDMs) from healthy controls and people with cystic fibrosis (pwCF) to examine how macrophages process and kill Mycobacterium abscessus (MABS). CF-MDMs showed reduced expression of phagocytosis-related pattern recognition receptors (TLR2, Dectin-1, Dectin-2, MARCO), reduced engulfment and lysosomal acidity, and additional mitochondrial dysfunction features that together supported intracellular MABS survival. These findings identify multiple macrophage defects in CF as mechanistic drivers of MABS persistence and suggest targets to improve intracellular antibacterial immunity in pwCF.

Tarique AA, Emming S, Kelk D et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

PRRSV NSP2 hijacks host lipophagy via a LIPE-PNPLA2-AMPK-MTOR axis to promote viral replication.

This study examined how porcine reproductive and respiratory syndrome virus (PRRSV) uses its nonstructural protein NSP2 to promote viral replication by hijacking host lipophagy. PRRSV infection triggered lipophagy with lipid droplet depletion and increased free fatty acids, and NSP2 was required by directly interacting with lipid-associated lipases LIPE and PNPLA2 to activate a LIPE–PNPLA2–AMPK–mTOR axis. These mechanistic findings identify a host metabolic signaling pathway that PRRSV exploits, suggesting potential antiviral strategies targeting lipophagy regulation.

Zhu Z, Lin Q, Zhang X et al. · Autophagy · (2026) · View on PubMed ↗

Monitoring viral evolution and epidemiological characteristics of SARS-CoV-2 during 2022-2023 using Integrated Genomic Surveillance.

This study used Germany’s Integrated Molecular Surveillance for SARS-CoV-2 (IMSSC2) network to monitor SARS-CoV-2 genomic evolution and epidemiological characteristics during 2022–2023, combining routine whole-genome sequencing with epidemiological and laboratory phenotype data. The integrated approach enabled timely detection and characterization of emerging variants alongside changes in transmissibility and immune-evasion–related properties. This provides a scalable surveillance framework for public health decision-making by linking viral genotype, phenotype, and population-level epidemiology.

Mache C, Kerber R, Schulze J et al. · Communications medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Hantavirus infection: A narrative review focusing on epidemiology, diagnosis, infection control and treatment in the era of globalisation.

This narrative review studied the epidemiology, diagnosis, infection control, and treatment of hantavirus infections in the context of globalisation, with emphasis on Andes virus (ANDV) in South America. It found that hantaviruses are zoonotic RNA viruses transmitted mainly via inhalation of aerosolized rodent excreta, and that ANDV uniquely shows sustained person-to-person transmission in Argentina and Chile. The review highlights clinically important implications for intensive care management and infection prevention strategies for HCPS, especially for ANDV outbreaks.

Chediack V, Calvo M, Cunto E et al. · Medicina intensiva · (2026) · View on PubMed ↗

Volatile signaling in plant-Metarhizium-insect interactions: Implications for nitrogen cycling.

This study examined plant–Metarhizium–insect interactions to determine how nitrogen cycling is influenced by volatile compounds produced during symbiosis. The key finding was that the endophytic entomopathogenic fungus Metarhizium robertsii degrades the root antifungal caulilexin C to generate the volatile 1-methoxyindole, which is detected by the Drosophila Or74a olfactory receptor and attracts multiple Dipteran species. This is significant because it links microbial metabolism of plant defense compounds to insect behavior and ecosystem nitrogen cycling.

Tang X, Feng T, Yu C et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Perturbation of RNA homeostasis impairs mitochondrial respiration during poxvirus infection through excess RNA accumulation.

This study investigated how perturbing RNA homeostasis affects mitochondrial respiration during poxvirus infection, focusing on vaccinia virus infection and the role of viral decapping enzymes and host RNA exonuclease. The key finding was that impaired RNA degradation—via depletion of viral decapping enzymes or cellular exonuclease—caused excess RNA accumulation and severely compromised mitochondrial respiration. This is significant because it reveals a previously underappreciated host/viral RNA-processing requirement for maintaining mitochondrial function during poxvirus infection.

