PubMed Trending Research Digest — October 08, 2026

Automated digest · 97 articles · 15 research areas · October 08, 2026

Overview

Across this week’s digest, a dominant thread is the move from “one-size-fits-all” treatment toward mechanism- and biomarker-guided care. In oncology, multiple studies use immune profiling, spatial transcriptomics, and multi-omic atlases to explain resistance and identify actionable targets (e.g., cGAS-STING suppression via CHCHD3 in lung adenocarcinoma; macrophage metabolic reprogramming via GULP1 in gastric cancer; splicing signatures linked to checkpoint blockade phenotypes). Complementing these mechanistic efforts, several clinical trials and real-world studies test next-generation immunotherapies and combinations—ranging from neoadjuvant dual checkpoint blockade in recurrent glioblastoma to ADC immunomodulation frameworks and IL7R mRNA-LNP strategies—while also emphasizing practical endpoints like safety, response durability, and patient selection.

A second major theme is immunometabolism and inflammation as unifying biology across diseases. Host-targeted approaches appear repeatedly: inflammasome pathways as actionable levers in mpox macrophage infection; direct metabolic control of NLRP3 by L-arginine; and redox/mitochondrial checkpoints shaping outcomes in osteoporosis and neurodegeneration. Gut–liver and broader microbiome–metabolism links also feature prominently, including epigenetic “scarring” after intestinal inflammation that sustains susceptibility to fatty liver disease, and microbiome-derived metabolites (e.g., odd-chain fatty acid–producing bacteria) that modulate cholesterol handling and atherosclerosis.

Finally, several studies highlight advances in foundational biology and translational tools that enable better diagnosis, modeling, and intervention. These include improved genomic/epigenomic modeling of chromatin and DNA repair (DNA-PKcs in NHEJ; lactylation control of XPA), scalable sequencing workflows for repeat expansion disorders, and tissue-engineering/regenerative platforms (lung organoids for tissue-resident T cell immunity; tol-aLN for antigen-specific tolerance; AT2-to-airway regeneration cues). Together, the set reflects a broad shift toward quantitative, mechanistic, and personalized biomedical research—spanning from molecular regulation to clinical decision-making.

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Cardiopulmonary imaging & right-heart coupling

Prognostic Implications of Right Ventricular-Pulmonary Arterial Coupling Derived from Right Ventricular Strain in Secondary Tricuspid Regurgitation.

This study evaluated whether right ventricular free wall longitudinal strain (RVFWLS) normalized to pulmonary artery systolic pressure (PASP)—as an RV–pulmonary arterial coupling surrogate—predicts outcomes in patients with moderate-to-severe secondary tricuspid regurgitation, and compared its prognostic value against the established TAPSE/PASP ratio. The key finding was that the RVFWLS/PASP ratio derived from RV strain provided prognostic information about excess mortality and offered incremental value beyond TAPSE/PASP in this population. Clinically, this supports using RV strain–based RV–PA coupling metrics to better risk-stratify secondary TR patients and potentially guide management intensity.

Butcher SC, Galloo X, Fortuni F et al. · Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography · (2026) · View on PubMed ↗

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Oncology therapeutics (solid tumors) & clinical trials

Neoadjuvant niraparib monotherapy for unresectable, homologous recombination deficiency-positive, high-grade serous ovarian cancer (NANT): a multicentre, single-arm, phase 2 trial.

This multicentre, single-arm phase 2 trial tested neoadjuvant niraparib monotherapy as a chemotherapy-free approach in treatment-naïve, FIGO stage III–IV HRD-positive high-grade serous or endometrioid ovarian cancer initially unsuitable for primary debulking surgery. The study evaluates whether niraparib can achieve clinically meaningful outcomes in this HRD-positive population without interval debulking chemotherapy. If effective, it would support a biomarker-driven, chemotherapy-sparing neoadjuvant regimen using PARP inhibition for selected unresectable ovarian cancers.

Liu D, Peng Z, Zhang W et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Advances in Systemic Treatment of Breast Cancer.

This narrative review examined advances in systemic treatment for breast cancer since 2020, focusing on biomarker-guided strategies across hormone-receptor–positive/HER2-negative, HER2-positive, and other biologic subtypes. The key finding was that expanded molecular profiling and germline testing have enabled increasingly personalized therapy, with CDK4/6 inhibitors remaining foundational in HR+/HER2− disease while PI3K-pathway inhibitors, oral selective estrogen receptor degraders, and antibody-drug conjugates have meaningfully changed management after endocrine resistance. Scientifically and clinically, the article highlights how targeted agents and antibody-drug conjugates are being integrated based on tumor biomarkers to improve outcomes and treatment selection.

Hurvitz SA · The New England journal of medicine · (2026) · View on PubMed ↗

Perioperative Outcomes and Recovery After Robot-Assisted vs Open Radical Hysterectomy: A Secondary Analysis of the RACC Randomized Clinical Trial.

This secondary analysis of the multicenter, noninferiority phase 3 RACC randomized clinical trial compared perioperative outcomes and health-related quality of life after robot-assisted versus open radical hysterectomy in women with early-stage cervical cancer treated at tertiary centers in Europe. Robot-assisted radical hysterectomy showed perioperative safety and recovery outcomes that were evaluated against open surgery, with the study focusing on differences in surgical morbidity and HRQOL during recovery. These findings support evidence-based selection of minimally invasive (robot-assisted) radical hysterectomy approaches while addressing ongoing oncologic-safety concerns.

Salehi S, Norberg Hardie A, Smolders RGV et al. · JAMA surgery · (2026) · View on PubMed ↗

EACTS Expert Consensus Document on Iatrogenic Aortic Dissection.

This study tested whether inhibiting MEKK3 could halt cerebral cavernous malformation (CCM) progression by restoring endothelial integrity and modulating microglial activation, using mechanistic experiments supported by AI-assisted drug design and structural optimization. The key finding was that MEKK3 inhibition prevents CCM progression by targeting endothelial MEKK3-driven junctional disruption and fibrinogen leakage while restricting microglial MEKK3-dependent late-stage amplification of vascular injury via MEKK3–NF-κB-dependent uptake of damaged endothelial debris. Scientifically, it identifies MEKK3 as a therapeutic target and provides a rationale for MEKK3 inhibitors as potential disease-modifying treatments for CCM.

Luehr M, Nersesian G, Pitts L et al. · European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery · (2026) · View on PubMed ↗

Cadonilimab plus lenvatinib in advanced endometrial cancer: the multicenter single-arm phase II CLEAR-EC trial.

This study evaluated cadonilimab (a bispecific antibody targeting PD-1 and CTLA-4) plus lenvatinib in women with advanced endometrial cancer in the multicenter, single-arm phase II CLEAR-EC trial (NCT05824481). The trial assessed objective response rate as the primary endpoint with additional measures including progression-free survival and overall survival, following a safety run-in and then expansion to the recommended phase II dose. If efficacy and safety signals are favorable, this regimen could provide a new second-line or later option for platinum-refractory advanced endometrial cancer.

Zhou L, Zhao J, Li S et al. · Nature communications · (2026) · View on PubMed ↗

Neoadjuvant PD1 plus CTLA-4 immune checkpoint blockade in surgically resectable recurrent glioblastoma: a randomized surgical window-of-opportunity trial.

This randomized surgical window-of-opportunity trial studied neoadjuvant immune checkpoint blockade in surgically resectable recurrent glioblastoma, comparing nivolumab plus ipilimumab, nivolumab alone, or placebo. Neoadjuvant dual ICB with nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA-4) significantly increased tumor-infiltrating lymphocyte (TIL) density, meeting the primary endpoint for the dual-ICB arm. The results support dual checkpoint blockade as a strategy to enhance intratumoral immune infiltration before surgery in recurrent glioblastoma.

Sun L, Markus LF, Sanchez JC et al. · Nature communications · (2026) · View on PubMed ↗

Short-term risk prediction model for pancreatic cancer in type 2 diabetes: development and validation across two independent Chinese cohorts.

This retrospective longitudinal cohort study developed and validated a short-term pancreatic cancer risk prediction model for people with type 2 diabetes, including both new-onset and long-standing diabetes, using two independent Chinese cohorts (Tianjin Diabetes and Health Cohort for derivation/internal validation and an Xiamen Regional Electronic cohort for external validation). The key finding was that the model could stratify short-term pancreatic cancer risk across both diabetes durations, enabling more tailored screening prioritization. Scientifically and clinically, it supports more efficient pancreatic cancer screening strategies that go beyond models restricted to new-onset diabetes.

Zhu H, Fan H, Yang W et al. · Gut · (2026) · View on PubMed ↗

Efficacy of Cryotherapy in Preventing Taxane-Induced Neuropathy: The CryoPac Randomised Controlled Trial.

In the CryoPac randomized controlled trial, patients receiving taxane chemotherapy were assigned to cryotherapy (frozen gloves and socks during each taxane infusion) versus usual care to prevent chemotherapy-induced peripheral neuropathy (CIPN). The key finding was the trial’s assessment of whether cryotherapy reduces CIPN severity as measured by Total Neuropathy Score (TNS) and related outcomes compared with usual care. This is clinically important because it tests a practical, nonpharmacologic prevention strategy for a common dose-limiting toxicity of taxanes.

