PubMed Trending Research Digest — October 22, 2026
A curated digest of 93 trending PubMed articles, automatically categorised and summarised across 15 research areas.
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PubMed Trending Research Digest — October 22, 2026
Automated digest · 93 articles · 15 research areas · October 22, 2026
Overview
This week’s papers cluster around a few big momentum areas: (1) immunotherapy and immune modulation in cancer (notably CAR T engineering, epigenetic strategies to restore immune recognition, and immunosuppressive tumor microenvironments), and (2) mechanistic neurobiology linking immune signaling, protein/iron/mitochondrial dysregulation, and circuit-level control to neurodegenerative disease and recovery. Across these, a recurring theme is moving from descriptive biomarkers to actionable pathways—whether that’s IL-10–enhanced FAP CAR T to reduce fibrosis, CXCL16/CX3CR1-driven CD8+ neurodegeneration in organoids, or LRRK2/ABCA1/lysosome–trafficking axes that connect cellular stress to ferroptosis or cholesterol overload.
A second dominant thread is translational measurement and delivery: multiple studies develop or validate tools to predict risk and guide care (e.g., interpretable brain-metastasis models, proteomic signatures for AF/ALS, plasma p-tau217 interpretation, and radiographic RALE scoring), while others push therapeutic delivery platforms forward (dual-AAV reconstitution for cell-type targeting, programmable RNA editing via engineered AGO2/ALTER, compact ADAR-based “adaptamers,” and improved genome-editing efficiency by transient ATM inhibition). In parallel, clinical and real-world evidence continues to refine how interventions are deployed—ranging from EIT-guided ventilation to de-escalation strategies after PD-1–induced complete response in dMMR/MSI-H colorectal cancer.
Finally, infectious disease and host–pathogen interactions remain active, with work spanning viral immune evasion mechanisms (Zika NS5–STAT2), receptor-structure insights for viral entry (BVDV E2–CD46), and surveillance approaches that connect genomics to future risk (AMR Salmonella across food chains; zoonotic protozoa sentinel monitoring). Together, the digest reflects a field increasingly focused on mechanistic specificity—linking molecular interactions to system-level outcomes—and on building practical tools that can be validated in larger cohorts and clinical workflows.
Cancer immunotherapy (CAR T, bispecifics, immune modulation)
Epigenetic modulation of NKG2D ligands enhances NKG2D-CAR T cell efficacy in neuroblastoma.
This study evaluated whether epigenetic modulation can enhance neuroblastoma (NB) susceptibility to NKG2D-CAR T cells by increasing expression of NKG2D ligands (NKG2DL). The authors focused on the immune-evading mechanism whereby NB downregulates NKG2DL and tested epigenetic strategies to restore ligand expression, thereby improving CAR T efficacy (as indicated by the abstract’s rationale and objective). The clinical significance is that combining epigenetic therapies with NKG2D-CAR T cells could overcome tumor immune evasion and improve outcomes in high-risk pediatric NB.
Navarro-Zapata A, De Santisteban MO, Regojo-Zapata RM et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Nanotherapeutic macrophage reprogramming through immunometabolic and microbial modulation for sepsis treatment.
This study developed a glutathione-responsive nanotherapeutic platform that delivers the STING inhibitor 4-octyl itaconate and the DHODH inhibitor EA6 to reprogram macrophage immunometabolism and microbial-associated signaling for sepsis treatment, using integrated transcriptomic, metabolomic, and metagenomic analyses. It found that combined immunometabolic and microbial modulation reprograms macrophages toward a therapeutic state, improving the sepsis-relevant immune/metabolic environment. The work suggests a multi-target nanomedicine strategy that simultaneously addresses immune dysfunction and metabolic failure in sepsis.
Lu X, Wang W, Zhang B et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗
Bispecific antibodies in NSCLC: immune reengineering to neutralize adaptive tumor resistance.
This review article examined how bispecific antibodies (BsAbs) can reengineer immune responses in non-small cell lung cancer (NSCLC) to counter adaptive tumor resistance. It synthesizes evidence that BsAbs—through engineered dual targeting and immune-activation mechanisms—may outperform sequential single-agent strategies against heterogeneous resistance pathways. The work is significant for guiding rational BsAb design and selection of targets to improve durability of immunotherapy in NSCLC.
Li Z, Wang H, Diao M et al. · Trends in cancer · (2026) · View on PubMed ↗
FAP-targeting CAR T cells with constitutive IL-10 expression reduce kidney fibrosis in mice.
The study evaluated FAP-targeting CAR T cells engineered to constitutively express IL-10 in a mouse model of kidney fibrosis. The key finding was that IL-10–expressing FAP CAR T cells reduced kidney fibrosis compared with control CAR T approaches. This supports the scientific rationale that combining tumor/stromal targeting (FAP CAR) with anti-fibrotic immunomodulation (constitutive IL-10) can mitigate fibrotic remodeling in vivo.
Jardin BD, Liu F, Li L et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗
Cancer microenvironment & stromal biology
The Characteristics of Tumor Microenvironment by the Single Cell Profile in Endometrial Cancer of no Specific Molecular Profile (NSMP) Subtype.
This multi-omics study investigated the tumor microenvironment (TME) in endometrial cancer with no specific molecular profile (NSMP) subtype using single-nucleus RNA sequencing, spatial transcriptomics, and multiplex immunohistochemistry. The key finding was reduced immune infiltration with increased immune-suppressive populations, including SPP1+ macrophages and regulatory T cells (Tregs), along with more epithelial clusters showing high stemness scores in tumors collected before recurrence. Scientifically, it identifies TME and stemness-associated features that may help explain relapse risk in NSMP endometrial cancer and guide future biomarker or therapeutic strategies.
Yuan X, Zhai Z, Jing C et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗
P4HA1⁺ collagen-modifying fibroblasts are associated with pro-tumor niches and therapeutic vulnerabilities in colorectal cancer.
This study characterized colorectal cancer cancer-associated fibroblast (CAF) heterogeneity, focusing on P4HA1+ collagen-modifying fibroblasts, using single-cell RNA sequencing, spatial transcriptomics, and bulk transcriptomic integration. P4HA1+ CAFs were associated with pro-tumor spatial niches and displayed therapeutic vulnerabilities distinct from other CAF subsets. These findings nominate P4HA1+ fibroblasts as both a mechanistic niche marker and a potential target to disrupt tumor-promoting microenvironments in colorectal cancer.
Gui K, Chen Y, Du Q et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Neutrophil-epithelial niches arrest B-cell maturation in dysfunctional tertiary lymphoid structures of gastric cancer neoadjuvant immunochemotherapy.
In gastric cancer treated with neoadjuvant immunochemotherapy, this study integrated spatial transcriptomics, matched single-cell RNA-seq, multiplex tissue imaging, in vitro perturbations, and spatial proteomics (plus external cohorts >1100 patients) to define determinants of tertiary lymphoid structure (TLS) function. It identified neutrophil-epithelial niches that arrest B-cell maturation within dysfunctional TLS, disrupting germinal-center and plasma-cell trajectories associated with poor immune ecology. This mechanistic map is clinically significant because it links a specific microenvironmental niche to TLS failure and may guide interventions to restore effective anti-tumor immunity.
Wei C, Fu Q, Wei H et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗
Cancer genomics, resistance & therapeutic vulnerabilities
Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.
This review article synthesized evidence that ribosome biogenesis and selective translational control create oncogenic vulnerabilities in hematologic malignancies. It highlights how oncogenic signaling pathways such as MYC and PI3K/AKT/mTOR (and tyrosine kinase fusions) reprogram translation machinery toward selective synthesis of pro-survival, proliferative, and stemness proteins. The scientific significance is that it frames translation/ribosome pathways as actionable targets for therapeutic vulnerability exploitation in blood cancers.
Coelho-Silva JL, Machado-Neto JA · Molecular cancer · (2026) · View on PubMed ↗ · Free PDF ↗
Metabolic plasticity underlies ferroptosis resistance driven by mutant p53 in pancreatic ductal adenocarcinoma.
This study examined whether mutant p53 alters ferroptosis susceptibility in pancreatic ductal adenocarcinoma using isogenic pancreatic cancer cell models generated by CRISPR-Cas9 TP53 knockout and transient mutant p53 expression. Mutant p53 conferred ferroptosis resistance through metabolic plasticity that rewired cellular pathways to limit lipid peroxidation and ferroptotic execution. The results suggest mutant p53–dependent metabolic programs could be exploited to predict or overcome ferroptosis resistance in TP53-mutant PDAC.
Celesia A, Piccoli F, Wang T et al. · Molecular cancer · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗
Lineage plasticity-driven immunometabolic state transitions in advanced prostate cancer: biomarkers and therapeutic stratification.