Brahim Belhaouari D, Pant A, Navarro-Forero S et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

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Liver disease & hepatology (including SLD/PBC)

Membrane bridges and nanodomain partitioning govern membrane protein targeting to lipid droplets.

This study examined the physical mechanisms governing how ER membrane proteins are targeted to lipid droplets (LDs), focusing on membrane bridges and nanodomain partitioning. Using minimal fluorescence photon fluxes nanoscopy, highly inclined and laminated optical single-molecule tracking, and machine learning, the authors found that ER-to-LD targeting involves diffusion behaviors and partitioning governed by membrane-bridge/nanodomain organization for cargos including HSD17B13 and GPAT4 (and a model cargo). Scientifically, this clarifies the biophysical rules of LD protein trafficking and helps explain mislocalization of LD-targeted proteins implicated in steatotic liver disease.

Mizrak A, Kæstel-Hansen J, Matthias J et al. · Nature cell biology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

EASL position paper on preclinical models of steatotic liver disease.

This EASL position paper studied the adequacy and use of preclinical models for steatotic liver disease (SLD), including MASLD (formerly NAFLD), MetALD, alcohol-associated liver disease, and less common drug-induced, monogenic, and cryptogenic causes. It concluded that SLD is heterogeneous and that model selection should match the specific etiologic subtype and disease stage (steatohepatitis and progressive fibrosis). The consensus is significant for improving translational validity of preclinical studies and for guiding future therapeutic development across different SLD populations.

Gallage S, Castro RE, Estall J et al. · Journal of hepatology · (2026) · View on PubMed ↗

EASL-AASLD Delphi consensus statement on surrogate endpoints and real-world evidence in primary biliary cholangitis.

This EASL-AASLD Delphi consensus statement studied surrogate endpoints and real-world evidence (RWE) for primary biliary cholangitis (PBC) drug development, focusing on regulatory acceptance of biomarkers and patient-reported outcomes (PROs). It found that reliance on liver biochemistry and non-invasive fibrosis measures has limited regulatory validation as efficacy endpoints, and that PROs and RWE integration are not yet harmonized or standardized. The statement is clinically significant because it provides a framework to improve endpoint selection and evidence generation for achieving full regulatory approvals in PBC.

Journal of hepatology · (2026) · View on PubMed ↗

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Gastrointestinal disease & colorectal cancer screening

Colorectal cancer screening: An update to the American Cancer Society guideline, 2026.

This guideline update evaluated evidence for colorectal cancer (CRC) screening in the United States, including diagnostic performance of newly approved molecular tests such as multitarget stool RNA (mt-sRNA), next-generation mt-sDNA, and blood-based cell-free DNA assays. It updates the American Cancer Society (ACS) recommendations in light of regulatory approvals and modeling data, particularly as screening has expanded to average-risk adults starting at age 45. The update provides clinicians with an evidence-based framework for selecting modern stool- and blood-based screening options to reduce CRC incidence and mortality.

Wolf AMD, Hoffman RM, Walter LC et al. · CA: a cancer journal for clinicians · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

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Endocrine/metabolic interventions (GLP-1, ketogenic, supplements)

Effects of Coenzyme Q10 on Lipid, Glycemic, and Inflammatory Markers in Metabolic Disorders: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis assessed the effects of coenzyme Q10 (CoQ10) on lipid profile, glycemic control, and inflammatory markers by pooling randomized controlled trials (64 RCTs; 3422 participants). Using random-effects models, the analysis synthesized weighted mean differences/standardized mean differences to quantify changes in metabolic and inflammatory outcomes attributable to CoQ10. The findings inform evidence-based consideration of CoQ10 as a nutritional supplement strategy for metabolic disorders, while highlighting which biomarkers show the most consistent benefit.

Zhang Z, Liu Z, Geng Y et al. · Journal of diabetes research · (2026) · View on PubMed ↗ · Free PDF ↗

Very low-carbohydrate ketogenic diet in treatment-naïve women with endometrial cancer and overweight: a randomized feasibility study.