Lendorf ME, Bille MB, Krog SM et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗

First-line durvalumab and tremelimumab in poor-prognosis unresectable hepatocellular carcinoma: Phase IIIb single-arm SIERRA study.

This phase IIIb single-arm SIERRA study assessed first-line STRIDE therapy (tremelimumab plus durvalumab) in adults with poor-prognosis unresectable hepatocellular carcinoma (uHCC), including cohorts with impaired liver function (Child-Pugh B7/B8) and other poor prognostic features. The primary analysis reported safety and efficacy outcomes for STRIDE in these poor-prognosis patients, extending evidence from earlier early-safety reporting. The significance is that STRIDE may be a viable first-line option for uHCC patients who are often excluded from standard trials due to worse baseline prognostic factors.

Chan SL, Kudo M, Sangro B et al. · Journal of hepatology · (2026) · View on PubMed ↗

The expanding therapeutic landscape of β-thalassaemia.

This narrative review summarized the evolving therapeutic landscape for β-thalassaemia, focusing on disease-modifying approaches beyond transfusion and iron chelation. The key finding was that newer agents targeting erythroid maturation and red cell metabolism—specifically luspatercept and mitapivat—have expanded options for both transfusion-dependent and non-transfusion-dependent β-thalassaemia. The significance is that these therapies may reduce disease burden and improve outcomes, while also highlighting remaining gaps in access, safety, adherence, and curative feasibility.

Musallam KM, Sheth S, Locatelli F et al. · The Lancet. Haematology · (2026) · View on PubMed ↗

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Hematologic malignancies (myeloma/AML) & cellular therapies

Clinical Features and Outcomes of Therapy-Related Myeloid Neoplasms After CAR T-Cell Therapy.

This multicenter retrospective cohort study investigated whether therapy-related myeloid neoplasms (t-MN) occurring after chimeric antigen receptor (CAR) T-cell therapy confer an independent survival disadvantage compared with t-MN after autologous hematopoietic cell transplantation (auto-HCT) or standard chemotherapy/radiation. The key finding was that, in a latency-matched nearest-neighbor cohort, overall survival after post–CAR-T t-MN was worse (median OS 9.1 months) than after post-auto-HCT (16.9 months) or standard therapy (18.7 months). Scientifically and clinically, the study suggests that the post–CAR-T biology or treatment context may worsen prognosis, informing risk stratification and post–CAR-T surveillance strategies.

Jain MD, Ali A, Roman Diaz J et al. · Blood advances · (2026) · View on PubMed ↗

Translocation-induced enhancer rewiring reveals cryptic oncogenic circuits in multiple myeloma.

The study developed TransFinder to resolve cryptic immunoglobulin heavy chain (IGH) enhancer translocations in multiple myeloma (MM) by integrating SMRT long-read sequencing, Hi-C, H3K27ac ChIP-seq/CUT&Tag, and RNA-seq. Using this pipeline, the authors found that the canonical t(16;22)(q23;q11) translocation that activates MAF also hijacks enhancers to activate RAB36, and they uncovered additional cryptic translocations t(5;8)(q35;q24) activating MYC and t(1;22)(q25;q13) activating CBX. This improves mechanistic diagnosis of MM by mapping enhancer–promoter neo-loops at breakpoints to identify oncogenic drivers missed by routine testing.

Zheng E, Li Q, Dou X et al. · Science advances · (2026) · View on PubMed ↗

Extended follow-up of in vivo BCMA CAR-T therapy in relapsed/refractory multiple myeloma.

This study reports extended in vivo follow-up of the BCMA-targeted CAR-T product ESO-T01 in four patients with relapsed/refractory multiple myeloma, using a leukapheresis- and lymphodepletion-free approach. All patients developed dual-phase cytokine release syndrome (grades 1–3) and grade ≥3 hematotoxicities, with one patient experiencing grade 1 immune effector cell-associated neurotoxicity syndrome. These long-term safety/efficacy and pharmacokinetic/pharmacodynamic data support further clinical development of in vivo BCMA CAR-T strategies for heavily pretreated myeloma patients.

Xu J, Liu L, Xie W et al. · Nature medicine · (2026) · View on PubMed ↗

Venetoclax-based therapy versus hypomethylating agents alone in unfit patients with newly diagnosed acute myeloid leukemia: a real-world study from the PETHEMA registry.

This real-world PETHEMA registry analysis compared venetoclax (VEN)-based regimens versus hypomethylating agent (HMA) monotherapy in 2610 unfit patients with newly diagnosed acute myeloid leukemia. VEN-based therapy achieved higher composite complete remission (64.4% vs 20.0%) and lower 30- and 60-day mortality (4.8% vs 7.5%; 9.7% vs 15.7%), with improved median overall survival (11.4 vs 8.2 months; HR 0.66). The results strengthen evidence that adding venetoclax to HMAs improves early outcomes and survival in real-world, transplant-ineligible AML populations.

Aspas Requena G, Aguiar E, Brioso J et al. · Leukemia · (2026) · View on PubMed ↗

MAIA frailty subgroup analysis: long-term follow-up with daratumumab plus lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma.

This MAIA frailty subgroup analysis evaluated long-term outcomes of daratumumab plus lenalidomide/dexamethasone (D-Rd) versus lenalidomide/dexamethasone (Rd) in transplant-ineligible newly diagnosed multiple myeloma, stratifying patients by frailty using age, Charlson Comorbidity Index, and baseline ECOG performance status. After a median 64.5-month follow-up, D-Rd showed an overall survival benefit over Rd within frailty-defined subgroups (with the abstract reporting the updated OS benefit for D-Rd). The findings support using frailty-based risk stratification to guide daratumumab-containing therapy in older or medically vulnerable myeloma patients.

Facon T, Cook G, Usmani SZ et al. · Leukemia · (2026) · View on PubMed ↗

MK-4002, a B-cell maturation antigen-targeting T-cell engager, in relapsed or refractory multiple myeloma: a first-in-human, open-label, phase 1 study.

This first-in-human, open-label phase 1 study tested MK-4002, a trispecific B-cell maturation antigen (BCMA)-targeting T-cell engager, in adults with relapsed or refractory multiple myeloma. The key finding was the characterization of MK-4002’s safety, preliminary anti-myeloma activity, and pharmacokinetics in heavily pretreated patients. Scientifically and clinically, it provides early translational evidence for a next-generation BCMA T-cell engager and informs dose selection and further development in R/R multiple myeloma.

Madan S, Costello C, Lipe B et al. · The Lancet. Haematology · (2026) · View on PubMed ↗

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Immuno-oncology mechanisms & biomarkers

A preinvasive regulatory T cell axis for lung cancer interception.

This study used multi-omic, cross-tissue immune profiling in patients with preinvasive lung lesions surveilled by autofluorescence bronchoscopy and CT imaging to define how effector regulatory CD4+ T cells (eTreg) are remodeled during NSCLC development. The authors report a preinvasive T cell regulatory axis that becomes dysregulated as lesions progress toward lung cancer. These findings support interceptive strategies that track and therapeutically target early Treg-network changes before invasive NSCLC emerges.

Gamble S, Whiteman ZE, Peinador-Marín C et al. · Nature · (2026) · View on PubMed ↗

IL7R mRNA therapy enhances antitumor T cell immunity and suppresses tumor growth in preclinical tumor models.

This preclinical study evaluated IL7R mRNA therapy delivered in lipid nanoparticles (LNPs) via combined intratumoral and intravenous injection in syngeneic B16 melanoma and Lewis lung carcinoma (LLC) mouse models. The key finding is that IL7R mRNA increased IL7R expression and enhanced antitumor T cell immunity, suppressing tumor growth compared with empty LNP controls. These results support IL7R mRNA-LNP delivery as a strategy to boost T cell survival/homeostasis and improve tumor control.

Rehman AU, Khan MN, Akhtar A et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗

TCASIA: an integrative atlas linking alternative splicing landscapes for cancer immunotherapy.

This study developed TCASIA, an integrative atlas of alternative splicing landscapes for cancer immunotherapy, harmonizing >4000 samples across 29 cohorts. Using a “2-out-of-4” consensus framework (rMATS, MAJIQ, SUPPA2, SplAdder) with fuzzy matching, TCASIA produced high-confidence splicing signatures linked to immune checkpoint blockade clinical phenotypes. The atlas provides a resource for identifying splicing-based biomarkers and mechanistic targets to improve prediction and stratification for ICB.

Zhang Y, Guo Y, Wang H et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗

SLC39-driven zinc influx orchestrates pleiotropic tumor-immune system cross-talk to establish immune suppression in colorectal cancer.

The study analyzed how SLC39 family zinc transporters rewire tumor–immune interactions in colorectal cancer using bulk multi-omics, single-cell RNA-seq, spatial profiling, and functional assays across 258 patients. An SLC39-enriched tumor subtype showed immune-desert features, and SLC39-mediated zinc influx activated CDX2, which via a distal enhancer induced tumor-specific CD24 expression that promoted immune suppression. This identifies an SLC39–zinc–CDX2–CD24 axis as a mechanistic driver of tumor immune evasion and a potential therapeutic target.