This review studied how lineage plasticity and immunometabolic remodeling drive treatment resistance in advanced prostate cancer, integrating metastatic biopsies, longitudinal sampling, single-cell and spatial analyses for biomarker and therapeutic stratification. It found that androgen receptor (AR) pathway inhibition, chemotherapy, DNA-damage-directed therapy, and radioligand treatment select resistant clones while shifting lineage identity and metabolic/immune features, making AR-high, AR-low, double-negative, amphicrine, and treatment-emergent neuroendocrine phenotypes better modeled as evolving immunometabolic states. This is significant because it supports more dynamic biomarker frameworks and stratification strategies rather than treating these phenotypes as fixed histologies.
Wu H, Zhang W, Yan X et al. · Seminars in immunopathology · (2026) · View on PubMed ↗
Proteome-wide C-degron activity profiling connects conditional regulation of the CTLH E3 ligase complex to ribosome biogenesis.
This Molecular Cell study used a proteome-wide C-degron activity profiling approach to identify human protein substrates whose stability depends on C-terminal degron “capping,” linking conditional regulation to ribosome biogenesis. It characterized a leading candidate, ZMYND19, showing that its C-degron pathway is governed by the CTLH E3 ligase complex subunit Muskelin, and that TNF-α stimulation impairs CTLH-mediated degradation, with the abstract truncated before full mechanistic and phenotypic details. The significance is defining physiological C-degron substrates and connecting CTLH-dependent proteolysis to stress-responsive control of ribosome biogenesis.
Grant DW, Tan S, Ramage DE et al. · Molecular cell · (2026) · View on PubMed ↗ · Free PDF ↗
PSF3 recruits Polθ to stalled replication forks to promote DNA repair.
This study examined how the GINS complex subunit PSF3 recruits DNA polymerase theta (Polθ) to stalled replication forks in BRCA1/2-proficient and BRCA1/2-deficient tumor cells. PSF3 directly interacts with Polθ via Polθ recruitment to the PSF3 C-terminus, promoting fork restart, double-strand break end-joining repair after fork collapse, and lagging-strand gap filling in BRCA1/2-deficient contexts. These findings identify a PSF3–Polθ axis as a mechanistic driver of replication stress tolerance and tumor cell survival, with potential implications for targeting Polθ-mediated repair in BRCA1/2-defective cancers.
Vekariya U, Prather BL, Dunbrack RL et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Cancer biomarkers & risk prediction (imaging/proteomics/genomics)
Interpretable machine learning model for brain metastasis in breast cancer: a large-scale, multi-center study.
This study developed and validated an interpretable machine learning model to predict brain metastasis in breast cancer using a large retrospective, multi-center cohort including 186,351 patients from SEER, the National Cancer Database, and a Chinese cohort. The model identified high-risk patients for brain metastasis with stable performance across training and validation datasets. Clinically, an interpretable risk tool could improve early identification and stratification of breast cancer patients for surveillance and preventive interventions.
Yuan Q, Sha Y, Yu R et al. · Journal of translational medicine · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗
The landscape of gene loss and missense variation across the mammalian tree informs on gene essentiality.
This study developed two mammalian interspecies constraint metrics—GISMO (gene loss) and GISMO-mis (missense constraint)—across 462 mammalian species to infer gene essentiality. It found that GISMO and GISMO-mis strongly correlate with human loss-of-function, missense, and dosage constraint, while also identifying essential genes that were missed by prior approaches. The work is significant for improving the prioritization of essential genes in human genetics and for interpreting variant pathogenicity using evolutionary constraint.
Liao C, Ye R, Ivankovic F et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗
Association of Circulating Eosinophils With Systemic Immune Activation and Reduced Recurrence in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.
This study evaluated whether preoperative circulating eosinophil counts predict recurrence and immune activation in hormone receptor-positive/HER2-negative breast cancer. Using a multimodal discovery cohort (N=472) and a large propensity-score–weighted validation cohort (N=23,170), it assessed eosinophils as a noninvasive biomarker and tested additive predictive value alongside 21-gene recurrence scores (details truncated in the abstract). If validated, eosinophil count could provide a simple, blood-based tool to improve recurrence risk stratification in this common breast cancer subtype.
Li ZQ, Wu SY, Ge LP et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗
Neurodegeneration & neuroinflammation (Alzheimer’s, Parkinson’s, MS/NMOSD)
Direction-specific biomarker profiles and clinical significance of plasma p-tau217/amyloid PET discordance in cognitively normal adults.
This study analyzed cognitively normal adults from the Chinese Preclinical Alzheimer’s Disease Study (CPAS, n=594) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI, n=475) to characterize direction-specific plasma p-tau217 biomarker profiles relative to amyloid PET discordance. Using Centiloid-defined amyloid PET positivity (Centiloid ≥20) and PET-anchored, cohort-specific p-tau217 cutoffs with ≥0.90 specificity, the authors assessed cross-sectional relationships between discordant p-tau217 and amyloid PET groups. The results are clinically significant because they clarify the biological meaning of p-tau217/PET discordance in preclinical Alzheimer’s disease and can improve triage and interpretation of plasma-based amyloid testing.
Huang Y, Huang L, Cui L et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗
Capsaicin suppresses microglial inflammation through TRPV1-SSR4 interaction.
This work investigated how capsaicin modulates microglial inflammation and tested a mechanism involving TRPV1 and SSR4 protein-protein interaction. In the context of lipopolysaccharide (LPS)-induced neuroinflammation (as indicated by the methods description), capsaicin suppressed inflammatory microglial responses through TRPV1–SSR4 signaling. The study is significant because it links a defined receptor interaction (TRPV1–SSR4) to anti-inflammatory control in neuroinflammation, supporting translational strategies targeting microglial activation in neurodegenerative disease.
Hou Y, Wang S, Yang Y et al. · Translational neurodegeneration · (2026) · View on PubMed ↗ · Free PDF ↗
Aging-enhanced accumulation of fibroblasts excludes oligodendrocytes in demyelinated lesions.
This study examined how aging affects lesion cellular composition in a mouse model of central nervous system demyelination, focusing on fibroblast accumulation and oligodendrocyte exclusion. In young mice subjected to lysolecithin-induced demyelination, fibroblasts accumulated in spinal cord white matter lesions and were identified using immunofluorescence markers including PDGFRβ, collagen type 1α1, α-smooth muscle actin, periostin, and fibronectin. The findings are significant because they suggest fibroblast dysregulation may impair oligodendrocyte repair responses, with implications for age-dependent failure of remyelination.
Lozinski BM, Melchor GS, D’Mello C et al. · Journal of neuroinflammation · (2026) · View on PubMed ↗ · Free PDF ↗
Parkinson’s disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes.
This study investigated how LRRK2 mutations affect iron homeostasis, oxidative stress, and ferroptosis in human neurons and astrocytes, including models relevant to LRRK2-associated Parkinson’s disease. The authors found that LRRK2 mutation–driven dysregulation of iron handling promotes oxidative stress and ferroptotic cell death in these brain cell types. These findings support a mechanistic link between LRRK2-driven iron dyshomeostasis and ferroptosis as an early, potentially targetable pathway in Parkinson’s disease.
Mamais A, Batchelor RD, Chairmandurai A et al. · Molecular neurodegeneration · (2026) · View on PubMed ↗
Dysregulated cholesterol trafficking through ABCA1 drives neurodegeneration in Parkinson’s disease.
This study investigated the role of ATP-binding cassette transporter A1 (ABCA1) in Parkinson’s disease by examining postmortem substantia nigra tissue, a PD mouse model, and mechanistic effects of astrocytic ABCA1 on neuronal cholesterol handling. It found that ABCA1 is elevated in PD and that astrocytic ABCA1 drives excessive cholesterol efflux, leading to neuronal cholesterol overload, with neuronal ABCA1 localizing to lysosomes to facilitate cholesterol import and accumulation. This is clinically significant because it identifies ABCA1-mediated cholesterol trafficking as a mechanistic driver of neurodegeneration and a potential therapeutic target beyond cholesterol synthesis inhibition.
Ma FX, Zhao XX, Wang XX et al. · Nature neuroscience · (2026) · View on PubMed ↗
Genome-wide cross-trait analysis to compare genetic architecture between Parkinson’s disease and kidney-related traits.
This study performed genome-wide cross-trait analyses comparing Parkinson’s disease (PD) with five kidney-related traits using UK Biobank GWAS data in individuals of European ancestry. It found modest genome-wide genetic correlations (with a significant correlation for urinary potassium-to-creatinine ratio) but identified shared loci across 9 of 15 trait pairs using pleiotropy mapping, colocalization, and enrichment, with sex-combined and sex-stratified differences in how loci drive the traits. The work is significant because it clarifies the genetic architecture underlying epidemiologic links between kidney function and PD risk and helps prioritize shared biological mechanisms.