This randomized feasibility trial (NCT03285152) studied a very-low-carbohydrate ketogenic diet (VLCD) versus a standard diet in 19 treatment-naïve women with endometrial cancer and overweight/obesity over 21–28 days. The VLCD was feasible and well tolerated (high meal adherence, ~5.5% weight loss, and no grade 3/4 adverse events), with fasting glucose and insulin decreasing and exploratory tumor biology and circulating metabolic biomarkers assessed as secondary endpoints. These results support the practicality of ketogenic dietary intervention in this patient group and justify larger efficacy-focused trials.

Dantas E, Hootman KC, Moyer J et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Once-Weekly Semaglutide in Adults With Daily Cigarette Use: A Randomized Clinical Trial.

This phase 2a randomized clinical trial evaluated once-weekly semaglutide versus placebo in adults with daily cigarette use, with embedded human laboratory sessions at an academic medical center. The key finding was that semaglutide improved smoking-related outcomes (including cigarette use and craving) and also affected weight-related measures compared with placebo. Clinically, it supports the potential repurposing of the GLP-1 receptor agonist semaglutide as an adjunct pharmacotherapy for smoking cessation and cardiometabolic risk reduction.

Hendershot CS, Bremmer MP, Paladino MB et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

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Epigenetics & genome regulation

A Global Update on the Status of Prevention of Folic Acid-Preventable Spina Bifida and Anencephaly in Year 2024.

This study estimated the proportion of folic acid–preventable spina bifida and anencephaly (FAP SBA) prevented globally in 2024 under mandatory folic acid fortification of cereal grains (wheat flour, maize flour, rice) using country fortification data. The model used 69 countries with complete 2024 data and predicted the fraction of FAP SBA prevented based on assumed maternal folic acid intake thresholds (>150 mcg/day, truncated in the abstract). These findings provide a 2024 global public-health estimate of how effective mandatory folic acid fortification policies are for reducing neural tube defects.

Kancherla V, Wagh K, Pachón H · Birth defects research · (2026) · View on PubMed ↗

Structural basis of Wnt signalosome extracellular complex assembly.

The study used cryo-electron microscopy (cryo-EM) to determine the structural basis of extracellular Wnt signalosome assembly involving Wnt3a, Frizzled 8 (Fzd8), and LRP6. The authors resolved a Wnt3a/Fzd8/LRP6 complex in a 2:4:2 stoichiometry where Wnt3a forms a homodimer and each Wnt3a monomer binds two Fzd8 receptors and one LRP6 co-receptor, implying Wnt-induced Fzd cystine-rich domain (Fzd-CRD) tetramerization. This structural mechanism clarifies how simultaneous receptor engagement by Wnt3a can trigger canonical Wnt/β-catenin signaling.

Yue D, Sun G, Cao Y et al. · Cell · (2026) · View on PubMed ↗

PIWIL3-piRNA pathway controls rabbit oogenesis and embryogenesis via broad regulation of the transcriptome and proteome.

This study examined the role of the Piwi-piRNA pathway gene PIWIL3 in rabbit oogenesis and embryogenesis using CRISPR-Cas9 knockout and related functional assays. PIWIL3 is the predominant PIWI protein in rabbit oocytes, and PIWIL3 loss causes severe defects in oogenesis and impaired female fertility. The work establishes PIWIL3 as a conserved, functionally essential regulator of mammalian female reproduction and provides a rabbit model to study human PIWI-piRNA biology.

Gong Y, Shi S, Li L et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Epigenetic programming by H3K23ac defines lineage fate of Meg3+ haematopoietic stem cells and drives immune ageing.

This study investigated how epigenetic programming by H3K23ac shapes the lineage fate of Meg3+ hematopoietic stem cells (HSCs) during immune ageing. In aged Meg3+ HSCs, inflammatory signals increase H3K23ac and enhance PU.1 activity, driving expansion of a specific Meg3+ long-term HSC subset and skewing differentiation toward myeloid/megakaryocyte lineages at the expense of lymphocytes. These results link a defined histone modification to transcriptional control of HSC fate and identify a potential epigenetic lever to mitigate age-associated immune dysfunction.

Wei N, Zhan H, Deng Y et al. · Nature cell biology · (2026) · View on PubMed ↗ · Free PDF ↗

Selective cellular localization of UHRF1 safeguards mammalian zygotic genome activation and early embryonic development.