Hong SJ, Park S, Kim S et al. · Science advances · (2026) · View on PubMed ↗

CAR-engineered microglia harness phagocytosis to target brain tumor in organoid models.

The study engineered CAR-expressing microglia (CAR-MG) to harness phagocytosis against glioblastoma in organoid-based models, using human cortical organoid–derived microglia. CAR-MG expressing an EGFRvIII-targeting CAR selectively eliminated EGFRvIII-positive GBM cells through phagocytosis in 2D co-culture. This supports a cell-therapy strategy that repurposes innate phagocytes for targeted GBM killing using a tumor-specific antigen.

Choe MS, Yang WS, Cakir B et al. · Cell reports · (2026) · View on PubMed ↗

Single-Cell and Spatial Transcriptomics Reveal CHCHD3 as a Therapeutic Target to Activate cGAS-STING and Overcome Immunosuppression in Lung Adenocarcinoma.

This study analyzed clinical specimens from the CheckMate 816 trial using integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to define tumor immune microenvironment (TIME) features associated with resistance to neoadjuvant chemoimmunotherapy in lung adenocarcinoma (LUAD). It found that non-responders showed upregulation of the mitochondrial/chaperone gene CHCHD3, and mechanistically CHCHD3 promoted immunosuppression by sequestering cGAS and thereby dampening cGAS-STING innate immune activation. Identifying CHCHD3 as a therapeutic target suggests a strategy to overcome intrinsic resistance to chemoimmunotherapy in LUAD by restoring cGAS-STING signaling.

Zhang M, Li Z, Xiao Z et al. · Cancer research · (2026) · View on PubMed ↗

GULP1 Fuels Resistance to PD-1 Blockade through Lipid-Mediated Metabolic Reprogramming of Tumor-Associated Macrophages in Gastric Cancer.

This study investigated mechanisms of resistance to anti-PD-1 therapy in gastric cancer by integrating transcriptomic analyses of anti-PD-1-responsive versus anti-PD-1-resistant patient cohorts with mouse models and single-cell RNA-seq datasets, focusing on the role of GULP1 in tumor-associated macrophages. The key finding was that GULP1 promotes resistance to PD-1 blockade through lipid-mediated metabolic reprogramming of tumor-associated macrophages. Clinically, targeting the GULP1–macrophage metabolic axis could help overcome immune checkpoint inhibitor resistance in gastric cancer.

Zhang Z, Xu W, Yu K et al. · Cancer communications (London, England) · (2026) · View on PubMed ↗

Intestinal epithelial GSK3β governs fumarate-dependent neutrophil reprogramming to promote colorectal cancer.

This study used mouse models and multiomics profiling to define how intestinal epithelial GSK3β regulates fumarate-dependent neutrophil reprogramming in colorectal cancer. GSK3β-primed T3 neutrophils expressed FTH1 and PD-L1, promoting ferroptosis resistance and immune evasion, via nuclear GSK3β phosphorylation of linker histone H1FX leading to proteasomal degradation (through USP43 dissociation) and increased chromatin accessibility for glycolytic gene transcription. By connecting epithelial GSK3β signaling to neutrophil polarization and tumor immune escape, the work identifies a pathway that could be therapeutically targeted to overcome colorectal cancer resistance.

He XS, Yang XQ, Wan S et al. · Nature cancer · (2026) · View on PubMed ↗

T cell immunomonitoring: a comparative analysis of traditional and novel methods to quantify and characterize human antigen-specific T cells.

This Nature Protocols review compared traditional and newer methods for quantifying and characterizing human antigen-specific T cells for immunomonitoring. It synthesizes how different assay modalities capture the heterogeneity of antigen-specific T cell responses and how longitudinal monitoring can inform vaccine and cellular therapy development. The review is significant for standardizing and selecting immunomonitoring techniques that best reflect functional antigen-specific T cell activity in clinical studies.

Lazzaro S, Leroux-Roels G, Janetzki S et al. · Nature protocols · (2026) · View on PubMed ↗

Exploring the immunological effects of antibody-drug conjugates.

This Nature Reviews Clinical Oncology article reviewed the immunological effects of antibody-drug conjugates (ADCs) across cancers. It highlights that ADC efficacy can extend beyond direct payload cytotoxicity to include immunogenic cell death, antigen release, antibody-dependent cell-mediated cytotoxicity, dendritic cell activation, and tumor microenvironment reprogramming. The synthesis is clinically important because it frames ADCs as immunomodulatory agents, guiding rational combination strategies with immunotherapies.

Zagami P, Trapani D, Marra A et al. · Nature reviews. Clinical oncology · (2026) · View on PubMed ↗

Metal-organic framework nanovaccines for systemic tumour regression.

This preclinical study developed MOF-Vac, a metal-organic framework nanovaccine that co-delivers peptide antigens and STING agonists with phosphate-triggered intracellular release, and tested it in multiple murine tumor models. MOF-Vac enabled coordinated antigen presentation and innate immune activation, producing sustained T-cell priming and intratumoral effector function and driving systemic tumor regression across melanoma, colorectal cancer, triple-negative breast cancer, lung cancer, and oropharyngeal cancer models. The approach is significant because it addresses a key limitation of cancer vaccines—insufficient durability of T-cell activation within tumors—by coupling antigen delivery to STING-driven innate signaling.

Jiang X, Wang C, Yang K et al. · Nature biomedical engineering · (2026) · View on PubMed ↗

PRMT7 restricts CD8+ T cells expansion via the NF-ΚB pathway.

This study tested whether T cell-specific deletion of Prmt7 (using CD4-Cre) alters CD8+ T cell expansion and function, focusing on the NF-κB pathway. Prmt7 deficiency increased CD8+ effector differentiation, cytokine secretion, cytolytic activity, and anti-tumor responses, with transcriptional reprogramming driven by NF-κB activation and enhanced effector markers (e.g., CD25, CD69, IFNγ). The findings identify PRMT7 as a brake on CTL expansion that could be therapeutically targeted to improve cancer immunotherapy manufacturing and efficacy.

Srour N, Luo K, Allard D et al. · Nature communications · (2026) · View on PubMed ↗

Identification of expressed endogenous retroviral element associated long terminal repeats in devil facial tumour cells.

This study investigated devil facial tumour cells (DFT1/DFT2) to identify expressed endogenous retroviral element (ERV) long terminal repeat (LTR) sequences associated with specific LTR regions. The authors identified thousands of ERV LTR elements and highlighted a subset of expressed ERV LTRs linked to long terminal repeat activity in tumour cells. This provides candidate tumour-specific antigens for developing a vaccine against transmissible devil facial tumour disease.

Kruawan A, Stammnitz MR, Wilson R et al. · Open biology · (2026) · View on PubMed ↗

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Neurobiology & neurodegeneration biomarkers/therapeutics

Astrocytes regulate axonal mitochondrial transport deficits in C9ORF72 amyotrophic lateral sclerosis motor neurons.

This study used cocultures of human induced pluripotent stem cell (iPSC)-derived astrocytes carrying the C9ORF72 mutation with motor neurons to test how astrocytes affect axonal mitochondrial transport in ALS. Mutant astrocytes disrupted mitochondrial axonal transport and mitochondrial function, while isogenic gene-corrected astrocytes or boosting astrocytic mitochondrial bioenergetics rescued these deficits. The work establishes a non-cell-autonomous astrocyte mechanism for mitochondrial transport failure in C9ORF72 ALS models and suggests astrocyte-targeted metabolic interventions.

Stavrou M, Heffernan ÁB, Carter RN et al. · Nature neuroscience · (2026) · View on PubMed ↗

Attention-Deficit/Hyperactivity Disorder and Late-Life Cognitive Impairment.

The study assessed whether adult attention-deficit/hyperactivity disorder (ADHD) is associated with incident late-life cognitive impairment (mild cognitive impairment or dementia) using US All of Us electronic health record diagnoses and genetic liability measured by a genome-wide ADHD polygenic risk score (PRS). The analysis was designed to address diagnostic ascertainment and residual confounding by using both EHR-based outcomes and PRS within the same individuals. This clarifies the epidemiologic and genetic relationship between ADHD and later cognitive decline, informing risk stratification and causal hypotheses.

Bauer-Negrini G, Leffa DT, Ferreira PCL et al. · JAMA psychiatry · (2026) · View on PubMed ↗

Genetic evidence supports a cortical neuroprotective role of GLP-1 receptor activation in Alzheimer’s disease: A drug-target Mendelian randomization study.

This drug-target Mendelian randomization study used cis-expression quantitative trait loci (cis-eQTLs) for GLP-1 receptor (GLP-1R) from blood and brain cortex to test whether GLP-1R activation causally affects Alzheimer’s disease (AD) risk and related biomarkers. Genetic evidence supported a cortical neuroprotective role of GLP-1R expression, consistent with lower AD risk and/or favorable biomarker patterns linked to neuroprotection. These findings strengthen the rationale for GLP-1R–targeted therapies as potential disease-modifying approaches in AD beyond peripheral metabolic effects.