Chang L, Gawhary S, Maameri L et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
The EF1α promoter of cilta-cel drives a highly effective GZMK+ transcriptional program.
This study compared cilta-cel versus ide-cel CAR T cells in 87 multiple myeloma patients (50 cilta-cel, 37 ide-cel) using flow cytometry and single-cell multi-omics to determine how the cilta-cel EF1α promoter drives transcriptional programs. It found that the EF1α promoter in cilta-cel drives a highly effective GZMK+ transcriptional program associated with stronger CAR T cell expansion and persistence. These results support promoter choice as a determinant of CAR T cell efficacy and provide a mechanistic biomarker (GZMK program) for optimizing BCMA-directed therapies.
Herrera K, Mitra S, Sun Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Plasma Proteomic Signatures Predict Incident Amyotrophic Lateral Sclerosis: A Prospective Study Stratified by C9orf72 Expansion.
This prospective UK Biobank study quantified 2920 plasma proteins using the Olink Explore platform to predict incident amyotrophic lateral sclerosis (ALS), stratified by C9orf72 expansion status. Multivariable Cox models identified plasma proteomic signatures associated with future ALS onset, with predictive signals differing by C9orf72 expansion. These findings support plasma proteomics as a risk-stratification tool for preclinical ALS and suggest C9orf72-linked biology may shape early disease pathways.
Su WM, Duan QQ, Zhang N et al. · Journal of cachexia, sarcopenia and muscle · (2026) · View on PubMed ↗ · Free PDF ↗
Cerebrospinal fluid amyloid and neurodegeneration biomarkers in the diagnosis and prognosis of amyotrophic lateral sclerosis: a multicohort observational study.
In a multicohort observational study, 264 patients with ALS and 164 disease controls had baseline cerebrospinal fluid (CSF) biomarkers measured, including neurofilament light chain (NfL), amyloid-β peptides, phosphorylated tau (pTau181, pTau217), and GFAP. The study found that amyloid/tau and astrogliosis markers can complement NfL for diagnosis and prognosis, and that Alzheimer’s disease co-pathology influences ALS disease progression. These results suggest a multi-biomarker CSF panel may improve clinical stratification beyond NfL alone.
Obara K, Janelidze S, Ito D et al. · EBioMedicine · (2026) · View on PubMed ↗ · Free PDF ↗
More than just accuracy: A pathway-level framework for implementing blood and digital biomarkers for Alzheimer’s disease care.
This Neuron perspective proposed a pathway-level framework for implementing blood and digital biomarkers for Alzheimer’s disease care, focusing on how diagnostic accuracy translates into patient-centered outcomes. It argues that FDA-cleared/market-certified plasma tests and digital biomarkers should be evaluated by metrics such as diagnostic confidence, appropriate use of CSF/PET, time to diagnosis, and eligibility assessment for amyloid-targeting treatments, rather than accuracy alone. The significance is that it provides a practical blueprint for integrating biomarkers into clinical workflows to improve timely diagnosis and treatment access.
Perneczky R, Schöll M, Rauchmann BS et al. · Neuron · (2026) · View on PubMed ↗ · Free PDF ↗
Differential Trajectories of Brain Atrophy in Multiple Sclerosis, MOGAD, and AQP4 + NMOSD: The Role of Disease Activity in MOGAD.
This longitudinal imaging study compared brain atrophy trajectories across multiple sclerosis (MS), MOGAD, and AQP4-positive NMOSD, focusing on how disease activity relates to atrophy in MOGAD. It aimed to contrast global and regional atrophy patterns over time among these inflammatory demyelinating disorders and determine whether atrophy in MOGAD tracks disease course/activity (results truncated in the abstract). The work could clarify disease-specific neurodegeneration mechanisms and improve interpretation of progression biomarkers in MOGAD.
Cortese R, Bianchi A, de Mauro A et al. · Neurology · (2026) · View on PubMed ↗
CX3CL1 (fractalkine)-CX3CR1 interface drives CD8⁺ T cell-induced neurodegeneration in human brain organoids.
This PNAS study investigated how the CX3CL1 (fractalkine)–CX3CR1 interface mediates CD8+ T cell-induced neurodegeneration in human brain organoids. In human cortical organoids exposed to amyloid-β (Aβ), Aβ increased neuronal CX3CL1 expression, which recruited CX3CR1+ CD8+ T cells toward Aβ-treated organoids, linking this chemokine axis to immune-driven neurodegenerative stress (downstream findings truncated in the abstract). The results identify a specific immune–neuron signaling pathway that could be targeted to modulate T cell–mediated neurodegeneration in Alzheimer’s disease–related contexts.
Yang WS, Shin MS, Choe MS et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
ClC-7 links PIKfyve inhibition to Rab-dependent LRRK2 activity at lysosomes.
This study investigated how lysosomal perturbations communicate to leucine-rich repeat kinase 2 (LRRK2) signaling, focusing on the lysosomal lipid kinase PIKfyve and the chloride/proton antiporter ClC-7. It found that PIKfyve inhibition promotes LRRK2 recruitment and signaling at lysosomes through a pathway requiring ClC-7, which controls accumulation of multiple Rab GTPases on lysosomes, with Rab12 contributing substantially. These mechanistic links connect lysosomal lipid regulation to Rab-dependent LRRK2 activity, informing how cellular trafficking changes may drive Parkinson’s disease risk.
Clegg D, Bentley-DeSousa A, Roczniak-Ferguson A et al. · The Journal of cell biology · (2026) · View on PubMed ↗ · Free PDF ↗
Endothelial neo-antigen expression initiates CD8⁺ T cell-driven CNS vasculitis amplified by peripheral immune challenge.
The study developed a mouse model of primary CNS vasculitis using inducible, endothelial-biased neoantigen expression (brain endothelial ovalbumin, BrEndO) to examine how CD8+ T cells initiate and drive CNS vasculitis under different immune contexts. The key finding was that tamoxifen-induced ovalbumin expression in cerebral endothelial cells elicited a restrained endogenous CD8+ T cell response at the blood-brain barrier, whereas peripheral immune activation amplified disease severity. This provides mechanistic evidence that endothelial neo-antigen presentation can initiate CD8+ T cell-driven CNS vasculitis and that peripheral immune challenge can exacerbate it, informing model-based therapeutic targeting.
Schädlich IS, Nguyen DH, Thiem MW et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗
Neural circuits & behavior (learning, memory, sensorimotor)
From Genes to Neural Circuits: Genetic and Systems Mechanisms of Ethanol Sensitivity and Tolerance in Drosophila melanogaster.
This review studied genetic and systems mechanisms of ethanol sensitivity and tolerance in the fruit fly Drosophila melanogaster, synthesizing findings from behavioral assays, forward genetic screens, and neural-circuit analyses. The key finding is that conserved signaling pathways and defined neural circuits in Drosophila regulate ethanol-related behaviors such as sensitivity, tolerance, preference, and consumption. Scientifically, it highlights how Drosophila genetics can map molecular-to-circuit mechanisms relevant to alcohol use disorder biology.
Subedi A, Lee Y · BMB reports · (2026) · View on PubMed ↗
Comprehensive behavioral phenotyping of male Sulf1-deficient mice reveals reduced locomotor activity, altered forelimb gait, and reduced prepulse inhibition.
This study performed comprehensive behavioral phenotyping in male Sulf1-deficient (Sulf1 knockout) mice to define adult brain functions of the extracellular sulfatase Sulfatase 1 (Sulf1). Sulf1-deficient mice showed reduced locomotor activity, altered forelimb gait, and reduced prepulse inhibition compared with controls. These findings are scientifically important because they extend Sulf1’s role beyond learning/reward circuits to broader sensorimotor and behavioral regulation relevant to adult brain function.
Keino-Masu K, Chatzigiannis MM, Shoji H et al. · Molecular brain · (2026) · View on PubMed ↗ · Free PDF ↗
Two distinct projection pathways converge onto the same BLA neurons to contribute to fear memory retrieval.
This study examined neural circuitry for context-induced fear memory retrieval by testing whether projection pathways other than ventral hippocampus CA1 to basolateral amygdala (vCA1→BLA) contribute to retrieval. It found that two distinct projection pathways—specifically postrhinal cortex to BLA (POR→BLA) neurons and vCA1→BLA neurons—converge onto the same BLA neuron population to support fear memory retrieval. This is significant because it refines circuit-level targets for interventions aimed at preventing relapse in disorders such as PTSD.
Yang H, Xia T, Kuang S et al. · Molecular psychiatry · (2026) · View on PubMed ↗
Connexins are essential for the contribution of latent progenitors to healing after spinal cord injury.
