PubMed Trending Research Digest — September 13, 2026

Automated digest · 97 articles · 15 research areas · September 13, 2026

Overview

Across this week’s set, a dominant thread is mechanistic biology that links cellular “control points” to disease trajectories—especially via mitochondria, immune signaling, and compartmentalized receptor pathways. Multiple studies connect mitochondrial stress and homeostasis to outcomes (from C. elegans longevity to musculoskeletal disease and mitophagy regulation), while others show how metabolic cues (lactate sensing, glycolysis control, propionyl-CoA/ferroptosis resistance) reprogram immunity and cancer progression. In parallel, GPCR-focused work (including cryo-EM structures and receptor–β-arrestin stoichiometry/bias) emphasizes that where and how signaling occurs—at the membrane vs internal compartments—can determine biological output, offering a blueprint for more precise pharmacology.

A second major theme is immune modulation in complex microenvironments. Several papers highlight how to improve immunotherapy performance by reshaping the tumor or perioperative niche (TREM2-targeting after glioblastoma surgery, TAM-targeted mRNA delivery, stromal FAP targeting with bispecifics, and HER2-restricted 4-1BB agonism). Complementing this, studies in autoimmunity and inflammation (RA trajectories on JAK inhibitors, spatial immune niches in atopic dermatitis, FcRn blockade for pemphigus, and phenotype-based MAS distinctions) underscore the move toward stratified, mechanism-informed treatment selection. Microbiome/virome reviews and studies further broaden immune control to the gut-brain and antiviral axes, suggesting that microbial metabolites and viral components can tune neuroimmune homeostasis.

Finally, the digest includes clinically oriented evidence and implementation research spanning cardiometabolic risk, kidney disease, infection management, and digital/AI tools. Work on GLP-1-related outcomes (including muscle/lean mass considerations and real-world psychiatric safety signals), MASH fibrosis treatment guidance, and cross-population CVD risk model transferability all point to personalization beyond single-disease frameworks. Meanwhile, infection-focused studies (from HEV mouse models to toxin-targeting EVs for pneumococcal meningitis and improved SSTI triage) and pragmatic trial protocols (exercise for sarcopenia, AI-assisted prenatal ultrasound, safe-anastomosis training) reflect an emphasis on translating mechanistic insights into scalable, real-world care.

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Cancer precision oncology: targets, biomarkers, and resistance mechanisms

Neutrophil Senescence Induced by Tumor-Derived HMGB1 Promotes Hepatocellular Carcinoma Progression through Neutrophil Extracellular Trap-Mediated Suppression of CD8+ T Cell Immunity.

The study examined how tumor-derived HMGB1 induces neutrophil senescence and how aged neutrophils affect hepatocellular carcinoma (HCC) progression and CD8+ T cell immunity in analyses of public datasets (GSE149614, GSE189903) and a clinical cohort of 105 HCC patients and 41 healthy controls. Tumor-derived HMGB1 drove neutrophil extracellular trap (NET)-mediated suppression of CD8+ T cells, promoting HCC progression. These findings identify HMGB1–NET–CD8+ T cell immune suppression as a mechanistic axis and suggest aged neutrophil features as clinically relevant biomarkers/targets in HCC.

Duan Y, Yu S, Wang X et al. · Cancer communications (London, England) · (2026) · View on PubMed ↗

MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy.

The study investigated how methylmalonate semialdehyde dehydrogenase (MMSDH) regulates ferroptosis and gemcitabine (GC) resistance in pancreatic ductal adenocarcinoma (PDAC) under hypoxia, focusing on hypoxia-driven post-translational modifications and downstream ACSL4 regulation. Hypoxia induced GCN5-mediated lactylation of MMSDH at K113, enabling lactylated MMSDH to interact with ACSL4 to generate propionyl-CoA and promote KAT8-mediated ACSL4 K606 propionylation, which enhanced ACSL4-HSC70 binding and chaperone-mediated autophagic degradation of ACSL4, thereby counteracting ferroptosis and impairing PDAC chemotherapy efficacy. This mechanistic pathway (GCN5–MMSDH lactylation–ACSL4 propionylation–CMA) provides a metabolic target to overcome ferroptosis-linked chemoresistance in PDAC.

