PubMed Trending Research Digest — June 18, 2026

Automated digest · 97 articles · 15 research areas · June 18, 2026

Overview

Across this week’s set of papers, a dominant theme is the use of mechanistic biology to explain—and potentially control—disease trajectories. Multiple studies connect cellular “systems” (proteostasis, organelle contact biology, epigenetic locking of innate immune sensing, and senescence/inflammaging pathways) to functional outcomes: from meiotic crossover patterning and chromosome pairing to cardiac aging, neurodegeneration, and tumor progression. In parallel, several cancer papers emphasize immune evasion and microenvironmental control—showing how ECM glycosylation, stromal metabolic brakes, macrophage cholesterol/oxysterol signaling, and TGFβ pathway activation can suppress or reshape anti-tumor immunity.

A second major thread is translational and clinical decision support, spanning both therapeutic trials and risk stratification tools. Oncology appears repeatedly, including vaccine/maintenance strategies after transplant, neoadjuvant immunotherapy approaches in stage III NSCLC, and targeted therapies designed to overcome resistance (e.g., KRAS G12D inhibition resistance). Outside oncology, studies address cardiovascular risk prediction (including imaging- and biomarker-derived embeddings), medication safety signals, and standardized clinical frameworks (e.g., remission-oriented airway disease management, dynamic risk stratification in differentiated thyroid cancer, and consistent CIDP outcome definitions). Finally, several papers highlight emerging technologies—AI for prenatal cleft detection and autonomous EHR agents, plus advanced proteomics/spatial profiling and bioelectric sensors—suggesting that next-generation diagnostics and mechanistic mapping are increasingly converging to guide therapy selection and monitoring.

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Cancer immunotherapy & immune evasion

Bispecific Antibody Ivonescimab Added to Chemotherapy in EGFR-Variant Non-Small Cell Lung Cancer: The HARMONi-A Randomized Clinical Trial.

This randomized, double-blind, placebo-controlled phase 3 trial tested whether adding ivonescimab (a bispecific antibody targeting PD-1 and VEGF) to chemotherapy improves overall survival in patients with EGFR-variant nonsquamous NSCLC who progressed after prior EGFR TKI therapy. The study’s final overall results (HARMONi-A) assessed survival benefit in a China-based multicenter cohort of 55 sites. If positive, this would establish a new post-TKI treatment paradigm combining immune/angiogenic targeting with chemotherapy for EGFR-variant NSCLC.

Fang W, Zhao Y, Luo Y et al. · JAMA · (2026) · View on PubMed ↗

Targeting oncogenic TβRI signaling inhibits androgen-independent prostate cancer growth and metastasis.

The study developed fully human monoclonal antibodies designed to prevent proteolytic cleavage of the transforming growth factor-beta type I receptor (TβRI) by steric hindrance, thereby blocking ADAM17/TACE-mediated generation of the soluble TβRI intracellular domain (TβRI-ICD). In models of metastatic castration-resistant prostate cancer (mCRPC), inhibiting oncogenic TβRI signaling suppressed androgen-independent prostate cancer growth and metastasis. These findings are clinically significant because they support a receptor-cleavage blockade strategy to interrupt TGFβ-driven metastatic progression in advanced prostate cancer.

Flodbring Larsson P, Schmidt A, Mu Y et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

The IKKα-regulated microRNA miR-9-5p mediates lung cancer growth and invasiveness via CDH1/Wnt/β-catenin signalling.

In non-small cell lung cancer (NSCLC) cells, the study examined how silencing IKKα alters microRNA expression using Nanostring miRNome profiling and then tested miR-9-5p function in human lung cancer models. IKKα depletion upregulated miR-9-5p, and miR-9-5p overexpression increased migration, invasion, and EMT by reducing E-cadherin and activating the Akt1/β-catenin signaling axis. These findings position the IKKα→miR-9-5p→CDH1/Wnt/β-catenin pathway as a mechanistic driver of NSCLC aggressiveness and a potential therapeutic target.

Besta S, Roupakia E, Kanaki Z et al. · Cell death discovery · (2026) · View on PubMed ↗ · Free PDF ↗

SEMA6A inhibits tumor progression and boosts anti-tumor immunity via blocking the ISG15/TGFβ axis in colorectal cancer.

In colorectal cancer (CRC) models, the study investigated whether Semaphorin 6A (SEMA6A) affects tumor progression and anti-tumor immunity, using integrated RNA-seq/proteomics to identify downstream effectors. SEMA6A was downregulated in CRC and low expression associated with worse prognosis, and SEMA6A overexpression inhibited tumor growth in vitro and in vivo by blocking the ISG15/TGFβ axis, with ISG15 identified as a key downstream effector. This mechanistic link suggests restoring SEMA6A signaling could enhance anti-tumor immunity and counter CRC immune evasion.

Zhang F, Zhang R, Yan Z et al. · Molecular biomedicine · (2026) · View on PubMed ↗ · Free PDF ↗

Programmable mRNA 3’UTR engineering restores MHC-I and overcomes immune evasion in prostate cancer.

In prostate cancer, the authors developed a programmable RNA engineering platform (3’UTRCES) to manipulate mRNA alternative polyadenylation in vivo and restore MHC-I expression to overcome immune evasion. They identified tumor-specific 3’UTR shortening of the E3 ligase adaptor SPSB1 as a driver of MHC-I degradation via SPSB1-mediated ubiquitination (without affecting PD-L1), and used 3’UTRCES delivered by lipid nanoparticles to reverse this immune escape mechanism. This provides a targeted, antigen-presentation-restoring strategy that could sensitize prostate tumors to immunotherapy.

Huang F, Yuan F, Li K et al. · Nature biomedical engineering · (2026) · View on PubMed ↗

Targeting PID1 generates oxysterols to switch macrophage cell fates for improved antitumor immunity.

The study investigated how phosphotyrosine interaction domain-containing protein 1 (PID1) regulates tumor-associated macrophage (TAM) fate in human pan-cancers and tested the consequences of PID1 deficiency in myeloid cells. PID1 deficiency increased LDL receptor expression, promoting LDL uptake and intracellular free cholesterol accumulation that elevated reactive oxygen species (ROS) and drove cholesterol oxidation to oxysterols (including 5α,6α-epoxycholesterol and 7β-hydroxycholesterol), thereby switching macrophage cell fates toward improved antitumor immunity. These findings identify PID1–cholesterol–oxysterol signaling as a mechanistic target to reprogram TAMs for cancer immunotherapy.

Zheng Y, Wang Q, Dong C et al. · Nature cancer · (2026) · View on PubMed ↗

Neoadjuvant retlirafusp alfa (anti-PD-L1/TGF-β bifunctional fusion protein) with or without chemotherapy in unresectable stage III non-small cell lung cancer: updated results from the phase 2 TRAILBLAZER trial.

The study reported updated phase 2 TRAILBLAZER trial results evaluating neoadjuvant retlirafusp alfa (anti–PD-L1/TGF-β fusion protein) with or without chemotherapy in unresectable stage III non-small cell lung cancer (NSCLC) without EGFR or ALK alterations. The key finding was the trial’s updated efficacy and outcomes by treatment allocation strategy based on PD-L1 expression (retlirafusp alfa plus chemotherapy for non–high PD-L1; randomized retlirafusp alfa combination for high PD-L1), followed by surgery or radiotherapy and consolidation retlirafusp alfa. This informs neoadjuvant immunotherapy strategies for stage III NSCLC by clarifying how retlirafusp alfa regimens perform across PD-L1-defined subgroups.

Pan Y, Yang X, Zhou Q et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Glycosylated extracellular matrix drives immune suppression by modulating macrophage-T cell crosstalk in triple-negative breast cancer.

This study analyzed triple-negative breast cancer (TNBC) using comprehensive multi-omics profiling to determine how tumor extracellular matrix (ECM) glycosylation drives immune suppression through macrophage–T cell crosstalk. It identified that post-translational glycan modifications on ECM proteins mediate immunosuppressive behavior, and targeted enzymatic removal of these ECM glycans in decellularized TNBC samples altered macrophage–T cell interactions. This supports glycosylated ECM as a causal immunosuppressive mechanism in TNBC and suggests glycan-targeting strategies to enhance anti-tumor immunity.

Tarantola L, Tyler EJ, Liu Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer genomics, biomarkers & risk prediction

GWAS meta-analysis provides new insights into uveal melanoma risk.

Using germline data from nine studies (5 novel uveal melanoma GWAS plus four prior GWAS) totaling 5839 uveal melanoma cases and 349,863 controls, the authors performed fixed-effects inverse-variance weighted GWAS meta-analysis and follow-up TWAS to nominate risk genes. The meta-analysis identified new genetic insights into uveal melanoma susceptibility and used TWAS to prioritize candidate target genes at risk loci. This improves understanding of inherited risk architecture for uveal melanoma and can guide downstream functional studies of implicated genes.

D’Mellow M, Wang H, Palmer JM et al. · British journal of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Automated and personalized glioblastoma tumor organoid drug screening platform exposes sensitivity to proteasome and HDAC inhibitors.