Jiang L, Chen X, Qian J et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗

Using multi-trait polygenic scores to predict lithium responsiveness in patients with bipolar disorder.

This genetic prediction study developed multi-trait polygenic scores (mt-PGS) to predict lithium responsiveness in bipolar disorder patients using data from the International Consortium on Lithium Genetics (N=2367) who received lithium for at least 6 months. The mt-PGS approach improved prediction of lithium response measured by the Alda scale compared with more limited single-trait genetic approaches. Clinically, this supports moving toward more personalized lithium treatment selection using aggregated genetic risk information.

Sharew NT, Clark SR, Hartmann S et al. · The British journal of psychiatry : the journal of mental science · (2026) · View on PubMed ↗

Amyloid, p-tau, neurofilament light, and α-synuclein cerebrospinal fluid biomarkers across Alzheimer’s disease, dementia with Lewy bodies, and Parkinson’s disease.

This cross-disease biomarker study measured cerebrospinal fluid (CSF) amyloid beta (Aβ42/40), phosphorylated tau 181 (p-tau181), neurofilament light (NfL), and total α-synuclein using fully automated Elecsys immunoassays in 347 participants from the EPND cohort across Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and Parkinson’s disease (PD). It characterized overlapping and distinct CSF biomarker patterns across these neurodegenerative disorders and related amyloid/tau positivity to cognitive and motor function. The results are clinically important for improving differential diagnosis and for understanding shared pathology across AD, DLB, and PD.

Rizzo M, Teunissen CE, Zetterberg H et al. · Alzheimer’s & dementia (Amsterdam, Netherlands) · (2026) · View on PubMed ↗

Chronic Postnatal Chemogenetic Activation of Forebrain Excitatory Neurons Modulates Astrocyte-Associated Function and Metabolism in Adult Male Mice.

This preclinical study examined chronic postnatal chemogenetic activation of forebrain excitatory neurons in adult male mice and its effects on astrocyte-associated function and metabolism. It found that prolonged Gq-enhanced signaling in early postnatal life programs adult astrocyte-related metabolic and functional alterations. The results are significant because they connect early-life excitatory circuit modulation to long-term astrocyte dysfunction relevant to vulnerability for adult psychopathology.

Pradhan A, Pati S, Saba K et al. · The European journal of neuroscience · (2026) · View on PubMed ↗

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Neuro-immune interactions & CNS immune modulation

Immunoregulatory artificial lymph nodes restore antigen-specific tolerance in advanced multiple sclerosis.

This study engineered a 3D-printed tolerogenic artificial lymph node (tol-aLN) to restore antigen-specific tolerance in advanced multiple sclerosis by improving tolerogenic dendritic cell (tolDC) homing and durability. The key finding was that tolDCs loaded onto a porous gelatin methacrylate scaffold engineered for sustained CCL21 release created a protected immune niche that recruited naïve CD4+ T cells and shielded tolDCs from inflammatory lymph node conditions, with scaffold geometry optimization enhancing tolerogenic outcomes. Clinically, the work supports a next-generation antigen-specific immunotherapy concept that may overcome limitations of tolDC vaccines in inflamed lymphoid tissues.

Ji J, Wang X, Liu L et al. · Science translational medicine · (2026) · View on PubMed ↗

Neuro-immune interactions in tumors, immune-related disorders, and infections.

This article is a review summarizing evidence for neuro-immune interactions across tumors, immune-related disorders, and infections, focusing on mechanistic modes including local, reflex-level, and CNS-wide regulation. It highlights that limited mechanistic understanding and a shortage of candidate drugs have constrained therapeutic translation. The review frames neuro-immune pathways as emerging targets and provides a conceptual map to guide future drug discovery and mechanistic studies.

Zhuang QY, Zhang SW, Shao ZM et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗

A silent RAGE: The inflammatory pathway to dementia in Parkinson’s disease.

This narrative review examined how the receptor for advanced glycation end products (RAGE) may connect multiple neurodegenerative processes in Parkinson’s disease (PD), including α-synuclein pathology, amyloid-β and tau co-pathologies, and chronic neuroinflammation, to drive cognitive decline toward dementia. The key finding is the proposed role of RAGE as a multi-ligand orchestrator that bridges proteotoxic aggregates and damage-associated molecular patterns (DAMPs) to promote inflammatory cascades relevant to dementia progression. Scientifically, it highlights RAGE as a mechanistic target for interventions aimed at slowing or preventing PD-related cognitive deterioration.

Peixoto DO, Gasparotto J, Ojo OR et al. · Ageing research reviews · (2026) · View on PubMed ↗

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Infectious disease & zoonotic viruses

Fusion-loop-engineered Zika mRNA vaccine elicits convergent B cell immunodominance to uncouple protection from ADE in macaques.

This primate study engineered a fusion-loop (FL) variant Zika virus (ZIKV) M/E mRNA vaccine and assessed whether it protects against ZIKV challenge while minimizing dengue virus (DENV) antibody-dependent enhancement (ADE) in macaques. The vaccine induced predominantly ZIKV-specific B cells (>97%) dominated by a convergent population using a germline ortholog of human IGHV5-10-1, and it produced negligible DENV ADE. The findings provide primate-level validation that FL engineering can decouple protection from ADE risk, informing safer flavivirus vaccine design.

Yang C, Guo S, Lu Y et al. · Cell reports. Medicine · (2026) · View on PubMed ↗

Potential health impacts and costs of active case finding guided by Mycobacterium tuberculosis immunoreactivity survey results in Blantyre, Malawi: A mathematical modeling study.

The study used mathematical modeling to estimate the health impacts and costs of active tuberculosis (TB) case finding (ACF) in Blantyre, Malawi, comparing passive case finding (PCF), untargeted ACF, and targeted ACF guided by annual risk of TB infection (ARTI) derived from Mycobacterium tuberculosis immunoreactivity surveys in children under 5. ARTI-guided targeted ACF was evaluated for improved efficiency relative to untargeted strategies by leveraging local surveillance estimates across 33 urban neighborhoods. The work supports evidence-based allocation of ACF resources by quantifying where targeted screening could reduce transmission at lower cost.

Kim S, Can MH, Rickman HM et al. · PLoS medicine · (2026) · View on PubMed ↗

Global, regional, and national burden of tetanus in 204 countries and territories, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.

This Global Burden of Disease Study 2023 analysis estimated the global, regional, and national burden of tetanus from 1990 to 2023 across 204 countries and territories. It quantified trends in tetanus incidence, mortality, and disability-adjusted life years (DALYs) and highlighted persistent geographic disparities despite vaccination initiatives. These findings are significant for guiding public health prioritization and evaluating progress toward tetanus elimination goals.

EClinicalMedicine · (2026) · View on PubMed ↗

A divergent betacoronavirus with a functional furin cleavage site in South American bats.

This study characterized a newly identified betacoronavirus from South American bats (Pteronotus parnellii sampled in Brazil) by determining its complete genome and performing phylogenetic analyses. The virus was sufficiently divergent from recognized Betacoronavirus subgroups while retaining a functional furin cleavage site. This expands the known Americas betacoronavirus diversity and highlights furin-cleavage potential as a feature relevant to zoonotic risk assessment.

Takada K, Yamahoki N, Mifsud JCO et al. · Nature communications · (2026) · View on PubMed ↗

RSV prefusion F vaccine effectiveness in older adults with immunosuppression: a prespecified analysis of the DAN-RSV trial.

This prespecified subgroup analysis of the Danish pragmatic, open-label DAN-RSV trial evaluated effectiveness of a single dose of the bivalent RSV prefusion F protein-based vaccine (RSVpreF) in older adults (≥60 years) stratified by immunosuppression status. The key finding was that vaccine effectiveness differed according to immunosuppression, informing how well RSVpreF protects immunosuppressed versus non-immunosuppressed older adults. Clinically, this supports tailoring RSV prevention strategies and expectations of protection in immunocompromised elderly populations.

Reimer Jensen AM, Lassen MCH, Johansen ND et al. · The lancet. Healthy longevity · (2026) · View on PubMed ↗

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Inflammation, immunometabolism & inflammasomes

Early-life microbiota direct an epithelial S100 program required for neonatal immunity.

This mechanistic mouse study investigated how early-life microbiota shape neonatal immunity through epithelial S100 signaling, focusing on the calprotectin heterodimer S100A8/S100A9. The key finding was that newborn mice have high intestinal S100A8/A9 (calprotectin) levels driven by initial commensal bacterial exposure, and that impaired calprotectin expression or lack of microbiota colonization at birth increased susceptibility to sepsis and death after infection, while calprotectin administration rescued microbiota-depleted pups. The clinical significance is that early microbiome–S100 programming may be a targetable pathway to improve neonatal immune resilience.

Negi S, Hashimoto-Hill S, Waddell A et al. · Science translational medicine · (2026) · View on PubMed ↗

Infection of macrophages by mpox virus activates inflammasome and cell death, informing multitarget therapeutic strategies.

