PubMed Trending Research Digest — September 29, 2026

Automated digest · 97 articles · 15 research areas · September 29, 2026

Overview

Across this week’s set of studies, a dominant theme is the move toward mechanism-resolved, cell-type–specific understanding of disease. Multiple papers use single-cell and spatial multi-omics (e.g., human VSD atlases, ADPKD cyst transcriptomes, acute interstitial nephritis microenvironments, glioblastoma stem-like heterogeneity, and fibrosis-driving macrophage states) to map how local cellular niches and remodeling programs drive pathology. These datasets increasingly connect “where” and “which cells” to “what pathways,” enabling more precise biomarker discovery and therapeutic targeting.

A second major thread is immune regulation—both in cancer and in neuroinflammatory disease. Several studies identify actionable immune checkpoints or immune-evasion mechanisms (e.g., immunometabolic signatures in HNSCC, IFN-I autoantibodies in adult HSE, viral accessory proteins that suppress innate signaling, and cGAS roles beyond STING). In parallel, neuroimmune papers highlight how innate immune signaling and trafficking (microglial targets like PLXDC2, TREM1, SPP1–ITGB1, and peripheral CXCR3-dependent recruitment) can be reprogrammed to alter neurodegeneration, post-stroke pain, or cognitive outcomes.

Finally, many articles converge on cell-death and stress-response pathways—especially ferroptosis and related mitochondrial/lysosomal control—as therapeutic leverage points. From lactylation–HSPA5–VGLL3 axes in intracerebral hemorrhage to ferroptosis control in prostate cancer, ICC, and TNBC (including ECM-driven metabolic immune suppression), the work underscores that modulating regulated death and proteostasis can reshape disease trajectory. Complementing these biological advances, the digest also features translational progress in delivery and clinical implementation: next-generation CAR-T designs and microbiome-linked biomarkers, nanoparticle and hydrogel platforms, and updated guidelines/trials spanning diabetes–frailty care, pediatric UTI, perioperative cardiovascular management, and MASH/MASLD treatment selection.

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Cardiovascular development and remodeling

A Spatiotemporal Single-Cell Atlas Uncovers Dysregulated ECM Dynamics and Septal Remodeling Arrest in Human Ventricular Septal Defects.

This study built a high-resolution human single-cell transcriptomic atlas of isolated perimembranous ventricular septal defects (VSD) and integrated it with a reference-based spatial transcriptomic map across a 7–22 week developmental trajectory. It found aberrant cardiomyocyte hypertrophy together with a systemic failure of the non-myocyte microenvironment, including dysregulated extracellular matrix (ECM) regulatory programs and septal remodeling arrest. These findings provide a mechanistic, cell-type–resolved framework for how ECM dynamics and septal development go awry in human VSD, suggesting potential ECM-targeted strategies for future intervention.

Zhang X, Zhu L, Sun Z et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer immunotherapy prediction and biomarkers

Prolonged survival after systemic immune reactivation by aglatimagene besadenovec plus valacyclovir in immune checkpoint inhibitor-refractory non-small cell lung cancer.

This open-label phase 2a trial studied systemic immune reactivation using aglatimagene besadenovec (CAN-2409), a replication-defective adenoviral vector encoding herpes simplex virus thymidine kinase, plus valacyclovir in immune checkpoint inhibitor (ICI)-refractory non-small cell lung cancer (NSCLC) patients. The study reported prolonged survival after this combination therapy in the enrolled population. Scientifically and clinically, it supports the potential of CAN-2409/valacyclovir to generate durable systemic immune activation and improve outcomes for patients with limited options after ICI failure.

Aggarwal C, Sterman D, Dwyer J et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗

Immunometabolic Profiling of T Cells and Innate Lymphoid Cells Uncovers Therapeutic Targets to Enhance Immunotherapy in Head and Neck Cancer.

The study profiled tumor-infiltrating immune cells in head and neck squamous cell carcinoma (HNSCC) patients receiving neoadjuvant anti–PD-1 monotherapy or anti–PD-1 plus anti–IL-8 therapy using functional-metabolic flow cytometry, focusing on MAIT cells, CD8+ T cells, and innate lymphoid cells (ILCs). It found that CD39-negative OX40+ MAIT cells and CD8+ tumor-infiltrating lymphocytes were metabolically fit and less exhausted, whereas OX40− populations showed more evidence of metabolic stress/exhaustion. These immunometabolic signatures identify candidate therapeutic targets and biomarkers to enhance checkpoint blockade responses in HNSCC.

Rajakumar SA, Nanda N, Kim C et al. · Cancer immunology research · (2026) · View on PubMed ↗

Transketolase-like 1 potentiates PD-1 blockade in hepatocellular carcinoma by glycolysis to prime dendritic cell lactylation.

The study investigated how transketolase-like 1 (TKTL1) modulates immune checkpoint blockade (PD-1) efficacy in hepatocellular carcinoma (HCC) by linking tumor glycolysis to dendritic cell lactylation. Multi-omics analysis of anti–PD-1-treated HCC patients and mechanistic experiments in murine models identified TKTL1 as a dual-nature factor: TKTL1 overexpression predicted poor baseline prognosis yet potentiated PD-1 blockade response by priming dendritic cell lactylation. This suggests TKTL1 as both a biomarker and a mechanistic target to improve immunotherapy outcomes in PD-1–resistant HCC.

Cao H, Huang T, Chai Y et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Disitamab vedotin for HER2-positive breast cancer with liver metastases: phase 3 results from the RC48-C006 phase 2/3 trial.

This phase 2/3 randomized trial (RC48-C006; NCT03500380) studied disitamab vedotin (DV) versus lapatinib plus capecitabine (L+C) in 104 patients with HER2-positive advanced breast cancer with liver metastases (BCLM) previously treated with trastuzumab and taxanes. The phase 3 stage reported comparative efficacy outcomes including progression-free survival (PFS) assessed by blinded independent review, alongside safety, for the DV and L+C arms. These results are clinically significant because they test whether the HER2-targeted antibody-drug conjugate DV improves outcomes over an established HER2/chemotherapy regimen in a high-risk metastatic subgroup.

Wang J, Ouyang Q, Xie W et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Real-world outcomes of nivolumab-AVD and brentuximab vedotin-AVD in paediatric and adult advanced-stage Hodgkin lymphoma.

This multicentre retrospective real-world study across 17 US centers compared frontline regimens nivolumab-AVD versus brentuximab vedotin (BV)-AVD in 646 pediatric and adult patients with advanced-stage Hodgkin lymphoma. N-AVD was associated with higher rates of neutropenia and infections, while BV-AVD had more frequent dose reductions or omissions. These findings are clinically significant for optimizing toxicity management and regimen selection in routine practice beyond trial settings.

Chohan KL, Feng L, Cochran H et al. · British journal of haematology · (2026) · View on PubMed ↗ · Free PDF ↗

Perioperative Durvalumab for Resectable NSCLC: Updated Outcomes for Japanese Patients in AEGEAN.

This prespecified exploratory analysis of the phase 3 AEGEAN trial evaluated perioperative durvalumab plus neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone in 79 Japanese patients with resectable stage II–IIIB (N2) non-small cell lung cancer (NSCLC). The study updated event-free survival (EFS), disease-free survival (DFS), overall survival (OS), pathological complete response (pCR), and safety using interim and final analyses with specified data cutoffs. The results are important because they extend evidence for perioperative durvalumab in a defined Japanese subgroup, informing regional applicability of the perioperative immunotherapy strategy.

Mitsudomi T, Heymach JV, Horio Y et al. · Cancer science · (2026) · View on PubMed ↗ · Free PDF ↗

Insulin-Like Growth Factor Axis and Survival in Metastatic Hormone-Sensitive Prostate Cancer: Post-Hoc Analysis From the ENZAMET Phase 3 Trial.

This post-hoc analysis evaluated whether baseline circulating IGF-1 and IGFBP1 (and their ratio) predicted survival outcomes in 845 participants with metastatic hormone-sensitive prostate cancer enrolled in the ENZAMET phase 3 trial. Higher IGF-1:IGFBP1 was associated with worse survival/progression outcomes, supporting the prognostic value of the IGF axis in the context of enzalutamide plus androgen deprivation therapy (with or without docetaxel). These findings strengthen biomarker-driven risk stratification for mHSPC and suggest the IGF pathway may help identify patients less likely to benefit from standard intensification strategies.

Cilento MA, Lin HM, Yeung N et al. · The Prostate · (2026) · View on PubMed ↗ · Free PDF ↗

High-Density Type I Collagen Promotes IFN-γ+ CD8+ T Cell Exhaustion via SAT1-ASS1-Mediated Glutamine Accumulation and Ferroptosis in Triple-Negative Breast Cancer.

This study examined how high-density type I collagen in the tumor microenvironment influences immune dysfunction in triple-negative breast cancer (TNBC), focusing on IFN-γ+ CD8+ T cell exhaustion. It found that type I collagen density and lesion mechanics correlated with TNBC grade and progression, and mechanistic data indicated that high-density collagen promotes TNBC ferroptosis and drives CD8+ T cell exhaustion through SAT1–ASS1-mediated glutamine accumulation. These results connect ECM remodeling to metabolic immune suppression and ferroptosis, suggesting ECM-targeting strategies could improve immunotherapy responsiveness in TNBC.

Wang J, Pan S, Bai L et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Transformer-Based Multitask Framework Integrating Habitat and Deep Learning for Predicting Early Disease Control and Survival in Immunotherapy-Treated Hepatocellular Carcinoma.