Zheng P, Lin Y, Zhang M et al. · Nature cancer · (2026) · View on PubMed ↗

Tumor-derived CTHRC1 mediates ITGB3-dependent osteoclast differentiation to promote prostate cancer bone metastasis.

The study examined how tumor-derived CTHRC1 regulates ITGB3-dependent osteoclast differentiation to drive prostate cancer bone metastasis using in vitro co-culture systems and in vivo mouse models. Tumor-derived CTHRC1 promoted osteoclast differentiation and osteolytic lesion development by cooperating with RANKL signaling, enhancing osteoblast-derived RANKL-mediated osteoclastogenesis. This identifies the CTHRC1–ITGB3–RANKL axis as a potential therapeutic target to limit osteolytic bone metastasis in advanced prostate cancer.

Xie T, Peng T, Li Q et al. · Oncogene · (2026) · View on PubMed ↗

Propionyl-CoA catabolism is a metabolic gatekeeper for fatty acid oxidation in pancreatic cancer.

The study investigated whether propionyl-CoA catabolism controls fatty acid oxidation (FAO) dependency in pancreatic ductal adenocarcinoma (PDAC) by integrating patient plasma/tumor observations with mechanistic experiments in human PDAC cells and KPC mouse tumors (Pdx1-Cre; KrasG12D; Trp53R172H). PDAC patients and tumors showed decreased plasma propionyl-CoA intermediates and increased propionyl-CoA catabolic activity, with PDAC cells upregulating propionyl-CoA carboxylase (PCC) to accelerate propionyl-CoA catabolism and establish a PDAC-specific metabolic signature. PCC was required for PDAC growth, indicating propionyl-CoA catabolism as a metabolic gatekeeper and potential vulnerability for therapy.

Yu W, Wang B, Meng F et al. · Oncogene · (2026) · View on PubMed ↗

Dense RNA motif modifications enable robust in vivo prime editing and enhance efficiencies of diverse editing systems.

The study developed engineered prime editing guide RNAs (pegRNAs) containing densely modified RNA motifs and tested whether they enable robust in vivo prime editing across diverse editing systems. Systemic delivery of the prime editor as RNA via a single lipid nanoparticle injection achieved nearly 70% editing efficiency in vivo, improving performance without repeated dosing. This advances prime editing toward more clinically feasible delivery by increasing efficiency through pegRNA design.

Lei X, Chen D, Zhang K et al. · Nature biomedical engineering · (2026) · View on PubMed ↗

Malic enzyme 1 senses L-lactate to determine tumor heterogeneity.

This mechanistic cancer study investigated how malic enzyme 1 (ME1) senses L-lactate in tumor cells, focusing on direct binding to arginine 155 (R155) and downstream nuclear signaling. L-lactate binding promoted ME1 nuclear translocation via reduced acetylation at lysine 362 (K362) and karyopherin-α 4 (KPNA4)-dependent nuclear import, increasing metastatic potential through enhanced interaction with hepatoma-derived growth factor (HDGF) and epithelial–mesenchymal transition (EMT). Scientifically, it identifies ME1 as an L-lactate sensor that could be targeted to disrupt lactate-driven tumor heterogeneity and metastasis.

Cao SY, Hu K, Huang S et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Genome-wide CRISPR screens map synthetic lethal interactions across recurrent cancer driver alterations.

This study mapped synthetic lethal (SL) interactions across recurrent cancer driver alterations using genome-wide CRISPR screens in functionally validated isogenic cell lines and large-scale SL analysis integrating Cancer Dependency Map (DepMap) data. It charted SL interactions across 15 driver alterations (including FBXW7, CCNE1, CDK12, ARID1A, KMT2D, DNMT3A, TET2, KEAP1, STK11, IDH1, SF3B1, SRSF2, U2AF1, and chromosome 18q/13q losses) and validated several interactions such as ARID1A with GFPT1 and STK11 with a partner gene. The significance is that it expands actionable vulnerabilities for tumors driven by alterations that are not directly druggable, supporting target discovery for precision oncology.