The study combined clinical cohort evidence with direct experimental infection of human macrophages to determine how mpox virus (MPXV) triggers inflammation and cell death, and to inform multitarget therapeutic strategies. MPXV efficiently entered and replicated in human macrophages, activating AIM2 and NLRP3 inflammasomes and inducing pyroptosis, apoptosis, and necroptosis, while inflammasome inhibition reduced inflammation and cell death without reducing viral replication. These findings identify inflammasome pathways as actionable host targets to mitigate MPXV immunopathology.

Wang Y, Wang X, Tsikari T et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Evolutionarily conserved selective autophagy pathways.

This review studied evolutionarily conserved selective autophagy pathways across multiple model systems, focusing on seven major routes (mitophagy, xenophagy, pexophagy, lysophagy, ER-phagy, Golgiphagy, and ribophagy). It found that these pathways share conserved molecular recognition and regulatory principles that coordinate lysosomal degradation of specific intracellular substrates. The synthesis is significant because it provides a mechanistic map for identifying conserved targets that could be leveraged to modulate autophagy in disease.

Jipa A, Vincze V, Evdokimova D et al. · Autophagy · (2026) · View on PubMed ↗

L-Arginine inhibits NLRP3 inflammasome activation.

This mechanistic study investigated how the nutrient L-arginine (L-Arg) regulates NLRP3 inflammasome activation in macrophages and in mice. It found that L-Arg directly binds the Asp31 site of NLRP3, preventing NLRP3–ASC interaction and inflammasome assembly, while L-Arg deprivation promotes activation. The significance is that it identifies a direct metabolic control point of NLRP3 that could be exploited to modulate inflammatory disease.

Liu F, Zhuang W, Yang Y et al. · Nature metabolism · (2026) · View on PubMed ↗

Dysregulated tissue immunity in human fatal asthma.

This study profiled immune responses in human tissues from donors who died of fatal asthma (FA) versus unrelated causes, including donors with or without asthma history, across lymphoid organs, lungs, and intestines. Compared with controls, FA donors showed elevated plasma IgE and aberrant immune responses in mucosal-associated lymph nodes and lungs, including increased memory T and B cells and decreased Treg cells with age in the gut. These dysregulated tissue-immunity patterns in fatal asthma identify candidate immune-cell and pathway targets for understanding severity and improving risk stratification.

Lee YA, Wells SB, Yee DC et al. · Nature communications · (2026) · View on PubMed ↗

Pharmacological, clinical, and translational evidence for N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and zalsupindole: a systematic review.

This systematic review synthesized pharmacological, clinical, safety, and preclinical behavioral evidence for the tryptamine psychedelics N,N-dimethyltryptamine (N,N-DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and the putatively non-hallucinogenic analogue zalsupindole. The key finding was that these compounds differ in pharmacokinetics, receptor profiles, and phenomenology, with N,N-DMT and 5-MeO-DMT showing distinct profiles that may translate into different therapeutic and practical advantages. Scientifically, the review consolidates the evidence base needed to prioritize which short-acting tryptamines warrant further psychiatric therapeutic development and safety-focused trials.

Collyer C, Le GH, Hassan M et al. · Progress in neuro-psychopharmacology & biological psychiatry · (2026) · View on PubMed ↗

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Microbiome & host metabolism (gut–liver/atherosclerosis)

A gut microbial odd-chain fatty acid alleviates atherosclerosis in mice.

This mouse study tested whether administration of Bacteroides uniformis and its bioactive metabolite pentadecanoic acid (PA; C15:0) causally affect atherosclerosis and identified the hepatic target pathway. PA supplementation reduced atherosclerotic plaque burden by ~50% and alleviated disease via upregulation of hepatic low-density lipoprotein receptor (LDLR) expression. The results mechanistically link an odd-chain fatty acid–producing gut microbe to cholesterol handling and suggest a microbiome-derived metabolite strategy for atherosclerosis prevention.

Yin C, Chen Y, Lin G et al. · Nature · (2026) · View on PubMed ↗

Histone lactylation scarring transmits metabolic and epigenetic memory across the gut-liver axis.

This study investigated how prior intestinal inflammation influences later liver injury by mapping an epigenetic memory mechanism across the gut-liver axis. It found that LCN2+ colonic macrophages persist after colitis resolution with heightened glycolysis and durable histone H3K9 L-lactylation (H3K9la), then traffic to the liver to amplify steatosis under subsequent high-fat diet (HFD). The work links histone lactylation “scarring” to metabolic and epigenetic inheritance, explaining why UC remission does not eliminate susceptibility to MASLD.

Dong H, Li J, Yang D et al. · Cell metabolism · (2026) · View on PubMed ↗

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Genomics, epigenetics & chromatin/repair mechanisms

Human microglia clear intraneuronal α-synuclein aggregates by GPNMB-mediated trogocytosis.

This preclinical gene therapy study developed a strategy using split inteins and myotropic AAV vectors to deliver dysferlin in limb-girdle muscular dystrophy type R2 (LGMDR2), a disease caused by mutations in the DYSF gene. The key finding was that splitting the large dysferlin cDNA and reconstituting it via split inteins enabled effective AAV-mediated restoration of dysferlin expression despite AAV packaging limits. The scientific significance is that this approach provides a feasible gene-therapy platform for large-gene muscular dystrophies where full-length delivery is otherwise constrained.

Chueh HJ, Katsikoudi A, Aragón-González A et al. · Science translational medicine · (2026) · View on PubMed ↗

From a prion seed to a tree of discoveries: Byron Caughey’s RT-QuIC legacy in protein misfolding research.

This article is a scientific legacy review describing Byron Caughey’s contributions to prion detection and amplification, focusing on the Real-Time Quaking-Induced (RT-QuIC) approach and related cell-free prion conversion assays. It highlights how RT-QuIC was developed and refined to enable increasingly sensitive, specific, robust, and high-throughput detection and quantification of prion-like misfolded proteins. The work is significant because it provides a methodological foundation that has accelerated research across prion and other protein misfolding diseases.

Groveman BR, Vascellari S, Bongianni M et al. · Acta neuropathologica · (2026) · View on PubMed ↗

XPA lactylation is required for UV-induced DNA damage repair.

This mechanistic cancer biology study investigated how xeroderma pigmentosum group A (XPA) is regulated by lactylation in the context of UV-induced DNA damage repair. It showed that XPA is lactylated by the acyl-transferase KAT5 in the DNA-binding domain, and that UV-induced XPA lactylation enhances chromatin recruitment and nucleotide excision repair (NER), whereas lactylation-deficient XPA impairs NER and increases UV sensitivity in cancer cells. These findings identify XPA lactylation as a required regulatory step in UV damage repair and a potential vulnerability for targeting DNA repair pathways.

Yang J, Ding X, Zeng Z et al. · Nucleic acids research · (2026) · View on PubMed ↗

Nanopore sequencing combined with adaptive sampling and NanoExpansion enables accurate characterization of repeat expansion disorders.

This study evaluated targeted long-read nanopore sequencing combined with adaptive sampling and NanoExpansion to characterize short tandem repeat (STR) repeat expansion disorders in 132 participants, including myotonic dystrophy type 1 (DM1, n=51), DM2 (n=3), C9orf72-associated ALS (n=11; assessed by repeat-primed PCR for validation), and multiple spinocerebellar ataxia/cerebellar ataxia syndromes (SCA n=46; CANVAS n=13). The approach enabled accurate, comprehensive STR expansion characterization across these repeat expansion diseases, improving resolution beyond prior methods used for cohort stratification/validation. This supports nanopore-based, enrichment/adaptive workflows as a clinically scalable strategy for precise diagnosis of repeat expansion disorders such as DM1/DM2 and C9orf72-associated ALS.

Morandi L, Casadei F, De Fanti S et al. · NAR genomics and bioinformatics · (2026) · View on PubMed ↗

The 2026 World Health Organization Classification of Tumors of Soft Tissue and Bone: 6th Edition.

This article summarizes the 2026 World Health Organization Classification of Tumors of Soft Tissue and Bone (6th edition, STB6), detailing how updated “essential” and “desirable” diagnostic criteria incorporate recent molecular discoveries alongside pathology expertise. It reports that 19 new tumor entities were added and that diagnostic criteria were refined to improve accuracy across different resource settings. Scientifically and clinically, STB6 provides a standardized molecularly informed diagnostic framework that should improve consistency of tumor classification and downstream patient management.

Hornick JL, Bovee JVMG, Antonescu CR et al. · The American journal of surgical pathology · (2026) · View on PubMed ↗

Cell-cycle-driven noncanonical ubiquitination of METTL14 orchestrates RNA methylation.

This mechanistic study investigated how cell-cycle timing regulates mRNA N6-methyladenosine (m6A) methylation via ubiquitination of the m6A writer METTL14, focusing on the RLIM E3 ligase and the METTL3–METTL14 complex. RLIM deposits predominantly K27-linked ubiquitin on METTL14 in a cell-cycle-programmed manner, modulating complex assembly and RNA substrate engagement independently of METTL14 protein stability, with coordinated oscillations of transcriptome-wide m6A, K27-Ub on METTL14, and RLIM expression across the cell cycle. These findings define a cell-cycle-driven, noncanonical ubiquitination control layer for m6A regulation, linking temporal cell-cycle programs to epitranscriptomic output.

Cao J, Ying X, Zhou L et al. · Nature chemical biology · (2026) · View on PubMed ↗

Acetaminophen produces limited molecular and functional effects in human cortical organoids.

This study examined acetaminophen (APAP) effects on early human cortical development using induced pluripotent stem cell-derived cortical organoids (organoids from six independent iPSC lines). Across physiologically relevant APAP concentrations (25–100 μM) for 5 days starting at day 21 of differentiation, APAP produced limited molecular and functional changes in the organoids. These findings suggest that, at tested exposure levels and developmental timing, APAP may have modest direct effects on early cortical programs, informing mechanistic interpretation of inconsistent epidemiologic associations.

Trovò L, Kucera G, Gomez G et al. · Molecular psychiatry · (2026) · View on PubMed ↗

Near-atomistic simulations reveal the molecular principles that control chromatin structure and phase separation.

This study developed OpenCGChromatin, a high-performance coarse-grained computational model enabling near-atomistic simulations of chromatin structure and phase separation across condensates and chromatin fibers. OpenCGChromatin independently recapitulated linker-DNA-dependent chromatin structures seen in cryo-ET and predicted condensate thermodynamic stability consistent with biochemical assays, while also resolving histone-tail dynamics. The work provides a quantitative, physicochemical framework for predicting how chromatin properties govern genome organization and condensate behavior.

Russell K, Chen Y, Espinosa JR et al. · Nature communications · (2026) · View on PubMed ↗

DNA-PK driven nucleosome unwrapping enables NHEJ in chromatin.

This study investigated how DNA-dependent protein kinase catalytic subunit (DNA-PKcs) enables non-homologous end joining (NHEJ) in chromatin by using in vitro ligation assays with nucleosomes and cryo-EM structures of nucleosome-bound Ku and DNA-PK components. DNA-PKcs promoted NHEJ on nucleosomes with limited DNA accessibility by driving nucleosome unwrapping to expose DNA ends. These results clarify a mechanistic role for DNA-PKcs in overcoming chromatin barriers during DSB repair, with implications for genome stability and radiosensitivity.

Lu W, Vogt A, Lees-Miller SP et al. · Nature communications · (2026) · View on PubMed ↗

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Mitochondria, redox & mitochondrial transfer

Mitochondrial transfer protects against cisplatin-induced hearing loss by fumarate-mediated activation of mitophagy.

The study investigated whether mitochondrial transfer from mesenchymal stem/stromal cells (MSCs) protects against cisplatin-induced hearing loss in a mouse model and defined the downstream mechanism. MSCs homed to the cochlea, transferred mitochondria to damaged spiral ganglion neurons via tunneling nanotubes, increased intracellular fumarate, and activated mitophagy to remove dysfunctional mitochondria. This mechanistic link suggests that fumarate–mitophagy signaling is a therapeutic pathway for preventing cisplatin-associated sensorineural hearing loss.

Wu Y, Gu Y, Wang Y et al. · Cell reports · (2026) · View on PubMed ↗

Cellular Mechanisms Enabling Mitochondria Transfer and Transplantation.

This review studied cellular mechanisms that enable mitochondrial transfer and transplantation (mitoTT) in experimental systems, including endogenous routes such as tunneling nanotubes, extracellular vesicles, cell fusion, gap-junction communication, and phagocytosis-like internalization. It found that these routes differ in distance, directionality, cargo integrity, and regulatory control, and that preclinical exogenous mitochondria can transiently improve bioenergetics and reduce oxidative stress. The work is significant because it clarifies which mitoTT delivery mechanisms may be most physiologically relevant for therapeutic development.

Gokdemir FS, Ozendi Y, Kubat GB et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

Mitochondrial DNA damage elicits PINK1 upregulation in pontine cholinergic neurons in Parkinson’s disease.

This study investigated how mitochondrial DNA (mtDNA) damage regulates PINK1 expression in pontine cholinergic neurons in Parkinson’s disease, using ultra-deep whole-genome sequencing with stringent quality control. It found that mtDNA damage elicits PINK1 upregulation in these pedunculopontine nucleus neurons, consistent with a neuron-specific mitochondrial stress response. The finding is significant because it links mtDNA deletion burden to PINK1-mediated quality control in a specific Parkinson’s-relevant neuronal population.

Lu H, Pyle A, Steyn JS et al. · Brain : a journal of neurology · (2026) · View on PubMed ↗

OXR1 is a dual redox-mitochondrial checkpoint governing osteoclast differentiation and bone loss in an osteoporosis mouse model.

This study examined the role of the redox-mitochondrial checkpoint gene OXR1 in osteoclast differentiation and bone loss using mouse models of osteoporosis and mechanistic assays in osteoclast precursors. Oxr1 knockdown caused excessive ROS accumulation, mitochondrial damage, and impaired autophagic flux, and myeloid-specific loss of Oxr1 worsened bone loss. The work positions OXR1 as a protective regulator of osteoclast mitochondrial redox homeostasis, suggesting a potential target for limiting osteoporosis-associated bone destruction.

Chen X, Zhou C, Jin X et al. · Nature communications · (2026) · View on PubMed ↗

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Regenerative medicine & tissue engineering

Human lung organoid modelling of tissue-resident antiviral T cell responses.

This work generated long-term adult human distal lung organoids from intact tissue fragments in a 3D air-liquid interface system to model tissue-resident antiviral T cell responses. The key finding is that organoid infection can recapitulate epithelial infection–coupled, tissue-resident memory T cell (TRM) antiviral behaviors, enabling study of local versus secondary-lymphoid contributions. This provides a human in vitro platform to dissect mechanisms of TRM-mediated respiratory immunity and to test interventions that modulate tissue-resident T cell function.

Rathkey JK, Choi SS, van Unen V et al. · Nature · (2026) · View on PubMed ↗

Alveolar stem cells transdifferentiate to drive bronchiolar regeneration.

Using dual-recombinase-mediated lineage tracing in mice, this study examined whether alveolar type 2 (AT2) cells can cross anatomical compartments to repair bronchioles after injury. The authors found that AT2 cells migrate into injured bronchioles and transdifferentiate into club cells and ciliated cells, driven by immune-cell secretion of SPP1 that establishes a chemotactic gradient. This demonstrates a reciprocal alveolus-to-airway regenerative route and identifies SPP1 as a mechanistic cue for bronchiolar regeneration.

Liu K, Liu Z, Meng X et al. · Nature · (2026) · View on PubMed ↗

Optogenetic Therapy for Restoring Aspects of Visual Function.

This open-label study evaluated safety and visual-function effects of ganglion cell–directed optogenetic therapy in 10 participants with blindness due to advanced retinitis pigmentosa. The key finding was that a single intravitreal injection of an AAV vector encoding the red-shifted channelrhodopsin ChrimsonR was used to assess safety as the primary endpoint, with secondary outcomes including changes in light sensitivity measured by full-field stimulus testing. The clinical significance is that AAV-ChrimsonR optogenetics may provide a pathway to restore aspects of vision in late-stage inherited retinal degeneration while establishing early safety evidence.

Sahel JA, Futterknecht S, Audo I et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Targeted integration of extrachromosomal arrays in C. elegans using PhiC31 integrase.

The study tested whether the viral integrase PhiC31 can enable extremely efficient, targeted integration of extrachromosomal DNA arrays in Caenorhabditis elegans using attB/attP recombination. PhiC31-mediated integration (PhIAT) inserted transgene arrays at attB sites on three chromosomes, including a fluorescent landing pad, with high efficiency and targeted placement. This provides a less damaging alternative to x-ray or CRISPR-based integration for building stable, site-specific C. elegans transgenic lines.

Rich MS, Pellow R, Zhang Y et al. · Science advances · (2026) · View on PubMed ↗

Spatial transcriptomics reveals microenvironmental heterogeneity in osteoarthritic subchondral bone.

This study applied spatial transcriptomics to human osteoarthritic subchondral bone to map microenvironmental heterogeneity. It identified a spatially conserved osteogenic core–halo architecture with transcriptional reprogramming in sclerotic regions and found disrupted osteoblast–osteoclast spatial coupling, enhanced osteoblast–mesenchymal interactions, and candidate stromal-osteogenic signaling axes including FN1–SDC2 and COL1A1–DDR2. These spatially resolved molecular insights improve understanding of aberrant bone remodeling in osteoarthritis and nominate targets for modifying disease-associated subchondral remodeling.

Lin W, Xiao X, Tian D et al. · Nature communications · (2026) · View on PubMed ↗

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Reproductive health & developmental biology

A multiomic atlas reveals distinct immune landscapes in preterm and term chronic placental inflammation.

This multiomic atlas study profiled placental and extraplacental tissues from preterm and term pregnancies with chronic placental inflammation (CPI) using imaging mass cytometry, single-cell RNA sequencing, spatial transcriptomics, and T cell receptor repertoire mining. The key finding was that CPI forms a gestational age–dependent immune continuum rather than a single uniform inflammatory state, with preterm CPI characterized by distinct immune-cell infiltration patterns (including cytotoxic CD8+ T cells). Scientifically, the atlas provides a high-resolution map of CPI immune determinants across gestation, which could enable more precise biomarker stratification and mechanistic targeting of preterm inflammatory pathways.