This PNAS study tested whether connexins Cx26 and Cx43 are required for the contribution of latent ependymal progenitors to healing after spinal cord injury. Using specific genetic deletion approaches to disrupt connexin function, the authors found that connexins are essential for reactivation of the ependymal stem/progenitor niche and for effective post-injury healing (full phenotypes truncated in the abstract). The findings establish gap-junction signaling as a key regulator of regenerative progenitor responses after spinal cord injury.
Victoria Falco M, Fabbiani G, Prieto D et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Gene delivery & genome editing technologies
StitchR-based dual-AAV delivery strategies enable efficient transduction of defined neural cell populations.
This study developed four StitchR-based dual-AAV reconstitution strategies to enable efficient, targeted transduction of defined neural cell populations. By combining high-efficiency AAV serotypes with neuron- or glia-specific promoters, including an AAV11-hSyn-driven StitchR approach that achieved ≥94.44% specificity for local neurons and upstream projection neurons, the authors demonstrated improved targeting performance. The work is significant because it advances a practical gene-delivery platform for large-gene dual-AAV applications in neuroscience and gene therapy with cell-type specificity.
Luo N, Gao Y, Han Z et al. · Molecular brain · (2026) · View on PubMed ↗ · Free PDF ↗
Small variant calling in the era of long-read sequencing.
This review studied how small-variant calling methods have evolved for long-read sequencing across germline, de novo, somatic, and mosaic variant detection. It found that deep learning-based variant callers have increasingly replaced or complemented traditional approaches, and are now being integrated with alignment-, assembly-, and pangenome-based strategies to handle long-read error profiles and capture both DNA and RNA variants at different resolutions. The work is significant because it frames the current technical shift needed to accurately measure human genetic diversity and disease-relevant variation using long-read data.
Zheng Z, Sedlazeck FJ, Luo R · Nature reviews. Genetics · (2026) · View on PubMed ↗
Engineered human Argonaute 2 for targeted C-to-U RNA base editing.
This study engineered human Argonaute 2 (AGO2) as a programmable RNA targeting platform by fusing AGO2 to a C-to-U deaminase to create ALTER, tested using guide RNAs designed to remodel target RNA structure in human cells. It found that ALTER enables AGO-led targeted C-to-U RNA base editing with improved performance (reported on average 1.9-fold higher activity) and reduced nuclease activity, enhancing selectivity. This is clinically significant because using a human protein scaffold may reduce unintended effects seen with nonhuman RNA-editing systems and supports therapeutic translation of RNA base editing.
Lusi RF, Moncayo von Hase S, Model C et al. · Nature biotechnology · (2026) · View on PubMed ↗ · Free PDF ↗
Regulatable in vivo gene expression via adaptamers.
This Molecular Cell study developed “adaptamers,” a compact (<120 bp) RNA switch that couples small-molecule-responsive aptamers to endogenous ADAR-mediated RNA editing to regulate transgene expression in vivo. Ligand binding stabilizes a double-stranded RNA structure that recruits ADAR to convert a stop codon into a sense codon, restoring downstream protein translation, with the abstract truncated before reporting in vivo performance metrics. The significance is a potentially more translatable, reversible, and compact inducible gene control strategy for safer gene therapy applications.
Bryant J, Herron L, Doctor Y et al. · Molecular cell · (2026) · View on PubMed ↗
Transient ATM inhibition enhances knock-in efficiency in hematopoietic stem cells by attenuating the DNA damage response.
This study tested whether transient inhibition of ATM kinase enhances CRISPR/Cas9 knock-in efficiency in mouse hematopoietic stem cells (HSCs) using Cas9 RNP with AAV donor DNA. Transient ATM inhibition suppressed aberrant Cas9–AAV-induced ATM activation and downstream DNA damage response, reduced p53-dependent apoptosis, and increased survival and knock-in efficiency of edited HSCs. The work supports a practical genome-editing optimization strategy to improve therapeutic genome editing outcomes by mitigating DNA damage responses.
Natsagdorj ME, Hara H, Iida K et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Improving optogenetic control over Gi/o-coupled receptor signaling by optimized GIRK channel expression.
This study engineered optimized optogenetic constructs to improve control of Gi/o-coupled receptor signaling by coupling GIRK channel activity to light-activated Gi/o pathways. By creating expression cassettes that link GIRK subunit function to opsins (Opn4L/melanopsin, Opn1, parapinopsin, or Opn7b) and using the fast-activating GIRK1 F137S mutant, the authors enhanced selective Gi/o-mediated GIRK currents for more reliable optogenetic silencing. This advances the precision of optogenetic inhibition strategies by addressing GIRK channel availability as a key limiting factor.
Mücher B, Garrido-Charles A, Wietek J et al. · Science signaling · (2026) · View on PubMed ↗
Infectious disease & antiviral mechanisms
Whole-blood transcriptomic findings in emergency department patients with suspected cannabinoid hyperemesis syndrome: a pilot study.
This pilot study used genome-wide whole-blood RNA sequencing to compare transcriptomic profiles between 7 emergency department patients with suspected cannabinoid hyperemesis syndrome (CHS) and 7 matched controls. The authors identified differentially expressed genes and implicated dysregulated pathways relevant to CHS pathogenesis (with further analyses including digital isotype approaches, as described in the abstract). These findings provide preliminary, mechanism-oriented biomarkers and pathway targets for CHS that could be validated in larger cohorts.
Meltzer A, Cooper ZD, Heidish R et al. · Journal of cannabis research · (2026) · View on PubMed ↗ · Free PDF ↗
High-risk antimicrobial resistance genomic traits in multidrug-resistant Salmonella across China’s food chain: projections to 2050.
This study analyzed antimicrobial resistance (AMR) genomic traits in multidrug-resistant Salmonella enterica across China’s food chain using 2,536 MDR genomes from 15 provinces over 16 years, linking genomic surveillance to socioeconomic, climate, and health factors. It found that a machine-learning framework integrating genomic and risk assessment can identify high-risk AMR traits (clinically relevant, MDR, mobile) and that regression models relate trait prevalence to external drivers while projecting genomic trait prevalence to 2050. The findings are significant for guiding surveillance and intervention priorities to slow the future spread of MDR Salmonella.
Baker M, Lu X, Luo C et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Recovering anaerobic bacterial genomes in saliva, tumour and blood whole genome sequencing data from patients with prostate cancer.
This study aimed to recover anaerobic bacterial genomes from whole-genome sequencing data (including saliva, tumor, and blood) from patients in the PanProstate Cancer Group. It found that metagenomic assembly of non-human reads enables fine-scale microbial diversity and genome recovery across prostate cancer-associated clinical samples. This is scientifically significant because it improves access to microbial genomic features from standard clinical WGS datasets, supporting downstream causal hypotheses about microbiome contributions to prostate cancer.
Gihawi A, Bampalis A, Subramanian S et al. · NPJ biofilms and microbiomes · (2026) · View on PubMed ↗ · Free PDF ↗
Live imaging and interactome analysis of Zika and chikungunya viral RNAs via dual-action aptamer tag.
This study engineered dual-action Mango-II aptamer-tagged viral RNAs to enable live imaging and RNA interactome mapping of Zika and chikungunya viruses in live cells. It found that the aptamer tag supports high-resolution visualization of flavivirus RNA and replication-complex dynamics and enabled identification of >200 high-confidence host interactors of viral RNA. These results provide a platform for dissecting host–viral RNA interactions in real time, supporting antiviral target discovery for flaviviruses.
Jablunovsky A, Kropff BM, Narayanan A et al. · Nature communications · (2026) · View on PubMed ↗
Molecular survey of zoonotic protozoa in free-ranging marmosets (Callithrix penicillata) from Central Brazil: implications for One Health surveillance.
This molecular surveillance study assessed zoonotic protozoa in 232 free-ranging black-tufted marmosets (Callithrix penicillata) from central Brazil by quantitative PCR on liver samples collected from 2018–2023. It investigated Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Trypanosoma cruzi, but the abstract is truncated before providing prevalence results for each pathogen. Scientifically and for One Health, the findings support using adaptable NHPs as sentinel hosts to monitor transmission risk at the human–wildlife interface.
Melanie L, Dos Santos Pessoa VF, Sousa DER et al. · Parasitology international · (2026) · View on PubMed ↗ · Free PDF ↗
Structure of bovine viral diarrhea virus E2 glycoprotein in complex with CD46 reveals the molecular basis of virus-receptor recognition.
This structural biology study determined the crystal structure of bovine viral diarrhea virus (BVDV) E2 glycoprotein bound to the host receptor CD46 to define the molecular basis of virus–receptor recognition. The authors solved the BVDV-1 E2/CD46 complex at 3.1 Å resolution, showing that CD46 SCR1–2 domains engage E2 DII–DIV domains in an antiparallel orientation with interface interactions dominated by van der Waals contacts and limited hydrogen bonding. This provides a mechanistic template for understanding BVDV entry and can inform rational design of receptor-blocking antivirals or vaccines.