The study created an automated, personalized high-throughput drug screening platform using standardized patient-derived glioblastoma tumor organoids (TOs) from 11 glioblastoma patients. The key finding was that the organoid-based aHTS identified low-concentration sensitivities to proteasome inhibitors (carfilzomib, bortezomib, ixazomib) and histone deacetylase (HDAC) inhibitors (panobinostat and related agents, as reported in the abstract). This supports precision oncology by linking patient-specific GBM organoid phenotypes to actionable drug vulnerabilities.

Jungwirth G, Paul A, Wöllner A et al. · NPJ precision oncology · (2026) · View on PubMed ↗ · Free PDF ↗

A preoperative Artificial Intelligence model to estimate cancer-specific mortality in nonmetastatic kidney cancer patients.

The study developed and validated a preoperative, interpretable machine-learning model to estimate cancer-specific mortality in nonmetastatic kidney cancer patients using real-world clinical data. The key finding was that a survival-tree approach combining random survival forests with white-box modeling achieved performance in a cohort of 2536 patients and was externally validated in 580 patients using exactly eight preoperative features (e.g., tumor size and lymph node involvement). This enables more precise, pre-surgery risk stratification to support clinical decision-making in nonmetastatic renal cell carcinoma.

Larcher A, Traverso A, Scuri P et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

AKAP1 enhances glycogen accumulation and hepatocarcinogenesis through YTHDF2-mediated G6PC mRNA decay.

This study investigated the role of A-kinase anchoring protein 1 (AKAP1) in glycogen accumulation and hepatocarcinogenesis, using liver-specific AKAP1 depletion and overexpression mouse models. AKAP1 deficiency suppressed DEN/CCl4-induced and Akt/β-catenin oncogene-driven spontaneous hepatocellular carcinoma by reducing hepatic glycogen, while AKAP1 overexpression promoted glycogen accumulation and accelerated tumorigenesis via YTHDF2-mediated G6PC mRNA decay. These results connect AKAP1–YTHDF2–G6PC post-transcriptional control to cancer-associated glycogen metabolism, highlighting a mechanistic target axis for HCC prevention or therapy.

Yang T, Zhang J, Zhao Z et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Can switching between different types of myopia control spectacles enhance effectiveness? Findings from a real-world study.

This retrospective matched-cohort study evaluated whether switching myopia control spectacle types changes myopia progression in 1,012 children/adolescents, comparing a change-of-type group (n=253) versus a type-maintenance group (n=759) after 1:3 propensity score matching. The primary outcome was the annual rate of spherical equivalent refraction progression (D/year) before and after switching, and the analysis assessed within- and between-group differences. If switching shows benefit over maintaining the same spectacle type, it would inform real-world clinical decisions on optimizing myopia control regimens for pediatric patients.

Zhang J, Pan Q, Jin L et al. · The British journal of ophthalmology · (2026) · View on PubMed ↗

Long-Term Outcome of Molecularly Defined Oligodendrogliomas: Comparison of Grade 2 and 3 Tumors.

This institutional retrospective cohort study analyzed long-term outcomes of molecularly defined oligodendrogliomas, comparing WHO 2021 grade 2 (OG2) versus grade 3 (OG3) tumors. Across patients treated between 1996 and 2024, the study assessed natural history and management factors using baseline clinical features and MRI characteristics to determine which variables most strongly influenced outcome. These findings are significant for neuro-oncology because they refine prognostic expectations and management strategies for OG2 versus OG3 based on molecularly defined disease.

Bruno F, Pronello E, Bertero L et al. · Neurology · (2026) · View on PubMed ↗

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Cancer microenvironment, stroma & spatial tumor ecology

Spatial distribution of the proteome in the human body and in cancers.

This study profiled more than 13,000 proteins across 2,856 samples using data-independent acquisition mass spectrometry to map spatial proteome organization across 58 tissue types, 251 subtypes, and 25 carcinomas in humans. The authors generated a comprehensive, spatially resolved proteomic landscape that enables visualization of proteome trajectories across developmental (fetal), tumor, adjacent non-tumor, and healthy adult physiological states. This resource provides a high-resolution framework for understanding developmental biology and oncogenic progression and for identifying spatially linked cancer biology signatures.

Yue L, Jiang W, Li S et al. · Nature · (2026) · View on PubMed ↗

Fibroblastic aspartoacylase suppresses TGFβ-mediated responses and cancer progression.

This study examined how aspartoacylase (ASPA) in tumor stroma and cancer-associated fibroblasts (CAFs) regulates Transforming Growth Factor Beta (TGFβ)–dependent fibroblast programs. ASPA expression was repressed in CAFs, and reciprocal signaling was shown where TGFβ suppresses ASPA while ASPA restrains TGFβ-driven myofibroblast conversion and extracellular matrix (ECM) remodeling, thereby limiting cancer progression. These findings identify ASPA as a stromal metabolic brake on TGFβ signaling, suggesting a potential therapeutic strategy to modulate the tumor microenvironment rather than only tumor-cell metabolism.

Astobiza I, Capó-Serra C, Viera C et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Metabolic heterogeneity and niche rewiring in bone marrow plasma cells from patients with MGUS, solitary bone plasmacytoma and multiple myeloma.

This study used high-resolution MALDI-FT-ICR mass spectrometry imaging (MSI) on archived FFPE bone-marrow biopsies from patients with MGUS-like disease (MGUS and solitary bone plasmacytoma with minimal marrow involvement) and multiple myeloma (MM), integrating spatial metabolite maps with matched plasma-cell metabolomics. Spatial clustering defined plasma-cell-rich niches, and diversity metrics (Hill-based and β-diversity) quantified intra- and inter-niche metabolic heterogeneity across disease categories. The work links metabolic heterogeneity to bone-marrow niche rewiring in plasma-cell disorders, supporting niche-targeted metabolic biomarkers or therapies for MGUS/SBPmm versus MM.

Zhang G, Sun N, Chawla Y et al. · Blood cancer journal · (2026) · View on PubMed ↗ · Free PDF ↗

Cellular architecture and neighborhood-informed virtual spatial tumor profiling from histopathology.

This study introduced CANVAS (cellular architecture and neighborhood-informed virtual spatial tumor profiling), an AI platform that infers tumor ecological neighborhoods from hematoxylin and eosin (H&E) histopathology. Trained and validated using an atlas of >18 million cells from 41-plex spatial proteomics across 457 non-small cell lung cancer patients, CANVAS generated 10 reproducible cellular neighborhoods that capture conserved spatial organization of the tumor microenvironment. The clinical significance is improved, scalable spatial profiling from routine pathology slides to better characterize the tumor microenvironment and potentially inform prognosis and therapy response.

Li Y, Li Z, Quinton R et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

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Targeted cancer therapeutics & resistance mechanisms

Reversal of KRAS G12D inhibitor resistance by nimotuzumab via MEK/ERK-mediated unfolded protein response in pancreatic cancer.

This study tested the KRAS G12D inhibitor HRS-4642 in pancreatic ductal adenocarcinoma (PDAC) models and investigated mechanisms of acquired resistance, then evaluated combination reversal using nimotuzumab. While HRS-4642 showed potent and selective anti-tumor activity, resistance emerged in HRS-4642-resistant cell lines and was linked to MEK/ERK-mediated unfolded protein response (UPR) signaling, and nimotuzumab restored sensitivity by engaging this pathway. The work provides a rational combination strategy to overcome KRAS G12D inhibitor resistance in PDAC, potentially improving durability of targeted therapy.

Xue S, Xu H, Ma J et al. · Cancer letters · (2026) · View on PubMed ↗ · Free PDF ↗

FANCA-dependent FEN1 recruitment suppresses transcription-replication conflicts and PARPi sensitivity.

This in vivo CRISPR screen and mechanistic validation study examined synthetic lethality with PARP1 inhibitors (PARPi) and found that FANCA deficiency confers PARPi sensitivity through impaired FANCA-dependent recruitment of FEN1 to replication forks. The authors showed that FANCA loss does not primarily disrupt homologous recombination, but instead causes defective Okazaki fragment maturation, accumulation of lagging-strand single-strand DNA gaps, and RPA exhaustion upon PARPi treatment. Clinically, FANCA status may help expand PARPi use beyond classic HR deficiency by identifying tumors with replication-fork processing vulnerabilities.

Wang Q, Ellington SW, Guerra P et al. · Molecular cell · (2026) · View on PubMed ↗

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Hematologic malignancies & transplantation

WT1 peptide vaccines of post-allogeneic HSCT maintenance immunotherapy for pediatric acute leukemias: a phase II study.

This phase II trial evaluated post–allogeneic hematopoietic stem cell transplantation maintenance immunotherapy using two WT1 peptide vaccines (MCI-for) in 17 pediatric patients with refractory acute leukemia. The 3-year overall survival was 70.6% (95% CI 43.1–86.6%), exceeding a 30% historical control benchmark, and outcomes were driven by 12 clinical responders who maintained complete remission at year 1 after vaccination. The results support WT1 peptide vaccination as a potentially effective maintenance strategy after allo-HSCT in children, warranting further randomized validation.

Hashii Y, Oka Y, Sakata N et al. · Blood advances · (2026) · View on PubMed ↗

Final analysis of phase 2 clinical trial of ruxolitinib and azacitidine combination therapy in patients with myelodysplastic syndrome/myeloproliferative neoplasms.