Desjardins J, Bowlan J, Bernier C et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

Engineered Transformer Base Editor with Enhanced Editing Efficiency.

This engineering study developed an engineered transformer base editor (etBE) to improve cytosine base editing efficiency while reducing off-target (OT) mutations. The key finding is that etBE—created by rational deaminase engineering and fusion of a uracil DNA glycosylase inhibitor (UGI) domain to an engineered transformer base editor (tBE) architecture—achieved substantially enhanced editing efficiency compared with prior tBE approaches while maintaining improved OT profiles. This advances the translational potential of base editing by addressing a major bottleneck (insufficient efficiency) that limits broader clinical and research applications.

Chen B, Liang L, Xu R et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Insulin-like growth factor receptor signaling in physiology and disease.

This review summarized the insulin-like growth factor (IGF) signaling axis in physiology and disease, focusing on IGF ligands, IGF receptors (IGFRs), and IGF-binding proteins and their downstream pathways. It emphasized multilevel regulation that links upstream IGF/IGFR signaling to effectors such as PI3K–AKT and MAPK/ERK, and discussed how pathway dysregulation contributes to disease. The synthesis is significant for identifying therapeutic opportunities to modulate IGF/IGFR signaling in conditions where proliferation, differentiation, and redox homeostasis are disrupted.

Dilawar M, Malik A, Liao J et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

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Metabolic disease: obesity, diabetes, and liver fibrosis

Paediatric proteomic signatures of cardiometabolic disease-associated traits predict adult disease outcomes.

The study assessed whether pediatric circulating proteomic signatures reflecting 25 cardiometabolic disease (CKMD) traits in Hispanic/Latino children and adolescents (n=273; mean age 13.1 years) predict adult CKMD outcomes in a community adult cohort (n=685) and a much larger adult dataset (28,256 adults). Proteome signatures of CKMD in children were strongly associated with subsequent adult clinical CKMD outcomes. This supports proteomics-based early risk stratification for CKMD beyond adult-only thresholds, potentially enabling earlier intervention in children at high risk.

Landman JM, Highland HM, Perry AS et al. · Nature metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

International expert panel review for the use of resmetirom and semaglutide in the management of MASH-related fibrosis: clinical practice update.

This international expert panel review assessed clinical evidence for using resmetirom (Rezdiffra) and semaglutide (Wegovy) to treat MASH-related fibrosis in patients with significant fibrosis (F2–F3) without cirrhosis. It summarizes complementary mechanisms—resmetirom as a liver-directed thyroid hormone receptor-β agonist and semaglutide as a GLP-1 receptor agonist—and consolidates phase III trial data to support practice recommendations. The clinical significance is providing updated guidance for pharmacologic management of MASH with fibrosis in the post-FDA-approval era.

Mironova M, Ratziu V, Rinella ME et al. · Gut · (2026) · View on PubMed ↗

Orchestrated cell death pathways in cholangiopathies.

This review article examined orchestrated programmed cell death pathways in cholangiopathies, focusing on how epithelial stress and immune activation converge on cholangiocyte dysfunction and biliary fibrosis. It describes multiple regulated cell death modalities—apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death—triggered in a disease- and context-dependent manner in cholangiocytes. Scientifically, it frames cell-death pathway targeting as a potential strategy to interrupt progression of chronic bile duct injury and fibrosis.

Guicciardi ME, Pistorio V, Soret PA et al. · Gut · (2026) · View on PubMed ↗ · Free PDF ↗

Where the Future Lies: GLP-1 Receptor Agonists as Therapeutics for Dermatologic Comorbidities.