Duan Y, Lin S, Wang F et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Meta-analysis of 990 EBV genomes identifies EBER2 SNP7048 and its interaction with HLA-A*11:01 driving nasopharyngeal carcinoma risk.
This study analyzed 990 Epstein–Barr virus (EBV) genomes from Singapore, Hong Kong, and Guangdong/Guangxi (China) cohorts, integrating EBV whole-genome sequencing with matched host whole-exome sequencing to identify viral variants and host HLA interactions in nasopharyngeal carcinoma (NPC) risk. The meta-analysis identified a high-risk EBV strain signature involving the EBER2 SNP7048 and its interaction with the host HLA-A*11:01 allele. These results improve understanding of how specific EBV genetic variation and host immune genetics jointly shape NPC susceptibility, supporting more precise risk stratification and strain-focused epidemiology.
Wang CY, Yao F, Zhang X et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
A tunable immune-evasion function of Zika virus NS5 governs viral fitness and pathogenesis.
This study used multistep mutational scanning to map how Zika virus (ZIKV) nonstructural protein 5 (NS5) modulates type I interferon (IFN) signaling by controlling STAT2 degradation and viral RNA replication. It identified a single NS5 residue, L162, whose substitution uniquely abolishes STAT2 degradation while preserving intrinsic viral replication fitness. This provides a tunable, residue-level mechanism of immune evasion that links IFN antagonism to ZIKV pathogenesis, informing antiviral strategies that disrupt NS5–STAT2 immune escape.
Zhang Y, Zhang Y, Liu C et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Gut microbiota vesicle reprogramming by Ganoderma lucidum polysaccharide alleviates mycoplasmal pneumonia via the gut-lung axis.
This study investigated how the Ganoderma lucidum polysaccharide GLFP2 alleviates mycoplasmal pneumonia in mice by reprogramming gut microbiota-derived extracellular vesicles (GMEVs) along the gut–lung axis. Using targeted enzymatic fragmentation and multidimensional NMR, it resolved GLFP2 structure and identified β-(1→6)-linked galactosyl motifs as key features, and showed that oral GLFP2 reshaped gut microbiota and functionally reprogrammed GMEVs that could reproduce therapeutic effects. These findings suggest a microbiota-vesicle-mediated mechanism for polysaccharide-based anti-infective therapy and identify structural motifs that may be optimized for efficacy.
Zhang Z, Gong H, Zhang Z et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Vaccines & immunization strategies
Effectiveness of respiratory syncytial virus immunisation in practice.
This article reviewed real-world effectiveness of respiratory syncytial virus (RSV) immunization strategies across age groups, including infants, older adults, and adults at high risk. It reports that implementation is limited mainly by cost in higher-income settings, while real-world evidence shows high effectiveness and emerging benefits beyond respiratory outcomes (e.g., reduced cardiovascular events in older adults), though the abstract is truncated before detailing specific study results. The significance is that RSV prevention programs may deliver broader health gains and should be evaluated for impact on non-respiratory endpoints when planning immunization policy.
Groenendijk RW, Franck Z, Baral R et al. · The Lancet. Infectious diseases · (2026) · View on PubMed ↗
Jet-injected combinational adjuvants potentiate naked mRNA vaccines for protection against respiratory viral infections in mice.
The study tested clinically relevant adjuvants to enhance N1-methyl-pseudouridine-modified “naked” mRNA vaccines delivered by liquid jet injection into mouse skin for protection against respiratory viral infections. The key finding was that most screened adjuvants had little or inhibitory effects on humoral and cellular responses, but a specific adjuvant combination (identified in the truncated abstract) potentiated the jet-injected naked mRNA vaccine’s protective immunity. This suggests a potential strategy to improve the efficacy of less reactogenic, non-LNP mRNA vaccination approaches for respiratory viral disease.
Qiao N, Ishikawa J, Yasui F et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗
Cardiovascular disease & cardiac remodeling
Atorvastatin protects cardiomyocytes from doxorubicin toxicity by modulating YAP/TAZ signaling.
This experimental study investigated whether atorvastatin protects cardiomyocytes from doxorubicin-induced toxicity by modulating Hippo pathway signaling via YAP/TAZ. The key finding was that atorvastatin attenuated doxorubicin cardiotoxic effects through effects on YAP/TAZ signaling, linking a survival/apoptosis and mitochondrial-quality-control pathway to cardioprotection. Clinically, it suggests a potential mechanistic basis for repurposing atorvastatin to mitigate anthracycline cardiotoxicity.
Lim H, Jin S, Lee CJ et al. · BMB reports · (2026) · View on PubMed ↗
Aerobic exercise modulates macrophage polarization and promotes cardiac recovery after myocardial infarction in rats.
This study tested whether aerobic exercise improves cardiac recovery after myocardial infarction (MI) in rats and whether it does so by altering macrophage polarization. Using a left anterior descending coronary artery ligation model for chronic post-infarction remodeling and an 8-week aerobic training regimen after a recovery period, the authors assessed cardiac function/injury and macrophage polarization states. The scientific significance is that it links exercise-mediated immunomodulation (macrophage polarization) to improved post-MI cardiac outcomes, supporting exercise as a mechanistically informed adjunct therapy.
Zhu M, Zhou B, Peng J et al. · Journal of cardiothoracic surgery · (2026) · View on PubMed ↗ · Free PDF ↗
Total and beverage-specific alcohol use at mid-life and all-cause and cause-specific mortality: a prospective cohort study.
This prospective cohort study assessed whether insulin resistance–related indices (e.g., TyG, TyG-BMI, METS-IR, TG/HDL-C, eGDR, and CTI) predict recurrence after catheter ablation in patients with nonvalvular atrial fibrillation. Higher insulin resistance surrogate measures were associated with increased risk of AF recurrence after ablation, with CTI highlighted as a novel marker. The findings suggest routine biomarker-derived insulin resistance indices may help refine post-ablation risk stratification and follow-up intensity.
Li Z, Tan B, Desjardins C et al. · Nutrition journal · (2026) · View on PubMed ↗ · Free PDF ↗
Integrated proteomics and machine learning reveal AHNAK as a discriminative biomarker of atrial fibrillation in heart failure.
This study integrated label-free quantitative plasma proteomics with machine learning feature selection to identify biomarkers distinguishing atrial fibrillation (AF) in patients with heart failure. AHNAK emerged as a discriminative plasma protein biomarker for AF in this hospitalized acute decompensated HF cohort. If validated, AHNAK could enable earlier, blood-based AF detection in heart failure patients to guide timely management.
Zhu W, Gu Z, Huang Y et al. · BMC medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Plasma proteomic signatures of subclinical atherosclerosis progression for cardiovascular risk stratification: A cohort study.
This cohort study developed plasma protein risk scores (ProtRSs) to predict progression of subclinical atherosclerosis (SA) and to improve cardiovascular risk stratification. Using repeated SA assessments over 6 years in 903 individuals and selecting biomarkers from a 117-protein panel via LASSO regression, the authors constructed ProtRSs for SA progression and evaluated their incremental value for ASCVD risk prediction. The work supports proteomics-based risk scoring as a route to identify individuals with progressing SA who may benefit from earlier intervention.
Huang Y, Gao R, Li J et al. · PLoS medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Metabolic disease & obesity therapeutics
Oral Versus Injectable Incretin-Based Anti-Obesity Therapies: An Integrated Computational and Evidence-Based Comparison of Orforglipron, Semaglutide, and Tirzepatide.
This integrated computational and evidence-based comparison studied the weight-loss efficacy of incretin-based anti-obesity therapies—oral orforglipron versus injectable semaglutide and tirzepatide—using clinical trial evidence including the head-to-head SURMOUNT-5 trial plus network/pathway and multi-criteria decision analyses. The key finding was that tirzepatide produced significantly greater weight loss than semaglutide under the integrated, randomized-evidence framework, while orforglipron was evaluated comparatively using molecular descriptor and drug-target-disease network approaches. Scientifically and clinically, the work supports comparative effectiveness interpretation across oral and injectable GLP-1–based therapies for obesity by combining trial data with mechanistic computational analyses.
Sahu L, Nayak L, Tripathy A et al. · Omics : a journal of integrative biology · (2026) · View on PubMed ↗
Small-molecule modulation of VDAC enhances glucose-stimulated insulin secretion by promoting ATP flux.
This Cell Chemical Biology study investigated the small-molecule insulin secretagogue NPD976 and its structural analog DPEU (N-[2-(3,4-dimethoxyphenyl)ethyl]urea) in mouse, rat, and human β cells. It found that DPEU enhances glucose-stimulated insulin secretion, localizes to mitochondria, and directly interacts with the voltage-dependent anion channel (VDAC) to promote ATP flux, with the abstract truncated before detailing downstream mechanistic steps. Scientifically, it identifies VDAC modulation as a strategy to boost glucose-responsive insulin release, supporting DPEU/NPD976 as potential leads for diabetes therapeutics.