This phase 2 open-label trial studied the combination of azacitidine (AZA) plus ruxolitinib (RUX) in adult patients with myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN), reporting final long-term outcomes for the MDS/MPN diagnostic arm. The final analysis builds on an interim objective response rate of 57% and provides extended survival data for AZA+RUX in this overlap-syndrome population. These results support AZA+RUX as a clinically relevant disease-modifying strategy to improve durability of response and survival in MDS/MPN patients with limited prognostic options.

Arora S, Senapati J, Deshmukh I et al. · Journal of hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular imaging, cardiometabolic risk & biomarkers

Age-Related Distribution and Severity of Coronary Artery Stenosis Assessed by 640-Row Coronary Computed Tomography Angiography: A Cross-Sectional Study.

This single-center cross-sectional study assessed age-related distribution and severity of coronary artery stenosis using 640-row coronary computed tomography angiography (CCTA) in 390 consecutive patients with suspected coronary artery disease. It quantified stenosis severity by coronary segments and major vessel involvement and defined clinically significant stenosis by high-grade luminal narrowing thresholds (≥50% left main or ≥70% for other specified vessels). The findings clarify how coronary stenosis burden varies with age in contemporary CCTA practice, informing risk stratification and interpretation of imaging results.

Nguyen D, Duong SP, Tran TV et al. · Cureus · (2026) · View on PubMed ↗ · Free PDF ↗

Association Between Sleep Disorders and Adverse Cardiovascular Outcomes in Patients with Chronic Obstructive Pulmonary Disease: Insights from the UK Biobank.

Using UK Biobank data, this prospective cohort study examined whether sleep disorders are associated with adverse cardiovascular outcomes in 21,423 participants with chronic obstructive pulmonary disease (COPD). It tested the relationship between sleep disturbances and subsequent cardiovascular events, motivated by mechanisms such as intermittent hypoxia, systemic inflammation, and metabolic dysregulation. The results aim to strengthen causal risk assessment in COPD by identifying sleep health as a potentially modifiable contributor to cardiovascular morbidity.

An X, Chen Y, Wang Y et al. · International journal of chronic obstructive pulmonary disease · (2026) · View on PubMed ↗ · Free PDF ↗

Integration of triglyceride-glucose index and biological aging to predict cardiovascular disease risk in cardiovascular-kidney-metabolic syndrome stages 0-3: a multiple prospective cohort study.

This multiple prospective cohort study evaluated whether integrating the triglyceride-glucose (TyG) index with biological aging (KDM-BA) improves cardiovascular disease (CVD) risk prediction in people across cardiovascular-kidney-metabolic (CKM) syndrome stages 0–3 using UK Biobank, CHARLS, and a Sun Yat-sen Memorial Hospital cohort. The key finding was that the combined TyG index plus KDM-BA approach better stratified CVD risk than using either metabolic dysfunction or biological aging alone across CKM stages 0–3. Clinically, this integrated biomarker framework could enable earlier and more accurate identification of high-risk individuals for preventive cardiovascular interventions.

Shen R, Dong P, Fang S et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Multi-omic analysis of deep learning-derived phenotypes links ophthalmic imaging to cardiovascular and neurological traits.

Using UK Biobank data, the study developed a multi-omic pipeline integrating physiological, radiomic, metabolomic, and genomic information and trained retinal adversarial autoencoders to convert ophthalmic imaging (optical coherence tomography and color fundus photographs) into 256-dimensional embeddings. Retinal adversarial autoencoder-derived embeddings were associated with multiple cardiovascular and neurodegenerative traits, including ischemic heart disease and cerebrovascular disease, and also with Parkinson’s disease. This supports the scientific significance of deep-learning-derived retinal phenotypes as cross-domain biomarkers that may reflect shared biological axes underlying systemic disease risk.

Julian TH, Dou H, Duan J et al. · Nature cardiovascular research · (2026) · View on PubMed ↗ · Free PDF ↗

Role of systemic and epicardial adipose tissue in cardiometabolic disease.

This Nature Reviews: Cardiology article synthesized current evidence on how systemic adipose tissue and epicardial adipose tissue contribute to cardiometabolic disease, emphasizing depot-specific biology rather than total fat alone. It highlights that visceral, subcutaneous, and epicardial fat communicate with vasculature and myocardium through endocrine, paracrine, vasocrine, and neural pathways to shape cardiovascular inflammation and remodeling. The review frames adipose depot phenotyping and imaging (CT/MRI/DEXA with AI) as key to improving risk prediction and therapeutic targeting in cardiometabolic disease.

Khanna S, Mann G, Bhat A et al. · Nature reviews. Cardiology · (2026) · View on PubMed ↗

Comparison of Specific Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes Among Patients With Type 2 Diabetes.

This retrospective observational target-trial emulation study compared within-class kidney outcomes among adults with type 2 diabetes (T2D) at moderate cardiovascular risk using Medicare fee-for-service claims (OptumLabs) across different GLP-1 receptor agonists. The key finding was that GLP-1 receptor agonist choice showed differential associations with incident chronic kidney disease (CKD) and death, supporting within-class heterogeneity in kidney benefit. Clinically, these results can guide more evidence-aligned selection of specific GLP-1 receptor agonists for kidney risk reduction in T2D patients at moderate cardiovascular risk.

Neumiller JJ, Deng Y, Swarna KS et al. · American journal of kidney diseases : the official journal of the National Kidney Foundation · (2026) · View on PubMed ↗

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Cardiac aging & proteostasis/organellar maintenance

Life-span-dependent transcriptional dynamics of the human heart.

This study generated a single-nucleus RNA-sequencing atlas of 442,239 nuclei from 54 nonfailing human myocardial tissue samples across 29 individuals spanning development, adulthood, and aging (left and right ventricles). It found coordinated but cell type–specific transcriptional trajectories across major cardiac cell types that converge on progressive loss of gene expression homeostasis, with increasing stress-response and inflammatory signaling over the life span. These lifespan-resolved regulatory dynamics provide a cellular map for understanding mechanisms of cardiac aging and identifying targets to preserve cardiomyocyte function.

Jia H, Chen X, Chang Y et al. · Science advances · (2026) · View on PubMed ↗

Vacuolar H+-ATPase Preserves Cardiolipin Homeostasis Through the Lysosomal-Mitochondrial Axis to Restrain Cardiac Aging.

This study examined whether vacuolar H+-ATPase (v-ATPase) preserves cardiolipin (CL) homeostasis and restrains cardiac aging by regulating a lysosomal–mitochondrial axis. Using RNA sequencing and targeted lipidomics (and related functional assays, as described), it tested the idea that v-ATPase dysfunction disrupts CL metabolism, leading to mitochondrial decline and age-related cardiac changes. The findings position v-ATPase–dependent lysosomal acidification as a mechanistic lever for maintaining mitochondrial membrane integrity during cardiac aging.

Tie H, Hou M, Li Y et al. · Circulation · (2026) · View on PubMed ↗

Selective titin cleavage disrupts cardiac mechanical homeostasis to drive heart failure and fibrosis.

This work created a knock-in mouse model enabling in vivo cleavage of the elastic titin segment (“titin springs”) and assessed acute effects on cardiac mechanics using multimodal phenotyping including cardiac MRI, echocardiography, microscopy, and omics. Titin cleavage reduced chamber size and impaired ventricular filling without causing heart dilation, indicating that loss of titin stiffness acutely disrupts diastolic mechanical homeostasis. The results provide mechanistic insight into how proteolytic titin damage after ischemic or chemotherapy injury could drive heart failure and fibrosis.

Freundt JK, Hartmann P, Loescher CM et al. · Nature cardiovascular research · (2026) · View on PubMed ↗ · Free PDF ↗

Proteomic profiling of whole tissue sections in cardiac ATTR amyloidosis reveals increased extracellular matrix remodeling.

This study used quantitative mass spectrometry–driven proteomics on formalin-fixed paraffin-embedded (FFPE) whole cardiac tissue sections from cardiac transthyretin amyloidosis (ATTR-CA) cases and AL-CA controls to characterize disease-associated protein changes. Beyond transthyretin, it found over 500 upregulated proteins in ATTR-CA, including signatures consistent with increased extracellular matrix remodeling. These proteomic maps improve understanding of active remodeling processes in ATTR amyloidosis and may help identify biomarkers or therapeutic targets beyond amyloid deposition.

Vandendriessche A, Maia TM, Timmermans F et al. · Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology · (2026) · View on PubMed ↗ · Free PDF ↗

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Metabolism, mitochondria & organelle contact biology

Hepatocyte-to-intestinal stem cell remote communication regulates blood glucose homeostasis.

This study investigated how hepatocyte-to-intestinal stem cell (ISC) signaling regulates blood glucose homeostasis, focusing on fatty liver–associated hyperglycemia in mechanistic experiments. It found that hepatocyte-derived alkaline phosphatase (ALP) targets α2δ-1 in ISCs to promote Cav1.2 membrane translocation, increasing intracellular calcium, activating the calcineurin/NFATC2 pathway, and suppressing SOX21 to drive hyperglycemia independent of increased intrahepatic gluconeogenesis. The work identifies a specific liver–gut remote communication axis (ALP–α2δ-1–Cav1.2–calcineurin/NFATC2–SOX21) as a potential therapeutic target for metabolic dysregulation in fatty liver.

Ye J, Wan Q, Liu X et al. · Cell metabolism · (2026) · View on PubMed ↗

Chloroplast sunscreening by protein condensates confers high-light tolerance.