This review studied glucagon-like peptide-1 receptor agonists (GLP-1RAs) as potential therapies for dermatologic comorbidities in people with chronic inflammatory skin diseases. It found emerging clinical-trial and real-world evidence suggesting GLP-1RAs may improve outcomes in psoriasis, hidradenitis suppurativa, and atopic dermatitis while reducing cardiometabolic disease burden that often coexists with these conditions. Scientifically and clinically, this supports further mechanistic and interventional research on immunometabolic pathways linking GLP-1 signaling to skin inflammation.

DeCoster M, Narla S · Clinics in dermatology · (2026) · View on PubMed ↗

The evolving landscape of chronic pancreatitis in Japan: findings from a nationwide epidemiological survey in 2021.

This nationwide epidemiological survey in Japan studied the current burden and clinical characteristics of chronic pancreatitis (CP) using a two-stage design in patients treated at participating hospitals in 2021. It estimated 73,590 people with definite or probable CP in 2021 (prevalence 58.6 per 100,000) and 17,490 newly diagnosed cases (annual incidence 13.9 per 100,000), showing about a 30% increase in prevalence compared with 2016. The significance is that it updates national CP epidemiology and supports planning for prevention, diagnosis, and healthcare resource allocation.

Masamune A, Matsumoto R, Takikawa T et al. · Journal of gastroenterology · (2026) · View on PubMed ↗ · Free PDF ↗

Non-pharmacological therapies of traditional Chinese medicine in prediabetes: a systematic review and network meta-analysis of randomized controlled trials.

This systematic review and network meta-analysis compared six non-pharmacological traditional Chinese medicine (NPTTCM) interventions for prediabetes using randomized controlled trials. It evaluated acupuncture, acupoint catgut embedding (ACE), Baduanjin, electroacupuncture, massage, and Taiji, estimating mean differences and confidence intervals and ranking treatments via SUCRA. The significance lies in providing comparative efficacy evidence to guide selection of NPTTCM strategies for prediabetes risk reduction.

Qi X, Wang T, Liao L · Frontiers in endocrinology · (2026) · View on PubMed ↗ · Free PDF ↗

Reporting patterns of suicide- and self-injury-related events involving liraglutide, semaglutide, and tirzepatide: data from the European pharmacovigilance database.

This pharmacovigilance study analyzed the European pharmacovigilance database to characterize reporting patterns of suicide- and self-injury-related events associated with GLP-1 receptor agonists liraglutide and semaglutide and the dual GIP/GLP-1 agonist tirzepatide. It provides an updated assessment of psychiatric safety signals in post-marketing reports as these drugs are increasingly used for type 2 diabetes and chronic weight management. The clinical significance is improved real-world safety monitoring for suicidality/self-harm signals to inform clinicians and regulators while causality remains unproven.

Scavone C, Cerasuolo M, Gaio M et al. · Frontiers in pharmacology · (2026) · View on PubMed ↗ · Free PDF ↗

Obesity Increases Atherosclerosis Susceptibility via an Intertissue miR-30e-SLC7A11 Axis.

This study investigated how obesity increases susceptibility to atherosclerosis through an intertissue miR-30e–SLC7A11 axis linking adipose-derived signals to vascular endothelium. Using miRNA data mining and RT-PCR validation, it tested the proposed endocrine-like pathway in which adipose-derived miR-30e-5p influences SLC7A11 (a cystine/glutamate transporter) to promote endothelial atherogenic changes. Scientifically, it identifies a mechanistic miRNA–transporter axis that could be targeted to reduce obesity-driven atherosclerosis risk.

Wang C, She J, Qian X et al. · Circulation research · (2026) · View on PubMed ↗ · Free PDF ↗

Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists as Adjuncts to Insulin Therapy in Type 1 Diabetes Mellitus: An Overlap-Informed Umbrella Review.

This overlap-informed umbrella review synthesized evidence on glucagon-like peptide-1 receptor agonists (GLP-1RAs) used as adjuncts to insulin therapy in adults with type 1 diabetes mellitus (T1DM). The key finding is that the authors found the overall interpretation is complicated by substantial overlap among primary studies, methodological heterogeneity, and variable certainty of evidence, which affects conclusions about efficacy and safety. Scientifically and clinically, it clarifies the strength and limitations of current data to guide whether GLP-1RAs should be adopted broadly as adjuncts in T1DM.