Matsunaga K, Honda K, Ali M et al. · Cell chemical biology · (2026) · View on PubMed ↗
Renal disease & kidney injury/fibrosis
Finerenone versus Steroidal MRAs in Type 2 Diabetes and Chronic Kidney Disease without Prior Heart Failure.
This retrospective multi-center observational study used the TriNetX platform to compare finerenone versus steroidal mineralocorticoid receptor antagonists (spironolactone and eplerenone) in adults with type 2 diabetes and chronic kidney disease without prior heart failure. The key finding was the comparative real-world effectiveness and safety of finerenone relative to steroidal MRAs among patients who initiated MRAs after receiving an SGLT2 inhibitor as first-line therapy. Clinically, it provides evidence to inform MRA selection in T2D/CKD patients at risk for heart failure and death when prior heart failure is absent.
Kishimori T, Kato T, Iwasaki Y et al. · ESC heart failure · (2026) · View on PubMed ↗ · Free PDF ↗
HAMA microneedles patch loaded with muscle-targeting engineered apoptotic vesicles and attenuating sarcopenia by regulating mitochondrial homeostasis.
This study evaluated HAMA microneedle patches delivering muscle-targeting engineered apoptotic vesicles (ApoVs) to treat sarcopenia by regulating mitochondrial homeostasis. The treatment attenuated sarcopenia and improved mitochondrial function, consistent with ApoV-mediated modulation of oxidative stress and mitochondrial homeostasis in skeletal muscle. This supports a translational delivery strategy (HAMA microneedles + engineered MSC-derived ApoVs) for targeting mitochondrial dysfunction in age-related muscle loss.
Zhang J, Lin Z, Ding H et al. · Journal of nanobiotechnology · (2026) · View on PubMed ↗ · Free PDF ↗
Periplocin targets low density lipoprotein receptor-related protein 4 and protects against osteoarthritis.
This study investigated the natural product periplocin (a cardiotonic steroid from Periploca forrestii) in osteoarthritis by testing its effects on chondrocyte metabolism and cartilage degeneration. Periplocin targeted low density lipoprotein receptor-related protein 4 (LRP4) and promoted chondrocyte anabolism while protecting against osteoarthritis-related changes. Mechanistically, LRP4 is positioned as a therapeutic target for periplocin-based interventions in OA.
Liu J, Fu Q, Li C et al. · Cellular & molecular biology letters · (2026) · View on PubMed ↗ · Free PDF ↗
AI-Guided Identification of a Covalent SMAD3 Regulatory Mechanism of Celastrol in Diabetic Kidney Disease.
Using an AI-guided target-prioritization workflow (Uni-Mol deep learning) followed by biochemical validation, this study investigated celastrol as a therapeutic candidate in diabetic kidney disease (DKD) with a focus on transforming growth factor-β (TGF-β)/SMAD3 signaling. Activity-based protein profiling and a competitive iodoacetamide-based probe assay demonstrated that celastrol covalently targets SMAD3. Identifying SMAD3 as a direct covalent target provides a mechanistic basis for celastrol-like strategies to suppress renal fibrogenesis in DKD.
Chen P, Deng H, Wang W et al. · Pharmacological research · (2026) · View on PubMed ↗ · Free PDF ↗
CO-mediated restoration of mitochondrial redox homeostasis contributes to alleviating multiple programmed cell deaths in hepatic I/R injury.
This study examined whether carbon monoxide (CO) delivered to injured liver tissue can restore mitochondrial redox homeostasis and mitigate multiple programmed cell death pathways during hepatic ischemia–reperfusion injury (HIRI). Using a hyaluronic acid-modified, ROS-responsive nanoformulation (CPs@HA) for controllable CO delivery, the authors showed suppression of mitochondrial ROS burst and activation of the AMPK–SIRT1–PGC-1α axis with Ca2+ balance restoration, reducing ferroptosis, cuproptosis, and disulfidptosis occurring in parallel during HIRI. The work suggests a mechanistically grounded therapeutic strategy for HIRI by targeting mitochondrial dysfunction and broad cell-death programs.
Li J, Xu M, Zhou Q et al. · Redox biology · (2026) · View on PubMed ↗ · Free PDF ↗
Autoimmunity & inflammatory bowel disease (incl. Crohn’s/UC/PsA)
Epithelial NF-κB shapes protective Treg cell responses to restrain intestinal inflammation.
This study examined how intestinal epithelial NF-κB activity shapes regulatory T cell (Treg) responses in human ulcerative colitis (UC) biopsies and mouse colitis models using single-cell RNA sequencing and secretome analysis. It found that an NF-κB-driven epithelial pro-inflammatory secretome is paradoxically required for recovery and restrains unrestrained inflammation via CCL22-dependent Treg programming. These findings identify epithelial NF-κB/CCL22 signaling as a mechanistic target to promote resolution of intestinal inflammation rather than simply blocking inflammation.
Barleben L, Schneegans AJ, Uyar B et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Single-cell analysis reveals CXCL16+ dendritic cells and clonally expanded GZMK+ CD4 T cells driving joint inflammation in psoriatic arthritis.
Using multimodal single-cell sequencing of matched peripheral blood and synovial fluid from 6 psoriatic arthritis (PsA) patients (plus 1 RA patient and 6 healthy controls), this study identified immune cell programs driving joint inflammation. It found CXCL16+ dendritic cells and clonally expanded GZMK+ CD4 T cells enriched in synovial fluid, indicating a tissue-specific activated and clonally proliferating T-cell compartment. These findings clarify cellular drivers of PsA inflammation and nominate CXCL16+ DCs and GZMK+ CD4 T-cell clones as potential mechanistic targets.
Mullins BJ, Shwetar J, Herrera A et al. · Arthritis & rheumatology (Hoboken, N.J.) · (2026) · View on PubMed ↗
Long-lived plasma cells in rheumatic and selected antibody-mediated autoimmune diseases: biology, evidence, and therapeutic opportunities.
This review synthesized evidence on long-lived plasma cells (LLPCs) in rheumatic and other antibody-mediated autoimmune diseases and discussed therapeutic opportunities to target this compartment. It highlights that LLPC longevity is often inferred indirectly (e.g., kinetics, transcriptional state, or treatment resistance) rather than confirmed by human lineage tracing, and that no single surface phenotype (including CD19 loss) definitively identifies LLPCs. The significance is that better mechanistic understanding of LLPC biology could improve durable control of pathogenic autoantibodies when conventional immunosuppression or B-cell depletion fails.
Guo H, Xiang W, Zeng L et al. · Autoimmunity reviews · (2026) · View on PubMed ↗
Beyond the pelvis: redefining endometriosis as a systemic inflammatory disorder. A systematic review and meta-analysis.
This systematic review and meta-analysis evaluated whether endometriosis should be redefined as a systemic inflammatory disorder by assessing associations with autoimmune diseases, allergic conditions, chronic pain syndromes, and endocrine disorders. It used a comprehensive literature search and meta-analytic synthesis to quantify these cross-system comorbidities, but the abstract text provided is truncated before reporting pooled effect estimates. The clinical significance is reframing endometriosis as systemic immuno-inflammatory disease to better inform risk stratification, screening, and holistic management beyond pelvic pathology.
Zheng SH, Gao SJ, Cai JJ et al. · Autoimmunity reviews · (2026) · View on PubMed ↗
Gut-derived glucagon-like peptides attenuate T cell-induced intestinal injury.
This Cell Reports Medicine study tested whether endogenous gut-derived GLP-1R and GLP-2R signaling protects against T cell-induced intestinal injury in mice. It found that T cell activation–induced gut injury was increased in Glp1r-/- and Glp2r-/- mice and in mice with selective loss of intestinal proglucagon, indicating that GLP-1R/GLP-2R signaling is essential for protection. The significance is that enhancing endogenous GLP-1/GLP-2 pathways could be a therapeutic approach for T cell-mediated enteropathy.
Koehler JA, Baggio LL, Cao X et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗
CD47 fuels intestinal fibrosis by inducing fibroblast phagocytic evasion and represents a therapeutic target.
The study investigated how CD47-expressing fibroblasts and macrophage SIRPα signaling contribute to intestinal fibrosis in Crohn’s disease using single-cell and spatial transcriptomics. It found fibrosis-associated CD47hi fibroblasts coupled to SIRPAhi macrophages in fibrotic regions, with IL-1β mediating a profibrotic niche that promotes fibroblast phagocytic evasion, and that genetic disruption of fibroblast Cd47 or macrophage Sirpa enhanced fibroblast clearance. These findings identify the CD47–SIRPα axis as a therapeutic target to reduce intestinal fibrosis by restoring phagocytic clearance.