This study developed ECOS-Net, a transformer-based multitask model using CT-derived “habitat” features and 2.5D deep learning features to predict early disease control and overall survival in immune checkpoint inhibitor (ICI)-treated hepatocellular carcinoma (HCC) patients. In 832 ICI-treated patients for development (from eight institutions plus public databases), ECOS-DC achieved AUCs around 0.82–0.84 across training, internal validation, and external testing. Clinically, the model could help stratify HCC patients early on ICI therapy to guide treatment decisions and trial design.

Fu X, Guo Y, Gong B et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Neuroinflammation and innate immune regulation

Peripheral CXCR3 blockade mitigates T cell infiltration and neurodegeneration in a mouse model of tauopathy.

This mouse study investigated whether peripheral CXCR3 blockade affects T cell infiltration and neurodegeneration in tauopathy models, using genetic deletion or antibody-mediated blockade of CXCR3 and IFNγ-induced CXCL10/T cell recruitment paradigms. It found that CXCR3 deletion or blockade prevented IFNγ-induced T cell infiltration and that chronic systemic anti-CXCR3 treatment reduced parenchymal CD4+ and CD8+ T cell accumulation, attenuated neurodegeneration, and improved cognition. Scientifically, it implicates CXCR3-dependent peripheral immune trafficking as a modifiable driver of neuroinflammation in tauopathy.

Emmerson JT, Hu H, Savani V et al. · Neuron · (2026) · View on PubMed ↗

A microglial SPP1-ITGB1 feedback loop sustains thalamic hyperexcitability and post-stroke pain.

This mouse study identified a microglial signaling mechanism for central post-stroke pain (CPSP)-like behaviors by focusing on secreted phosphoprotein 1 (SPP1) and integrin β1 (ITGB1). It showed that hemorrhage-induced ATP activates P2X7 receptors to induce microglial SPP1, which then engages an autocrine SPP1–ITGB1 feedback loop that sustains a chemokine-rich pro-nociceptive environment and thalamic hyperexcitability. The significance is mechanistic and therapeutic: disrupting the microglial SPP1–ITGB1 loop could be a strategy to prevent chronic post-stroke pain chronification.

Dai R, Wu W, Zhou X et al. · Neuron · (2026) · View on PubMed ↗

Nuclear cGAS inhibits stimulation-induced inflammatory gene transcription via HDAC1.

The study investigated nuclear cyclic GMP-AMP synthase (cGAS) function in macrophages stimulated with lipopolysaccharide (LPS), focusing on inflammatory gene transcription control independent of STING. It found that nuclear cGAS acts as a transcriptional repressor that selectively suppresses primary response genes such as Cxcl1 and Tnf, requiring nucleosome binding but not cGAS enzymatic signaling. This clarifies a STING-independent role for cGAS in dampening inflammatory transcriptional programs.

Gao S, Li H, Yan S et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Hypothalamic microglial IL-4 signaling mediates cancer-associated cachexia via sympathetic activation.

This study investigated cancer-associated cachexia (CAC) in mice by manipulating hypothalamic interleukin-4 (IL-4) signaling using intracerebroventricular (ICV) delivery of anti-IL-4 antibody or recombinant IL-4. Using CX3CR1-creERT2 mice to knock down IL-4 receptor (IL-4R) in microglia, the authors found that hypothalamic microglial IL-4 signaling mediates CAC via sympathetic activation. The findings are clinically relevant because they identify a CNS immune-neuroendocrine axis that could be targeted to prevent or treat cachexia.

Kim S, Jang S, Park S et al. · Metabolism: clinical and experimental · (2026) · View on PubMed ↗ · Free PDF ↗

Remote Ischemic Post-Conditioning Preserves the Neurovascular Unit by Brain-Derived Gas6 That Drives Monocyte-Derived Macrophage Reprogramming via Axl and Vimentin after SAH.

This work investigated whether remote ischemic post-conditioning (RIPostC) protects the neurovascular unit after subarachnoid hemorrhage (SAH) by modulating monocyte-derived macrophages through the Gas6/Axl/Vimentin signaling axis in both rats and a clinical SAH cohort. RIPostC reduced CCR2+ cell infiltration and monocyte-derived macrophage burden, shifted macrophage polarization from M1-like to M2-like, and preserved blood–brain barrier integrity via Gas6/Axl/Vimentin-dependent reprogramming. Clinically, the study links CSF leukocyte burden with functional outcomes and mechanistically supports RIPostC as a potential immunomodulatory therapy to limit early brain injury after SAH.

Zhu Y, Huang Z, Rong X et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

AI-Designed TREM1-Targeted LYTAC Nanoparticles Reprogram the Neuroimmune Microenvironment in Traumatic Brain Injury.

This study identified the TREM1-expressing cell population in traumatic brain injury (TBI) human and mouse brains and tested whether pharmacologic TREM1 targeting can reprogram neuroimmune inflammation. TREM1 deletion attenuated neuroinflammation, preserved neurovascular integrity, and improved neurological/behavioral recovery, and an AI-designed TREM1-binding peptide was engineered into a mannose-6-phosphate lysosome-targeting LYTAC delivered by an Angiopep-2-functionalized pH-responsive dendrimer nanoparticle. The approach provides a targeted LYTAC nanomedicine strategy to suppress TREM1-driven secondary neuroinflammation after TBI.

Huang Y, Liu Y, Peng H et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Salvianolic Acid a Disrupts the HSP90α-AKT-PERK Ternary Complex to Alleviate Atherosclerosis by Activating Endoplasmic Reticulum Stress of Senescent Vascular Smooth Muscle Cells.

The study examined whether salvianolic acid A (SAA) modulates heat shock protein 90 alpha (HSP90α) signaling in senescent vascular smooth muscle cells (VSMCs) using HSP90α overexpression/knockdown in vitro and adeno-associated virus (AAV)-mediated VSMC-specific HSP90α manipulation in ApoE-/- mice fed a high-fat diet. SAA inhibited HSP90α, disrupting an HSP90α–AKT–PERK ternary complex and promoting apoptosis of senescent VSMCs while alleviating atherosclerosis in vivo. These findings suggest SAA may be a therapeutic strategy for atherosclerosis by targeting HSP90α-dependent endoplasmic reticulum stress programs in senescent VSMCs.

Guan X, Lu M, Cui X et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Extracellular Vesicle Packaged TDP43 Derived From ECs Exacerbates Cigarette Tar-Related Atherosclerosis Progression via Enhancing Macrophage Extracellular Traps.

The study tested how extracellular vesicles (EVs) carrying TDP43 from cigarette tar (TAR)–treated endothelial cells (ECs) affect atherosclerosis progression in TAR-injected ApoE-/- mice and in macrophage co-culture systems. TAR increased EC EV secretion and exacerbated atherosclerotic plaques, while EV inhibition with GW4869 reduced lesions; mechanistically, TAR promoted macrophage extracellular trap (MET) formation, and EV-associated TDP43 enhanced this process. This indicates that EC-derived, TDP43-containing EVs are a mechanistic link between cigarette tar exposure and immune-driven plaque progression via METs.

Zhu X, Chen Y, Meng W et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

LAPTM5 Downregulation-Driven VAMP8 Phosphorylation Impairs Autophagosome-Lysosome Fusion and Aggravates Septic Acute Lung Injury.

The study examined the role of lysosomal-associated protein transmembrane 5 (LAPTM5) in macrophage autophagy during septic acute lung injury (ALI) by analyzing peripheral blood mononuclear cells (PBMCs) from septic ALI patients and alveolar macrophages from septic mice, and then manipulating Laptm5 using macrophage-specific depletion and AAV overexpression. LAPTM5 was downregulated in septic ALI and inversely correlated with SOFA score, and altering Laptm5 expression worsened or improved ALI phenotypes; mechanistically, LAPTM5 downregulation drove VAMP8 phosphorylation, impairing autophagosome–lysosome fusion. These findings identify a LAPTM5–VAMP8 axis as a potential therapeutic target to restore autophagic flux and mitigate septic lung inflammation.

Jiang L, Li Q, Liu H et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

PLXDC2 siRNA-Mediated Intervention Attenuates Microglial Senescence Through cGAS-STING Signaling.

This study used a single-cell atlas of the human substantia nigra to identify PLXDC2 upregulation in Parkinson’s disease (PD) microglia and then tested PLXDC2 siRNA delivered via a biomimetic nanoplatform. The HFn-GM@siPLXDC2/DFO/CeO2 nanoparticles attenuated microglial senescence by engaging cGAS–STING signaling, while combining BBB-penetrating ferritin/microglial membrane targeting with iron chelation (deferoxamine) and antioxidant CeO2. Scientifically and therapeutically, it links a specific microglial target (PLXDC2) to innate immune senescence pathways and proposes a BBB-capable, multi-modal delivery strategy for PD.

Lu H, Zheng Z, Wang F et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Ilexoside K Ameliorates Atherosclerosis by Suppressing CD72hi Macrophages and Blocking CXCL12-CXCR4 Axis to Inhibit Endothelial Pyroptosis.

This study characterized a c-Rel-driven CD72hi macrophage subset in human and murine atherosclerotic plaques using single-cell transcriptomics and functional assays. It showed that CD72hi macrophages promote endothelial pyroptosis, oxidative stress, and dysfunction via pathological CXCL12–CXCR4 signaling, and that the natural triterpenoid saponin Ilexoside K (IK) blocks this axis to ameliorate atherosclerosis. The work supports IK and the CD72hi–CXCL12/CXCR4–pyroptosis pathway as potential anti-inflammatory targets to reduce residual inflammatory risk in atherosclerotic cardiovascular disease.