This study investigated how selective nuclear localization of the epigenetic factor UHRF1 regulates zygotic genome activation (ZGA) in mouse embryos using an Nlrp14-deficient model that disrupts UHRF1 and DNMT1 zygotic localization. Nuclear exclusion of UHRF1 (and DNMT1) was required for proper LINE1 DNA demethylation and for successful ZGA and early embryonic development. These findings identify a specific spatial “gating” mechanism controlling DNA demethylation during mammalian ZGA, linking UHRF1 localization to early developmental epigenetic reprogramming.

Yan R, Cheng X, Long X et al. · Cell discovery · (2026) · View on PubMed ↗ · Free PDF ↗

Design principles of a membrane-spanning ubiquitin ligase.

The study used cryo-electron microscopy plus biophysical and functional assays to define the structure and signaling mechanism of a human membrane-spanning ubiquitin ligase complex composed of MEGF8, MOSMO, and the intracellular RING-family protein MGRN1 in the context of Hedgehog pathway signaling. The MEGF8–MOSMO–MGRN1 (MMM) complex attenuates Hedgehog signaling by ubiquitylating the GPCR Smoothened (SMO), with a long helix engaging SMO via an intramembrane degron and extending to the cytoplasm to regulate SMO activation. This structural mechanism clarifies how extracellular morphogen signals are converted into SMO ubiquitylation and provides a blueprint for targeting receptor-type E3 ligases in Hedgehog-driven disease.

Williams C, Nocka LM, Hedger G et al. · Molecular cell · (2026) · View on PubMed ↗

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Bioengineering, imaging & computational methods

Genomic and population analyses reveal asymmetric subgenome evolution and local adaptation in the polyploid Lycopus lucidus.

This study generated a chromosome-level genome assembly and population genomic datasets for the polyploid medicinal plant Lycopus lucidus to determine how asymmetric subgenome evolution drives local adaptation across China. The genome revealed a recent whole-genome triplication, with three subgenomes showing unequal transposable element accumulation, gene retention, and evolutionary rates, where subgenome B was stabilized by strong purifying selection while subgenomes A and C underwent dynamic reorganization. The findings clarify how subgenome asymmetry after polyploidization contributes to ecological adaptation, informing evolutionary genomics of medicinal polyploid species.

Zhang R, Wang M, Jiang F et al. · Communications biology · (2026) · View on PubMed ↗

Open-channel block of human TRPV6 by polyamine spermine.

This study characterized the structural and functional mechanism of how the polyamine spermine blocks the human TRPV6 ion channel. Using calcium imaging, electrophysiology, cryo-electron microscopy, mutagenesis, and molecular dynamics simulations, the authors found that spermine produces a voltage-dependent block of TRPV6-mediated currents. This provides a mechanistic basis for polyamine regulation of TRPV6, which is relevant to TRP-channel roles in pain, inflammation, and cancer.

Neuberger A, Veretenenko II, Shalygin A et al. · Nature communications · (2026) · View on PubMed ↗

Modeling the thermal behavior of photopolymers for in-space fabrication.

This study modeled and experimentally validated the thermal behavior of photopolymer-based processes for in-space fabrication under microgravity conditions. Using International Space Station (ISS) experiments and a parabolic flight campaign, the authors combined measurements with modeling to address heat management challenges that can cause defects like surface blistering and deformation. The results support more reliable photopolymer manufacturing in microgravity by enabling predictive control of curing-related thermal effects.

Ericson J, Widerker D, Stibbe E et al. · NPJ microgravity · (2026) · View on PubMed ↗

Spatiotemporal transcriptome atlas of human embryos after gastrulation.

This study created a spatiotemporal transcriptome atlas of human embryos after gastrulation by profiling gene expression across 77 sagittal sections of 13 whole-human embryos (Carnegie stages 12–23) using Stereo-seq and integrating results with single-nucleus RNA sequencing. It revealed cellular heterogeneity underlying organ-specific differentiation and produced regulatory profiles for development of 50 organs and 198 substructures. This atlas provides a high-resolution reference for mapping human developmental gene programs and identifying candidate regulatory events relevant to congenital disease origins.