Zhao X, Wang Y, Wang D et al. · Cell reports. Medicine · (2026) · View on PubMed ↗ · Free PDF ↗
A genetically regulated SKAP2 switch modulates human T lymphocyte adhesion and migration.
This study examined the functional consequences of genetically regulated SKAP2 expression in human T lymphocytes, including analyses of T cells from individuals with allelic variants or engineered modulation of endogenous SKAP2 levels. SKAP2 promoted T cell adhesion while restraining migration in a nonredundant manner with SKAP1, indicating distinct roles for the SKAP2 and SKAP1 adapters in immune cell trafficking. These results connect a Crohn’s disease risk-associated regulatory change in SKAP2 to specific T cell behaviors relevant to inflammatory disease pathogenesis.
Spinella MC, Gualdrini F, Leoni C et al. · The Journal of experimental medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Reproductive biology & developmental biology
Spatial multi-omic atlas profiles early organogenesis of a Carnegie stage 12 human embryo.
This study profiled a Carnegie stage 12 (CS12) human embryo using spatial transcriptomics and spatial metabolomics co-registered to embryonic anatomy. It found 17 spatially resolved cell populations spanning major organ primordia, including spatially separable hepatocyte- and cholangiocyte-lineage priming programs. The results are scientifically significant because they provide an integrated spatial multi-omic map of early human organogenesis that can guide mechanistic studies of developmental lineage specification.
Wang LJ, Yang H, Song J et al. · Nature cell biology · (2026) · View on PubMed ↗ · Free PDF ↗
Single-oocyte proteome-transcriptome co-profiling reveals a role of dysregulated lactate metabolism in oocyte aging.
This study used single-cell proteome/transcriptome co-profiling of GV/MII-aged oocytes from mice and humans to define molecular drivers of oocyte aging, focusing on how proteomic changes relate to RNA expression. It found species- and stage-specific dysregulation with uncoupled proteomic versus transcriptomic alterations, indicating that aged-oocyte proteome changes are not primarily driven by RNA levels. This advances mechanistic understanding of female infertility by highlighting proteome-level dysregulation (including lactate metabolism) as a key feature of oocyte aging.
Cao L, Wu H, Jiang Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
RNF220 safeguards meiotic synapsis and male fertility by antagonizing SYCE1 ubiquitination.
This study investigated RNF220, a RING-type E3 ubiquitin ligase, in spermatogenesis by using a Stra8-Cre germ cell-specific conditional knockout mouse model. It found that RNF220 loss causes male subfertility with testicular atrophy, oligozoospermia, abnormal sperm morphology, and severe defects in homologous chromosome synapsis and DNA damage repair, consistent with elevated apoptosis. The work identifies RNF220 as a safeguard of meiotic synapsis and male fertility through antagonism of SYCE1 ubiquitination, highlighting a specific ubiquitin-regulatory mechanism underlying infertility.
Cha J, Lin H, Xia Y et al. · Cell death & disease · (2026) · View on PubMed ↗ · Free PDF ↗
Clinical trials, protocols & real-world evidence (non-mechanistic)
Mixed Presentation of Hyperglycemic Hyperosmolar State and Diabetic Ketoacidosis in a Pediatric Patient: a Case Report and Literature Review.
This case report and literature review studied a 16-year-old female with myelomeningocele, neurogenic bladder, obesity, and insulin resistance who presented with a mixed hyperglycemic crisis (diabetic ketoacidosis plus hyperglycemic hyperosmolar state) after self-discontinuing metformin, atorvastatin, and allopurinol. The key finding was that the patient’s presentation was initially consistent with isolated DKA but ultimately reflected coexisting DKA and HHS, a pattern associated with higher complication risk. Clinically, the report emphasizes that mixed DKA/HHS in pediatrics is rare and potentially fatal and should be actively considered to avoid misclassification and delayed management.
Ordoñez-González I, García-Couturier R, Gómez Pérez AP et al. · Journal of clinical research in pediatric endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗
Study protocol of a prospective, non-interventional cohort study evaluating the benefits of transjugular intrahepatic portosystemic shunt in patients with hepatocellular carcinoma receiving first-line atezolizumab plus bevacizumab (NISTIPS TRITICC-4, IKF092).
This prospective, non-interventional cohort study protocol evaluated whether transjugular intrahepatic portosystemic shunt (TIPS) improves outcomes in patients with hepatocellular carcinoma receiving first-line atezolizumab plus bevacizumab, as in the NISTIPS TRITICC-4 (IKF092) study. The key finding is the study’s rationale that TIPS may reduce clinically significant portal hypertension and thereby enable safer continuation of immunotherapy plus bevacizumab despite bleeding risk from bevacizumab. Scientifically, it will generate real-world evidence on the role of portal-pressure–reducing procedures in immuno-oncology regimens for advanced HCC.
Angendohr C, Weigel C, Kunstein A et al. · Future oncology (London, England) · (2026) · View on PubMed ↗ · Free PDF ↗
Long-term outcome of stenting for the iliac vein stenosis with ipsilateral arterio-venous graft; a case series.
This single-center retrospective case series studied hemodialysis patients with lower-extremity arteriovenous grafts who developed symptomatic iliac vein stenosis and were treated with bare metal stents (BMS). The key finding was the technical feasibility and clinical outcomes (including adverse events and imaging/clinical follow-up) of BMS placement in this specific vascular-access–related setting. The results are significant for nephrology practice because they inform the evidence base for managing central venous stenosis in patients dependent on ipsilateral dialysis access.
Shi Y, Bao X, Fu X et al. · Renal failure · (2026) · View on PubMed ↗ · Free PDF ↗
Diagnostic Performance of the Radiographic Assessment of Lung Edema Score for Acute Respiratory Distress Syndrome-Post Hoc Analysis of the “Validating Acute Lung Injury Biomarkers for Diagnosis” Study.
This post hoc analysis studied the diagnostic performance and interobserver reliability of the Radiographic Assessment of Lung Edema (RALE) score for acute respiratory distress syndrome (ARDS) in adult ICU patients receiving invasive ventilation for at least two consecutive days with available chest radiographs on the first two ICU days. The key finding was the RALE score’s diagnostic accuracy for ARDS and how consistently different experienced raters applied the scoring across early radiographs. Clinically, it supports whether RALE can be used reliably as a radiographic tool for ARDS diagnosis in critical care settings.
Zimatore C, Jabaudon M, Pisani L et al. · Critical care explorations · (2026) · View on PubMed ↗ · Free PDF ↗
Sleep, inflammation, and pain in musculoskeletal rehabilitation: a structured integrative review of neurobiological mechanisms and non-pharmacological pain management strategies.
This structured integrative review studied the neurobiological mechanisms linking sleep disturbance, inflammation, and pain in the context of musculoskeletal rehabilitation and identified non-pharmacological pain management strategies. The key finding was that evidence across 57 included studies supports a reinforcing cycle among sleep disruption, inflammatory processes, and persistent pain that can undermine rehabilitation outcomes. Scientifically and clinically, it consolidates mechanistic targets and intervention options (non-pharmacological) to improve rehabilitation by addressing sleep and inflammation alongside pain.
de Freitas EM, Silva A, Esteves AM · Pain management · (2026) · View on PubMed ↗
ABCD-Trial: study protocol for a randomized, double-blind, placebo-controlled study in patients with Amyotrophic lateral sclerosis for the evaluation of efficacy and safety of B-Cell Depletion with rituximab (ABCD).
This article describes the protocol for the ABCD-Trial, a randomized, double-blind, placebo-controlled study in patients with amyotrophic lateral sclerosis (ALS) evaluating B-cell depletion with rituximab. The trial is designed to assess rituximab’s safety and efficacy by targeting CD20-positive antibody-producing B-cells in the cerebrospinal fluid, motivated by neuroinflammation and autoantibody-related mechanisms in ALS. The clinical significance is that it tests a repurposed immunotherapy strategy grounded in ALS immunopathology, potentially informing future disease-modifying approaches.
Ufer F, Rössling R, Spottke A et al. · Trials · (2026) · View on PubMed ↗ · Free PDF ↗
Impact of socioeconomic factors and birth-related conditions on autism spectrum disorder, Down syndrome, and attention deficit/hyperactivity disorder.
This retrospective hospital-based study examined associations between socioeconomic factors and maternal birth-related conditions and diagnoses of autism spectrum disorder (ASD), Down syndrome (DS), and attention deficit/hyperactivity disorder (ADHD) in children. Maternal medication use during pregnancy (excluding dietary supplements) was significantly associated with higher odds of ASD, with other socioeconomic/birth variables evaluated via multivariable logistic regression. The results highlight modifiable maternal exposures and contextual risk factors that may inform prevention and risk counseling for neurodevelopmental disorders.
Al-Khlaiwi T, Alhakbany M, Aldossary MK et al. · BMC pediatrics · (2026) · View on PubMed ↗ · Free PDF ↗
A multicentre phase III clinical trial of dual-epigenetic therapy plus CHOP compared with CHOP in previously untreated patients with peripheral T-cell lymphoma.
This multicenter phase III trial studied whether adding dual epigenetic therapy—azacitidine plus chidamide—to CHOP (AC-CHOP) improves outcomes versus CHOP alone in previously untreated peripheral T-cell lymphoma (PTCL) patients in China. In 128 enrolled patients (AC-CHOP n=84; CHOP n=44), the primary endpoint was not met, with numerically higher ORR and CR in AC-CHOP but no statistically significant difference, while a trend toward improved progression-free survival was observed. Clinically, the trial informs the risk–benefit and efficacy expectations of azacitidine/chidamide intensification in frontline PTCL.
Wei C, Su L, Wang X et al. · Blood cancer journal · (2026) · View on PubMed ↗ · Free PDF ↗
Ociperlimab and tislelizumab in advanced esophageal squamous cell carcinoma (AdvanTIG-203): a phase II study.
This phase II randomized study evaluated ociperlimab plus tislelizumab versus placebo plus tislelizumab in advanced esophageal squamous cell carcinoma (AdvanTIG-203), enrolling 125 patients (ociperlimab arm n=62; control n=63). The primary endpoint was not met, with investigator-assessed ORR of 30.6% in the ociperlimab arm versus 20.6% in the control arm, and no statistically significant difference. Scientifically and clinically, the trial indicates that adding ociperlimab to tislelizumab did not produce a clear efficacy advantage in this setting.
Wang F, Lin CY, Sun JM et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
The Safety of Melasma Treatment in Vitiligo Patients: An International E-Delphi Study.
This international E-Delphi study synthesized evidence and expert consensus on safe management of melasma in patients with concomitant vitiligo. It found that only one study supported oral tranexamic acid as safe in this context, and experts generally favored prioritizing vitiligo treatment—especially when active—while incorporating patient preferences. The consensus provides practical guidance for clinicians facing the treatment dilemma created by therapies that may destabilize vitiligo or melasma.
Abdallah M, Ezzedine K, Passeron T et al. · Pigment cell & melanoma research · (2026) · View on PubMed ↗
Effect of electrical impedance tomography-guided positive end-expiratory pressure optimisation on postoperative pulmonary complications in laparoscopic colorectal surgery: a randomised controlled trial.
In a single-centre randomized controlled trial, adults at intermediate-to-high risk for postoperative pulmonary complications (ARISCAT score ≥26) undergoing laparoscopic colorectal surgery were assigned to electrical impedance tomography (EIT)-guided individualized PEEP titration versus fixed PEEP of 5 cm H2O. EIT-guided ventilation reduced clinically relevant postoperative pulmonary complications compared with conventional fixed PEEP. This provides evidence that EIT can improve lung-protective ventilation strategies to lower postoperative respiratory morbidity in higher-risk surgical patients.
Wang TH, Liu HC, Tang W et al. · British journal of anaesthesia · (2026) · View on PubMed ↗
Clinical Outcomes of Bladder-sparing Management Versus Early Radical Cystectomy in cT1 Micropapillary Bladder Cancer: A Systematic Review and Meta-analysis.
This systematic review and meta-analysis compared bladder-sparing management (including Bacillus Calmette-Guerin, BCG) versus early radical cystectomy in patients with clinical T1 (cT1) micropapillary bladder cancer. Across included studies of carefully selected patients, bladder-sparing approaches showed oncologic outcomes that were comparable to early radical cystectomy in the pooled analysis. The results support a potential role for initial bladder preservation in selected cT1 micropapillary cases, while highlighting the need for consistent selection criteria and follow-up.
Patel SR, Rauf M, Geng Y et al. · European urology oncology · (2026) · View on PubMed ↗
Observation versus maintenance immunotherapy after PD-1-induced clinical complete response in dMMR/MSI-H colorectal cancer managed non-operatively: a multicenter cohort study.
This multicenter cohort study in China evaluated patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer who achieved clinical complete response (cCR) after PD-1 inhibitor therapy and then entered non-operative management. Patients managed with observation were compared with those receiving maintenance immunotherapy, assessing associations with survival outcomes and treatment-related toxicity. The study addresses whether maintenance immunotherapy is necessary after PD-1-induced cCR, informing safer de-escalation strategies in this biomarker-defined population.
Gao X, Wang Q, Zhang Z et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗
Safety outcomes of semaglutide by chronic kidney disease severity in the FLOW trial.
In a prespecified secondary analysis of the FLOW trial (NCT03819153), safety outcomes of once-weekly subcutaneous semaglutide 1.0 mg were assessed across baseline chronic kidney disease (CKD) severity strata defined by eGFR in participants with type 2 diabetes and CKD. The analysis evaluated serious adverse events and adverse events leading to discontinuation by baseline eGFR category. These findings are important for clinicians to balance renal-risk–dependent tolerability when using semaglutide in CKD patients.
Tuttle KR, Andersen MR, Arici M et al. · Kidney international · (2026) · View on PubMed ↗
Comparative efficacy and safety of treatments for eosinophilic esophagitis: Systematic review and network meta-analysis of randomized controlled trials.
This systematic review and network meta-analysis compared randomized controlled trial treatments for eosinophilic esophagitis (EoE) across children and adults, evaluating pharmacologic, dietary, and mechanical interventions. Across 48 RCTs, it synthesized comparative efficacy and safety using random-effects network meta-analysis with GRADE certainty, but the provided abstract text is truncated before reporting specific relative rankings or effect sizes. Clinically, the work aims to guide evidence-based selection among EoE therapies by clarifying which options balance symptom/endoscopic outcomes and adverse events for different age groups.
Roldan Y, Silang I, Rayner D et al. · The Journal of allergy and clinical immunology · (2026) · View on PubMed ↗ · Free PDF ↗
Real-world effectiveness and safety of cenobamate in children and adolescents with drug-resistant epilepsy: a systematic review, meta-analysis, and meta-regression.
This systematic review and meta-analysis evaluated real-world effectiveness and safety of adjunctive cenobamate in children and adolescents (≤18 years) with drug-resistant epilepsy. Across included single-arm studies, the pooled analysis assessed seizure outcomes and adverse events, with meta-regression used to explore heterogeneity (details truncated in the abstract). The results support evidence-based consideration of cenobamate’s pediatric off-label use by quantifying real-world benefit–risk in pediatric DRE populations.
Samanta D, Ramani PK, Jain P · Epilepsy & behavior : E&B · (2026) · View on PubMed ↗ · Free PDF ↗
Germline pharmacogenetic variants associated with trastuzumab deruxtecan-induced interstitial lung disease in advanced breast cancer: PROCURE project.
The PROCURE project studied germline pharmacogenetic variants associated with trastuzumab deruxtecan (T-DXd)-induced interstitial lung disease (ILD) in patients with advanced HER2-positive or HER2-low breast cancer. It aimed to identify toxicity-associated variants beyond the previously implicated UGT1A1 polymorphisms by analyzing multicenter translational pharmacogenomic data (specific variants and results are truncated in the abstract). Clinically, defining germline predictors of T-DXd ILD could enable risk stratification and safer use of this effective HER2-targeted therapy.
Arenas A, Saura C, Alva-Bianchi M et al. · ESMO open · (2026) · View on PubMed ↗ · Free PDF ↗
Recanalization After Acute Cervical Artery Dissection: A Multicenter International Study.
This multicenter international retrospective study analyzed recanalization after acute cervical artery dissection (CeAD) in imaging-confirmed patients enrolled in the Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection study. It quantified the 6-month rate of complete recanalization and identified clinical/imaging factors associated with recanalization, and assessed recurrent ischemic stroke risk by recanalization status (full results truncated in the abstract). The findings help refine prognosis and may guide follow-up and management strategies after CeAD based on recanalization outcomes.
Romoli M, Muppa J, Lee EM et al. · Neurology · (2026) · 1 citations · View on PubMed ↗
Familial hypercholesterolaemia and thymic ageing in a Chinese cohort.
This study evaluated the relationship between familial hypercholesterolemia (FH), thymic ageing, and the potential reversibility by lipid-lowering therapy in a Chinese cohort. In 562 heterozygous FH patients (treatment-naïve vs on lipid-lowering therapy) and 295 age-matched healthy controls, it assessed thymic output using circulating CD4+ recent thymic emigrant measures and examined how lifelong LDL exposure relates to thymic function. The findings aim to clarify whether lipid-lowering therapy can mitigate FH-associated thymic ageing, with implications for broader health effects beyond atherosclerotic risk.
Li F, Zhang J, Deng J et al. · European heart journal · (2026) · View on PubMed ↗
Generated automatically on October 22, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.