He X, Li S, Chen J et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration and proteinopathy

BAG3 coordinates astrocytic proteostasis of Alzheimer’s disease-linked proteins via proteasome, autophagy, and retromer interactions.

The study examined how the astrocyte-enriched proteostasis regulator BAG3 coordinates Alzheimer’s disease–linked protein handling by integrating proteasome, autophagy, and retromer pathways, using single-nucleus RNA sequencing and CRISPR/Cas9 editing in human induced pluripotent stem cell–derived models. BAG3 loss caused greater disruption of astrocytic proteostasis, with proteomic and transcriptomic profiling identifying altered interactions across proteasome/autophagy/retromer systems. These findings position BAG3 as a mechanistic node controlling astrocytic clearance of AD-relevant proteins and suggest potential therapeutic leverage points for neurodegenerative disease.

Augur ZM, Fogo GM, Benoit CR et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

MRI Characteristics of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Review.

This review studied the MRI characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) by summarizing hallmark imaging features, lesion distribution, and lesion evolution relevant to the 2023 diagnostic criteria. It emphasizes that variability in MRI parameters and an underrecognized imaging spectrum can delay diagnosis and treatment. Scientifically and clinically, the synthesis helps clinicians interpret MRI findings more accurately and differentiate MOGAD from multiple sclerosis and AQP4+ neuromyelitis optica spectrum disorder.

Flanagan EP, Banwell BL, Cacciaguerra L et al. · JAMA neurology · (2026) · View on PubMed ↗

Genetic architecture and molecular pathogenesis of Parkinson’s disease: emerging mechanisms and therapeutic targets.

This review studied the genetic architecture and molecular pathogenesis of Parkinson’s disease (PD) by synthesizing emerging mechanisms and therapeutic targets linked to α-synuclein Lewy body pathology and dopaminergic neuron loss in the substantia nigra pars compacta (SNpc). It highlights interconnected pathways including impaired protein homeostasis, mitochondrial dysfunction, oxidative stress, lysosomal-autophagic defects, and chronic neuroinflammation. The synthesis supports a multi-target therapeutic direction informed by genetics and convergent molecular mechanisms underlying PD.

Yildirim S · Metabolic brain disease · (2026) · View on PubMed ↗

Targeting LDHA Palmitoylation Sensitizes GBM to Chemoradiotherapy via Suppressing Palmitic Acid Induced Glycolytic Reprogramming.

The study examined how the E3 ubiquitin ligase LRSAM1 regulates TDP-43 localization and degradation in amyotrophic lateral sclerosis (ALS). In postmortem spinal cord tissue from sporadic ALS patients and healthy controls, immunohistochemistry showed LRSAM1 preferentially associated with TDP-43 pathology, supporting a role in TDP-43 proteostasis. These findings are significant because they implicate LRSAM1-mediated ubiquitin pathways as potential therapeutic targets to modulate pathogenic TDP-43 handling in ALS.

Gao Z, Zhao R, Chen Z et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Lewy Body Disease Across Aging: Clinical and Neuropathological Correlates in a Population Brain Bank.

This population brain bank study assessed how Braak-staged Lewy body disease (LBD) relates to age, mixed neuropathology, and clinical features within a single cohort. Using autopsied participants (n=2480) from the Biobank for Aging-related studies, the authors evaluated correlations between LBD staging and both neuropathological co-pathologies and clinical manifestations. The significance is that it clarifies how LBD staging maps onto real-world aging and mixed pathology, improving interpretation of biomarkers and prognostic expectations across ages.

Paes VR, Pereira FL, Silva CM et al. · Movement disorders : official journal of the Movement Disorder Society · (2026) · View on PubMed ↗ · Free PDF ↗

Evaluating the neurofilament light chain-derived gap between biological and chronological age in multiple sclerosis and controls.

The study compared chronological age versus neurofilament light chain (NfL)-derived age in multiple sclerosis (MS) patients and controls, and tested clinical correlates of the “age gap” in a real-world retrospective cohort. The key finding was that NfL-derived age differed from chronological age in MS, and the magnitude of the NfL age gap associated with clinical measures, supporting NfL as a biomarker of biological aging in MS. This is significant for risk stratification and monitoring disease-related neurodegeneration beyond conventional clinical timelines.

Nicolella V, Polito C, Criscuolo V et al. · Journal of neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Cannabinoid CB1 Receptor in Nociceptors Mediates Postoperative Analgesia via ASIC3 Inhibition.

This study used a mouse plantar incision postoperative pain model combined with nociceptor-selective Cnr1 knockout and site-specific pharmacology to test how the cannabinoid type-1 receptor (CB1R; Cnr1) regulates peripheral analgesia. CB1R activation in primary sensory neurons robustly reduced postoperative mechanical allodynia by inhibiting the proton-sensing ion channel ASIC3, with CB1R colocalizing and physically associating with ASIC3 in CGRP+ peptidergic nociceptors. The results identify a peripheral CB1R–ASIC3 mechanism that could be exploited to develop analgesics that reduce pain without central side effects.

Xu K, Ji L, Yang H et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

14-3-3γ Protects Against Postoperative Cognitive Dysfunction by Regulating Tau Thr205 Phosphorylation and Synaptic Integrity.

This study assessed whether 14-3-3γ protects against postoperative cognitive dysfunction (POCD) by regulating tau Thr205 phosphorylation and synaptic integrity, using CSF proteomics (SomaScan 7K) in the ADNI cohort and a prospective surgical cohort plus mechanistic mouse and AAV-based experiments. Higher perioperative/cognitive vulnerability–linked 14-3-3γ levels were associated with better cognitive outcomes, and mechanistically 14-3-3γ reduced tau Thr205 phosphorylation and preserved synaptic integrity in models of surgery-induced cognitive impairment. The work supports 14-3-3γ as a biomarker and potential therapeutic target to prevent POCD via tau-pathway modulation.

Zhu S, Han X, Zhang H et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Hederagenin Attenuates Morphine Addiction via GABAA1-Mediated Modulation of Ca2 +-CaMK-CREB Signaling in Ventral Tegmental Dopaminergic Neurons.

This study tested whether hederagenin (HE) modulates morphine-associated contextual reward learning in both sexes and identified the relevant target and signaling pathway in ventral tegmental dopaminergic neurons. HE attenuated morphine conditioned place preference (CPP) acquisition and reduced established CPP expression, with chemical proteomics prioritizing the GABAA receptor α1 subunit (GABAA1; gene GABRA1) and implicating Ca2+-CaMK-CREB signaling downstream. The findings suggest a GABAA1-mediated mechanism by which HE may reduce maladaptive opioid-context associations and support adjunct strategies for opioid addiction.

Jiang H, Zhou Z, Xue N et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Ambroxol in Gaucher disease and GBA1-related Parkinson disease: an updated systematic review.

This PRISMA 2020 systematic review evaluated evidence for ambroxol (ABX), a CNS-penetrant compound that can increase glucocerebrosidase activity, in Gaucher disease (GD) and GBA1-related Parkinson disease (GBA1-PD). Across searched databases and clinical trial registries up to 19 August 2026 (with additional revision searching), the review synthesized clinical and methodological findings and assessed risk of bias by study design. The review clarifies the current state of ambroxol’s therapeutic potential and evidence quality for targeting lysosomal dysfunction in GD and GBA1-PD.

Lipiński P, Jezela-Stanek A, Tylki-Szymańska A · Acta neurologica Belgica · (2026) · View on PubMed ↗ · Free PDF ↗

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Cell death pathways (ferroptosis/mitophagy/apoptosis)

Next-generation brain organoids: neural complexity from cellular diversity to functional networks.

The study investigated whether lactylation activates an HSPA5–VGLL3 signaling axis to inhibit mitophagy-dependent ferroptosis after intracerebral hemorrhage (ICH). In ICH models, VGLL3 expression increased and loss-of-function experiments showed that VGLL3 silencing worsened ferroptosis phenotypes, consistent with a protective pathway driven by lactylation-mediated HSPA5 activation. This is significant because it connects a specific post-translational modification (lactylation) to ferroptosis control in ICH, suggesting VGLL3/HSPA5 as mechanistic and therapeutic candidates.

Duan CH, Wang YK, Tang TS et al. · Brain : a journal of neurology · (2026) · View on PubMed ↗

Lactylation-mediated activation of HSPA5 upregulates VGLL3 expression to inhibit mitophagy-dependent ferroptosis following intracerebral hemorrhage.

The study focused on lactylation-mediated activation of HSPA5 and its downstream effect on VGLL3 to suppress mitophagy-dependent ferroptosis following intracerebral hemorrhage. The key finding was that the HSPA5–VGLL3 axis promotes neuroprotection in ICH models, with functional experiments indicating that disrupting VGLL3 exacerbates ferroptosis-related injury. This work is significant because it identifies a modifiable molecular pathway linking lactylation, mitophagy, and ferroptosis in a major cause of neuronal death after ICH.

QiXiang Z, QiKai T, BaoFeng W et al. · Autophagy · (2026) · View on PubMed ↗ · Free PDF ↗

Paeoniflorigenone triggers TRIM28 phosphorylation-dependent ferroptosis and immune activation to suppress intrahepatic cholangiocarcinoma.