Lee O, Son Y, López-Gil JF et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗

ALKBH5 activates creatine-driven thermogenesis by stabilizing CKB mRNA in response to cold.

This study investigated how the m6A demethylase ALKBH5 regulates non-shivering thermogenesis in response to cold by stabilizing CKB mRNA in adipose tissue. It found that cold/adrenergic stimulation increases ALKBH5 activity, fat-specific Alkbh5 knockout reduces thermogenic capacity and worsens obesity susceptibility and glucose homeostasis in male and female mice, while ALKBH5 overexpression increases energy expenditure and improves systemic metabolism; ALKBH5 expression inversely correlates with obesity in humans. The mechanism is significant because it identifies an ALKBH5–CKB mRNA stabilization pathway as a potential therapeutic target for obesity and metabolic disease independent of UCP1.

Zhang Y, Du C, Qiao W et al. · Nature metabolism · (2026) · View on PubMed ↗

The transcription factor C/EBPβ promotes hyperglycemia-elicited glycolysis and liver cancer progression.

This study examined how the transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) drives hyperglycemia-elicited glycolysis and liver cancer progression in hepatocellular carcinoma. It found that high glucose activates C/EBPβ transcription via a ROS-dependent PERK–eIF2α–ATF4 pathway, and that the LAP isoforms of C/EBPβ (not LIP) promote glycolytic gene programs that support tumor progression. These mechanistic links between hyperglycemia signaling and C/EBPβ-dependent metabolism suggest potential therapeutic strategies to slow liver cancer in patients with diabetes.

Luo Y, Qian Z, Yuan G et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Beyond Fat Loss: Addressing the Sarcopenia Challenge of Incretin-Based Therapies.

The article reviewed how incretin-based therapies for type 2 diabetes and obesity (including GLP-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists) affect body composition, particularly lean mass and sarcopenia risk. It highlights that weight loss commonly reduces lean mass, but lean loss does not necessarily equate to true skeletal muscle contractile impairment or sarcopenia. Clinically, it emphasizes the need for better assessment of muscle quality and sarcopenia outcomes when using incretin-based regimens.

Kim JY, Kim NH · Diabetes & metabolism journal · (2026) · View on PubMed ↗ · Free PDF ↗

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Infection, inflammation, and antimicrobial/antitoxin strategies

Comparison of new and recurring post-acute infection syndrome - results from a German population-based cohort.

This cross-sectional study compared first versus recurring post-acute infection syndrome (PAIS) episodes in a German population-based digital cohort (DigiHero; DRKS00025600), using retrospective self-reports from 2,801 participants who reported a respiratory infection between Sept 2024 and Aug 2025 with symptoms lasting ≥12 weeks. Among PAIS cases, the study found differences in symptom burden/impairment and episode duration between new and recurring PAIS episodes (with 57% reporting PAIS recurrence among detected cases). These findings improve recognition and clinical management of PAIS relapse patterns by quantifying how recurring episodes differ from initial episodes.

Frost J, Peter F, Glaser N et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗

Long-term safety of first-line osimertinib plus platinum-pemetrexed in EGFR-mutated advanced NSCLC: FLAURA2.

This systematic review and meta-analysis studied randomized controlled trials in adults (≥18 years) in emergency departments with acute respiratory failure (ARF), comparing high-flow nasal oxygen (HFNO) versus conventional oxygen therapy (COT) or non-invasive ventilation (NIV). The primary outcome was the need for endotracheal intubation and mechanical ventilation, with secondary outcomes including ICU admission, hospital length of stay, dyspnoea scores, physiological/biochemical parameters, and mortality. Clinically, the pooled evidence is intended to guide ED oxygenation strategy selection to reduce escalation to invasive ventilation in ARF.

Planchard D, Jänne PA, Yang JC et al. · Lung cancer (Amsterdam, Netherlands) · (2026) · View on PubMed ