PubMed Trending Research Digest — June 11, 2026

Automated digest · 98 articles · 15 research areas · June 11, 2026

Overview

This week’s digest is dominated by mechanistic biology that links cellular state changes to disease—especially via immune regulation, organelle dysfunction, and stress responses. Multiple studies connect innate immune activation to specific molecular “switches”: hypoxia-driven RNF126–ABCD3 pexophagy in hepatocellular carcinoma, KAT7–H3K14ac–CMPK2 signaling driving mtDNA-driven microglial inflammation in Alzheimer’s disease, and mitochondrial architecture/cGAS–STING pathways contributing to heart failure. In parallel, stress granule clearance is framed as a therapeutic lever (DNAJB1/HSP70), while cytokine exposure is shown to create context-specific cancer vulnerabilities (IFNγ/TNF-induced GPI transamidase dependencies). Together, these papers emphasize that targeting the right node in a dynamic pathway may be more effective than broad inhibition.

A second major theme is precision intervention—spanning both therapeutics and diagnostics. In oncology, spatial and single-cell technologies (SPACE-seq, spatial transcriptomics after insufficient RFA, meningioma atlases) are used to connect lineage history and microenvironment architecture to progression and treatment opportunities. Several clinical studies and real-world datasets refine how to choose or sequence therapies: QFR-guided PCI durability, HR-guided β-blocker management after MI, and multiple cancer treatment effectiveness/response benchmarks (e.g., epcoritamab in routine practice, HER2-mutant NSCLC second-line patterns, KRAS Q61 heterogeneity). Outside cancer, guideline and policy updates for cardiovascular–kidney–metabolic syndrome and for fibrosis detection in steatotic liver disease highlight a shift toward integrated risk frameworks and earlier stratification.

Finally, the digest underscores the growing importance of microbiome and metabolic context in shaping disease risk and treatment response. Dietary exposures (sweetened beverages, diet-induced obesity effects on mucus and bile-acid metabolism) and microbiota-targeted strategies (nanocellulose in intrahepatic cholestasis of pregnancy; SCFA-focused host–pathogen modulation) repeatedly appear as upstream drivers of inflammation and organ outcomes. Across these diverse areas—immunity, metabolism, and tissue context—the common thread is that disease trajectories are increasingly understood as emergent properties of interacting systems, and interventions are moving toward more targeted, state-aware strategies.

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Cancer immunotherapy & tumor microenvironment

Molecular glue degraders of HuR suppress BRAF-mutant colorectal cancer.

This study focused on BRAF-mutant colorectal cancer and used rational chemical library design plus parallel proteomic screening to identify a targeted RNA-binding protein degrader strategy. It reports dHuR as a molecular glue degrader of HuR (human antigen R), an RNA-binding protein that drives tumor growth and therapy resistance, aiming to overcome limitations of BRAF inhibitors such as encorafenib that fail due to MAPK reactivation from BRAF dimerization. If validated clinically, HuR degradation via molecular glue chemistry could provide a new therapeutic route for BRAF(V600E)-driven CRC and potentially reduce resistance and relapse.

Lu X, Wang X, Yang Z et al. · Nature · (2026) · View on PubMed ↗

Iron-mediated ferroptosis impairs CAR-T cell function and antitumor efficacy.

This study analyzed clinical samples from multiple myeloma and acute lymphoblastic leukemia patients treated with CAR-T cells and tested mechanisms in female mouse cancer models and ex vivo cultures. It found that after rapid CAR-T expansion, a “diminution” phase characterized by ferroptosis-associated features and elevated serum iron coincided with impaired CAR-T function, and that excess intracellular iron promoted ferroptosis in CAR-T cells. These results identify iron-mediated ferroptosis as a driver of CAR-T dysfunction and suggest that targeting iron handling or ferroptosis pathways could improve CAR-T persistence and antitumor efficacy.

Kong D, Yang T, Zhao M et al. · Nature cancer · (2026) · View on PubMed ↗

TQB2618 plus penpulimab, alone or in combination with chemotherapy, for recurrent or metastatic nasopharyngeal carcinoma: a multicentre, two-cohort, phase 2 trial.

This multicentre, two-cohort phase 2 trial tested dual immunotherapy targeting TIM-3 and PD-1 using TQB2618 plus penpulimab, either alone or combined with chemotherapy, in recurrent or metastatic nasopharyngeal carcinoma. In the TP cohort (post–PD-(L)1 progression), and the TPGC cohort (treatment-naïve), the study evaluated safety and efficacy endpoints including objective response rate and progression-free survival. The trial’s design and reported outcomes inform whether TIM-3/PD-1 blockade—alone or with gemcitabine/cisplatin—can improve outcomes in this patient population.

Xu C, Wang SY, Nie M et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗

Single-nucleus interrogation of primate small intestinal aging reveals NCoR1 decline as a conserved feature that is reversed by metformin.

This study used single-nucleus interrogation of primate small intestine to profile cellular aging and identified NCoR1 (NCOR1) decline as a conserved feature of aging that is reversed by metformin. It found that aging shifts intestinal barrier dysfunction, chronic inflammation, and stem cell differentiation away from absorptive toward secretory lineages, and that manipulating NCoR1 in human intestinal epithelial cells and organoids recapitulates or rescues aging phenotypes (including senescence, disrupted junctions, and lineage imbalance). The significance is that NCOR1 loss is a mechanistic aging driver in the gut and a potential therapeutic target, with metformin showing reversal of the aging-associated transcriptional program.

Li J, Lu X, Tong T et al. · Nature aging · (2026) · View on PubMed ↗

FOLFOX plus nivolumab combination therapy for cisplatin-unfit patients with untreated advanced esophageal squamous cell carcinoma.

This clinical study evaluated FOLFOX (oxaliplatin-based) plus nivolumab for cisplatin-unfit patients with untreated advanced esophageal squamous cell carcinoma (ESCC). It found that the combination was feasible and assessed for effectiveness and safety specifically in patients who cannot receive cisplatin due to renal/cardiac dysfunction or older age. The significance is that it supports an alternative first-line regimen for a clinically important subgroup lacking standard cisplatin-based options.

Ogura N, Yamamoto S, Morita R et al. · Esophagus : official journal of the Japan Esophageal Society · (2026) · View on PubMed ↗ · Free PDF ↗

Adjuvanted inactivated rabies virus-vectored Lassa virus vaccine in healthy adults: a phase 1 trial.

This Phase 1 randomized, controlled dose-escalation trial studied an adjuvanted inactivated rabies virus-vectored Lassa virus vaccine (LASSARAB; Josiah strain glycoprotein complex) in healthy adults. It found that participants received two intramuscular doses with antigen doses of 700, 1,400, or 2,800 relative units formulated with the TLR-4 agonist 3D-6-acyl PHAD-SE adjuvant (or a licensed rabies vaccine control) and that the interim analysis reports primary safety with secondary immunogenicity outcomes. The significance is advancing a candidate Lassa vaccine toward licensure by demonstrating early safety and immune responses in a controlled human study.

Ortiz JR, Kurup D, Kaufman AC et al. · Nature medicine · (2026) · View on PubMed ↗

SPACE-seq integrates spatial transcriptomics and lineage tracing in native tissues.

The study introduced SPACE-seq, a platform that integrates CRISPR-based lineage tracing barcodes with spatial transcriptomics (via slide-seq) in native tissues. Using SPACE-seq, the authors uncovered intratumor transcriptional diversification among clonally related cells and identified tumor–stroma crosstalk that reciprocally reshapes behaviors of malignant and stromal populations. This provides a powerful method to link lineage history to spatial cell states, enabling mechanistic mapping of how tumors evolve within their tissue microenvironment.

Jia Y, Sun D, Weir JA et al. · Cell stem cell · (2026) · View on PubMed ↗

Prognostic factors and survival outcomes in relapsed/refractory aggressive B-cell lymphomas treated with epcoritamab.

The study analyzed real-world prognostic factors and survival outcomes in 157 adult patients with relapsed/refractory aggressive B-cell lymphomas treated with the bispecific antibody epcoritamab outside clinical trials across 9 US centers (2023–2025). Epcoritamab produced a best overall response rate of 49.6% and best complete response rate of 31.9%, with 1-year progression-free survival and overall survival of 29% and 38%, respectively. The results provide clinically relevant effectiveness and outcome benchmarks for epcoritamab in routine practice and help identify factors associated with response and survival in R/R aggressive B-cell lymphoma.

Bock AM, Feng L, Chauhan A et al. · Blood advances · (2026) · View on PubMed ↗ · Free PDF ↗

Dihydrotanshinone I inhibits PHGDH to suppress serine synthesis and remodel TME in NSCLC.

The study investigated whether the natural product dihydrotanshinone I inhibits PHGDH (phosphoglycerate dehydrogenase) to suppress serine synthesis and remodel the tumor microenvironment (TME) in non-small cell lung cancer (NSCLC). Dihydrotanshinone I targeted PHGDH to reduce serine biosynthesis and thereby altered the TME to support anti-tumor effects, including improved responsiveness to immunotherapy approaches. This positions dihydrotanshinone I as a natural-product PHGDH inhibitor with a mechanistic rationale for combination strategies that reprogram serine-dependent tumor immunity.

Qian C, Han H, Wan L et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

High resolution spatial transcriptomics identifies insufficient radiofrequency ablation induces hepatocellular carcinoma progression via CEBPD / CXCL2 axis.

This study used high-resolution spatial transcriptomics to analyze tumor microenvironment architecture in hepatocellular carcinoma (HCC) arising after insufficient radiofrequency ablation (iRFA) and to identify transcriptional mechanisms driving progression. Insufficient RFA induced an immunosuppressive microenvironment and promoted tumor progression via a CEBPD/CXCL2 axis. Scientifically, mapping spatial gene programs after sublethal heat stress highlights CEBPD/CXCL2 as a mechanistic target to reduce recurrence after inadequate RFA.

Lin K, Zhang N, Zhang Z et al. · Hepatology (Baltimore, Md.) · (2026) · View on PubMed ↗ · Free PDF ↗

Impact of preoperative radiotherapy on the risk of postpancreatectomy haemorrhage and major morbidity after resection of pancreatic adenocarcinoma including arterial divestment or arterial resection.

This study assessed the association between preoperative radiotherapy and postpancreatectomy haemorrhage (PPH) and major morbidity in patients undergoing pancreatic adenocarcinoma resection with arterial divestment or arterial resection after chemotherapy. Preoperative radiotherapy was evaluated for its impact on surgical bleeding and major complications in this high-arterial-involvement subgroup. If confirmed, the results would inform perioperative treatment sequencing by clarifying whether preoperative radiotherapy increases operative risk in complex pancreatic resections.

Stoop TF, van ‘t Land FR, Seelen LWF et al. · BJS open · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer genomics, biomarkers & precision oncology

Molecular and clinical characteristics of patients with non-small cell lung cancer (NSCLC) harboring KRAS Q61 mutations to assess therapeutic responses.

This study characterized molecular and clinical features of non-small cell lung cancer (NSCLC) patients harboring KRAS Q61 mutations and assessed therapeutic response using next-generation sequencing (NGS) data linked to clinical records. Among 8862 analyzed probes, 487 patients (5.5%) had KRAS Q61 mutations, and further analyses of 365 patients evaluated associations between KRAS Q61 subtypes (e.g., Q61H and Q61L) and time-to-event outcomes. The results clarify the heterogeneity of KRAS Q61–mutant NSCLC and can guide more tailored treatment decisions and prognostic counseling.

Ruge L, John F, Verheyen M et al. · Clinical cancer research : an official journal of the American Association for Cancer Research · (2026) · View on PubMed ↗

Acquired BRAF-AGK Fusion Following Osimertinib Plus Savolitinib in EGFR-Mutated MET-Amplified Non-Small-Cell Lung Cancer: Durable Response to Gefitinib and Trametinib in a Case Report.

This case report studied treatment evolution in a 59-year-old woman with stage IV EGFR L858R-mutated, MET-amplified non-small-cell lung cancer who received osimertinib plus savolitinib and later developed an acquired BRAF–AGK fusion. After dual EGFR/MET inhibition, the patient achieved a durable response to gefitinib and trametinib despite the new fusion alteration (specific response metrics truncated in the abstract). The report suggests that secondary, targetable fusions such as BRAF–AGK can emerge after osimertinib-based therapy and that targeted combinations may retain clinical relevance.

Lee AF, Wu SY · OncoTargets and therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative efficacy of CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib in HR+/HER2- advanced breast cancer.

This retrospective clinical study compared real-world efficacy of CDK4/6 inhibitors—palbociclib, ribociclib, and abemaciclib—in 240 patients with HR+/HER2- advanced breast cancer treated between January 2022 and June 2023, all combined with fulvestrant. Patients were grouped by drug regimen (palbociclib n=69, ribociclib n=72, abemaciclib n=99), and the study aimed to identify factors influencing treatment outcomes (primary endpoint/results truncated in the abstract). The comparison is clinically relevant for selecting among CDK4/6 inhibitors in HR+/HER2- advanced breast cancer based on observed effectiveness and prognostic factors.

Hou B, Zhang Y · American journal of cancer research · (2026) · View on PubMed ↗ · Free PDF ↗

Spatially resolved single-cell analyses of human meningioma identify novel cell states influencing tumor microenvironment and progression.

The study characterized tumor-intrinsic heterogeneity in human meningioma by profiling 712 samples using single-nuclear RNA sequencing and high-resolution spatial transcriptomics, alongside bulk DNA methylation/RNA sequencing, bulk proteomics, and plasma methylation. It found that myeloid cell states vary across molecular subtypes and influence the tumor microenvironment and progression, defining novel cell states linked to disease behavior. This provides a single-cell/spatial map of meningioma microenvironment drivers that could inform subtype-specific therapeutic strategies.

Landry AP, Yefet LS, Wang JZ et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

New perspectives on endocrine therapy suitability for hormone receptor-positive metastatic breast cancer in clinical practice.

The article reviewed clinical considerations for endocrine therapy (ET) suitability in hormone receptor-positive metastatic breast cancer, focusing on how biomarkers and tumor genetics guide ET selection and sequencing alongside CDK4/6 inhibitors. It emphasizes that standard first-line therapy is ET plus CDK4/6 inhibitors, while emerging biomarkers such as ESR1 and PIK3CA mutations (and other clinical characteristics) can inform expected response and optimal treatment order across lines. This helps clinicians personalize ET-based strategies in HR+/HER2− advanced breast cancer as the treatment landscape evolves.

Rugo HS, Curigliano G, Cescon DW et al. · Breast (Edinburgh, Scotland) · (2026) · View on PubMed ↗ · Free PDF ↗

Real-world clinical characteristics and outcomes in patients with HER2-mutant non-small cell lung cancer (NSCLC) who received second-line treatment: A nationwide database analysis in Japan.

The study used Japan’s Center for Cancer Genomics and Advanced Therapeutics nationwide database to characterize patients with HER2-mutant NSCLC receiving second-line treatment and to describe treatments and outcomes. It focused on real-world endpoints including overall response rate (ORR), disease control rate (DCR), time on treatment (ToT), and reasons for discontinuation in this second-line setting. These data help define effectiveness and clinical patterns of HER2-targeted strategies in routine practice for HER2-mutant NSCLC after first-line therapy.

Uehara Y, Ikegami M, Kohsaka S et al. · Lung cancer (Amsterdam, Netherlands) · (2026) · View on PubMed ↗ · Free PDF ↗

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Antiviral mechanisms & vaccine development

RNF138-Mediated Ubiquitination and Degradation of NS5 Restricts Tick-Borne Encephalitis Virus Infection.

This mechanistic study investigated how the host E3 ubiquitin ligase RNF138 restricts tick-borne encephalitis virus (TBEV) infection by targeting the viral RNA-dependent RNA polymerase NS5. The key finding was that RNF138 directly interacts with NS5, catalyzes K48-linked polyubiquitination, and induces degradation of NS5, with ubiquitination sites including K372, K462, and K470 identified by ubiquitin-remnant profiling and mutational analyses. Scientifically, it reveals an RNF138–NS5 axis as an intrinsic antiviral restriction mechanism and a potential target for antiviral strategies.

Sun J, Yang W, Zhou H et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

LRP4 is an entry receptor for multiple encephalitic alphaviruses.

The study investigated LDLR-related protein 4 (LRP4) as an entry receptor for encephalitic alphaviruses, testing its role in cells infected with Eastern equine encephalitis virus (EEEV) and related viruses (Western equine encephalitis, Semliki Forest, and Sindbis) using a CRISPR-based activation screen. LRP4 was identified as a mediator of viral attachment and internalization, explaining residual infection in receptor-deficient cells. This supports LRP4 as a mechanistic entry target for multiple encephalitic alphaviruses and provides a basis for antiviral strategies that block receptor-dependent uptake.

Tian S, Ma B, Guo H et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

A macrophage-targeted bivalent saRNA vaccine protects against ocular and cutaneous HSV-1 infection in mice.

The study developed a macrophage-targeted bivalent self-amplifying RNA (saRNA) vaccine (MTL-bivalent-IL12) encoding HSV-1 glycoproteins gD and gB, formulated in ganglioside GM3-engineered lipid nanoparticles (LNPs) targeting CD169+ macrophages, and evaluated protection against ocular and cutaneous HSV-1 infection in mice. The vaccine induced protective immunity that reduced HSV-1 infection outcomes in both eye and skin models. This supports a macrophage-directed saRNA/IL-12 vaccination strategy as a potential approach to prevent recurrent HSV-1 disease by strengthening immune control at relevant entry sites.

Li Y, Zhang Z, Zhu Z et al. · Journal of controlled release : official journal of the Controlled Release Society · (2026) · View on PubMed ↗

Consecutive catalytic steps of viral RNA polymerase and exonuclease suggest a way to overcome intrinsic nucleotide analogue resistance.

This study used structural biology to examine how viral RNA polymerase and exonuclease coordinate consecutive catalytic steps, aiming to explain and potentially overcome intrinsic resistance to nucleotide analogues (NAs). Structural evidence supported a mechanistic basis for sequential inhibition of RNA synthesis and repair in RNA viruses that encode exonuclease domains, including Coronaviridae and Arenaviridae. The significance is a rational strategy for designing NA-based antivirals that target both polymerization and excision to reduce resistance.

Shannon A, Fattorini V, Sartre C et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration & brain inflammation

The 25-Year Evolution of Lithium as a Disease-Modifying Agent in Dementia: A Narrative Review.

This narrative review evaluated evidence that lithium, a long-standing bipolar disorder therapy, may act as a disease-modifying agent in neurodegenerative conditions such as mild cognitive impairment (MCI) and Alzheimer disease (AD). The review highlights lithium’s multi-pathway cellular effects, including upregulation of the anti-apoptotic gene/protein BCL2, enhanced brain-derived neurotrophic factor (BDNF) signaling, inhibition of glycogen synthase kinase-3β (GSK-3β), mitochondrial stabilization, and reduced oxidative stress. Clinically, these convergent mechanisms provide a rationale for further trials testing lithium’s potential to slow neurodegeneration rather than only treating symptoms.

Moore GJ, Bose N, Henter ID et al. · JAMA psychiatry · (2026) · View on PubMed ↗

Mitochondrial Dysfunction as a Driver of Neurodegeneration in Parkinson’s and Huntington’s Disease: Molecular Insights and Emerging Interventions.

This molecular review synthesized evidence that mitochondrial dysfunction drives neurodegeneration in Parkinson’s disease and Huntington’s disease, focusing on gene-linked mitochondrial quality control and dynamics. In Parkinson’s disease, it emphasizes mutations in PINK1 and Parkin affecting mitochondrial quality control and the role of α-synuclein aggregation in worsening mitochondrial damage, while in Huntington’s disease mutant huntingtin disrupts mitochondrial dynamics, transport, and ATP production. The convergence of mitochondrial impairment across both disorders supports emerging therapeutic strategies targeting mitochondrial pathways.

Kuwar OK, Khan S, Maloo A et al. · Molecular neurobiology · (2026) · View on PubMed ↗

Loss of STMP1 Perturbs Mitochondrial Cristae and Drives Cellular Inflammation and Heart Failure.

The study investigated how loss of STMP1 affects mitochondrial cristae integrity and triggers cellular inflammation and heart failure, with emphasis on mitochondrial DNA–mediated activation of the cGAS–STING pathway and type I interferon responses. STMP1 loss was reported to perturb mitochondrial cristae and drive inflammation via cGAS–STING/IFN-I signaling, contributing to cardiac dysfunction (experimental details truncated in the abstract). This mechanistic link between mitochondrial architecture and innate immune activation may identify STMP1 and the cGAS–STING axis as targets to mitigate inflammation-driven heart failure.

Ruberto FP, Lee CJM, Ackers-Johnson M et al. · Circulation · (2026) · View on PubMed ↗

The entropic brain today.

This narrative review studied the entropic brain hypothesis in humans, focusing on how brain entropy relates to levels of phenomenal consciousness across multiple altered states (e.g., meditation, flicker light, near-death-like experiences, REM sleep, pre-ictal aura, unmedicated early psychosis, and psychedelic drug states). It reported that expansive states show increased brain entropy while states with no or reduced consciousness show decreased entropy. The significance is a unifying mechanistic account linking consciousness level to measurable neural complexity, with implications for interpreting neuropsychiatric and anesthetic/clinical states.

Carhart-Harris RL · Brain : a journal of neurology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

The pharmacology of gepants in migraine: A scoping review on mechanisms, clinical applications, and combination strategies.

This scoping review studied gepants—calcitonin gene-related peptide (CGRP) receptor antagonists—in migraine, synthesizing evidence on mechanisms, clinical applications, safety, and combination strategies. It found that gepants act via CGRP receptor blockade and have expanding roles for acute and preventive migraine treatment, with emerging data on combination approaches. The significance is that it consolidates the pharmacologic rationale and practical evidence needed to optimize gepant-based regimens and potential polytherapy.

Iannone LF, Silvestro M, Munafò A et al. · Headache · (2026) · View on PubMed ↗

Hyperglycosylation is a metabolic driver of Alzheimer’s disease.

The study investigated whether hyperglycosylation drives Alzheimer’s disease (AD) using transgenic AD mouse models and post-mortem human AD brain samples, integrating spatial metabolomics, lipidomics, and glycomics with spatial isotopic tracing pulse-chase of N-linked glycans. It found that increased glycan biosynthesis causes a conserved brain hyperglycosylation phenotype, and that genetic knockdown of glycan biosynthetic enzymes improves cognitive outcomes in AD mice. These results identify hyperglycosylation as a mechanistic metabolic driver and suggest glycan-biosynthesis enzymes as potential therapeutic targets for AD.

Hawkinson TR, Liu Z, Ribas RA et al. · Nature metabolism · (2026) · View on PubMed ↗

Semaglutide attenuates neuroinflammation in male mice.

The study tested whether the GLP-1 receptor agonist semaglutide attenuates lipopolysaccharide (LPS)-induced neuroinflammation in male mice and sought the cellular mechanisms involved. Semaglutide prevented neutrophil brain infiltration, reduced excessive cytokine release, and suppressed neuroinflammation-associated transcriptional signatures specifically in microglia and endothelial compartments. This mechanistically links semaglutide’s anti-inflammatory effects to coordinated resolution of neuroinflammation in key brain-resident and vascular immune interfaces.

Belmont-Rausch DM, Ludwig MQ, Bentsen MA et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer’s disease pathogenesis.

The study investigated how the histone acetyltransferase KAT7 (HBO1) regulates mitochondrial DNA (mtDNA)-driven innate immune activation in microglia in Alzheimer’s disease, using 5×FAD mice and human AD brain samples. KAT7 and its histone mark H3K14ac were elevated in AD microglia and promoted transcription of Cmpk2, a mitochondrial kinase required for mtDNA synthesis, with KAT7 loss reducing mtDNA-driven mitochondrial immunity. This identifies an epigenetic KAT7–H3K14ac–CMPK2 axis as a mechanistic driver of chronic neuroinflammation and a potential therapeutic target to slow AD pathogenesis.

Liu Y, Ye Y, Fan M et al. · Neuron · (2026) · View on PubMed ↗ · Free PDF ↗

Human J-domain proteins promote stress granule disassembly and suppress neurodegeneration-linked protein aggregation.

This study examined how human J-domain proteins (JDPs) regulate stress granule disassembly and suppress neurodegeneration-linked protein aggregation. The authors found that HSP70 and JDPs localize to stress granules, that inhibiting these chaperones slows granule disassembly, and that overexpressing JDPs—especially DNAJB1—accelerates disassembly without changing assembly; in vitro, HSP70 and DNAJB1 partition into G3BP1 condensates and reduce aggregation. Scientifically, the work implicates DNAJB1/HSP70-driven clearance of stress granules as a potential therapeutic lever to mitigate pathological protein aggregation.

Mastromarco GJ, Earnshaw R, Moore G et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurobiology, stroke recovery & neurorehabilitation

Diagnostic and prognostic accuracy of Berg Balance Scale and Mini-Balance Evaluation Systems Test in individuals with stroke: A systematic review and meta-analysis.

This systematic review and meta-analysis evaluated diagnostic and prognostic accuracy of the Berg Balance Scale (BBS) and the Mini-BESTest in individuals with stroke, focusing on how cutoff values perform against specified reference standards. The pooled evidence supported that both balance tests can discriminate outcomes, with accuracy varying by the reference standard used for diagnosis or prognosis. Clinically, the findings help clinicians select appropriate BBS or Mini-BESTest cutoff thresholds to better predict functional outcomes after stroke.

Kobayashi S, Kamo T, Ogihara H et al. · Physiotherapy theory and practice · (2026) · View on PubMed ↗

Remote Ischemic Postconditioning in Endovascular Thrombectomy for Stroke: The EnTRIPS Randomized Clinical Trial.

This multicenter, randomized, controlled, outcome-assessor-blinded trial studied ultra-early remote ischemic postconditioning (RIPC) delivered after endovascular treatment (EVT) in patients with acute ischemic stroke undergoing mechanical thrombectomy. The key finding was the efficacy and safety comparison of ultra-early RIPC versus control in improving clinical outcomes after EVT (primary results are truncated in the provided abstract). Clinically, it tests whether a simple conditioning intervention can add neuroprotection when applied immediately after reperfusion therapy.

Cheng Y, Chen W, Chang M et al. · Stroke · (2026) · View on PubMed ↗

Early versus Late Ventricular Intervention Study (ELVIS) in post-hemorrhagic ventricular dilatation: Bayesian reanalysis of brain injury and outcomes.

The study reanalyzed data from the Early versus Late Ventricular Intervention Study (ELVIS) in 126 preterm infants with post-hemorrhagic ventricular dilatation (PHVD) using Bayesian logistic regression. It compared early intervention (ventricular index >97th percentile) versus late intervention (VI >97th percentile +4 mm) and generated posterior estimates for secondary brain injury and death or neurodevelopmental impairment (NDI) at 2 years under multiple prior assumptions. This Bayesian reanalysis aims to better quantify probability of benefit and harm for timing of ventricular intervention in PHVD.

Cizmeci MN, de Vries LS, Whitelaw A et al. · Pediatric research · (2026) · View on PubMed ↗

Scg2 drives corticospinal circuit reorganization with spinal premotor interneurons and astrocytes for motor recovery after stroke in mice.

The study examined how the secretory protein Scg2 drives corticospinal circuit reorganization after stroke in male mice, focusing on connectivity with spinal premotor V2a interneurons and astrocytes. Scg2-dependent structural and functional reconnection of corticospinal axons to denervated cervical cord premotor circuits promoted motor recovery, with chemogenetic silencing showing these pathways contribute to improved function. These findings identify Scg2 as a potential therapeutic lever to enhance spinal circuit rewiring and recovery after stroke.

Sato T, Nakamura Y, Hoshina K et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular risk, prevention & clinical guidelines

Outcomes of Cardiovascular Surgery in Patients With Multiple Sclerosis.

This study used the US National Inpatient Sample to assess nationwide morbidity and mortality after cardiovascular surgery in patients with multiple sclerosis (MS) undergoing coronary artery bypass grafting, valve surgery, aortic surgery, or combined procedures from 2016–2022. The key finding (as framed by the study objective) is that MS is associated with perioperative risk, consistent with concerns about autonomic dysregulation and hemodynamic instability, though the abstract is truncated before reporting effect sizes. Clinically, the results aim to inform surgical risk stratification and perioperative management for MS patients undergoing major cardiovascular operations.

Diz Ferre JL, Zhou G, Cabulong A et al. · JAMA surgery · (2026) · View on PubMed ↗

Ultrasound-guided musculoskeletal interventions and professional boundaries: an international expert opinion.

This international expert opinion (structured consultation among 20 Physical and Rehabilitation Medicine physicians from 14 countries) studied the patient-safety, ethical, and medicolegal implications of musculoskeletal ultrasound (US)-guided interventions being performed by allied health professionals without comprehensive medical training. It found that clear professional boundaries, appropriate training/credentialing, and governance are necessary to mitigate risks when non-physicians perform US-guided procedures. The significance is that it provides a cross-country framework to improve safety and accountability for US-guided musculoskeletal care delivered by mixed professional teams.

Abdulsalam AJ, Grabljevec K, Ince B et al. · European journal of physical and rehabilitation medicine · (2026) · View on PubMed ↗

Cardiac Amyloidosis: Pathogenesis, Diagnosis, and Treatment.

This review studied the pathogenesis, diagnostic evaluation, and treatment of cardiac amyloidosis, emphasizing systemic amyloid types—especially light-chain (AL) and transthyretin (ATTR) amyloidosis with cardiac involvement. It found that misfolded beta-pleated-sheet proteins form insoluble fibrils that deposit in the interstitium, driving organ dysfunction, and that recent treatment advances target these underlying mechanisms. The significance is improved clinical decision-making for diagnosing and selecting therapy in a condition with substantial administrative prevalence (~50 per 100,000 person-years).

Beckmann S, Akin I, Haghikia A et al. · Deutsches Arzteblatt international · (2026) · View on PubMed ↗

Surgeons’ stress assessment after surgical mortality: first international validated survey (STRESSURG study).

The STRESSURG study assessed post-traumatic stress symptoms in surgeons after unexpected perioperative death using an international, cross-sectional online survey. It evaluated prevalence and severity of post-traumatic stress symptoms and tested associations with professional, demographic, and institutional factors among surgeons who experienced intraoperative or early postoperative deaths. The study provides validated evidence to quantify psychological impact in surgical practice, informing interventions that may improve surgeon well-being and patient safety.

Morató O, Peña-Salazar C, Grande L et al. · Langenbeck’s archives of surgery · (2026) · View on PubMed ↗ · Free PDF ↗

Single-cell profiling unveils an exhaustion trajectory of ZNF683hi tissue-resident alveolar CD8+ T cells in checkpoint inhibitor pneumonitis.

The study reviewed global advances in health artificial intelligence and framed AI adoption as a workforce imperative rather than a clinician replacement strategy. It highlights that generative AI tools embedded in documentation, triage, and workflow can reduce administrative overload and burnout amid a projected global shortage of health professionals. This is significant for guiding responsible deployment of AI to preserve clinical expertise and improve care delivery capacity.

Zhou X, Jiang Z, Ren Y et al. · Med (New York, N.Y.) · (2026) · View on PubMed ↗ · Free PDF ↗

Effectiveness of Digital Health Interventions to Improve Self-Care in Patients With Chronic Diseases: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis evaluated randomized controlled trials to determine whether digital health interventions (e.g., mobile apps, telemonitoring, connected devices) improve self-care in adults with chronic diseases. Across included RCTs, the analysis assessed overall effects on self-care outcomes rather than disease-specific endpoints. The findings clarify the magnitude of benefit of digital self-care tools and inform evidence-based implementation for chronic disease management.

Longhini J, Pedrotti D, Foladori F et al. · Journal of medical Internet research · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular disease outcomes & interventional cardiology

Angiographic Quantitative Flow Ratio-Guided Coronary Intervention: 5-Year Follow-Up From the FAVOR III China Randomized Trial.

This 5-year follow-up analysis of the FAVOR III China randomized trial compared quantitative flow ratio (QFR)–guided percutaneous coronary intervention (PCI) versus angiography-guided PCI in patients with coronary artery disease. The long-term results assessed whether the earlier improvements in outcomes with QFR guidance persisted through 5 years and evaluated ongoing safety. Scientifically and clinically, sustained benefit would support QFR-guided PCI as a durable strategy to improve revascularization decision-making beyond short-term follow-up.

Zhang H, Guan C, Jin Z et al. · Journal of the American College of Cardiology · (2026) · View on PubMed ↗

Conservative Oxygen for Unresponsive Patients after Cardiac Arrest.

This randomized clinical trial studied conservative versus liberal oxygen therapy in unresponsive adults after cardiac arrest who were receiving mechanical ventilation in the ICU, using pulse oximetry–guided SpO2 targets (lower limit 90% for both groups). The key finding was that conservative oxygen (upper SpO2 alarm 95% with FiO2 reduced to 0.21 when possible) improved survival with favorable functional outcome compared with liberal oxygen (full outcome details are truncated in the provided abstract). Clinically, it supports oxygen titration strategies to limit hyperoxia exposure in post–cardiac arrest patients who remain unresponsive.

Hodgson CL, Mackle D, Mather AM et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Hospital Policy of Tranexamic Acid to Reduce Transfusion in Major Noncardiac Surgery.

This multicenter, double-blind, cluster-randomized, placebo-controlled trial studied whether a hospital-wide policy of intraoperative tranexamic acid reduces red-cell transfusion in patients undergoing major noncardiac surgery who were at high risk for transfusion. The key finding was that the policy approach safely reduced the need for red-cell transfusion compared with placebo (specific effect estimates are truncated in the provided abstract). Clinically, it supports implementing system-level tranexamic acid protocols to improve blood conservation and potentially reduce transfusion-associated risks.

Houston BL, McIsaac DI, Breau RH et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Heart Rate and Cardiovascular Outcomes in Post-Myocardial Infarction Patients Treated by β-Blockers: A Secondary Analysis of the ABYSS Trial.

This prespecified secondary analysis of the ABYSS trial evaluated how baseline heart rate (HR) relates to cardiovascular outcomes and to the effect of β-blocker continuation versus interruption in 3698 stable post–myocardial infarction patients (left ventricular ejection fraction ≥40%). The key finding was that HR stratified by tertiles (<60, 60 to <68, ≥68 bpm) was associated with cardiovascular outcomes and modified the impact of β-blocker interruption/continuation (outcome specifics are truncated in the provided abstract). Clinically, it suggests HR may help personalize β-blocker management in the modern reperfusion era after MI.

Zeitouni M, Procopi N, Cayla G et al. · Circulation · (2026) · View on PubMed ↗

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Cardio-renal-metabolic syndrome & metabolic health

2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

This guideline report studied prevention, detection, evaluation, and management strategies for cardiovascular-kidney-metabolic syndrome in the intended clinical audience of clinicians caring for patients with interrelated obesity/type 2 diabetes, chronic kidney disease, and cardiovascular disease. It found that the 2026 AHA/ACC/ADA/ASN guideline retires and expands the 2013 overweight/obesity guideline to provide updated, integrated recommendations across the cardio-renal-metabolic spectrum. The significance is that it standardizes care pathways for a high-risk, multi-organ syndrome rather than treating obesity, diabetes, kidney disease, and cardiovascular disease in isolation.

Ndumele CE, Rodriguez F, Dixon DL et al. · Journal of the American College of Cardiology · (2026) · View on PubMed ↗

Corylin promotes healthy aging via RAGA-mTOR suppression and sex-dependent activation of SIRT3.

The study investigated whether Corylin, a flavonoid from Psoralea corylifolia, promotes healthy aging and defined its molecular pathways in mice. Mid-life Corylin improved metabolic function, muscle integrity, and physical performance, extended median lifespan in female mice (11.9% increase; higher survival at 125 weeks), and showed sex-dependent effects with mechanistic links to RAGA-mTOR suppression and activation of SIRT3. These findings support Corylin as a potential sex-specific geroprotective intervention and identify RAGA-mTOR and SIRT3 as candidate targets for healthy longevity.

Cheng SF, Lin YT, Wang TH et al. · Nature communications · (2026) · View on PubMed ↗

Joint association of genetic risk and accelerometer-based step count with cardiovascular disease: a UK-Biobank cohort study.

This UK Biobank prospective cohort study examined the joint association of genetic cardiovascular risk and accelerometer-measured daily step count with incident cardiovascular disease (CVD) in participants without prevalent CVD at baseline. Genetic risk categories (low to high) and step-count categories (low <6,500, moderate 6,500–12,499, high ≥12,500 steps/day) were analyzed together to determine whether physical activity modifies genetic risk for coronary artery disease and ischemic stroke. The findings are intended to support risk-informed prevention by quantifying how step-based activity levels relate to genetically determined CVD risk.

Birmpili P, Brocklebank L, Portas L et al. · European journal of preventive cardiology · (2026) · View on PubMed ↗ · Free PDF ↗

2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

This article is a guideline report that synthesizes evidence for the prevention, detection, evaluation, and management of cardiovascular-kidney-metabolic syndrome for clinicians. It updates and expands prior obesity-related guidance and provides recommendations across interconnected metabolic risk factors (including obesity and type 2 diabetes), chronic kidney disease, and cardiovascular disease. Scientifically and clinically, it standardizes care pathways and risk-based management strategies for a multi-organ syndrome rather than treating each condition in isolation.

Ndumele CE, Rodriguez F, Dixon DL et al. · Circulation · (2026) · View on PubMed ↗

Use of Predicted Risk and Expected Benefit to Guide Decision-Making in Cardiovascular-Kidney-Metabolic Syndrome for the Primary Prevention of Cardiovascular Disease: A Scientific Statement From the American Heart Association and American College of Cardiology.

This scientific statement addresses how predicted risk and expected benefit should guide decision-making for primary prevention of cardiovascular disease in cardiovascular-kidney-metabolic syndrome. It discusses using quantitative risk assessment tools—such as the PREVENT (Predicting Risk of Cardiovascular Disease Events) equations—to align initiation and intensification of preventive therapies with individual risk. The significance is a framework for more precise, benefit-targeted prevention decisions rather than relying on uniform thresholds.

Khan SS, Bhave N, Blumenthal RS et al. · Circulation · (2026) · View on PubMed ↗

Cardiac Autonomic Neuropathy is Associated with the Incidence and Progression of Cardiovascular-Kidney-Metabolic Syndrome.

This study investigated whether cardiac autonomic neuropathy (CAN) predicts the incidence and progression of cardiovascular-kidney-metabolic (CKM) syndrome. In discovery and validation cohorts including UK Biobank, CAN measured by cardiovascular autonomic reflex tests showed increasing prevalence across CKM stages and was associated with incident CKM syndrome and progression in multi-state models. These results position CAN as a clinically measurable risk marker for CKM syndrome development and worsening.

Yang T, Fang D, Wu T et al. · European journal of preventive cardiology · (2026) · View on PubMed ↗

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Infectious disease, microbiome & host–pathogen interactions

Dietary fat alters goblet cell function and microbial bile acid metabolism to promote intestinal lipid absorption in mice.

This study used mouse models of diet-induced and genetic obesity to test how dietary fat reshapes the colonic mucus niche and host–microbiota bile acid metabolism. Excess dietary lipids impaired goblet-cell glutamine metabolism and redox homeostasis, thinning the mucus layer, depleting Akkermansia muciniphila, and expanding the bile-acid-transforming bacterium Clostridium scindens, with downstream enterohepatic bile-acid changes activating FXR–PLIN2 signaling. These findings identify the mucus niche as an early, diet-sensitive driver of metabolic dysfunction and suggest bile-acid/FXR pathway modulation as a mechanistic target to improve diet-associated intestinal lipid absorption and metabolic disease risk.

Liang X, Zhang Y, Xie W et al. · Nature microbiology · (2026) · View on PubMed ↗

Gut microbiota-derived short-chain fatty acids (SCFAs): immunomodulatory effects and therapeutic potential in infections.

This comprehensive analysis reviewed how gut microbiota-derived short-chain fatty acids (SCFAs) modulate host immunity and barrier function and assessed their interaction with 11 key gut pathogens, including bacteria (e.g., Staphylococcus aureus, Clostridioides difficile, Salmonella spp., Campylobacter jejuni, Klebsiella pneumoniae, Vibrio cholerae), fungi (Candida albicans), and viruses (SARS-CoV-2, influenza virus, respiratory syncytial virus, rotavirus). The key finding was that SCFAs act as immunomodulatory signaling molecules with potential therapeutic relevance across multiple pathogen classes (specific effect sizes and mechanisms are truncated in the provided abstract). Scientifically, the review supports targeting SCFA pathways as a strategy to influence infection susceptibility and immune responses.

Yu J, Li W, Xu Y et al. · Clinical microbiology reviews · (2026) · View on PubMed ↗

Carbapenemases: epidemiology, detection and management in a changing global landscape.

This review studied the epidemiology, detection, and management of carbapenemase-producing Gram-negative bacteria in the context of changing global antimicrobial resistance patterns. It summarizes how carbapenemase genes have disseminated internationally via plasmids, transposons, and integrons, with current dominance of KPC, NDM, VIM, IMP, and OXA-type enzymes and rising metallo-beta-lactamase prevalence beyond hospitals (management specifics truncated in the abstract). The synthesis is clinically significant for guiding surveillance, diagnostic selection, and treatment strategies against last-line beta-lactam resistance.

Macesic N, Harris PNA, Mo Y et al. · JAC-antimicrobial resistance · (2026) · View on PubMed ↗ · Free PDF ↗

The skin microbiome as a key regulator of psoriasis: From dysbiotic drivers to host-directed therapeutics.

This review synthesized evidence that the skin microbiome regulates psoriasis pathogenesis by shifting from dysbiotic drivers toward host-directed therapeutic opportunities. Across studies, psoriatic lesions show increased pro-inflammatory taxa (e.g., Corynebacterium, Staphylococcus aureus), decreased commensals (e.g., Cutibacterium), higher bacterial load, and reduced community diversity, with downstream effects on skin barrier function and immune dysregulation. The article highlights the skin microbiome as a modifiable contributor to psoriasis and supports development of host- and microbiome-targeted interventions beyond conventional anti-inflammatory therapy.

Xie T, Hao Y, Qin L · Microbiological research · (2026) · View on PubMed ↗

Risk prediction of Helicobacter pylori strains across Correa’s cascade via intelligent analysis of genome-wide SNPs.

This study analyzed 528 Helicobacter pylori whole-genome sequences spanning nonatrophic gastritis (NAG), atrophic gastritis (AG), intestinal metaplasia (IM), and gastric cancer (GC) to predict strain-level risk across Correa’s cascade. Using genome-wide association analyses with adjustment for population structure and a random forest model incorporating advanced-lesion-associated variants, it derived an H. pylori Genomic Risk Score (HpRS). Clinically, HpRS could enable genome-informed identification of H. pylori strains most likely to progress to advanced lesions and cancer.

Song X, Wang X, Zhang S et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

A fungal natural product that inhibits plant cellulose biosynthesis by disrupting cellulose synthase complexes.

This study identified and characterized a fungal natural product, 8-methyldichlorodiaporthin (MDD), as a plant cellulose biosynthesis inhibitor acting on cellulose synthase complexes (CSCs). Structure–activity relationship analyses in Arabidopsis thaliana showed that methylation on the isocoumarin ring and chlorination of the side chain are critical for MDD growth inhibition, and a chemical forward genetic screen implicated disruption of CSC function. The results support MDD as a broad-spectrum cellulose biosynthesis inhibitor and a tool for herbicide development and mechanistic studies of CSC biology.

Wu Z, Liu L, Han W et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Higher BMI is associated with vaginal microbiome alterations in women with PCOS.

This study assessed whether higher body mass index (BMI) is independently associated with vaginal microbiome alterations in women with polycystic ovary syndrome (PCOS). Using full-length 16S rRNA Nanopore sequencing of vaginal and anorectal swabs from 75 women (55 PCOS, 20 controls) stratified by BMI, the authors found BMI-related differences in microbial diversity and composition. Clinically, the findings suggest that BMI is an important driver of vaginal microbiome variation in PCOS, informing how metabolic status may modulate reproductive tract microbiology.

Spochacz-Santoro M, Szeliga A, Durda-Masny M et al. · Reproduction & fertility · (2026) · View on PubMed ↗

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Liver disease, hepatitis B & hepatocellular carcinoma

A first-in-class pulsatile FXR agonist for bile-acid-related liver diseases.

This work developed and tested linafexor, a first-in-class pulsatile (rapidly cleared) non-bile-acid FXR agonist, in preclinical models of bile-acid-related liver diseases. Linafexor was engineered for rapid systemic clearance to enable pulsatile FXR activation and showed robust efficacy across multiple metabolic dysfunction–associated steatohepatitis and liver fibrosis models, aiming to avoid the reduced efficacy/toxicity seen with continuous FXR activation. The study supports a pharmacokinetic “pulsing” strategy for nuclear receptor therapeutics and positions linafexor as a candidate approach for treating FXR-relevant cholestatic and metabolic liver disorders.

Zang Y, Shi J, Zhao G et al. · Nature · (2026) · View on PubMed ↗

Artificially Sweetened and Sugar-Sweetened Beverage Intake and Risk of Liver Cancer.

This pooled analysis of 11 prospective US cohort studies examined whether artificially sweetened beverage (ASB) and sugar-sweetened beverage (SSB) intake was associated with incident liver cancer overall and by subtype (hepatocellular carcinoma [HCC] and intrahepatic cholangiocarcinoma [ICC]). Higher ASB and/or SSB consumption was associated with increased risk of liver cancer, with subtype-specific associations reported for HCC and ICC. These findings support limiting sugar-sweetened and artificially sweetened beverages as a potentially modifiable dietary exposure to reduce liver cancer risk.

Watling CZ, Zhao L, Zhang X et al. · JAMA network open · (2026) · View on PubMed ↗

Diagnostic innovation and models of care to improve fibrosis detection and risk stratification in steatotic liver disease.

This Series paper studied diagnostic innovation and models of care to improve fibrosis detection and risk stratification in steatotic liver disease (SLD) across the continuum of care in Europe. It highlights expanding non-invasive fibrosis assessment options—including blood biomarkers, imaging, automated lab algorithms, and artificial intelligence-enabled tools—while noting inconsistent implementation due to limited awareness and constrained resources (truncated). The work is significant for improving early identification of fibrosis, enabling better prognostication and management of SLD-related outcomes.

Pugliese N, White TM, Brennan PN et al. · The Lancet regional health. Europe · (2026) · View on PubMed ↗ · Free PDF ↗

Assessing Europe’s policy readiness to confront the MASLD/MASH public health threat.

This policy-focused paper studied Europe’s readiness to address metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced form, metabolic dysfunction-associated steatohepatitis (MASH). It reports that MASLD is highly prevalent in Europe (estimated 30.4% in EU/UK adults) but remains weakly represented or absent from health policy and development agendas, despite links to obesity and type 2 diabetes (clinical guideline coverage truncated). The findings are significant for informing public health prioritization and strengthening clinical practice guideline integration for MASLD/MASH.

Lazarus JV, White TM, Agirre-Garrido L et al. · The Lancet regional health. Europe · (2026) · 3 citations · View on PubMed ↗ · Free PDF ↗

Bepirovirsen induces innate immune activation in the liver potentially through TLR8 signaling.

The study examined whether bepirovirsen, an unconjugated antisense oligonucleotide in Phase 3 for chronic hepatitis B virus (HBV), induces innate immune activation in the liver via Toll-like receptor 8 (TLR8) signaling. Using cytokine profiling of Phase 2a patient samples and mechanistic testing with PBMCs from healthy donors, the authors assessed innate cytokine responses consistent with PRR-mediated activation. This is clinically significant because it helps define the immunostimulatory mechanism underlying bepirovirsen dosing responses and informs safety/management of HBV antisense therapy.

Ermler ME, Delahaye JL, Jordan W et al. · JHEP reports : innovation in hepatology · (2026) · View on PubMed ↗

Nanocellulose Alleviates Intrahepatic Cholestasis of Pregnancy via Gut Microbiota-Mediated Bile Acid Homeostasis.

This preclinical study tested prophylactic nanocellulose—especially cellulose nanofibers (CNF)—as a gut microbiota-targeted dietary intervention in a rat model of intrahepatic cholestasis of pregnancy (ICP). CNF reduced maternal total bile acids (TBA), improved offspring survival, and was associated with enrichment of probiotic taxa alongside suppression of bile acid-transforming bacteria, supporting restored bile acid homeostasis. These findings suggest a microbiome-mediated, non-drug dietary strategy that could complement current ICP management by targeting bile acid dysregulation.

Yu M, Dai H, Zhong X et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗

HBsAg seroclearance further reduces hepatocellular carcinoma but not hepatic decompensation in patients with cirrhosis and complete viral suppression.

This cohort study evaluated whether hepatitis B surface antigen (HBsAg) seroclearance adds benefit beyond complete viral suppression in nucleos(t)ide analogue (NA)-treated adults with cirrhosis, using entecavir/tenofovir-treated patients. Compared with complete viral suppression alone, HBsAg seroclearance further reduced hepatocellular carcinoma (HCC) risk but did not significantly change hepatic decompensation risk. Clinically, HBsAg seroclearance may serve as an additional prognostic marker for HCC risk stratification in NA-treated cirrhosis.

Hui VW, Tang JC, Wong VW et al. · Hepatology (Baltimore, Md.) · (2026) · View on PubMed ↗

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Inflammation, immune regulation & cytokine signaling

Interleukin-10 Autoantibodies and HLA-DRB1*01:03 in Inflammatory Bowel Disease.

This study evaluated whether neutralizing interleukin-10 (IL-10) autoantibodies contribute to inflammatory bowel disease (IBD) and assessed genetic association with HLA-DRB1*01:03. Using a cellular IL-10 reporter assay, confirmatory competitive ELISA, and an in vitro cytokine-release bioassay in a subgroup, the authors tested serum from IBD patients in the Oxford and UK IBD BioResource cohorts and controls. The work clarifies the immunogenetic and autoantibody basis of IL-10 pathway disruption in IBD, supporting targeted diagnostic and potentially therapeutic strategies for IL-10 phenocopy syndromes.

Gharahdaghi N, Yeh PJ, Ceron-Gutierrez L et al. · The New England journal of medicine · (2026) · View on PubMed ↗

High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury: The VICTORY Randomized Clinical Trial.

This phase 3 randomized, double-blind, placebo-controlled trial studied whether high-dose intravenous vitamin C reduces mortality and organ dysfunction in adults (≥18 years) with deep second- or third-degree burns covering ≥20% total body surface area requiring skin grafting across 24 burn centers in North/Central/South America, Europe, and Asia. The key finding was that high-dose IV vitamin C did not improve clinical outcomes compared with placebo (details truncated in the provided abstract). The results provide high-level evidence to guide whether vitamin C should be used as an adjunct therapy for severe burn–associated systemic inflammation and multiple organ dysfunction.

Stoppe C, Hill A, Cancio LC et al. · JAMA · (2026) · View on PubMed ↗

Carbocisteine or Hypertonic Saline for Acute Respiratory Failure.

This multicenter, open-label, randomized 2×2 factorial trial studied the mucoactive agents carbocisteine (750 mg three times daily enterally) and 6% or 7% nebulized hypertonic saline (4 mL four times daily) in critically ill, mechanically ventilated patients ≥16 years with acute respiratory failure and difficult-to-clear secretions. The key finding was the comparative effect on duration of mechanical ventilation and related outcomes across usual care, carbocisteine, hypertonic saline, or both (primary outcome and results are truncated in the provided abstract). The trial informs evidence-based use and safety considerations for mucoactive therapy in acute respiratory failure.

Connolly B, Dickson N, Campbell C et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Transcriptomic analysis identifies novel ferroptosis-related biomarkers and therapeutic targets in pulmonary arterial hypertension.

This study used transcriptomic data from human pulmonary arterial hypertension (PAH) and control lung tissue (from GEO) combined with ferroptosis-related gene sets (from MsigDb and FerrDb) to identify ferroptosis-related biomarkers and therapeutic targets, and then performed differential expression, enrichment, and hub-gene analyses. The key finding was identification of novel ferroptosis-related biomarkers and candidate therapeutic targets associated with PAH pathobiology (specific genes/biomarkers are truncated in the provided abstract). Scientifically, it highlights ferroptosis as a mechanistic pathway in PAH and provides targets for future validation and drug development.

Ji H, Ma S, Bao W et al. · Journal of hypertension · (2026) · View on PubMed ↗

Preclinical and clinical advances in pulmonary hypertension associated with systemic sclerosis.

This narrative review synthesized preclinical and clinical advances in pulmonary hypertension associated with systemic sclerosis (SSc-PH), focusing on mechanisms (immune dysregulation, endothelial injury, metabolic reprogramming, fibroproliferative remodeling), risk stratification, and treatment targets. The key finding was that an integrated early-detection and risk-stratification approach—combining refined cardiac imaging metrics and other emerging tools—may improve management of SSc-PH (details truncated in the provided abstract). Clinically, it frames current and potential therapeutic targets to reduce morbidity and mortality in this high-risk autoimmune complication.

Birnhuber A, Zeder K, Kwapiszewska G · Current opinion in pulmonary medicine · (2026) · View on PubMed ↗

Endothelial SHMT2 Drives Pulmonary Vascular Remodeling Through Noncanonical Pathway in Pulmonary Hypertension.

The study investigated whether endothelial serine hydroxymethyltransferase 2 (SHMT2) drives pulmonary vascular remodeling in pulmonary hypertension using proteomic profiling of hypoxia-treated human pulmonary artery endothelial cells, patient lung samples, and rodent PH models. SHMT2 was identified as a key endothelial factor and was linked to pulmonary vascular remodeling through a noncanonical pathway (details truncated in the abstract). These findings position endothelial SHMT2 as a mechanistic target for developing therapies to prevent or reverse pulmonary hypertension–associated vascular remodeling.

Wang Q, Tian J, Liu D et al. · Circulation · (2026) · View on PubMed ↗

Inflammasome-Primed Neutrophils Aggravate Atherosclerosis in Cigarette Smoking.

The study examined how cigarette smoke exposure primes neutrophils to aggravate atherosclerosis in mice, focusing on whether neutrophil alarmin release drives systemic myelopoiesis and vascular inflammation. In wild-type mice exposed to inhaled cigarette smoke or cigarette smoke extract, immune cell composition across lung, bronchoalveolar lavage, blood, spleen, and bone marrow was assessed by flow cytometry to test this mechanism (key results truncated in the abstract). The work supports a lung-to-system inflammatory axis in smoking-related atherosclerosis and highlights neutrophil priming/alarmin signaling as a potential intervention point.

Chattopadhyay D, Nitin N, Jaggers RM et al. · Circulation research · (2026) · View on PubMed ↗

Mepolizumab Efficacy in COPD: Insights from Longitudinal Patterns of Blood Eosinophil Counts and Their Variability Across Three Clinical Trials.

This pooled analysis studied mepolizumab efficacy in chronic obstructive pulmonary disease (COPD) patients stratified by longitudinal patterns and variability of blood eosinophil counts (BEC) across three Phase 3 randomized, double-blind, placebo-controlled trials (METREX, METREO, MATINEE). It found that mepolizumab 100 mg reduced annualized moderate/severe exacerbations in ways that depended on BEC pattern/variability, supporting BEC as a dynamic biomarker for treatment response. The significance is more precise use of mepolizumab in COPD by accounting for how BEC changes over time rather than relying on a single measurement.

Criner GJ, Watz H, Han MK et al. · American journal of respiratory and critical care medicine · (2026) · View on PubMed ↗

Inflammatory cytokines induce new cancer dependencies.

The study examined how inflammatory cytokines create new cancer dependencies by running in vitro genome-scale CRISPR loss-of-function screens in eight cancer models exposed to interferon-γ (IFNγ), interferon-β, or tumor necrosis factor. It identified components of the glycosylphosphatidylinositol (GPI) transamidase complex as inflammation-induced vulnerabilities, indicating that cytokine-driven transcriptional/cell-state changes can expose specific genetic dependencies. These results suggest that cytokine signaling can be exploited to predict and target context-specific therapeutic vulnerabilities in tumors.

Cheruiyot CK, Kim SY, Dubrot J et al. · Nature genetics · (2026) · View on PubMed ↗

GPR84 blockade in macrophages mitigates sepsis-induced liver injury via PPARα-driven metabolic reprogramming and M2 polarization.

The study investigated the role of the fatty-acid-activated receptor GPR84 in sepsis-associated liver injury (SLI) using murine models and mechanistic profiling, including single-cell RNA sequencing and immunohistochemistry. Gpr84 blockade in macrophages mitigated SLI by promoting PPARα-driven metabolic reprogramming and shifting macrophage polarization toward an M2 phenotype. This identifies a macrophage GPR84–PPARα axis as a potential therapeutic target to reduce liver damage during sepsis.

Chen Y, Zhou Y, Guo S et al. · Metabolism: clinical and experimental · (2026) · View on PubMed ↗

m6A-Mediated Glycolysis by IL-37 Drives T Cell Metabolic Reprogramming to Regulate Colitis.

The study investigated how the anti-inflammatory cytokine IL-37 regulates colitis by linking m6A RNA methylation to T-cell metabolic reprogramming. IL-37 reduced global m6A levels and reshaped CD4+ T-cell metabolism via SIGIRR signaling, inhibiting IRAK4/JNK phosphorylation and NF-κB p65 activation, which downregulated METTL14 and decreased m6A deposition at the A2445 site in the 3′UTR of SLC2A1, destabilizing i[ncomplete in abstract]. This mechanistic IL-37–SIGIRR–METTL14–m6A–SLC2A1 pathway provides a targetable axis for controlling T-cell-driven inflammation in inflammatory bowel disease.

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

Shared CD4+ T cell receptor specificity groups in Crohn’s disease and ulcerative colitis.

This study analyzed how HLA-DRB1 genetic risk shapes CD4+ T cell receptor (TCR) specificity in inflammatory bowel disease (IBD), comparing Crohn’s disease (CD) and ulcerative colitis (UC). Using HLA-DRB1 genotyping and profiling 3.13 million TCRβ sequences from circulating memory CD4+ T cells in 33 IBD patients (20 UC, 13 CD) and 14 healthy controls, the authors applied GLIPH2 to identify shared CD4+ TCR specificity groups across disease contexts. The findings link HLA-DRB1-associated MHC class II variation to convergent TCR specificity patterns, advancing understanding of shared immune drivers in UC and CD.

Chan JE, Mohsin A, Krijgsman J et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗

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Autoimmunity & immune-mediated disorders

Real-world efficacy of eculizumab in generalized myasthenia gravis patients with poor early response to efgartigimod: a prospective cohort study.

This prospective cohort study evaluated whether sequential therapy with the complement C5 inhibitor eculizumab benefits generalized myasthenia gravis (gMG) patients who had poor early response to the FcRn inhibitor efgartigimod. It followed 103 gMG patients longitudinally after one cycle of efgartigimod to assess clinical benefit from eculizumab in this poor-responder subgroup (key outcomes truncated in the abstract). The results are significant for guiding treatment sequencing in gMG when initial FcRn inhibition is insufficient.

An X, Zhu L, Huang X et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment - update 2026.

This European consensus guideline update (Part 2: Treatment) evaluated evidence and expert recommendations for managing invasive cutaneous squamous cell carcinoma (CSCC) in immunocompetent and immunosuppressed patients. It provides updated first-line treatment recommendations (notably surgical approaches for common primary CSCC) and guidance for subsequent management based on current literature and consensus. The guideline standardizes care pathways across European specialties to improve outcomes and decision-making in invasive CSCC.

Stratigos AJ, Dessinioti C, Garbe C et al. · European journal of cancer (Oxford, England : 1990) · (2026) · View on PubMed ↗

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Genetic epidemiology & psychiatric genetics

Mutation-dependent responses to sleep and exercise in clonal haematopoiesis.

This study examined how lifestyle factors (sleep and exercise) affect clonal haematopoiesis (CH) in humans and mice across specific CH driver mutations in Jak2, Tet2, Trp53, and Dnmt3a. The authors found mutation-dependent responses, with mutant cells uniquely sensitive to lifestyle; in human datasets, moderate-to-vigorous physical activity correlated with lower prevalence of non-DNMT3A-driven CH, and in atherogenic mice with Jak2V617F or Tet2 LOF, uninterrupted sleep (but not Trp53 LOF or Dnmt3aR878H) influenced CH-related outcomes. These results imply that CH clone biology is shaped by behavioral exposures in a mutation-specific manner, informing risk stratification for atherosclerosis and potential lifestyle interventions tailored to CH genotype.

Gerhardt T, Jacob W, Gaebel L et al. · Nature · (2026) · View on PubMed ↗

Changes in Genetic Contributions to ASD and ADHD by Year of Diagnosis.

This cohort study assessed how genetic risk contributions for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) changed by year of diagnosis using population genetic risk profiling in individuals diagnosed over time. The genetic risk profile differed across diagnosis years compared with expectations under simulated scenarios, suggesting that changes in underlying genetic risk (not only diagnostic practices) may contribute to rising incidence. Scientifically, the results motivate re-evaluating etiologic models for ASD/ADHD and may inform future risk stratification and prevention strategies.

LaBianca S, Lousdal ML, Dybdahl Krebs M et al. · JAMA psychiatry · (2026) · View on PubMed ↗

Cariprazine for Autism-A Case Report.

This case report studied the use of cariprazine in a 10-year-old girl with autism spectrum disorder (ASD), focusing on safety and effectiveness for behavioral symptoms. The authors report one of the earliest accounts of cariprazine being safe and effective in this patient, described as “metabolic-friendly,” targeting behavioral facets of ASD (details truncated in the abstract). Clinically, it supports further investigation of cariprazine as a potential pharmacologic option for ASD-related behavioral difficulties.

Naguy A, Pridmore S, Alamiri B · Psychopharmacology bulletin · (2026) · View on PubMed ↗ · Free PDF ↗

Genome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestry.

The study performed a genome-wide association meta-analysis of quantitatively measured generalized anxiety symptom severity in 693,869 individuals of European ancestry across 14 cohorts. It identified 80 independent genome-wide significant variants in 74 loci (39 newly associated) with SNP-based heritability of 5.9%, and polygenic scores that predicted anxiety symptom severity and disorder across European, African, and South Asian ancestry samples. The findings refine the genetic architecture of generalized anxiety on a symptom continuum and support cross-ancestry polygenic risk modeling.

Skelton M, Mitchell BL, Assary E et al. · Nature human behaviour · (2026) · View on PubMed ↗ · Free PDF ↗

Pleiotropic shared heritability quantifies the shared genetic variance of common diseases.

The study introduced a statistical method, pleiotropic shared heritability with bias correction (PHBC), to quantify the liability-scale genetic variance of a target disease shared with selected auxiliary diseases. Using a Monte Carlo bias-correction approach on genetic correlation matrices, PHBC estimated shared heritability across 15 UK Biobank diseases and showed how shared genetic variance contributes to disease architectures. This advances genetic epidemiology by enabling more accurate, targeted estimation of pleiotropic overlap relevant to comorbidity and shared mechanisms.

Zhao Y, Strober B, Hou K et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

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Developmental biology & congenital/genetic disorders

Single-cell analysis of fetal testis reveals dysfunction of human Leydig cells in Klinefelter syndrome.

This study used single-cell transcriptome analysis to define fetal testis cellular dysfunction in Klinefelter syndrome (KS), focusing on Leydig cells. In fetal KS versus control testicular cells, Leydig cells showed increased proliferation and immature differentiation with elevated MAPK signaling and increased expression of the X-linked gene EIF1AX, while Sertoli cell clusters also differed (including an XIST-negative cluster with altered cell-cycle features). These results identify specific developmental defects in human fetal Leydig cells in KS that may contribute to infertility and guide targeted research into sex-chromosome aneuploidy mechanisms.

Yan T, Chen G, Zhang J et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

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Cell biology & molecular mechanisms (incl. ubiquitin, stress granules, organelles, genome editing)

Mitochondria directly interact with the nuclear pore complex.

This study investigated whether mitochondria physically interact with the nuclear pore complex (NPC) and identified candidate molecular mediators. Using two unbiased proteomic approaches (GST pulldown and BioID), the authors found VDAC1 as a top mitochondrial candidate interacting with a filamentous nuclear pore component, supporting direct mitochondria–NPC contacts. The discovery links mitochondrial function to nuclear transport/control at the NPC and provides a new mechanistic framework for how organelle crosstalk can regulate gene expression and cell fate.

Menendez-Montes I, Marin-Vicente C, Mukherjee S et al. · Nature · (2026) · View on PubMed ↗

RNA structure programs endogenous ADAR for precise and efficient editing.

This study developed LEAPER 3.0, an engineered ADAR-recruiting RNA (arRNA) platform, to program endogenous ADAR1/ADAR2 for precise RNA editing. By integrating AlphaFold 3 structural predictions with biochemical and cellular assays, the authors defined the molecular interface between ADAR1 or ADAR2 and double-stranded RNA and used these insights to rationally optimize arRNAs for improved editing efficiency and precision. This advances programmable, enzyme-free RNA editing by leveraging endogenous ADAR activity and provides a mechanistic blueprint for designing safer and more accurate therapeutic RNA editors.

Song D, Liu G, Zhang W et al. · Cell · (2026) · View on PubMed ↗

Long-term reversal of Duchenne muscular dystrophy via circular arRNA-guided exon skipping in monkeys and humans.

This study applied LEAPER 2.0, using circular ADAR-recruiting RNAs (circ-arRNAs) to harness endogenous ADAR for programmable exon skipping in the DMD gene. In DMD nonhuman primates and humans with hotspot mutations, a single administration achieved long-term reversal of Duchenne muscular dystrophy phenotypes by restoring dystrophin expression through ADAR-dependent and ADAR-independent mechanisms that bypass out-of-frame mutations. These results provide strong translational evidence that circ-arRNA-guided endogenous ADAR editing can produce durable therapeutic benefit in a large-animal model and in patients.

Guo W, Tang H, Yi Z et al. · Cell · (2026) · View on PubMed ↗

eIF3 Orchestrates a Biphasic Stress Response Linking Translational Control to Mitochondrial Integrity in Skeletal Muscle.

This experimental study investigated how the eukaryotic translation initiation factor 3 (eIF3) complex coordinates a biphasic stress response that links translational control to mitochondrial integrity in skeletal muscle under distinct stress modes. The authors found that specific eIF3 dynamics regulate translation programs in a stress-phase–dependent manner and preserve mitochondrial function during skeletal muscle stress. These mechanistic insights identify eIF3 as a potential target for interventions aimed at improving muscle resilience and mitochondrial health.

Lin Y, Xia J, Li M et al. · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · (2026) · View on PubMed ↗

CRISPR-Based Gene Therapy for Brain Disease.

This review article examined the use of CRISPR-Cas9–based gene therapy approaches for treating brain diseases caused by pathogenic gene mutations. It summarizes how CRISPR enables precise genome editing across diverse cell types and discusses preclinical and translational strategies for neurological targets. The scientific significance is that CRISPR-based gene therapy is positioned as a platform for disease-modifying interventions in otherwise hard-to-treat neurogenetic disorders.

Khajouei F, Ghaemi A, Abnous K et al. · Molecular neurobiology · (2026) · View on PubMed ↗

Onasemnogene Abeparvovec in Patients With SMA: Interim Results of the RESTORE Registry in Japan.

This interim real-world post-marketing surveillance study (RESTORE registry; NCT04174157) studied onasemnogene abeparvovec (OA; Zolgensma) in Japanese patients with spinal muscular atrophy (SMA). It found that 80 patients received OA (with 30% monotherapy and 54% bridge/switch), and reported 5-year interim outcomes on safety and effectiveness consistent with ongoing clinical monitoring in routine practice. The significance is that it provides longer-term, Japan-specific effectiveness and safety data for a one-time AAV gene replacement therapy in SMA.

Saito K, Benguerba K, Tsuchida K et al. · Annals of clinical and translational neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Efficient prime editors for heritable multiplex precision genome editing in soybean.

The study developed and tested an optimized prime editing system for soybean (GmPEplus) to enable efficient heritable multiplex precision genome editing in dicot plants. GmPEplus achieved up to 81.3% editing efficiency in stable transgenic lines, and further improved performance by nicking the non-edited strand with an additional sgRNA using a tRNA processing system and independent AtU6 expression. This provides a high-efficiency, heritable prime-editing platform for soybean trait engineering and functional genomics.

Su F, Dong Y, Guo R et al. · Nature plants · (2026) · View on PubMed ↗

Spatially resolved m6A profiling using m6A-ARTR-DBiT.

The study developed m6A-ARTR-DBiT, a spatial m6A profiling assay that uses reverse-transcription-based detection and deterministic barcoding to map transcriptome-wide N6-methyladenosine (m6A) distribution in intact tissue. Applying it to mouse embryonic tissues and adult brains produced spatially resolved m6A landscapes and revealed region-associated m6A features, with positive correlations between spatial m6A levels and expression patterns from spatial transcriptomes. This technique enables tissue-context mapping of RNA methylation regulation and links m6A spatial patterns to functional gene expression domains.

Xiao Y, Bai Z, Zou Z et al. · Nature methods · (2026) · View on PubMed ↗

Nek1 defines a branch of centriolar microtubule length control parallel to CP110-Cep97.

The study investigated how the kinase Nek1 regulates centriolar microtubule length, identifying a pathway parallel to the CP110–Cep97 distal cap complex. Nek1 localized to the distal centriole with CP110 and Cep97, interacted with Cep97 and Cep78, and its loss caused pronounced centriolar microtubule shortening, indicating Nek1 works with CP110–Cep97 to control centriole length. This clarifies a conserved regulatory branch for centriole architecture that is important for centrosome function and ciliogenesis.

Streubel JMS, Karasu OR, Munoz IM et al. · Nature communications · (2026) · View on PubMed ↗

Prion-based protein self-assembly tunes mutagenesis to enable rapid adaptation.

The study examined whether prion-based self-assembly can create reversible, heritable “mutagenesis switches” by altering DNA repair and recombination protein activity in Saccharomyces cerevisiae populations from laboratory and clinical ecological niches. Frequent prion switching tuned mutagenesis rates and improved short-term adaptive evolution under strong selection pressure. These findings support a mechanism for rapid, reversible evolvability mediated by self-templating protein assemblies, with implications for understanding adaptation and genome stability control.

Van Elgort A, Jakobson CM, Chen YR et al. · Cell · (2026) · View on PubMed ↗

Mechanisms of ubiquitylation of the mitotic regulatory protein Cdc20.

This mechanistic study investigated how the mitotic regulatory protein Cdc20 is ubiquitylated by the anaphase-promoting complex/cyclosome (APC/C), focusing on whether ubiquitylation occurs via an intramolecular “cis” mechanism. Using experimental approaches to test Cdc20–APC/C interactions and ubiquitylation outcomes, the authors dissected the molecular basis of Cdc20 ubiquitylation during mitotic exit. The work clarifies how APC/C recognizes and modifies Cdc20, informing broader models of how ubiquitin signaling controls cell-cycle transitions.

Sitry-Shevah D, Miniowitz-Shemtov S, Liburkin Dan T et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

RNF126 is a peroxisomal fate switch enabling redifferentiation therapy in hepatocellular carcinoma.

This study investigated how the hypoxia-inducible E3 ubiquitin ligase RNF126 regulates peroxisome loss and hepatocyte redifferentiation in hepatocellular carcinoma (HCC). Under hypoxia, HIF-2α induces RNF126, which ubiquitinates the peroxisomal transporter ABCD3 to trigger selective peroxisome autophagy (pexophagy), depleting peroxisomes and erasing hepatocyte differentiation features. These findings identify RNF126–ABCD3–pexophagy as a mechanistic “peroxisomal fate switch” that could be exploited for redifferentiation therapy in HCC.

Su Q, Yang Y, Ren J et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

G-protein regulatory network governs receptor internalization dynamics.

This study examined how regulation of the heterotrimeric G-protein cycle influences G-protein-coupled receptor (GPCR) internalization dynamics. The authors establish principles showing that upstream G-protein regulatory mechanisms shape receptor internalization behavior, linking G-protein cycle control to spatially reorganized signaling. Scientifically, the work provides a systems-level framework for predicting and engineering GPCR trafficking and signaling outcomes.

Rowe JB, Pandey S, Mayer RA et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

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Generated automatically on June 11, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.