This preclinical study tested paeoniflorigenone (PFG), a monomer from total glucosides of paeony, in multi-dimensional intrahepatic cholangiocarcinoma (ICC) models to define its mechanism of action. Transcriptomic profiling and functional assays indicated that PFG triggers TRIM28 phosphorylation-dependent ferroptosis along with immune activation to suppress ICC malignant phenotypes. The work is scientifically significant because it links a specific ferroptosis pathway (TRIM28 phosphorylation) to anti-tumor immune effects, supporting PFG as a mechanistically guided therapeutic candidate for ICC.

Lin K, Lu Y, Lin Z et al. · Pharmacological research · (2026) · View on PubMed ↗ · Free PDF ↗

FBP1-Mediated Compartmentalization of Glycolytic Enzyme Complexes Suppresses PKM2 Function to Ameliorate MASLD Progression.

This study examined how fructose-1,6-bisphosphatase 1 (FBP1) regulates hepatocyte glycolysis during metabolic dysfunction-associated steatotic liver disease (MASLD) progression in clinical specimens and preclinical MASLD models. FBP1 was downregulated from MASL to MASH and directly interacted with glycolytic enzymes PKM2, ENO1, and LDHA to form compartmentalized complexes that suppress PKM2 activity, thereby restricting excessive glycolysis and lipid accumulation. These findings identify an FBP1–PKM2 axis and enzyme-compartmentalization mechanism as a potential therapeutic target to ameliorate MASLD progression.

Wang B, Tang Y, Li N et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Platycodon grandiflorus-Derived Nanovesicles Sensitize Gastric Cancer to T Cell Killing via Ferroptosis-Driven Membrane Mechanical Remodeling.

This study examined whether Platycodon grandiflorus-derived nanovesicles (PGNs) can sensitize gastric cancer to T cell killing by inducing ferroptosis and altering membrane mechanics. PGNs promoted ferroptosis-driven plasma membrane mechanical remodeling by reprogramming tumor lipid composition—coordinately suppressing the SLC7A11–GPX4 antioxidant axis while delivering polyunsaturated fatty acids, especially gamma-linolenic acid—leading to glutathione depletion, lipid peroxidation, and ferroptotic cell death that enhanced immune attack. The findings suggest a plant-nanovesicle strategy to overcome intrinsic resistance to cytotoxic T-cell killing via ferroptosis induction.

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

Dual Compartmentalization of GSTA4 Suppresses Ferroptosis to Drive Antiandrogen Resistance in Prostate Cancer.

This study investigated how glutathione S-transferase alpha 4 (GSTA4) suppresses ferroptosis to drive antiandrogen resistance in castration-resistant prostate cancer (CRPC) using integrated multi-omics of resistant models and patient specimens. GSTA4 was identified as a pivotal ferroptosis suppressor associated with adverse outcomes and was shown to drive antiandrogen resistance via dual compartmentalization that detoxifies the lipid peroxidation product 4-hydroxynonenal in the cytosol. These results define a mechanistic ferroptosis-evasion program centered on GSTA4 compartmentalization as a potential target to overcome antiandrogen resistance.

Luo Y, Zhuang W, Li Z et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

A Hepatocyte-to-Stellate Cell Axis Couples Alternate-Day Fasting to Liver Fibrosis Resolution via ATG7 S-Nitrosylation.

The study assessed a hepatocyte-to-stellate cell signaling axis in human fibrotic liver samples and mouse models, focusing on hepatocyte endothelial nitric oxide synthase (eNOS) and how alternate-day fasting (ADF) influences liver fibrosis resolution via autophagy-related gene 7 (ATG7) S-nitrosylation. Hepatocyte-specific eNOS deletion worsened injury and fibrosis, and ADF’s anti-fibrotic effects depended on this intercellular pathway, with ATG7 S-nitrosylation coupling hepatocyte signals to stellate cell quiescence and reduced fibrogenesis. These results support ADF as a mechanistically grounded, eNOS–ATG7–mediated strategy to promote liver fibrosis resolution.

Wang X, Zeng M, Sun C et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Stimulation of OGG1 Enhances Oxidative DNA Damage Repair and Protects Against Acute Liver Failure by Acetaminophen.

The study investigated whether pharmacologically stimulating the DNA glycosylase OGG1 can enhance oxidative DNA damage repair and protect against acetaminophen-induced acute liver failure in hepatocytes. It identified the small molecule CMM-98, which binds the OGG1 active site to robustly promote AP-site processing by rewiring OGG1’s catalytic outcome under oxidative stress, thereby improving oxidative DNA damage resolution and hepatocyte viability. This supports OGG1-targeted small-molecule modulation as a potential therapeutic approach for acetaminophen-associated acute liver failure driven by oxidative DNA lesions.

Zhao Z, Upadhyay R, Eddershaw A et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Epigenetics and transcriptional regulation

H3K27me3 loss and METTL3-m6A converge to upregulate SOX11/SMARCA4 and drive H3K27-altered spinal cord glioma stemness and proliferation.

The study used patient-derived spinal cord H3K27-altered diffuse midline glioma (H3-DMG) stem-like spheres and differentiated models, applying multi-omics including single-cell RNA-seq, spatial transcriptomics, RNA m6A profiling, CUT&Tag, and ATAC-seq. It found that H3K27me3 loss and METTL3-mediated m6A converge to upregulate SOX11 and SMARCA4, promoting H3K27-altered glioma stemness and proliferation. This links epigenetic loss (H3K27me3) with epitranscriptomic regulation (METTL3–m6A) to define a pathway driving aggressive spinal cord glioma biology.

Yan H, Jin J, Chang Y et al. · Neuro-oncology · (2026) · View on PubMed ↗

A redox switch on CDC48 regulates peroxisomal function via controlling peroxisome-associated protein degradation.

The study examined how a redox-regulated switch on the AAA-ATPase CDC48 complex controls peroxisomal function through regulation of peroxisome-associated protein degradation in Arabidopsis. The authors identified the peroxisomal membrane protein PEX22 as a direct substrate of the CDC48 complex and showed that CDC48/NPL4/UFD1 promotes ubiquitin-dependent PEX22 turnover, linking CDC48 activity to peroxisome biogenesis and physiological function. This mechanistic insight clarifies how ubiquitin-proteasome control interfaces with peroxisomal redox homeostasis, highlighting CDC48–PEX22 axis as a regulatory node.

Li J, Wang Y, Pan R et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Histone H4 lysine 20 tri-methylation safeguards breast cancer lineage fidelity and unfolded protein response.

The study examined how histone H4 lysine 20 tri-methylation (H4K20me3) regulates breast cancer lineage fidelity and the unfolded protein response (UPR) in triple-negative breast cancer (TNBC). Pharmacologic inhibition of H4K20me3 methyltransferases KMT5B and KMT5C with A-196 reduced H4K20me3, altered lineage-identity and stress-response gene programs, suppressed tumor growth in vivo, and promoted mesenchymal features alongside UPR activation. These findings highlight H4K20me3 as an epigenetic control point that can be therapeutically targeted to reshape TNBC cell state and stress signaling.

Li Z, Tawawalla A, Foidart P et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Single-cell/spatial omics atlases and microenvironments

A human single-cell atlas identifies OLR1+ scar-associated macrophages as a potential therapeutic target for chronic liver disease.

This study generated a human liver single-cell atlas from 42 healthy and 35 chronic liver disease (CLD) patients to define fibrosis-driving macrophage states, focusing on TREM2+ scar-associated macrophages (SAMac) and the scavenger receptor OLR1. It identified two disease-expanded TREM2+ SAMac subtypes, including a pro-inflammatory OLR1+ population that spatially accumulates in the CLD fibrotic niche and whose high hepatic OLR1 expression was associated with worse outcomes. These findings nominate OLR1+ scar-associated macrophages as a potential therapeutic target for chronic liver fibrosis and provide a cellular biomarker framework for patient stratification.

Papachristoforou E, Kong K, Colella F et al. · Nature genetics · (2026) · View on PubMed ↗

The Polycystic Kidney Disease Cyst Transcriptome Defined by Integrating Spatial, Single Nuclear, and Bulk Transcriptomics.

The study defined the autosomal dominant polycystic kidney disease (ADPKD) cyst transcriptome by integrating spatial transcriptomics (10x Genomics Visium), single-nucleus RNA-seq, and bulk transcriptomics in an ADPKD patient sample. By preserving cyst morphology with spatial sampling and combining it with single-nucleus and bulk data, the authors characterized cyst size–related transcriptional heterogeneity and enabled retrograde cyst transcriptome analysis. This improves mechanistic resolution of cyst biology and supports more precise identification of pathways driving ADPKD progression.

Khan MI, Robichaud JH, Afrin H et al. · Kidney360 · (2026) · View on PubMed ↗

Stem cell morphology defines functional heterogeneity and therapeutic vulnerabilities in glioblastoma.

The study investigated glioblastoma stem-like cells (GSLCs) by integrating cell morphology with transcriptomic identity to define functional heterogeneity and therapeutic vulnerabilities in glioblastoma. Using CellShape-seq (spatial transcriptomics coupled to morphology), the authors found that distinct morphological states correspond to different functional programs and reveal specific vulnerabilities that are not fully captured by transcriptional profiling alone. Scientifically, this provides a morphology-informed framework for identifying actionable GSLC subtypes and guiding targeted therapeutic strategies in GBM.

Barelli C, Bonfanti M, Mirabella F et al. · Neuro-oncology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Spatial analysis reveals cellular microenvironments and mechanisms of inflammation and injury in acute interstitial nephritis.

The study used high-resolution imaging mass cytometry and single-cell spatial transcriptomics to map cellular microenvironments and inflammatory/injury mechanisms in human acute interstitial nephritis (AIN) compared with acute tubular injury (ATI) and reference tissue. It found that interferon-γ–induced CXCL9–CXCR3 signaling was markedly increased in AIN, with enriched predicted T cell–T cell amplification networks in lymphoid aggregates, while injured proximal tubules (notably VCAM1+ cells) upregulated complement components. These results identify spatially organized immune–tubular pathways that could guide targeted therapies for AIN beyond corticosteroids.

Baker ML, Kakade VR, Budiman T et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Integrated Multi-Omics Reveals Cellular States and Microenvironmental Remodeling in Coexisting DCIS and IDC.

This study used integrated spatial transcriptomics, single-cell RNA sequencing, and single-cell DNA sequencing to compare cellular states and microenvironmental remodeling in coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) samples. It identified candidate progression-limiting genes including MGP, PLAT, and SERPINA3 and delineated malignant epithelial meta-programs (MPs) associated with distinct transcriptional states between DCIS and IDC. The multi-omics framework and candidate genes provide leads for understanding and potentially intercepting the DCIS-to-IDC transition.

Zhang N, Wan T, Zhang S et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

DUET-seq: An Open-Source Droplet Platform for High-Fidelity Joint Chromatin and Transcriptome Profiling Reveals Temporal Regulatory Decoupling in Single Cells.

The study developed DUET-seq, an open-source droplet microfluidic platform for joint chromatin accessibility and transcriptome profiling from the same nucleus, and evaluated it for capturing temporal regulatory relationships in single cells. DUET-seq used programmable dissolvable dual-linker hydrogel beads and one-step intra-droplet RT-PCR to co-index RNA and transposed chromatin fragments within ~12 hours, revealing temporal regulatory decoupling between chromatin accessibility and gene expression. This provides a lower-cost, higher-fidelity method to directly connect regulatory elements to transcriptional output in time-resolved single-cell studies.

Cheng D, Meng Z, Wei L et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer genomics, resistance, and targeted therapy mechanisms

Opposing functions of gut immunomodulatory metabolites on CAR-T therapy.

The study investigated how ATM deficiency affects PARP inhibitor (PARPi) cytotoxicity in mammalian cells, focusing on DNA replication restart/repriming at endogenous base lesions. It found that loss of ATM permits unrestrained PRIMPOL-dependent repriming at oxidative base lesions, generating post-replicative DNA gaps that activate PARP, driven by aberrant BRCA1 recruitment to stalled forks and suppression of HLTF/ZRANB3-mediated repriming control. This mechanistically links ATM to replication fork lesion processing and clarifies why PARPi kill ATM-deficient tumors.

Perl M, Guetter S, Shah D et al. · Cell · (2026) · View on PubMed ↗

A transient MXD4-dependent proliferative pause enables survival of brain micrometastases.

The study examined brain micrometastasis initiation in aggressive cancer models and identified a transient MXD4-dependent proliferative pause during early brain colonization. It found that metastatic cells temporarily restrain proliferation via the MYC antagonist MXD4 before vascular co-option outgrowth, and that MXD4 disruption reduces micrometastasis survival and progression to macrometastases, with validation in human brain micrometastasis analyses. This reveals a targetable survival program that could be exploited to prevent metastatic outgrowth in the brain.

García-Gómez P, Retana D, Hernández-Oliver C et al. · Cancer cell · (2026) · View on PubMed ↗

A Paired Tumor Organoid-Stroma Biobank Reveals PLAU⁺ Fibroblasts as Drivers of Chemoresistance in Lung Adenocarcinoma.

The study created a paired tumor organoid–stroma biobank from treatment-naïve lung adenocarcinoma patients and co-cultured lung cancer organoids with cancer-associated fibroblasts (CAFs) to model chemoresistance. It identified PLAU (plasminogen activator urokinase) as a marker of chemoresistance-associated CAFs and showed that tumor cells polarize fibroblasts toward a PLAU+ state that reduces organoid drug sensitivity and links to poor patient survival. This supports PLAU+ fibroblasts as mechanistic drivers and potential therapeutic targets for overcoming LUAD chemoresistance.

Li S, Zhang Z, Lv Q et al. · Cancer research · (2026) · View on PubMed ↗

Inhibition of Translesion DNA Synthesis Sensitizes BRCA-Deficient Ovarian Cancer to PARP Inhibitors.

The study investigated whether inhibiting translesion DNA synthesis (TLS) can sensitize BRCA-deficient ovarian cancer to PARP inhibitors by probing mechanisms of PARPi resistance. The authors report that TLS contributes to PARPi resistance by enabling replication across DNA lesions, and that blocking TLS increases PARPi sensitivity in BRCA-deficient contexts. This provides a rationale for combination strategies targeting TLS to overcome PARP inhibitor resistance in BRCA1/2-mutated ovarian cancer.

Li N, Lavudi K, Ge Q et al. · Cancer research · (2026) · View on PubMed ↗

TgDDP is a novel DIX domain protein that plays an essential role in Toxoplasma endodyogeny.

The study investigated the function of TgDDP, a previously unannotated DIX-DnaJ domain protein, in Toxoplasma gondii daughter cell formation (endodyogeny). Using endogenous tagging and functional characterization, the authors found TgDDP is essential for endodyogeny, linking its DIX and DnaJ domain architecture to the parasite’s cell-division machinery. This work is significant because it identifies a new apicomplexan-specific regulator of parasite replication that could be exploited for future anti-toxoplasmosis strategies.

Gaji RY, Mandadi P, Ali D et al. · mBio · (2026) · View on PubMed ↗ · Free PDF ↗

Real-World Landscape of BRCA Deleterious Alterations in Advanced Prostate Cancer: Insights From a Nationwide Genomic Database.

This nationwide genomic database study analyzed 2,815 patients with advanced prostate cancer undergoing tissue-based tumor-only comprehensive cancer genomic profiling (CGP) from Dec 2020 to Nov 2024 to characterize BRCA1/BRCA2 (BRCA) deleterious alterations. It focused on how BRCA variant types and co-occurring gene alterations relate to clinical features such as age and family history in metastatic castration-resistant or androgen-indifferent prostate cancer, including neuroendocrine prostate cancer. The results are clinically significant because they refine real-world expectations for BRCA-driven biology in patients selected for tumor-only CGP, informing precision oncology and potential eligibility for targeted therapies.

Tsumura H, Koguchi D, Tabata KI et al. · The Prostate · (2026) · View on PubMed ↗

PTBP1-Mediated Alternative Splicing of DNAJB6 Promotes Everolimus Resistance in Clear Cell Renal Cell Carcinoma via EIF4B/PKIB/AKT/mTOR Positive Feedback Loop.

This study investigated how PTBP1-mediated alternative splicing of DNAJB6 contributes to everolimus resistance in clear cell renal cell carcinoma (ccRCC) through an EIF4B/PKIB/AKT/mTOR positive feedback loop. Using single-cell transcriptomics, patient-derived samples, animal models, and in vitro assays, the authors showed that PTBP1 promotes a splicing program that activates the AKT/mTOR pathway network and sustains everolimus resistance. The findings identify PTBP1–DNAJB6 splicing and the EIF4B/PKIB/AKT/mTOR loop as actionable mechanisms to overcome resistance to mTOR inhibition.

Pan XW, Zheng HF, Li MC et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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CAR-T engineering, delivery, and microbiome/immune reconstitution

ATM safeguards DNA replication by restraining pathological repriming at endogenous base lesions.

The study analyzed patient gut microbiomes in 129 individuals across three German centers using shotgun metagenomics and targeted mass spectrometry to relate immunomodulatory metabolites to CAR-T outcomes. Reduced short-chain fatty acids—especially valeric acid—before CAR-T correlated with higher risk of disease progression, while higher indole metabolites (e.g., indole-3-carboxaldehyde, indole-3-acetic acid) and the branched-chain fatty acid isovaleric acid were associated with better outcomes. These findings suggest metabolite-based biomarkers and potential microbiome-targeted interventions to improve CAR-T efficacy.

Sommerova L, King A, Chapman JR · Molecular cell · (2026) · View on PubMed ↗

Advancing In Vivo Chimeric Antigen Receptor T-Cell Engineering to Accelerate Clinical Translation.

This review article summarizes advances in in vivo chimeric antigen receptor (CAR) T-cell engineering aimed at improving clinical translation. It highlights strategies to program T cells directly in the body to reduce dependence on complex ex vivo manufacturing, improve T-cell fitness, enable more flexible dosing, and potentially reduce or avoid lymphodepletion. The significance is that it frames how next-generation CAR designs and delivery approaches may overcome current manufacturing and control barriers in CAR-T therapy.

Bai Z, Yi M, Hu S et al. · MedComm · (2026) · View on PubMed ↗ · Free PDF ↗

Respiratory Viral Infections Following CAR-T Cell Therapy for Lymphoma and Myeloma: Severity and Immune Correlates.

This retrospective cohort study analyzed laboratory-confirmed respiratory viral infections (RVIs) in 563 commercial CAR-T recipients with lymphoma or myeloma treated between 2018 and 2024. It characterized RVI severity (URTI vs LRTI, CTCAE v5.0 grading, and respiratory-support needs) and assessed immune reconstitution markers as time-dependent covariates using multivariable Andersen–Gill models. The findings are clinically significant because they define when and how RVIs occur after CAR-T and identify immune correlates that could guide monitoring and preventive interventions.

Einarsdottir S, Fei T, Sotelo-Alva MI et al. · International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · (2026) · View on PubMed ↗ · Free PDF ↗

A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.