This study examined how chloroplast protein condensates mediate singlet oxygen (¹O₂) responses and photoprotection, identifying METHYLENE BLUE SENSITIVITY1 (MBS1) as a key mediator. The authors found that MBS1, containing a zinc-finger (ZnF) domain flanked by intrinsically disordered regions, senses ¹O₂ via ZnF conformational change and phase transition from liquid-like droplets to lower-dynamic condensates, and that these condensates attenuate photodamage under high light. Scientifically, it reveals a conserved condensate-based mechanism for rapid chloroplast photoprotection and ¹O₂ signaling.

Shao N, Chen M, Xu N et al. · Cell · (2026) · View on PubMed ↗

Ion transport peptide regulates larval body water balance via a receptor guanylyl cyclase in Drosophila.

In Drosophila melanogaster, this study investigated how the short amidated isoform of ion transport peptide (saITP) regulates larval body water balance through the receptor guanylyl cyclase Gyc76C in the hindgut. It showed that saITP, secreted from brain neurosecretory cells, forms a brain–hindgut neuroendocrine axis, and that both ITP and Gyc76C are essential for larval survival. These findings define a conserved endocrine signaling pathway controlling osmotic/ionic homeostasis during development.

Watanabe A, Koyama T, Kubrak O et al. · iScience · (2026) · View on PubMed ↗ · Free PDF ↗

Semaglutide targets muscle mitochondria to regulate glutamine metabolism and treat osteoarthritis.

This iScience study tested the mechanism of semaglutide’s osteoarthritis (OA) effects by using cross-tissue single-cell RNA sequencing and multi-omics approaches in mice. It found that semaglutide improves muscle mitochondrial metabolic dysfunction under high-fat diet and OA conditions and targets muscle mitochondria to regulate glutamine metabolism, with intramuscular injection of semaglutide-prestimulated C2C12 mitochondria alleviating pain and cartilage damage. The work links a GLP-1–based drug to mitochondrial glutamine control in OA, suggesting a mechanistic basis for muscle-targeted therapeutic effects.

Tian Y, Zheng Z, Ma Y et al. · iScience · (2026) · View on PubMed ↗ · Free PDF ↗

Structural insights into OSTα/β-mediated transport of bile acids and steroid conjugates.

This structural biology study used high-resolution cryo-electron microscopy (cryo-EM) to determine how the human organic solute transporter OSTα/β transports bile acids and steroid conjugates and how inhibitors bind. The key finding was that OSTα/β forms a tetrameric organization (a homodimer of heterodimers) required for membrane activity, with substrate binding in a surface-exposed tunnel sealed by palmitoyl chains on a conserved intracellular loop (IL2), and that two chemically distinct inhibitors (including fidaxomicin) bind in inhibitor-bound states. These mechanistic insights are significant for rational drug design targeting OSTα/β to modulate enterohepatic circulation and related metabolic or pharmacologic processes.

Sun X, Tian T, Low M et al. · Nature structural & molecular biology · (2026) · View on PubMed ↗

Targeting intracellular cholesterol imbalance rescues sarcomere-ER contact site signaling and ER remodeling in dilated cardiomyopathy.

This research used induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), patient-derived heart tissue, and living adult cardiomyocytes to study dilated cardiomyopathy (DCM) and heart failure (HF) mechanisms, focusing on intracellular cholesterol imbalance. Lipidomics showed abnormal intracellular cholesterol in iPSC-CMs carrying DCM-causing sarcomere mutations (tropomyosin and troponin T), and targeting cholesterol imbalance rescued sarcomere–ER contact site signaling and ER remodeling. The work is significant because it links lipid dysregulation to organelle contact signaling defects and suggests cholesterol-targeted interventions for DCM/HF.

Ignatyeva N, Cheruiyot C, Saleem HN et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Structural evidence that a lipid plug controls K2P6.1(TWIK-2) function.

The authors used cryo-electron microscopy (cryo-EM) to determine structural mechanisms of lipid regulation in the human K2P6.1 (TWIK-2) leak potassium channel, including mutant structures in nanodiscs and detergent environments. They observed an unusual conformation in the first selectivity filter and identified a pair of two-chain lipids within the channel cavity (“lipid plug”) that controls channel function. This structural evidence clarifies how specific lipid occupancy can gate ion channel activity and provides a framework for targeting lipid–channel interactions therapeutically.

Mondal A, Niranjan S, Minor DL · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

EasySCP unveils extensive liver zonation at single-cell proteomics resolution.

EasySCP, a high-throughput single-cell proteomics workflow combining FACS-based single-cell sorting, single-step 384-well digestion, and sensitive mass spectrometry, was applied to individual HEK293 cells and female murine liver hepatocytes. The method identified ~5000 proteins per HEK293 cell and achieved spatially informed hepatocyte zonation profiling in mice, detecting ~3500 proteins per hepatocyte and zonation patterns for 3277 of 5267 proteins using 215 conserved zonation markers. This provides a scalable proteomics platform to map liver microanatomy and discover zonation-specific biology relevant to metabolism and liver disease.

Hao B, Wei J, Xu J et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

SRP orchestrates protein biogenesis beyond initial ER membrane targeting.

The study investigated how the signal recognition particle (SRP) functions during protein biogenesis beyond its canonical role in targeting nascent proteins to the ER membrane in Saccharomyces cerevisiae. The key finding was that SRP binds strongly to emerging transmembrane domains (TMDs) from the ribosomal tunnel but only to a minority of cleavable signal peptides, and the authors identified nascent-chain features enabling a predictive algorithm for SRP binding and showed SRP triages nascent ER proteins into distinct downstream routes (as summarized in the abstract). This expands mechanistic understanding of SRP-mediated substrate selection and improves models of how cells route nascent proteins to the ER.

Kotan IE, Sartori S, Bose R et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

FGF21 reduces ER stress by enhancing the unfolded protein and integrated stress responses through increased sulfide signaling.

This study examined fibroblast growth factor 21 (FGF21) action on endoplasmic reticulum (ER) stress using proximity labeling to map signaling at its receptor β-klotho (KLB) and related pathways. It found that FGF21 increases enzymatic sulfide (H2S) production, enhances—but does not initiate—the unfolded protein response (UPR), and is associated with ER protein folding and stress responses. The results suggest a physiological mechanism linking FGF21–KLB signaling to integrated stress response modulation via sulfide signaling, with potential implications for treating ER-stress–linked metabolic disorders.

Grandl G, König AC, Metzger F et al. · Cell metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Activation of PPARγ/FGF21 signaling axis with Puerarin reprograms tumor lipid metabolism, attenuating malignancy in colon cancer.

This study examined whether the isoflavone puerarin (from Pueraria lobata) can modulate tumor lipid metabolism in colorectal cancer (CRC) and investigated the PPARγ/FGF21 signaling mechanism. Puerarin activated the PPARγ/FGF21 axis, reprogramming CRC lipid metabolism (including reduced lipid-droplet accumulation) and attenuating malignant phenotypes. These findings support the PPARγ–FGF21 pathway as a mechanistic target for potential CRC therapies using puerarin or related lipid-metabolism modulators.

Tang Y, Zhou P, Ding Y et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

Elevated mitochondrial protein import in acute myeloid leukemia increases reliance on mitochondrial protease LONP1.

This study investigated mitochondrial protein import in acute myeloid leukemia (AML) cells and how it affects reliance on the mitochondrial protease LONP1. Using gene expression analyses and functional assays, the authors found increased mitochondrial protein import in AML compared with normal hematopoietic cells, with upregulated mitochondrial unfolded protein response (UPRmt) and increased LONP1 expression correlating with the import increase. The work is clinically relevant because it identifies the mitochondrial import–UPRmt–LONP1 axis as a potential vulnerability that could be therapeutically targeted in AML.

Tcheng M, Voisin V, Thomas GE et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration, brain aging & neuroinflammation

Human iPSC-NSC-Derived Extracellular Vesicles Can Alleviate Alzheimer’s Disease-Linked Impairments in Mitochondria, mTOR Signaling, Autophagy, and Hippocampal Neurogenesis.

This preclinical study tested whether intranasally administered extracellular vesicles (EVs) derived from human induced pluripotent stem cell–derived neural stem cells (hiPSC-NSC-EVs) could reverse Alzheimer’s disease–linked impairments in 3-month-old male and female 5xFAD mice. The key finding was that hiPSC-NSC-EVs alleviated multiple neuropathological and cellular dysfunctions, including mitochondrial deficits, mTOR signaling alterations, autophagy changes, and impaired hippocampal neurogenesis. These results are significant because they extend EV-based neurotherapeutic potential beyond microglia/astrocyte-driven neuroinflammation toward broader mechanisms relevant to progressive cognitive decline.

Madhu LN, Attaluri S, Kotian S et al. · Aging cell · (2026) · View on PubMed ↗ · Free PDF ↗

Inhibiting fear memory recall-induced oligodendrogenesis rescues PTSD-like behaviors.

The study used a repeated fear recall mouse model to mimic PTSD-like re-experiencing symptoms and examined whether blocking fear memory recall-induced oligodendrogenesis could alter downstream brain plasticity and behavior. Inhibiting recall-driven oligodendrogenesis rescued PTSD-like behaviors, linking impaired myelin/oligodendrocyte dynamics to symptom expression after traumatic memory reactivation. These results suggest a mechanistic therapeutic direction for PTSD that targets adult white-matter remodeling rather than only fear circuitry.

Feng J, Huang NX, Liu K et al. · Molecular psychiatry · (2026) · View on PubMed ↗

The oocyte-enriched metabolite serotonin alleviates cellular senescence and aging phenotypes in the mouse.

The study profiled the metabolite landscape of mouse oocytes versus cleavage-stage embryos and tested the role of the oocyte-enriched metabolite serotonin (5-hydroxytryptamine, 5-HT) in aging and cellular senescence phenotypes in mice. The key finding was that serotonin alleviated senescence/aging phenotypes via dual mechanisms: signaling through the serotonin receptor 5HTR1B to modulate mitochondrial function and a non-canonical pathway that promotes protective effects (details truncated in the abstract). Scientifically, it identifies oocyte-derived serotonin as a causal, developmentally enriched regulator of aging biology.

Xu Y, Zhang L, Liao X et al. · The EMBO journal · (2026) · View on PubMed ↗ · Free PDF ↗

TGFb signaling promotes astroglial activation and TDP-43 proteinopathy in organoid models of frontotemporal lobar degeneration.

This study used induced pluripotent stem cell (iPSC)-derived cortical organoids to model frontotemporal lobar degeneration and examined how TGFβ signaling affects astroglial activation and TDP-43 proteinopathy in GRN loss-of-function contexts (GRN-/- and GRNR493X). It found that GRN mutations cause precocious astrogliosis that promotes neuronal stress and synaptic loss, with single-cell transcriptomics and histopathology implicating robust activation of TGFβ signaling. These results mechanistically connect GRN-driven glial changes to TDP-43 pathology, suggesting TGFβ-pathway modulation as a potential therapeutic strategy in FTLD-GRN.

Ramsey AC, Tang XY, Macias MJ et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochondria and brain aging: From cell-specific dysfunction to intercellular cooperation.

This Neuron review synthesized evidence on how mitochondrial dysfunction contributes to brain aging across neurons, glia, and vascular cells, emphasizing cell-type and subcellular compartment differences. It highlights intercellular mitochondrial transfer as a form of metabolic cooperation and discusses therapeutic concepts such as mitochondrial transplantation. The review’s significance is to frame mitochondrial aging biology as a networked, cell-to-cell process rather than a neuron-only decline, guiding future therapeutic development.

Grimm A, Lang U, Eckert A · Neuron · (2026) · View on PubMed ↗ · Free PDF ↗

Detecting amyloid-β pathology in subjective cognitive decline using plasma and CSF biomarkers.

This study evaluated plasma and cerebrospinal fluid (CSF) biomarker panels for detecting amyloid-β (Aβ) pathology in 143 individuals with subjective cognitive decline (SCD) from the β-AARC cohort. Aβ status was defined by CSF Aβ42/40, and the work compared performance across multiple platforms for Aβ, tau, synaptic function, neurodegeneration, and glial reactivity markers, including novel CSF tau variants (e.g., p-tau205, p-tau217, p-tau231, p-tau235, and NTA-tau). The results are clinically relevant because they identify which blood/CSF biomarker combinations best detect preclinical Alzheimer-type Aβ pathology in SCD, informing earlier diagnosis and trial enrichment.

Contador J, Pozzi FE, Sánchez-Benavides G et al. · EBioMedicine · (2026) · View on PubMed ↗ · Free PDF ↗

Cognitive Aging and Brain Health: A Comparison of Super Movers vs Nonsuper Movers.

This retrospective study compared cognitive aging and brain health in older adults classified as “super movers” versus “nonsuper movers” using data from HRS-INS, the LonGenity Study, and RUSH MAP. Super movers (age ≥80 with gait speeds ≥1.5 SDs above age- and sex-adjusted means) were evaluated for incident cognitive impairment risk, cognitive decline trajectories, and brain health outcomes. The results are clinically significant because they test whether exceptional mobility in late life is associated with better cognitive trajectories and brain health, supporting mobility as a modifiable risk marker.

Jayakody O, Milman S, Barzilai N et al. · Neurology · (2026) · View on PubMed ↗

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Neurodevelopmental & neuropsychiatric epidemiology

Incidence, prevalence, and global burden of attention-deficit/hyperactivity disorder from 1990 to 2021 across 204 countries in individuals under age 20: data, with critical appraisal, from the 2021 Global Burden of Disease study.

This global population-based analysis used Global Burden of Disease (GBD) 2021 data to estimate ADHD incidence, prevalence, and disability-adjusted life years (DALYs) from 1990–2021 in individuals under age 20 across 204 countries and territories. In 2021, ADHD prevalence was estimated at 46,890,733 cases (95% uncertainty interval 32,136,904–67,271,064), with corresponding estimates of incidence and DALY burden over time and by geography. The findings are clinically and policy significant for targeting child and adolescent mental health resources and for monitoring trends in a major neurodevelopmental disorder.

Cortese S, Kim MS, Han JH et al. · Molecular psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗

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Infectious disease, vaccines & host-pathogen interactions

Precision-engineered STING agonist nanoparticles enable coordinated mucosal-systemic immunity for durable pan-β-coronavirus protection.

This study engineered NanoCF501, a precision-engineered nanoparticle STING agonist formulated with a 2-ethyl-2-oxazoline polymer, and tested it in rats and mice using intranasal co-administration with multivalent pan-β-coronavirus antigen fragments. NanoCF501 enhanced mucus penetration and localized respiratory retention with reduced systemic exposure (via pharmacokinetics in rats) and, in mice, induced coordinated mucosal and systemic immunity that protected against homologous and heterologous pan-β-coronaviruses. The work supports STING-agonist nanoparticle design as a strategy for durable, low-toxicity mucosal vaccines against broad coronavirus targets.

Liu Z, Zhou J, Gao R et al. · Nature nanotechnology · (2026) · View on PubMed ↗

Structural basis and immunogenic efficacy of porcine circovirus type 3 virus-like particle.

The authors determined high-resolution cryo-EM structures of porcine circovirus type 3 (PCV3) capsid protein assembled into virus-like particles (VLPs) and of PCV3 VLPs bound to the PCV3-specific antibody 2B5, then evaluated immunogenicity in mice and pigs. Structural analysis revealed PCV3-specific surface loop differences from PCV2 and defined a conserved 2B5 epitope involving the BC, EF, and HI loops, and PCV3 VLP immunization induced sustained antibody responses that prevented viremia in a pig challenge model. This structural and preclinical efficacy evidence supports PCV3 VLPs as a rational vaccine candidate with defined antigenic targets.

Su J, Tong X, Jiang Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

A CRISPR knockout mouse library for functional genomics in influenza research.

This study developed a CRISPR knockout mouse library for influenza A research by generating 84 gene-modified mouse lines targeting prioritized host factors from literature and in vitro siRNA screens. Using this in vivo platform, the authors identified 17 host factors whose genetic ablation conferred resistance to influenza A virus infection and then began functional follow-up on two factors. The resource is significant for accelerating whole-animal validation of host dependency factors, improving translation from cell-based findings to influenza pathogenesis and therapeutic target discovery.

Ueki H, Tomita Y, Duong C et al. · Cell · (2026) · View on PubMed ↗

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Microbiome, gut barrier & metabolite-mediated immunity

Combined acetaldehyde metabolism burden modifies IBD susceptibility to alcohol consumption.

This prospective cohort study (n=455,417) tested whether alcohol consumption modifies inflammatory bowel disease (IBD) risk according to alcohol metabolic capacity using a genetically derived acetaldehyde burden score. The key finding is that acetaldehyde metabolism burden—constructed from genetic variants in alcohol dehydrogenase and aldehyde dehydrogenase and supported by eQTL and proteomic validation—modifies the association between alcohol intake and IBD susceptibility. This suggests that host alcohol-metabolism genetics and acetaldehyde exposure may help explain inconsistent alcohol–IBD relationships and could refine risk stratification.

Chen J, Guo Y, Hu J et al. · Gut · (2026) · View on PubMed ↗

Guar Gum, Partially Hydrolyzed Guar Gum, and Human Gut Health: A Narrative Review.

This narrative review summarizes evidence on guar gum and partially hydrolyzed guar gum (PHGG) as “guar fiber” and their effects on human gut health. It focuses on outcomes across the gastrointestinal tract, gut microbiota, gut–brain axis, and liver steatosis, synthesizing findings from clinical and related literature. The review highlights PHGG/guar fiber as a promising dietary intervention with multi-system relevance, while identifying areas where further clinical trials are needed.

Scarpellini E, Roselli F, Scarcella M et al. · Reviews on recent clinical trials · (2026) · View on PubMed ↗

The bacteroidal metabolite O-LysoPE facilitates hepatocyte-mediated immunosuppression in autoimmune hepatitis.

Researchers investigated autoimmune hepatitis (AIH) by comparing gut microbiota and hepatic immune regulation in self-healing mouse hepatitis models versus AIH patients, focusing on Bacteroides acidifaciens and its metabolite 1-oleoyl-sn-glycero-3-phosphoethanolamine (O-LysoPE). O-LysoPE was depleted in AIH patients but enriched in self-healing models, and it promoted hepatocyte-driven active immunosuppression by engaging a specific downstream target pathway (truncated in the abstract). This identifies a gut-derived lipid metabolite as a potential precision immunosuppressive strategy to improve efficacy while reducing systemic side effects of broad immunosuppressants.

Xu M, Luo K, Zhou Z et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

The Prodromal Synucleinopathy Rating Scale: An Assessment in Patients With REM Sleep Behavior Disorder.

This study assessed the clinicometric properties and reliability of the Prodromal Synucleinopathy Rating Scale (PSRS) in 348 North American Prodromal Synucleinopathy (NAPS) cohort participants without overt Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA). PSRS ratings were analyzed across visits from August 2022 to June 2025 to evaluate how consistently clinicians could quantify prodromal synucleinopathy burden. Standardizing PSRS measurement is scientifically significant because it can improve outcome tracking and patient selection in upcoming disease-modifying clinical trials targeting prodromal PD/DLB/MSA.

Boeve BF, Nie Y, Lu R et al. · Neurology · (2026) · 1 citations · View on PubMed ↗

Fecal Microbiota Transplantation in Parkinson Disease: A Systematic Review, Meta-Analysis, and Meta-Regression.

This systematic review and meta-analysis evaluated the efficacy and safety of fecal microbiota transplantation (FMT) for Parkinson disease (PD) by synthesizing clinical evidence across studies. The analysis (following PRISMA guidance with protocol registration in PROSPERO) pooled outcomes to determine whether FMT improves PD-related clinical endpoints and whether it is tolerable. The findings are important for the gut-brain axis field because they clarify the current evidence base and safety profile of FMT as a potential adjunct therapy in PD.

Pereira MAOM, Tudella GCN, Klostermann AU et al. · Neurology · (2026) · View on PubMed ↗

Microbial metabolites at the front line: Orchestrating gastrointestinal and systemic barrier immunity across the lifespan.

This review synthesized evidence from mouse models and human studies on how microbiota-derived metabolites regulate barrier immunity across the lifespan. It highlights that metabolites such as short-chain fatty acids, tryptophan catabolites, and bile acid derivatives modulate epithelial integrity, innate immune tone, and adaptive immunity/tolerance, and that metabolite dysregulation is linked to diseases including inflammatory bowel disease, asthma, and atopic dermatitis. The work is significant because it consolidates mechanistic pathways that could be leveraged for metabolite-targeted therapies to restore mucosal and systemic immune balance.

Koren O, Collado MC, Chassaing B et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

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Inflammation, senescence & innate immune signaling

Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.

The study used single-cell RNA sequencing to profile FOXP3+ regulatory T cells (Tregs) in synovial tissue from patients with rheumatoid arthritis (RA) and compared them with blood Tregs. It identified two enriched synovial Treg states—CD25hiCXCR6pos Tregs and dysfunctional CD25loAREGpos Tregs—where fibroblast-activated cortisol drove amphiregulin (AREG) expression, impairing suppressive function and promoting an inflammatory phenotype in synovial fibroblasts. These findings define a cortisol–AREG axis that destabilizes Treg function in RA and suggest a mechanistic target to restore immune regulation in autoimmune arthritis.

Koh B, Gal Oz ST, Sato R et al. · Nature immunology · (2026) · View on PubMed ↗

Meiotic pairing through barcode-like satellite DNA repeats.

The study examined how non-coding satellite DNA repeats with a “barcode-like” arrangement influence meiotic homolog pairing in Drosophila, using satellite DNA deletion, duplication, and translocation strains. Repeat mismatches disrupted meiotic pairing, especially at centromeres and pericentromeres, and pairing defects were also observed in progeny from natural populations with satellite divergence. These findings reveal a recombination-independent, sequence-architecture mechanism for homolog pairing that refines our understanding of chromosome recognition during meiosis.

Skrutl L, Chavan A, Sintsova A et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Nuclear export of R-loop by the DDX1 and XPO1 complex promotes senescence-associated secretory phenotype and inflammaging.

The study examined how R-loops are exported from the nucleus to the cytoplasm by a DDX1 and XPO1 complex and how this promotes senescence-associated secretory phenotype (SASP) and inflammaging. It found cytoplasmic accumulation of nuclear-derived R-loops in senescent cells, enriched in alpha-satellite repeats, which localized to cytoplasmic chromatin fragments and activated the cGAS–STING pathway to drive SASP. These results identify DDX1/XPO1-mediated R-loop nuclear export as a mechanistic control point for inflammaging and senescence-driven inflammation.

Hao X, Zhao B, Yan Q et al. · Nature aging · (2026) · View on PubMed ↗ · Free PDF ↗

Epigenetic compartmentalization of mitotic chromosomes by phase-separation-driven repulsion between WDR5 and the chromosomal passenger complex.

The study examined how epigenetic regulators organize mitotic chromosomes by showing that liquid-liquid phase separation (LLPS) of WDR5 can compartmentalize mitotic chromatin. The key finding was that WDR5 LLPS, driven by multivalent charged and hydrophobic interactions in its N-terminal region, repels the chromosomal passenger complex (CPC) to help establish spatial organization during mitosis. This provides a physical mechanism linking histone-mark recruitment machinery (WDR5/H3K4 methyltransferase complexes) to mitotic protein patterning and accurate chromosome segregation.

Wang Y, Jiang X, Liu X et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Epigenetic lockdown of type I interferon sensing and signalling in human pluripotent cells.

This study examined epigenetic control of type I interferon (IFN-I) sensing and signaling in human pluripotent cells by depleting MPP8 in human induced pluripotent stem cells (iPSCs) and comparing responses in iPSC-derived neural progenitor cells (NPCs). iPSCs showed an attenuated IFN-I pathway, and MPP8 depletion induced young LINE-1 elements and IFN-I pathway genes, including double-stranded RNA sensors and interferon-stimulated responses. The findings reveal how the HUSH complex (via MPP8) epigenetically “locks down” IFN-I activation during early development, informing how innate immune sensing is regulated in pluripotent states.

Holt JH, Enriquez-Gasca R, Wilson RP et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

ZNF512B safeguards genome integrity at regulatory regions to repress the SASP and inflammation.

This study investigated how the zinc-finger protein ZNF512B regulates cellular senescence outputs by suppressing the senescence-associated secretory phenotype (SASP) and inflammation. Using a SASP reporter and a CRISPR-Cas9 screen targeting active regulatory elements, the authors found that ZNF512B loss induces DNA damage, activates cGAS-STING signaling, and drives inflammatory transcriptional reprogramming, while ZNF512B normally promotes preferential DNA repair at regulatory regions to limit SASP induction. The work identifies ZNF512B as a genome-integrity safeguard that could be targeted to dampen SASP-driven inflammation in aging and senescence-associated diseases.

Sahu SK, Memczak S, Thakurela S et al. · Cell stem cell · (2026) · View on PubMed ↗

Ubiquitin-proteasome system regulates pro-crossover protein dynamics during meiosis in Caenorhabditis elegans.

This study examined how the ubiquitin-proteasome system (UPS) regulates pro-crossover protein dynamics during meiosis in Caenorhabditis elegans. Knockdown of the ubiquitin-activating enzyme E1 or proteasome increased pro-crossover protein levels and crossover designation, indicating UPS control of crossover patterning via ubiquitination-dependent regulation of pro-crossover proteins. These findings identify a conserved proteostasis mechanism that can tune meiotic recombination outcomes, with implications for understanding how chromosome segregation fidelity is maintained.

Zhang H, Liang W, Li M et al. · PLoS biology · (2026) · View on PubMed ↗ · Free PDF ↗

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Bioelectricity & neural/epithelial signaling tools

Red-shifted GRAB acetylcholine sensors for multiplex imaging in vivo.

The study developed red fluorescent, G-protein-coupled receptor activation-based acetylcholine (ACh) sensors (including the high-affinity rACh1h) to enable multiplex in vivo imaging across mouse brain regions. The key finding was that rACh1h reliably detects ACh release with a wide detection range and expanded spectral profile suitable for simultaneous imaging with other neuromodulators. This advances circuit neuroscience by providing genetically encoded tools for real-time, multiplex measurement of cholinergic signaling in vivo.

Xie S, Miao X, Li G et al. · Nature neuroscience · (2026) · View on PubMed ↗

Epithelial cells fire voltage spikes.

This study investigated whether epithelial cells generate bioelectric voltage spikes by using multielectrode arrays in primary human keratinocytes and MDCK epithelial monolayers after localized laser injury. The authors found voltage spikes with depolarization, repolarization, and hyperpolarization phases lasting 1–2 seconds, occurring at 4–12 spikes per minute for over 60 minutes postinjury, with nonmonotonic spatial dependence on distance from the injury site. These findings are significant because they establish that epithelial tissues can use neuron-like spike dynamics for injury signaling, opening new avenues for understanding epithelial bioelectric control of repair and immunity.

Yu SM, Granick S · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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Clinical trials, pharmacovigilance & clinical management frameworks

Towards autonomous medical artificial intelligence agents.

This work evaluated whether an autonomous clinical AI agent, MIRA (Medical Intelligence for Reasoning and Action), can manage patient cases with physician-level performance in a sandboxed electronic health record (EHR) environment. The key finding is that MIRA operates within governed access to patient data and can initiate permitted EHR actions under defined safety constraints while performing at a level intended for clinical decision-making. If validated broadly, this approach could move beyond narrow “copilot” chat tools toward safer, workflow-integrated autonomous medical agents.

Ferber D, Hilgers L, Höper C et al. · Nature · (2026) · View on PubMed ↗

Benzylpenicillin versus flucloxacillin or cloxacillin for the treatment of penicillin-susceptible Staphylococcus aureus bacteraemia (SNAP): an international, multicentre, open-label, non-inferiority randomised controlled trial.

This international, multicentre, open-label, non-inferiority randomized controlled trial compared benzylpenicillin versus anti-staphylococcal penicillins (cloxacillin or flucloxacillin) for treating penicillin-susceptible Staphylococcus aureus (PSSA) bacteremia in adults. The trial’s central finding (as designed to test non-inferiority) is that benzylpenicillin is evaluated as an alternative to standard anti-staphylococcal penicillins, addressing concerns about undetected penicillin resistance while potentially improving pharmacokinetics and adverse-effect profiles. Clinically, the results aim to inform first-line antibiotic choice for PSSA bacteremia and optimize safety and effectiveness.

Lancet (London, England) · (2026) · View on PubMed ↗

Management of Differentiated Thyroid Cancer.

This article reviewed and proposed a clinical framework for risk-adapted management of differentiated thyroid cancer across the full care pathway from nodule detection through surveillance, treatment, and follow-up. The key finding is the emphasis on dynamic, ongoing risk stratification that integrates clinicopathological staging with molecular tumor risk characterization and treatment response to guide therapeutic decisions over time. This framework is significant because it standardizes how clinicians balance risks and benefits while adapting management to individual patient trajectories.

Hegedüs L, Wirth LJ, Tuttle RM · The New England journal of medicine · (2026) · View on PubMed ↗

Cefazolin for Methicillin-Susceptible Staphylococcus aureus Bacteremia.

This Bayesian adaptive platform trial compared cefazolin with an antistaphylococcal penicillin (flucloxacillin or cloxacillin) in adult patients with methicillin-susceptible Staphylococcus aureus bacteremia, using death from any cause within 90 days as the primary outcome. The key finding is the trial’s ongoing randomized evaluation of whether cefazolin is non-inferior or superior to antistaphylococcal penicillins for mortality in this population. If cefazolin performs as well or better, it could shift standard-of-care antibiotic selection for MSSA bacteremia.

Lee TC, Barina LA, Walls G et al. · The New England journal of medicine · (2026) · View on PubMed ↗

The translational potential of drug-induced hypothermia in acute ischemic stroke.

This translational study assessed the feasibility and safety of drug-induced hypothermia and hypometabolism for acute ischemic stroke using chlorpromazine plus promethazine (C+P) in preclinical and clinical contexts. In mice, C+P induced hypothermia and suppressed brain glucose metabolism, and it reduced infarct volumes and improved neurological deficits. The significance is that C+P represents a potential noninvasive pharmacologic strategy to achieve sustained neuroprotective hypothermia/hypometabolism in acute stroke.

Xu S, Wang Q, An H et al. · Science translational medicine · (2026) · View on PubMed ↗

Ropeginterferon alfa-2b-njft treatment in essential thrombocythemia across different driver mutations: results from a North American, single-arm, multicentre study (EXCEED-ET).

This multicenter, single-arm phase 2b study (EXCEED-ET) evaluated ropeginterferon alfa-2b-njft (ropeg) in essential thrombocythemia across different driver mutation contexts in North America, including both treatment-naïve and hydroxyurea-pretreated patients. Patients were required to have platelet counts >450×10^9/L at screening, and the trial assessed ropeg efficacy and safety across enrolled subgroups regardless of prior cytoreductive therapy status. By extending ropeg evidence beyond the largely Asian SURPASS-ET setting, the study informs mutation-agnostic and region-relevant use of interferon therapy in ET.

Reeves BN, El Chaer F, Foltz L et al. · Lancet regional health. Americas · (2026) · View on PubMed ↗ · Free PDF ↗

Patient capacity and constraints in managing multimorbidity: a qualitative study in primary care settings in Kerala, India.

This qualitative study used semi-structured interviews to explore patient capacity and constraints for managing multimorbidity among 42 patients with two or more chronic conditions attending primary care settings in Kerala, India. The study identified practical barriers and facilitators shaping patients’ ability to handle treatment burden, including constraints related to day-to-day management and care access. These insights are significant for designing patient-centered, feasible interventions for multimorbidity management in low- and middle-income primary care contexts.

Kripa SVS, Neelamana SK, Krishnan A et al. · BMC primary care · (2026) · View on PubMed ↗ · Free PDF ↗

Remission in Global Airway Diseases: EUFOREA Consensus Paper.

The EUFOREA consensus paper reviewed evidence and expert guidance on achieving remission in global airway diseases, focusing on severe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and allergic rhinitis (AR). The key finding was consensus on practical principles for inducing and maintaining remission using disease-modifying therapies such as biologics and allergen immunotherapy, shifting goals from symptom control to remission. This provides a standardized, actionable framework to guide clinicians worldwide in remission-oriented management of chronic airway disease.

Virchow JC, Bertels X, Backer V et al. · Allergy · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative Effects of Antidiabetic Drugs on Body Composition: A Systematic Review and Network Meta-Analysis.

This systematic review and frequentist random-effects network meta-analysis compared how major antidiabetic drugs affect body composition by synthesizing randomized controlled trials (41 trials; 2906 participants) and estimating changes in fat mass (FM) and lean body mass (LBM). The key finding was that different antidiabetic drug classes produced distinct, quantifiable effects on FM and LBM, indicating that body-composition impacts vary by therapy. Scientifically and clinically, these comparative estimates can inform selection of glucose-lowering treatments when preserving muscle/lean mass and limiting fat gain are important for metabolic and functional outcomes.

Rakhsha SS, Shahinfar H, Ebrahimi-Mousavi S et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗

Menopausal Hormone Therapy: A Narrative Review of Contemporary Evidence.

This narrative review synthesized contemporary evidence on menopausal hormone therapy (MHT) for vasomotor and genitourinary symptoms, addressing how to select therapy and manage safety in individualized care. The key finding was that, despite historical declines after the Women’s Health Initiative (WHI), evidence-based approaches support appropriate MHT use with careful risk stratification and individualized management. Clinically, the review aims to reduce misconceptions and improve appropriate utilization of MHT where benefits outweigh risks.

Finks SW, Cieri-Hutcherson NE, Vernon V et al. · Pharmacotherapy · (2026) · View on PubMed ↗

Opportunities, risks and challenges integrating artificial intelligence into optometry education: A qualitative interview study.

This qualitative interview study explored stakeholder views on integrating artificial intelligence (AI) into optometry education by interviewing eyecare practitioners, students, educators, regulators, and AI technology experts. The key finding was that stakeholders saw both opportunities and risks in AI integration, emphasizing the need to define educational priorities and curriculum content before implementation. This is significant for shaping evidence-informed, competency-based optometry training that prepares learners for AI-enabled clinical practice.

Buckmaster F, van Staden D, Coetzee L · Optometry and vision science : official publication of the American Academy of Optometry · (2026) · View on PubMed ↗ · Free PDF ↗

Dexmedetomidine use in Infants undergoing Cooling due to neonatal Encephalopathy (DICE trial): safety and pharmacokinetics.

The DICE trial (phase II, multicenter, open-label, randomized safety and pharmacokinetics study) evaluated dexmedetomidine versus morphine in 48 infants undergoing therapeutic hypothermia for neonatal encephalopathy. The key finding was characterization of dexmedetomidine safety and pharmacokinetics in this specific cooled infant population using nonlinear mixed-effects modeling with NONMEM 7.5. This is clinically important because it informs dosing and safety considerations for using dexmedetomidine as a sedation/analgesia alternative to morphine during neonatal encephalopathy treatment.

Baserga MC, Bahr TM, Yang MJ et al. · Pediatric research · (2026) · View on PubMed ↗

GLP-1 Receptor Agonists for Obesity Management in Older Adults: A Scoping Review on the Risk of Sarcopenia and Sarcopenic Obesity.

This scoping review synthesized evidence on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for obesity management in older adults, focusing on mechanistic and clinical links to sarcopenia and sarcopenic obesity. The review concludes that while GLP-1 RAs produce effective weight loss, muscle mass loss is common, creating a clinically important risk for sarcopenia. The findings highlight the need for careful patient selection and monitoring of lean mass when using GLP-1 RAs in older populations.

Simsek H, Ucar A · Current nutrition reports · (2026) · View on PubMed ↗ · Free PDF ↗

Implications of wait times for sentinel node biopsy on melanoma disease progression, micrometastatic tumour burden and survival outcomes in the modern treatment era.

In a UK retrospective cohort of 1625 patients listed for sentinel node biopsy (SNB) between 2010–2023, the study assessed whether SNB wait time affects melanoma progression, micrometastatic tumor burden, and disease-specific survival, including stratification by early (≤90 days) versus late (>90 days) and adjustment for adjuvant systemic therapy (AST) use. Longer wait times were evaluated for thresholds associated with worse survival outcomes, with subgroup analyses considering AST era effects (2017–2023). Clinically, the work informs how scheduling delays for SNB may influence staging accuracy and outcomes in modern melanoma care.