Levenson D, Romero R, Pique-Regi R et al. · Science translational medicine · (2026) · View on PubMed ↗

Rapid protamine evolution suppresses meiotic drive in Drosophila.

The study examined how rapid evolution of the Drosophila protamine gene Mst77F affects spermatogenesis and meiotic drive in Drosophila melanogaster using in vivo gene replacement with divergent orthologs and engineered sex-chromosome fusions. Replacing or dosage-altering Mst77F caused DNA compaction defects in X-bearing sperm, reducing mature X-bearing sperm and producing male-biased progeny, while increasing ortholog dosage rescued the bias. These findings show that protamine evolution can actively suppress meiotic drive, linking fast-evolving sperm chromatin proteins to sex-chromosome transmission outcomes.

Chang CH, A de la Cruz AF, Lai HY et al. · Science advances · (2026) · View on PubMed ↗

Endogenous retrovirus control of calbindin is essential for human early embryogenesis.

The study investigated how human endogenous retrovirus HERVH regulatory sequences control calbindin (CALB1) during human early embryogenesis, focusing on a HERVH integration at 8q21.3. HERVH integration coincided with acquisition of CALB1 expression in Homininae evolution, and the authors showed that HERVH-derived cis-regulatory control is essential for proper early embryonic development. These results establish a functional role for an endogenous retroviral element in regulating a host developmental gene, with implications for understanding HERV dysregulation in disease.

Pape J, McCarthy A, Serna-Morales E et al. · Science advances · (2026) · View on PubMed ↗

Single-cell study of human ovarian response to phthalate exposure reveals glial cell susceptibility and disruption of adhesion and mitochondrial pathways.

This study used adult human ovarian tissue explants from seven donors to test whether mono(2-ethylhexyl) phthalate (MEHP), the metabolite of di(2-ethylhexyl) phthalate (DEHP), alters ovarian cell states using single-cell RNA sequencing after 6 days of exposure at 20.51 nM and 20.51 μM. MEHP exposure revealed susceptibility of glial cells and disrupted adhesion and mitochondrial pathways. These findings provide mechanistic, cell-type-specific evidence that phthalate exposure can impair ovarian tissue function, informing reproductive toxicology and regulation of DEHP/MEHP.

Panagiotou EM, Méar L, Rooda I et al. · EBioMedicine · (2026) · View on PubMed ↗

Early neuroendocrine signatures of polyendocrine metabolic ovarian syndrome risk: Pubertal programming, social brain signals, and novel therapeutic targets.

This review examined early neuroendocrine antecedents of polyendocrine metabolic ovarian syndrome (PMOS; formerly PCOS) during puberty, focusing on girls at risk and the developmental timing of central neuroendocrine pathway dysregulation. The key finding was that pubertal programming—particularly kisspeptin–GnRH dysregulation and altered central metabolic signaling—may precede post-menarche clinical diagnosis and represent novel therapeutic target biology. The significance is that identifying these early neuroendocrine signatures could enable earlier risk stratification and development of mechanism-based interventions.

Oğuz SH, Yildiz BO · Journal of neuroendocrinology · (2026) · View on PubMed ↗

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Endocrinology, obesity & metabolic disease

Intensive vs Standard Blood Pressure Lowering in People With and Without Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis synthesized randomized clinical trials of intensive versus standard blood pressure lowering in adults with and without chronic kidney disease (CKD), assessing cardiovascular and kidney outcomes with subgroup analyses by CKD status. Intensive BP lowering produced standardized effects on cardiovascular disease and kidney failure risk, with effect modification evaluated according to whether participants had CKD. The results clarify how treatment intensity should be tailored for CKD patients to balance cardiovascular benefit against potential kidney-related harms.

Iatridi F, Roddick AJ, Staplin N et al. · JAMA cardiology · (2026) · View on PubMed ↗

Plasma proteomic signatures of biological aging and metabolic dysfunction-associated steatotic liver disease risk: a prospective cohort study.

This prospective cohort study in 52,131 UK Biobank participants used plasma proteomics (2911 proteins) to test whether multi-dimensional biological aging indicators—telomere length, frailty index, Klemera-Doubal method biological age, and phenotypic age—predict incident metabolic dysfunction-associated steatotic liver disease (MASLD) and identify mediating biomarkers. The analysis identified plasma proteomic signatures linking biological aging to increased MASLD risk, implicating specific proteins in the aging–MASLD axis. These biomarkers and mechanistic links could improve risk stratification and point to therapeutic targets for preventing MASLD in biologically aged individuals.

Cao TR, Wu LJ, Yang XH et al. · Hepatology international · (2026) · View on PubMed ↗

Obesity and the Development of Cardiometabolic Multimorbidity: A Cross-Lagged Panel Network Analysis of Three National Chinese Cohorts.

This cross-lagged panel network analysis used three nationally representative Chinese cohorts—CHARLS (2011–2015, n=12,491), CHNS (2004–2015, n=8,412), and CFPS (2010–2022, n=22,193)—to examine bidirectional longitudinal associations between obesity and cardiometabolic multimorbidity (hypertension, diabetes, ischaemic heart disease, and cerebrovascular disease) in adults aged ≥45 years. The key finding was that obesity and cardiometabolic diseases show bidirectional, time-lagged relationships that can be mapped as a replicable network across cohorts. This supports obesity as a dynamic driver of cardiometabolic multimorbidity risk and informs timing-focused prevention strategies.

Fang Z, Liu J, Zhang L · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗

Weight Loss or Muscle Loss? Cellular Mechanisms and Clinical Strategies for Preserving Lean Mass During GLP-1-Based Therapy.

This review examined cellular and tissue-level mechanisms that could explain lean mass changes during GLP-1 receptor agonist and newer dual/triple incretin-based therapies, with attention to clinical contexts such as older adults and those at risk for sarcopenia. The key finding is that reductions in fat-free/lean mass during GLP-1-based therapy do not necessarily equate to loss of contractile skeletal muscle, and multiple mechanisms may contribute to observed body-composition shifts. Clinically, it highlights strategies to preserve skeletal muscle/lean mass during GLP-1-based weight loss to reduce sarcopenia risk.

Sukurica E, Sengul GF, Uysal Cinar F · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗

Effect of Short-Rest Interval versus Traditional Multiple-Set Resistance Training Combined with Endurance Training in Patients with Cardiovascular Disease: A Randomized Clinical Trial.

This randomized clinical trial studied short-rest interval resistance training (3/7 RT) versus traditional multiple-set resistance training (3×9 RT) combined with endurance training in patients with cardiovascular disease undergoing 12-week cardiac rehabilitation. It found that VO2peak and quadriceps strength improved similarly between groups, with comparable changes in functional performance (e.g., 30-sit-to-stand) and lean mass. The significance is that shorter-rest resistance protocols may achieve similar cardiometabolic and strength benefits, potentially improving training efficiency in cardiac rehab.

Gillet A, Lamotte M, Forton K et al. · American journal of physical medicine & rehabilitation · (2026) · View on PubMed ↗

CGM has Similar Predictive Performance to OGTT for Monitoring Early-Stage Type 1 Diabetes.

This study compared continuous glucose monitoring (CGM) with oral glucose tolerance testing (OGTT) and HbA1c for predicting progression to stage 3 type 1 diabetes in early-stage T1D individuals. It found that CGM metrics—particularly time above 140 mg/dl (TA140)—had similar predictive performance to OGTT for stage 3 monitoring, with comparable specificity for key thresholds. The significance is that CGM could support earlier risk monitoring and potentially streamline follow-up in early-stage T1D.

Steck AK, Dong F, Pyle L et al. · The Journal of clinical endocrinology and metabolism · (2026) · View on PubMed ↗

Longer lipids mark aging and constrain lifespan.

This cross-species, multi-tissue lipidomics study examined how lipid remodeling changes with aging in mice, Caenorhabditis elegans, Drosophila, and humans. It found a conserved aging hallmark of lipid acyl-chain elongation (with depletion of shorter species) that constrains lifespan, while dietary restriction shortened cardiac lipids in mice. The ratiometric shift toward longer lipids provides a mechanistic biomarker and potential intervention target for age-associated decline and age-related heart disease.

Li W, Schomakers BV, Trętowicz MM et al. · Nature aging · (2026) · View on PubMed ↗

Major Adverse Cardiovascular Events in Men with High-risk Localized or Metastatic Prostate Cancer Starting Long-term Hormone Therapy in the STAMPEDE Trial.

This post hoc analysis of the STAMPEDE trial evaluated cardiovascular safety in men with high-risk localized or metastatic prostate cancer starting long-term hormone therapy, comparing androgen receptor pathway inhibitors (abiraterone acetate plus prednisolone, with/without treatment intensification) and assessing SCORE2 performance. The study focused on major adverse cardiovascular events (MACE) and how well SCORE2 predicted 10-year cardiovascular risk in this treated prostate cancer population. Clinically, it helps determine whether ARPIs and other intensification strategies meaningfully increase cardiovascular risk and whether SCORE2 is valid for risk stratification in these patients.

El-Taji O, Dutey-Magni P, Brown M et al. · European urology · (2026) · View on PubMed ↗

Design and baseline characteristics of the CagriSema cardiovascular outcomes trial (REDEFINE 3).

This article describes the design and baseline characteristics of the REDEFINE 3 trial evaluating the fixed-dose combination cagrilintide-semaglutide (CagriSema; 2.4 mg/2.4 mg weekly) versus placebo in participants with established cardiovascular disease (CVD) with BMI ≥25.0 kg/m2, with or without type 2 diabetes. The trial’s key finding at this stage is the randomized, double-blind, placebo-controlled setup intended to test cardiovascular outcomes and confirm safety objectives including noninferiority. The significance is that it will generate definitive evidence on whether CagriSema improves cardiovascular outcomes in a high-risk CVD population.

Cavender MA, Jastreboff AM, Cheng AYY et al. · American heart journal · (2026) · View on PubMed ↗

Cell-type-specific repression reveals MC4R neurons as a site of action for ciliary obesity genes.

This in vivo study used a Cre-dependent CRISPR interference (CRISPRi) approach to temporally and cell-type-specifically repress obesity-associated ciliary genes in melanocortin-4 receptor (MC4R) neurons. The key finding was that MC4R neurons represent a functional site of action for ciliary obesity genes, linking ciliary gene biology to hypothalamic energy regulation. This advances mechanistic obesity genetics by pinpointing the neuronal circuitry through which these genes influence body weight.

Diener Blake A, Zhang Z, Alexandre C et al. · Molecular metabolism · (2026) · View on PubMed ↗

Associations of RAS inhibitors and Calcium Channel Blockers with Liver Stiffness Dynamics and Long-term Liver-Related Events in MASLD.

Using data from the VCTE-Prognosis international multicenter cohort with serial vibration-controlled transient elastography (VCTE) measurements, this study assessed whether renin-angiotensin system inhibitors (RASi) or calcium channel blockers (CCBs) affect liver stiffness dynamics and long-term liver-related events (LREs) in metabolic dysfunction-associated steatotic liver disease (MASLD). The key finding was that specific antihypertensive drug classes were associated with differences in liver stiffness progression/regression and subsequent LRE risk. This is significant because it suggests a potentially modifiable medication strategy to influence liver disease trajectory in MASLD patients with hypertension.

Zhou XD, Chen QF, Kim SU et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · (2026) · View on PubMed ↗

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Autoimmunity, dermatology & rheumatology therapeutics

Diagnostic accuracy of the straight leg raise test for lumbosacral radicular pain: a systematic review with meta-analysis.

This systematic review and meta-analysis studied the diagnostic accuracy of the straight leg raise and crossed straight leg raise tests for lumbosacral radicular pain in patients with low back-related leg pain, using eligible diagnostic accuracy and prediction model studies with reference standards such as imaging, electrodiagnosis, surgery, or clinical diagnosis. The key finding was that the review synthesized available evidence on test performance (sensitivity/specificity and related diagnostic metrics) and assessed study bias using QUADAS-2/PROBAST, concluding with an overall estimate of diagnostic accuracy across included studies. Clinically, these results inform how reliably bedside straight leg raise–type maneuvers can support diagnosis of lumbosacral radicular pain and guide interpretation alongside confirmatory testing.

Nee RJ, Boyd BS, Sierra-Silvestre E et al. · Musculoskeletal science & practice · (2026) · View on PubMed ↗

Comparative Effectiveness of Treatments for Relapse Prevention in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

This multicenter comparative effectiveness study analyzed prospectively collected data from 13 US pediatric neuroimmunology centers to determine which maintenance therapies best prevent relapses after a first myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) event in pediatric-onset patients. The key finding was an evidence-based comparison of relapse-prevention effectiveness across maintenance regimens in children with MOG-IgG positivity by cell-based assay and aquaporin-4 IgG negativity, using prospectively collected real-world treatment data. Clinically, the results aim to guide selection of maintenance therapy to reduce post–first-event relapse risk in pediatric MOGAD.

Virupakshaiah A, Schoeps VA, Race J et al. · Neurology · (2026) · View on PubMed ↗

Efficacy of acupuncture for tinnitus with anxiety: a systematic review and meta-analysis.

This systematic review and meta-analysis assessed the efficacy of acupuncture for tinnitus with comorbid anxiety by searching nine databases (including PubMed and major Chinese databases) through January 15, 2026. The analysis found that acupuncture can alleviate tinnitus symptoms and improve anxiety outcomes in patients with tinnitus accompanied by anxiety. These findings support acupuncture as a potential adjunctive non-pharmacologic option for managing tinnitus-related anxiety, while also motivating higher-quality trials to confirm effect sizes and durability.

Peiyun W, Shuaihui Q, Yi C et al. · Frontiers in neurology · (2026) · View on PubMed ↗

Outcomes of Tapering Biologic and Targeted Synthetic DMARDs in Rheumatoid Arthritis: A Multicenter Randomized Non-Inferiority Trial.

This multicenter, randomized, open-label non-inferiority trial studied structured tapering of biologic or targeted synthetic DMARDs (b/tsDMARDs) in rheumatoid arthritis patients who had achieved sustained low disease activity (DAS28-ESR-defined) for at least 6 months. The key finding was that stepwise dose tapering maintained DAS28-ESR low disease activity at week 24 with non-inferior efficacy compared with continuing the same b/tsDMARD dose. This provides evidence-based guidance for safely reducing treatment intensity in RA patients in sustained low disease activity.

Park DJ, Choi SE, Kang JH et al. · Arthritis & rheumatology (Hoboken, N.J.) · (2026) · View on PubMed ↗

UVB-Induced Repigmentation in Vitiligo: Hair Follicle Melanocyte Stem Cell Migration and Its Molecular Mechanisms.

This review focused on UVB-induced repigmentation in vitiligo, emphasizing how hair follicle melanocyte stem cell (McSC) migration to the interfollicular epidermis contributes to restoration of epidermal melanocytes. The key finding is that UVB phototherapy promotes McSC migration and that multiple molecular mechanisms regulate this process, making it central to repigmentation. Clinically, understanding these pathways can guide improved UVB-based or targeted therapies to enhance repigmentation in vitiligo patients.

Baiyi Z, Guanying L, Xin H et al. · Pigment cell & melanoma research · (2026) · View on PubMed ↗

Efficacy and Safety of Delgocitinib and Its Impact on Patient’s Perspective for Moderate-to-severe Chronic Hand Eczema in Adults: A 16-week Real-world Prospective Multicentre Study.

This real-world prospective multicenter study evaluated delgocitinib, a pan–Janus kinase inhibitor, in 149 adults with moderate-to-severe chronic hand eczema across 20 Italian dermatology centers. It found clinically meaningful improvements by week 4 (PGA-chronic hand eczema 0/1 and HECSI-75) that increased further by later follow-up, with safety assessed over the 16-week period. The study is significant because it provides practical effectiveness and tolerability data for delgocitinib outside randomized trials.

Pezzolo E, Luyo Saboya RA, Ortoncelli M et al. · Acta dermato-venereologica · (2026) · View on PubMed ↗

Real-world effectiveness of dupilumab in COPD: a German multicenter analysis.

This multicenter real-world analysis studied dupilumab treatment effectiveness in COPD patients in Germany, including comparisons between COPD-only versus COPD with comorbid asthma and between patients with versus without chronic bronchitis. It found that dupilumab outcomes were assessed using annualized moderate-to-severe exacerbation rates as the primary endpoint along with lung function and CAT score changes. The significance is that it extends evidence for dupilumab’s COPD benefit into routine clinical practice and stratifies outcomes by type 2 comorbidity and chronic bronchitis status.

Abdo M, Skowasch D, Greulich T et al. · Respiratory research · (2026) · View on PubMed ↗

Real-world Treatment Patterns Among Patients with Generalized Myasthenia Gravis in the United States.

This US real-world study characterized treatment patterns among adults with generalized myasthenia gravis (gMG) using the Komodo Research Data and tracked MG-related clinical events such as exacerbations and crises. It found how commonly used therapies (e.g., acetylcholinesterase inhibitors, corticosteroids, non-steroidal immunosuppressants) and newer options (B-cell depleting agents, C5 inhibitors, and FcRn blockers) were utilized in practice. The significance is that it documents real-world adoption and event burden across the evolving gMG therapeutic landscape.

Grover K, Cloutier M, Coteur G et al. · Neurology and therapy · (2026) · View on PubMed ↗

EFFICACY AND SAFETY OF ADVANCED THERAPIES AS INDUCTION THERAPY FOR ULCERATIVE COLITIS: AN UPDATED SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

This updated systematic review and network meta-analysis synthesized phase 3 randomized controlled trials to compare advanced therapies for ulcerative colitis (UC) as induction therapy in moderate-to-severe disease. The key finding was a comparative ranking of efficacy and safety across multiple advanced therapy options using pairwise meta-analyses and frequentist random-effects network meta-analysis. Clinically, it helps guide treatment selection when head-to-head trials are limited by providing an evidence-based hierarchy of induction effectiveness and tolerability.

Olivera PA, Lasa JS, Singh S et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · (2026) · View on PubMed ↗

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Generated automatically on October 08, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.