This study developed a multi-targeting “Bicephali” CAR-T platform for non-small cell lung cancer (NSCLC) to overcome antigen heterogeneity and T cell exhaustion. The dual-transmembrane CAR uses two distinct extracellular antigen-binding domains targeting CD276 and NKG2D ligands (NKG2DLs) with a shared 4-1BB/CD3ζ intracellular signaling module, and Bicephali CAR-T cells showed superior tumor killing versus conventional BB002 CAR-T in vitro and in vivo. This platform provides a strategy to broaden antigen coverage in heterogeneous NSCLC while maintaining potent co-stimulation for improved therapeutic efficacy.

Wang L, Zhang Y, Peng S et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Clinical trials, guidelines, and real-world evidence (non-oncology)

EASL-EASD-EASO Guidance for the Use of Resmetirom and Semaglutide as MASH-Targeted Therapy.

This guidance document synthesized evidence for using resmetirom and semaglutide as MASH-targeted therapy in adults with metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH), using non-invasive fibrosis tests such as vibration-controlled transient elastography (VCTE), magnetic resonance elastography (MRE), and enhanced liver fibrosis (ELF) score. It provides updated recommendations for identifying high-risk patients for major adverse liver-related outcomes (MALO) based on specific NIT thresholds (e.g., VCTE 10–20 kPa, MRE 3.1–5.0 kPa, ELF 9.8–11.3) and for considering pharmacotherapy accordingly. The significance is practical: it standardizes how clinicians select patients for resmetirom and semaglutide without relying on liver biopsy.

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

Leniolisib and rapamycin in Activated PI3-Kinase-δ-syndrome: a retrospective ESID registry-based analysis.

This retrospective ESID registry-based analysis assessed real-world treatment indications, clinical course, immunologic changes, and tolerability in patients with activated PI3K-delta syndrome (APDS) treated with rapamycin and/or the selective PI3Kδ inhibitor leniolisib. The key finding was characterization of how these therapies were used in routine care and their associated immunologic and clinical effects in APDS patients. Clinically, the results inform comparative effectiveness and safety expectations for targeted PI3Kδ inhibition versus rapamycin in a rare immunodeficiency.

Rivalta B, Wolkewitz M, Kusters M et al. · The Journal of allergy and clinical immunology · (2026) · View on PubMed ↗

Efficacy and safety of garetosmab, an activin A-blocking antibody, in fibrodysplasia ossificans progressiva (OPTIMA): a randomised, double-blind, placebo-controlled, phase 3 trial.

This randomized, double-blind, placebo-controlled phase 3 trial evaluated garetosmab, an activin A-blocking antibody, in adults with fibrodysplasia ossificans progressiva (FOP) caused by heterozygous gain-of-function mutations in ACVR1 (activin receptor type 1A). The study tested whether blocking activin A would prevent or reduce heterotopic ossification progression and associated disability compared with placebo. The significance is that it provides high-level clinical evidence for a mechanism-based therapy targeting the ActA–ACVR1 pathway in a devastating ultrarare genetic disorder.

Papa R, Rhee S, Delai P et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer (CHN HYPOPMRT): 10-year outcomes from a randomised, non-inferiority, open-label, phase 3 trial.

This randomized, non-inferiority, open-label phase 3 trial compared hypofractionated versus conventional fractionated postmastectomy radiotherapy in women aged 18–75 years with high-risk breast cancer after modified radical mastectomy and axillary dissection, reporting 10-year outcomes. The key finding was that hypofractionated postmastectomy radiotherapy achieved non-inferior long-term efficacy with an adverse event profile comparable to conventional fractionation. This long-term evidence supports hypofractionation as a durable standard option for high-risk postmastectomy regional nodal irradiation.

Sun GY, Chen SY, Tang Y et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Surgery and tile-based radiation therapy versus surgery and stereotactic radiation for newly diagnosed brain metastases (ROADS): a randomized, open-label, phase 3 trial.

The ROADS phase 3 randomized open-label trial studied patients with newly diagnosed brain metastases undergoing surgical resection, comparing resection plus cesium-131 collagen tile-based radiation therapy (R+TBRT) versus resection plus stereotactic radiation (R+SRT). The key finding was that TBRT using cesium-131 tiles was evaluated for non-inferiority in safety and efficacy relative to standard post-operative SRT in this surgical population. Clinically, the trial tests whether immediate, tile-based focal radiation can match outcomes while potentially improving logistics after resection.

Weinberg JS, Imber BS, DiNapoli V et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

2026 AHA/ACC/ACS/ASNC/HRS/SCA/SCCT/SCMR/SVM Guideline for Perioperative Cardiovascular Management for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

This guideline article studied perioperative cardiovascular evaluation and management strategies for adult patients undergoing noncardiac surgery by synthesizing human-subject evidence from a comprehensive literature search (Aug 2022–Mar 2023). It provides structured, evidence-based recommendations spanning preoperative risk assessment, intraoperative management, and postoperative care for noncardiac surgical patients. Clinically, it standardizes cardiovascular decision-making to reduce perioperative morbidity and improve outcomes across diverse surgical settings.

Thompson A, Fleischmann KE, Smilowitz NR et al. · Circulation · (2026) · View on PubMed ↗

Hearing Intervention for Older Adults With Mild Cognitive Impairment: The CHOICE Randomized Clinical Trial.

The CHOICE randomized clinical trial studied whether hearing intervention could reduce dementia-level impairment incidence in older adults with coexisting hearing loss and mild cognitive impairment (MCI). Over 24 months of follow-up, the trial evaluated whether improving hearing would stabilize or improve cognitive outcomes compared with standard care (open-label, multicenter design). If effective, hearing intervention would represent a scalable, modifiable strategy to slow cognitive decline in a high-risk population.

Chen Y, Shi H, Xiang M et al. · JAMA neurology · (2026) · View on PubMed ↗

Vibegron, mirabegron, and other add-on therapies for persistent overactive bladder symptoms in α1-blocker-treated men with benign prostatic hyperplasia: a systematic review and Bayesian network meta-analysis.

This systematic review and Bayesian network meta-analysis studied add-on therapies for persistent overactive bladder (OAB) symptoms in men with benign prostatic hyperplasia (BPH) already treated with an α1-blocker, comparing vibegron, mirabegron, and other options. Across 18 included trials (16 contributing quantitative data), the analysis used indirect vibegron–mirabegron comparisons and estimated efficacy and adverse event odds ratios to rank treatments. Clinically, it informs evidence-based selection of second-line OAB medications for α1-blocker–treated men by integrating comparative effectiveness and safety.

Yajima S, Okumura G, Yoshida S et al. · World journal of urology · (2026) · View on PubMed ↗

Clinical Practice Guideline for the Diagnosis and Treatment of Urinary Tract Infection in Children From 8 Days to 5 Years of Age.

This article is a clinical practice guideline updating evidence and recommendations for diagnosing and treating urinary tract infection (UTI) in children aged 8 days to 5 years. It synthesizes updated literature to provide practical diagnostic and management guidance for pediatric clinicians across low–medical complexity settings. The guideline is significant because it standardizes care for a common pediatric infection and is intended to improve diagnostic accuracy and treatment decisions in young children.

Alverson BK, Hains DS, Downs SM et al. · Pediatrics · (2026) · 2 citations · View on PubMed ↗

Efficacy and Safety of Biologic Therapies Targeting Type 2 and Epithelial-Alarmin Pathways in Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

This systematic review and network meta-analysis compared the efficacy and safety of biologic therapies targeting type 2 and epithelial-alarmain pathways in chronic obstructive pulmonary disease (COPD). It synthesized randomized controlled trial evidence for seven monoclonal antibodies across IL-4/13, IL-5/IL-5Rα, IL-33/ST2, and TSLP pathways, updating cross-agent rankings with newer pivotal and alarmin-trial data. The clinical significance is improved comparative guidance on which biologic targets may best reduce exacerbations and balance safety for COPD patients with type 2/eosinophilic inflammation.

Khoshaim YA, Almaghrabi AR, Alruwaythi AA et al. · Cureus · (2026) · View on PubMed ↗ · Free PDF ↗

Persistence, Safety and Pharmacokinetics of Vedolizumab After Switching to the Subcutaneous Route in a Prospective French National Cohort Study.

The study assessed persistence, safety, efficacy, and pharmacokinetics of vedolizumab after switching from intravenous (IV) to subcutaneous (SC) administration in a prospective French national cohort of ulcerative colitis (UC) and Crohn’s disease (CD) patients in remission. At Week 52, SC-vedolizumab persistence was reported for the cohort, with the analysis also characterizing pharmacokinetic behavior and safety after the route switch. Clinically, the findings inform real-world expectations for durability and tolerability of SC-vedolizumab following IV-to-SC conversion in IBD care.

Hupé M, Mathieu N, Amiot A et al. · Alimentary pharmacology & therapeutics · (2026) · View on PubMed ↗

Effectiveness of Adding GLP-1 Receptor Agonists to SGLT2 Inhibitor Therapy in Chronic Kidney Disease: A Population Based Study.

The study evaluated, in adults with chronic kidney disease (CKD), the effectiveness of adding a GLP-1 receptor agonist (GLP-1RA) to existing sodium-glucose co-transporter-2 inhibitor (SGLT2i) therapy using a retrospective population-based cohort from the TriNetX Global Collaborative Network. After propensity score matching, the combined-therapy group showed differences in kidney and cardiovascular outcomes compared with SGLT2i alone, supporting potential benefit of the add-on strategy. This provides real-world evidence to inform treatment sequencing decisions for CKD patients considering GLP-1RA escalation on top of SGLT2i.

Salim H, Qureshi S, Gulsin GS et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Plastic Stent-Based Management Versus Metal Stent Exposure for Lifelong Biliary Drainage in Unresectable Malignant Hilar Biliary Obstruction.

This retrospective causal-inference study compared plastic stent-based management versus metal stent exposure for intended lifelong biliary drainage in 608 patients with unresectable malignant hilar biliary obstruction (MHBO) undergoing initial endoscopic drainage at 22 Japanese tertiary centers (Jan 2020–Mar 2024). The analysis modeled self-expandable metal stent (SEMS) use as a time-varying exposure to estimate failure of lifelong drainage compared with plastic stents (PS). The results are clinically significant because they address which stent strategy best sustains biliary patency over the remaining course of disease in patients with prolonged survival from chemotherapy.

Masuda A, Kobayashi T, Takenaka M et al. · Endoscopy · (2026) · View on PubMed ↗ · Free PDF ↗

Impact of pediatric connective tissue diseases on olfactory and gustatory functions.

This case-control study assessed olfactory and gustatory function in 25 pediatric patients with connective tissue diseases versus 25 age-matched healthy controls. Olfaction was measured with Sniffin’ Sticks and Sniffin’ Kids tests, and taste was evaluated with the ODOFIN Taste Test, then related to disease clinical features. The findings are important because they quantify sensory dysfunction in pediatric connective tissue diseases and may support earlier recognition and symptom-directed care.

Celik S, Kilic O, Slipcevic B et al. · International journal of pediatric otorhinolaryngology · (2026) · View on PubMed ↗

Copper-Driven Epithelial Barrier Disruption: A Novel Mechanism of COPD Acute Exacerbations Mediated by the TNF-α/ATP7A Axis.

This study investigated the relationship between serum copper levels and acute exacerbations of COPD (AECOPD) using NHANES 2011–2012 cross-sectional data, a hospital case-control cohort (30 AECOPD vs 30 controls), and a one-year prospective follow-up, and then explored mechanisms in copper-manipulated COPD models. Higher copper levels were associated with more frequent exacerbations and earlier recurrence, and mechanistic experiments supported a copper-driven epithelial barrier disruption pathway mediated by the TNF-α/ATP7A axis. These results implicate copper homeostasis and ATP7A-linked inflammatory signaling as drivers of AECOPD and potential therapeutic targets.

Xiao X, Hao Y, Ding Z et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Scaling of an evidence-based intervention program in older people with diabetes and frailty in Latin America. Diabfrail-Latam clinical trial protocol.

This clinical trial protocol describes Diabfrail-Latam, a multimodal, scalable intervention for older adults with type 2 diabetes mellitus (T2DM) and frailty in Latin America. The program combines multicomponent physical exercise (based on VIVIFRAIL), nutritional education, and therapeutic target adjustments, using an international, multicenter, single-blind design with 1:1 randomization to intervention versus usual care. If validated, it will provide evidence-based guidance for implementing integrated diabetes–frailty care across Latin American settings.

Laosa O, Cano-Gutierrez CA, Sepulveda-Loyola W et al. · The Journal of frailty & aging · (2026) · View on PubMed ↗ · Free PDF ↗

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Infectious disease immunology and antiviral mechanisms

Zinc mediates the allosteric activation of Shiftless to suppress programmed -1 ribosomal frameshifting.

The study examined how the interferon-stimulated zinc finger protein Shiftless (SHFL) regulates programmed -1 ribosomal frameshifting (-1 PRF) across viral and cellular contexts. It found that SHFL orthologs broadly suppress -1 PRF in a conserved manner, and that inhibition requires zinc ions and zinc finger function, demonstrating zinc-mediated allosteric activation of SHFL. This mechanistic insight explains how SHFL restricts -1 PRF used by viruses like HIV-1 and SARS-CoV-2 and may guide antiviral strategy development.

He ST, Zheng Y, Ying R et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Autoantibodies neutralizing type I IFNs underlie ~5% of herpes simplex encephalitis in adults.

The study examined whether neutralizing autoantibodies against type I interferons (IFN-I) occur in Danish adults with herpes simplex encephalitis (HSE) and how they affect antiviral immunity. In 16 of 339 adults, serum (and in some cases cerebrospinal fluid) contained IgG-mediated neutralizing activity against IFN-I (0.1–10 ng/ml), and patient serum impaired exogenous IFN-I protection of fibroblasts from HSV-1 infection in vitro. These findings indicate that IFN-I autoimmunity explains ~5% of adult HSE and supports considering IFN-I autoantibody testing to guide targeted immunologic management.

Jensen JA, Skouboe MK, Gervais A et al. · The Journal of experimental medicine · (2026) · View on PubMed ↗

NS1-Induced PARP1 Phase Transitions Prolongs Host Transcriptional Pausing to Promote Influenza A Virus Replication.

This study examined how influenza A virus (IAV) nonstructural protein NS1 promotes viral replication by regulating host PARP1 phase behavior and transcriptional pausing. CRISPR screening identified PARP1 as a proviral factor, ATAC-seq showed NS1 drives PARP1-dependent promoter-proximal chromatin remodeling, and NS1 binding to PARP1’s helical domain induced hyper-condensed, gel-like PARP1 condensates that prolonged RNA polymerase II (Pol II) pausing by enriching pausing factors (e.g., SPT5-PLD). These mechanistic insights link viral NS1–PARP1 liquid/phase transitions to host transcriptional control, highlighting PARP1 as a potential antiviral target.

Ma S, Kang C, Liu X et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Sarbecoviruses Suppress Innate Immunity by Recruiting PPM1A to Modulate STAT2 and ORF9b Phosphorylation.

This study investigated how the Sarbecovirus accessory protein ORF9b suppresses innate immunity by recruiting the host phosphatase PPM1A to modulate STAT2 and ORF9b phosphorylation. It found that ORF9b consistently dampens antiviral signaling across Sarbecoviruses by engaging PPM1A, with PPM1A acting through dual regulatory effects on phosphorylation events. These mechanistic insights identify a conserved viral immune-evasion strategy that could be exploited for host-targeted or viral-protein–targeted antiviral therapies.

Xie L, Huang Z, Zhang Z et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Renal disease mechanisms and kidney injury

Compound Abrus cantoniensis Extract Alleviates AFB1-Induced Liver Injury by Regulating PI3K-AKT Pathway and Gut Microbiota/Butyrate Metabolism.

This study evaluated whether Abrus cantoniensis extract (ACCE) protects against aflatoxin B1 (AFB1)-induced liver injury in vivo and in vitro, and investigated underlying mechanisms using integrated transcriptomic, microbiomic, and metabolomic analyses. ACCE attenuated AFB1 hepatotoxicity by modulating the PI3K–AKT signaling pathway and improving gut microbiota/butyrate-related metabolism, reducing hepatic and intestinal damage in AFB1-exposed models. The work supports ACCE as a candidate hepatoprotective intervention and links PI3K–AKT and gut butyrate biology to AFB1 injury mitigation.

Hu H, Cheng M, Zheng S et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

SIRT5-Mediated Desuccinylation of ACAA2 Protects Against Calcium Oxalate-Induced Kidney Injury by Regulating Fatty Acid Oxidation to Suppress Mitochondrial Oxidative Injury and Ferroptosis.

The study investigated how SIRT5-mediated desuccinylation affects calcium oxalate (CaOx) crystal–induced kidney injury in renal tubular epithelial cells (RTECs) and in mouse models, using multi-omics (succinylomics, lipidomics, proteomics) to identify affected fatty acid oxidation (FAO) enzymes. SIRT5 was reduced in CaOx stones, and SIRT5 deficiency impaired FAO, increased polyunsaturated fatty acid accumulation and phospholipid remodeling, and promoted mitochondrial oxidative injury and ferroptosis. This work links SIRT5 desuccinylation of FAO enzymes to ferroptosis control, highlighting a potential molecular target to prevent nephrolithiasis-associated tubular damage.

Jiang Q, Dong C, Liu Y et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Inflammatory bowel disease and gut-immune therapies

Assembled Hyaluronic Acid Therapeutics for Targeting M1 Macrophages and Regulating Immune Homeostasis for Ulcerative Colitis Treatment.

This study developed an oral, drug-free self-assembling hyaluronic acid (HA) therapeutic for ulcerative colitis by targeting and attenuating hyperactivated M1 macrophages. Using HA conjugated to unsaturated fatty acids via dynamic covalent boronate–catechol ester bonds, the assembled formulation accumulated in inflamed colon and reduced M1-like activation to rebalance colonic immune homeostasis. The work suggests a non-biologic, macrophage-targeted platform that may improve efficacy while minimizing off-target effects in inflammatory bowel disease.

Wan J, Ma A, Zhang Y et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

A Gut-Brain Axis Underlying Succinate-Associated Compulsive-Like Behavior.

The study explored whether succinate is causally linked to compulsive-like behavior in mice using a gut microbiota–gut-brain framework and examining neural changes in glutamatergic neurons in the relevant brain region. Succinate exposure/association correlated with significant compulsive-like behaviors and disrupted glutamatergic neuronal function, extending prior observations that OCD patient fecal microbiota increased succinate in colonized mice. This suggests succinate may be a microbiota-derived metabolite that drives OCD-like phenotypes through glutamatergic circuitry, offering a potential biomarker or intervention target.