Breeze SO, Heaton MJ, Snelling AP et al. · British journal of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Risk of medication-related osteonecrosis of the jaw during romosozumab treatment.

The study assessed the risk of medication-related osteonecrosis of the jaw (MRONJ) during romosozumab treatment by conducting a retrospective new-user, active-comparator propensity score–matched cohort analysis in women using romosozumab versus parathyroid hormone (PTH) analogs (teriparatide or abaloparatide) within the TriNetX Global Collaborative Network. The key finding was the comparative MRONJ risk estimate between romosozumab and PTH analog users in this matched real-world population. Clinically, the results help quantify MRONJ risk for osteoporosis patients when choosing between romosozumab and anabolic PTH-based therapies.

Stokar J, Szalat A · Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · (2026) · View on PubMed ↗ · Free PDF ↗

Potent and biased agonists of class B1 GPCRs from a heterochiral design strategy.

The study used a heterochiral design strategy to generate potent, biased agonists for class B1 GPCRs by creating heterochiral analogues of glucagon and PTH(1-34) with selected L-α-amino-acid residues replaced by D-α-amino-acid residues to destabilize the bound-state α-helix. The key finding was that these heterochiral peptides retained strong agonist potency while producing biased receptor signaling for glucagon and PTH(1-34) receptors. This provides a structure-guided route to engineer next-generation peptide therapeutics with tailored signaling profiles for diabetes and osteoporosis.

Gibadullin R, Tran LM, Niu J et al. · Nature chemistry · (2026) · View on PubMed ↗ · Free PDF ↗

Artificial intelligence for detecting fetal orofacial clefts and advancing medical education.

This study evaluated an artificial intelligence system for prenatal detection of fetal orofacial clefts using ultrasound images from 22 hospitals, training on 45,139 images from 9,215 fetuses. The AI achieved sensitivity and specificity above 93% and 95%, respectively, performing at or above senior radiologists and better than junior radiologists. This demonstrates clinically deployable AI for earlier, more reliable prenatal diagnosis of orofacial clefts, potentially improving timely intervention and reducing morbidity.

Zhang Y, Huang Y, Dou H et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Tirzepatide for Obesity in Adults ≥ 65 Years: A Post Hoc Analysis of the SURMOUNT and SUMMIT Clinical Trials.

This post hoc analysis assessed tirzepatide (a once-weekly GLP-1/GIP receptor agonist) for obesity in adults aged ≥65 years using data from Phase 3 SURMOUNT trials (SURMOUNT-1 through -5, including the 3-year extension) plus SURMOUNT-OSA and SUMMIT. Efficacy and safety outcomes were compared between participants aged ≥65 and <65 across trials. The study clarifies whether tirzepatide’s weight-loss benefits and tolerability extend to older adults, supporting evidence-based dosing and risk–benefit decisions in this underrepresented population.

Alfaris N, Kushner RF, Li J et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Alcohol-associated Liver Disease in the MENA Region: A 16-Country Survey of Healthcare Provider Perspectives.

This 16-country cross-sectional survey studied healthcare provider perceptions and clinical experiences with alcohol-associated liver disease (ALD) among clinicians involved in liver disease management across the MENA region. Providers reported region-specific perceived ALD prevalence, diagnostic and care patterns, and sociocultural/access barriers that varied across Gulf, North Africa, and Levant & Turkey subregions. The findings highlight practical, system-level obstacles to ALD recognition and management in MENA that can inform targeted improvements in screening, referral pathways, and culturally appropriate care delivery.

El-Kassas M, Awad A, Medhat MA et al. · Annals of hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Surrogacy of Intermediate Clinical Endpoints for Overall Survival in Patients With Localized Muscle-Invasive Bladder Cancer.

This multicenter analysis studied whether intermediate clinical endpoints—pathologic complete response (pCR), pathologic objective response (pOR), and disease-free survival (DFS)—can serve as surrogates for overall survival (OS) in 4,828 patients with localized muscle-invasive bladder cancer (cT2-T4N0M0) undergoing radical cystectomy with or without neoadjuvant chemotherapy across 29 European centers. The study found that certain intermediate endpoints (evaluated via surrogate validation using inverse probability of treatment weighting) did not fully capture OS, limiting their reliability as validated surrogates. Scientifically, the work informs which perioperative endpoints may or may not accelerate randomized trial completion for localized MIBC without compromising OS interpretability.

Scilipoti P, de Angelis M, Thibault C et al. · Journal of the National Comprehensive Cancer Network : JNCCN · (2026) · View on PubMed ↗

Consensus Definitions of Disease Activity and Clinical Outcomes in Patients With Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

This consensus study developed standardized definitions for disease activity status and clinical outcomes in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Using a GBS|CIDP Foundation International task force of 17 CIDP experts plus guest specialists and patient representatives, the group iteratively reviewed and voted on terminology such as “No Evidence of Disease Activity,” relapse, response, refractory disease, and remission. Establishing uniform CIDP definitions is scientifically and clinically significant because it improves comparability across trials and supports consistent treatment decision-making.

Allen JA, Eftimov F, Querol L et al. · Neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Virion display reveals MD-1 as an endogenous agonist for the orphan receptor GPRC5B.

This study used virion display to deorphanize the human orphan GPCR GPRC5B by identifying endogenous protein ligands. The authors engineered recombinant viruses displaying the four GPRC5 family receptors and screened them against a human proteome array, then focused on GPRC5B, which had prior links to obesity. The approach is scientifically significant because it provides a generalizable, proteome-wide method for GPCR deorphanization and advances understanding of GPRC5B ligand biology.

Johansen E, Syu GD, Wan Z et al. · Science signaling · (2026) · View on PubMed ↗

On-Scene, Residential Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest: Operational and Logistical Considerations.

This report described the first on-scene, residential extracorporeal cardiopulmonary resuscitation (ECPR) performed in North America for refractory out-of-hospital cardiac arrest (OHCA). A 66-year-old woman with witnessed ventricular fibrillation underwent immediate venoarterial ECMO cannulation on scene by a mobile ECMO team in a confined residential bedroom setting. The operational and logistical insights are clinically important because they demonstrate feasibility of rapid, prehospital ECPR initiation to reduce low-flow time in selected refractory OHCA cases.

Dinh K, Witkov R, Liu J et al. · ASAIO journal (American Society for Artificial Internal Organs : 1992) · (2026) · View on PubMed ↗

Analysis signals of disproportionate reporting associated with donanemab: A retrospective pharmacovigilance study using the FAERS database.

This retrospective pharmacovigilance study analyzed adverse event reports for donanemab in the FDA Adverse Event Reporting System (FAERS) from Q3 2024 to Q2 2025 using reporting odds ratio (ROR), proportional reporting ratio (PRR), Multi-item gamma poisson shrinkage (MGPS), and Bayesian confidence propagation neural network (BCPNN). The key result was the identification of disproportionate reporting signals (SDRs) for specific adverse events associated with donanemab, along with descriptive characterization of time-to-onset patterns. Clinically, these SDRs can guide targeted safety monitoring and hypothesis generation for confirmatory studies of donanemab-associated risks.

Zhang Y, Gong Q, Yu J et al. · Science progress · (2026) · View on PubMed ↗ · Free PDF ↗

Effects of gliflozins on bone health of patients with chronic kidney disease: a systematic review.

This systematic review evaluated the effects of SGLT2 inhibitors (gliflozins) on bone health in patients with chronic kidney disease (CKD) by synthesizing randomized controlled trials and observational cohort studies. Across included studies, the authors summarized skeletal safety outcomes (e.g., osteoporosis, fractures, falls, amputations) and bone mineral markers, concluding an overall assessment of skeletal risk and metabolic effects of SGLT2i in CKD populations. Scientifically and clinically, the review addresses a key uncertainty in CKD management by clarifying whether gliflozins meaningfully alter bone outcomes.

Cassani de Oliveira M, Rufino L, Mendes Lourenço AL et al. · Journal of nephrology · (2026) · View on PubMed ↗

Restoring the interplay between the endoplasmic reticulum and mitochondria by gene therapy improves Charcot-Marie-Tooth type 2A disease.

This proof-of-concept gene therapy study targeted Charcot-Marie-Tooth disease type 2A (CMT2A) caused by dominant MFN2 mutations by restoring endoplasmic reticulum–mitochondria interplay in neurons. Neuronal overexpression of a therapeutic construct improved ER–mitochondria contacts and mitigated downstream mitochondrial dysfunction and axonal degeneration phenotypes in the MFN2 disease context. The findings are significant because they provide a rationale for treating CMT2A by correcting organelle contact biology rather than only boosting mitochondrial function.

Tessier M, Hamze Z, Bonello-Palot N et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

DMD-Null mice exhibit severe muscle weakness, impaired regeneration, and deficient satellite cell function.

This study characterized the phenotype of DMD-null mice to model Duchenne muscular dystrophy (DMD) and assess muscle weakness, regeneration, and satellite cell function. DMD-null mice showed severe muscle weakness, impaired regenerative capacity, and deficient satellite cell function compared with expectations from milder dystrophic models. The results are important for selecting and interpreting preclinical DMD models that better reflect human disease severity and for evaluating regenerative or stem-cell–targeted therapies.

Wilton-Clark H, Shah MNA, Leckie J et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on June 18, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.