Pan J, Li Y, Lin Z et al. · Nature · (2026) · View on PubMed ↗

Universal transcriptomic hallmarks of mammalian ageing and mortality.

This study integrated over 11,000 transcriptomes from more than 25 tissues across four mammals (mouse, rat, macaque, human) to derive universal transcriptomic biomarkers of chronological age and expected mortality. It found conserved, interpretable ageing-related signatures across species and cell types, including CDKN1A and LGALS3, and used these to predict lifespan-modulating interventions, time to death, chronic disease risk, and rejuvenation outcomes. The work provides cross-species molecular hallmarks that can be used to benchmark interventions and improve prediction of ageing and mortality trajectories.

Tyshkovskiy A, Kholdina D, Davitadze M et al. · Nature · (2026) · View on PubMed ↗

β-Arrestin condensates regulate G-protein-coupled receptor function.

The study examined how β-arrestin 1 and β-arrestin 2 regulate G-protein-coupled receptor (GPCR) signaling by forming liquid-liquid phase separation (LLPS) condensates in cells. The authors found that β-arrestins undergo LLPS to create condensates that localize near GPCRs via β-arrestin oligomerization, thereby modulating GPCR function. This mechanistic link between β-arrestin condensates and GPCR signaling provides a new framework for understanding drug-targetable GPCR regulation and biased signaling.

Anderson PJ, Xiao P, Zhong YN et al. · Nature · (2026) · View on PubMed ↗

Stem-Cell-Derived Biologic Ventricular Assist Tissue in Heart Failure.

The study investigated the safety and early efficacy of stem-cell-derived biologic ventricular assist tissue (BioVAT) in an open-label phase 1–2 trial in patients with heart failure and left ventricular ejection fraction ≤35%. BioVAT, composed of engineered heart muscle units made from allogeneic induced pluripotent stem cell–derived cardiomyocytes and stromal cells, was transplanted at 5, 10, or 20 units to achieve cardiac remuscularization. This work is clinically significant because it tests a scalable, off-the-shelf regenerative tissue approach for improving function in advanced systolic heart failure.

Zimmermann WH, Ensminger S, Kutschka I et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Death following high-dose AAV9 gene therapy in a patient with advanced SMA-PME.

This first-in-human case report studied intravenous AAV9 gene therapy delivering the human ASAH1 coding sequence in a 15-year-old female with advanced spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) carrying heterozygous ASAH1 mutations (c.456A>C and c.918-2A>G). The patient experienced marked clinical deterioration and death following high-dose AAV9 administration (2.2×10^14 vector genomes/kg), despite no detectable anti-AAV9 neutralizing antibodies. The report is clinically significant because it highlights a serious safety risk for AAV9-based ASAH1 gene therapy in advanced disease and underscores the need for careful risk mitigation and monitoring in future trials.

Boespflug-Tanguy O, Valent A, Rambaud J et al. · Molecular therapy : the journal of the American Society of Gene Therapy · (2026) · View on PubMed ↗

Personalized neoadjuvant treatment regimen selection in locally advanced rectal cancer based on regimen-specific response modeling.

This study developed and validated a deep learning framework to personalize neoadjuvant regimen selection for locally advanced rectal cancer (LARC) by estimating patient-specific probabilities of pathological complete response (pCR) across multiple treatment options. Using a multicenter cohort and a hard-gated mixture-of-experts model integrating pretreatment multiparametric MRI and clinical variables, the system generated regimen-specific pCR probabilities to support clinician-led decision-making with strong predictive performance (reported via AUC). This approach could reduce over- or undertreatment by moving rectal cancer neoadjuvant selection from population-based rules toward individualized, data-driven modeling.

Liu X, Tang Y, Zhang S et al. · NPJ digital medicine · (2026) · View on PubMed ↗ · Free PDF ↗

SlSAM3 interacts with SlACS4 to facilitate brassinosteroid signaling-mediated tomato (Solanum lycopersicum) fruit coloring.

This study tested how the brassinosteroid (BR) signaling pathway controls tomato fruit coloring by identifying protein interactions involving SlSAM3 and SlACS4. Exogenous 24-epibrassinolide (EBR) induced SlSAM3 expression and promoted fruit coloration and ethylene production, and SlSAM3 knockout/overexpression showed SlSAM3 is required for BR-mediated coloration. The study further reports that SlSAM3 interacts with SlACS4 to facilitate BR signaling output, positioning this module as a regulator of climacteric fruit ripening.

Xuetong W, Ailing L, Huan C et al. · Communications biology · (2026) · View on PubMed ↗ · Free PDF ↗

Uncovering spatially resolved functional genomics with CRISPR screen sequencing.

This study developed spatial CRISPR screen sequencing (SPAC-seq) and the TARDIS statistical toolkit to link gene perturbations to spatial phenotypes in tissues. Using SPAC-seq/TARDIS, it found that Icam1 loss in tumor cells promotes metastasis via immune suppression and macrophage polarization, and it identified Cd44’s role in CD8+ T cells (with additional spatial pathway mapping). The approach is scientifically significant because it enables systematic, spatially resolved functional genomics to prioritize genes and pathways driving tumor–immune interactions.

Zhang H, Zhang Z, Wang P et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Structural basis for RISC assembly of human Argonaute2.

The study determined how human Argonaute 2 (AGO2) assembles the RNA-induced silencing complex (RISC) by solving four cryo-electron microscopy structures of AGO2 bound to an siRNA duplex and capturing assembly intermediates. The structures show that the MID-PIWI lobe secures one duplex end while α-helix 14 stabilizes it, and that N-domain engagement triggers passenger-strand removal from the 5’ end while keeping the guide seed paired, with the PAZ domain engaging the guide 3’ end. These mechanistic insights into AGO2 RISC assembly improve the molecular understanding of siRNA strand selection, informing therapeutic design of RNAi-based interventions.

Zhang H, Adhav VA, Kehling AC et al. · Molecular cell · (2026) · View on PubMed ↗ · Free PDF ↗

Uncovering the initial response: Intra-mitochondrial surveillance activates the UPRmt.

The study used a chemogenetic approach in yeast to induce mild, intra-mitochondrial hydrogen peroxide (H2O2) stress and test how the mitochondrial unfolded protein response (UPRmt) is activated under physiologic-like conditions. Mild oxidative stress triggered UPRmt independently of cytosolic damage signals, identifying an initial mitochondrial surveillance step (presequence-dependent) that initiates the response. This reframes UPRmt activation as an intra-mitochondrial sensing process during gradual oxidative stress (e.g., aging or chronic respiratory defects), with implications for understanding mitochondrial proteostasis and stress adaptation.

Taskin AA, Shankar S, Peselj C et al. · Molecular cell · (2026) · View on PubMed ↗ · Free PDF ↗

Plug-and-play assembly of biodegradable ionizable lipids for potent mRNA delivery and gene editing in vivo.

This study investigated a plug-and-play combinatorial chemistry approach to assemble biodegradable ionizable lipids for mRNA delivery and in vivo gene editing, using screening and machine learning to optimize lipid structures and testing in wild-type and genetically modified mice. The key finding was that after screening 500 ionizable lipids, the authors derived structure–activity relationships and identified a lead ionizable lipid that formed potent lipid nanoparticles delivering multiple gene-editing tools in vivo. This is significant because it provides a scalable lipid design platform that can improve mRNA-based gene editing therapeutics by enhancing delivery efficiency.

Han X, Xu Y, Ricciardi AS et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Effect of Electroacupuncture on Postherpetic Neuralgia: A Randomized Clinical Trial.

This multicenter, randomized, sham-controlled clinical trial studied electroacupuncture for postherpetic neuralgia (PHN) in patients enrolled at 7 tertiary hospitals in China. The key finding was that electroacupuncture reduced PHN pain severity compared with sham electroacupuncture while maintaining an acceptable safety profile. Clinically, the results provide higher-quality evidence that electroacupuncture can be an effective and safe nonpharmacologic option for refractory neuropathic pain.

Chen L, Liu Q, Pei L et al. · JAMA neurology · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on May 28, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.