Li Y, Zhang YD, Wang W et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Integrating Genetics With Epidemiological Measurements Identifies Burden QTLs of Inflammatory Bowel Disease across 20 Countries.

The study integrated Global Burden of Disease (GBD) epidemiological data (1990–2021) with 1000 Genomes Project genotypes (2,621,978 SNPs; 2414 unrelated individuals) across 20 countries to identify burden quantitative trait loci (bQTLs) for inflammatory bowel disease (IBD). It identified 1074 IBD bQTLs, with 384 significantly associated with both age-standardized prevalence and incidence, and highlighted rs7633471 (chr3:30698616:C>A) as the strongest effect signal. These findings connect population-level genetic architecture to cross-country IBD burden heterogeneity, improving understanding of genetic drivers of disease epidemiology.

Sun C, Wei S, Tao J et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

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Biomaterials, drug delivery, and imaging/biomarkers

Cargo crosslinking nucleates AP-1 lattice formation.

The study used cryo-electron microscopy to determine how the human adaptor protein complex AP-1 binds a cargo containing tandem sorting motifs in vitro. A single cargo molecule bridged two neighboring AP-1 complexes, nucleating formation of an AP-1 lattice at 3.5–4.0 Å resolution. This provides a structural mechanism for how cargo directly promotes coat assembly, informing models of vesicle trafficking and cargo selection.

Deng H, Jia G, Yang Q et al. · Cell · (2026) · View on PubMed ↗

Non-invasive control of gene editing in vivo by photoswitchable Cas12f and focused ultrasound.

The study engineered compact photoswitchable Cas12f (psCas12f) proteins co-delivered with sgRNA in a single AAV particle and tested non-invasive, focused-ultrasound–controlled gene editing in vivo. Key findings were that psCas12f enables spatiotemporal control of CRISPR editing deep in tissue using external light/ultrasound activation while maintaining AAV co-delivery feasibility. This advances safer, location- and timing-restricted genome editing strategies compatible with clinical delivery constraints.

Song D, Malinao MG, Wu X et al. · Cell · (2026) · View on PubMed ↗

Cnidarian mechanosensory cells as ancestors of vertebrate hair cells: Molecular targeting of an ancient mechanotransduction complex.

The study investigated the evolutionary relationship between cnidarian nematocyte mechanosensory cells and vertebrate inner-ear hair cells by examining the ancient mechanotransduction complex and the roles of TMC1/TMC2-like components. The authors report that cnidarian nematocyte hair-bundle structures and molecular targeting implicate an evolutionarily conserved mechanotransduction machinery analogous to the vertebrate mechanoelectrical transduction complex (METC). This supports a conserved origin of METC channel function and provides a molecular framework for tracing how vertebrate hair-cell mechanosensation evolved.

Banday ZZ, Randich AM, Hulse RE et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Increasing Lipid Nanoparticle mRNA Copy Number Improves Transfection Potency.

The study investigated how modifying lipid nanoparticle (LNP) formulation via a two-step dialysis process affects mRNA transfection potency in LNP systems. Increasing LNP mRNA copy number improved transfection potency, with the work linking dialysis-driven changes (ionizable lipid charge state conversion and fusion at different ionic strengths) to altered complex/vesicle behavior. These findings provide a formulation lever to enhance mRNA delivery efficiency for RNA therapeutics using optimized LNP dialysis and higher payload loading.

Zhang Y, Leung J, Cheng J et al. · Advanced materials (Deerfield Beach, Fla.) · (2026) · View on PubMed ↗ · Free PDF ↗

Predicting Clinical Improvement in Chronic Low Back Pain Using Exercise-Induced IVIM Perfusion: Threshold Evaluation and Disability-Dependent Effects.

The study evaluated whether exercise-induced intravoxel incoherent motion (IVIM) MRI parameters (diffusion D and pseudodiffusion D*) can predict clinical improvement in chronic low back pain (LBP) and whether disability level modifies these thresholds in people with LBP. Key results showed that specific IVIM threshold values in D and D* after acute exercise could stratify individuals likely to improve versus not, with disability-dependent effects on predictive performance. This supports using post-exercise IVIM MRI as a noninvasive biomarker to personalize rehabilitation response prediction in chronic LBP.

Dupuis F, Berry DB, Havandjian L et al. · NMR in biomedicine · (2026) · View on PubMed ↗ · Free PDF ↗

Immune Checkpoint Inhibitor as a Fifth Component of Lipid Nanoparticles Enables Lymph Node-Targeting and Augments mRNA Vaccine Efficacy.

This study engineered mRNA lipid nanoparticles (LNPs) by incorporating a biphenyl-structured amphiphilic PDL1 inhibitor as a “fifth component” (using an ALC0315-based LNP platform) to enhance lymph node targeting and mRNA vaccine efficacy. The PDL1 inhibitor–incorporated LNPs increased lymph node delivery and augmented antigen-specific immune responses compared with conventional LNP formulations. The approach provides a modular strategy to improve therapeutic/vaccine performance by combining organ targeting with immune checkpoint modulation within the same nanoparticle.

Ha M, Kim J, Kim S et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Persistent Zn2+ Influx-Mediated Deacetylation of ANXA2 Regulates the “Zn2+-Autophagic Flux” and Alleviates Intervertebral Disc Degeneration.

This study investigated how persistent Zn2+ influx regulates autophagy and intervertebral disc degeneration (IVDD) by focusing on zinc transporter ZIP14 (SLC39A14) and annexin A2 (ANXA2) deacetylation at lysine 302 (K302). Integrating single-cell RNA-seq, mRNA-seq, and LC-MS identified ZIP14 as a key regulator, and mechanistic experiments showed Zn2+-driven ANXA2 K302 deacetylation controls a “Zn2+-autophagic flux” pathway that alleviates IVDD. The findings connect senescence-associated ion imbalance to autophagy regulation and nominate the ZIP14–ANXA2 axis as a therapeutic target for degenerative disc disease.

Jin Y, Chen Y, Xie Y et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

An Extracellular Pore‑Targeting Peptide Defines a Designable Allosteric Site in TRPV2.

This study developed and characterized Depiv2, an extracellular pore-targeting peptidic inhibitor of the ion channel TRPV2, using structure-guided design and biophysical electrophysiology. Cryo-EM showed Depiv2 binding to the TRPV2 extracellular pore domain remodels the pore and stabilizes a closed, non-conductive state, and patch-clamp recordings demonstrated nanomolar potency with subtype selectivity by reducing open probability and single-channel conductance. These results establish a designable allosteric site in TRPV2’s extracellular pore and provide a rational framework for selective TRPV2 modulation.

Zhu A, Wang H, Wang J et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

In Situ Photo‑Crosslinked Functional Bilayer Hydrogel Modulates Local Microenvironment and Remyelination After Optic Nerve Injury.

The study developed an in situ photo-crosslinked functional bilayer hydrogel (GO/GI@MPDA-Cle) for optic nerve injury repair, using an outer layer for optic nerve sheath sealing and an inner layer delivering drug-loaded nanoparticles (MPDA-Cle) to modulate the local microenvironment and support remyelination. The hydrogel was designed to provide stable adhesion and sustained local nanoparticle release, aiming to improve remyelination and functional recovery after optic nerve injury. This platform suggests a biomaterial strategy to overcome limitations of current therapies by simultaneously stabilizing the injury site and actively shaping the remyelination microenvironment.

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

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Public health epidemiology and burden of disease

Postpandemic Trends in Pediatric Respiratory Virus Hospitalizations: A Multicenter Study, 2019-2025.

This multicenter retrospective study evaluated postpandemic trends in pediatric hospitalizations for respiratory viruses (including RSV and influenza) across 16 hospitals in Italy from 2019–2025, with particular attention to the 2024–2025 RSV season after nirsevimab immunoprophylaxis implementation. The key finding was that pediatric respiratory virus hospitalization patterns showed marked temporal variability after the COVID-19 pandemic, with RSV season dynamics in 2024–2025 occurring in the context of nirsevimab use. Clinically, the results help interpret how RSV immunoprophylaxis may influence real-world hospitalization burden and guide future pediatric infection prevention planning.

Attaianese F, Campani S, Trapani S et al. · Influenza and other respiratory viruses · (2026) · View on PubMed ↗

Global burden of cancer attributable to infections in 2024: a worldwide incidence analysis.

This worldwide incidence analysis estimated the global cancer burden attributable to infections in 2024 by calculating population-attributable fractions (PAFs), absolute case numbers, and age-standardized incidence rates using GLOBOCAN Cancer Today data. It quantified attributable cancer incidence for 12 IARC Group 1 carcinogenic infectious agents, providing a comprehensive global snapshot of infection-related cancer risk. The significance is public-health oriented: it identifies where prevention of specific infectious agents could yield measurable reductions in cancer incidence.

Rumgay H, Georges D, Huang Y et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Global burden of venous thromboembolism: incidence and outcome estimates of deep-vein thrombosis and pulmonary embolism.

This multinational review estimated the global incidence and outcomes of venous thromboembolism (VTE), focusing on deep-vein thrombosis and pulmonary embolism, using available epidemiologic data from 2012–2016. The authors found that reliable data were available for only a limited set of countries (mainly Northern America, Western Europe, and Oceania) with notable regional differences. The work is scientifically important because it quantifies the worldwide VTE burden while highlighting major geographic gaps needed to improve prevention, risk stratification, and resource allocation.

Bikdeli B, Rashedi S, Pfeferman M et al. · Nature reviews. Cardiology · (2026) · View on PubMed ↗

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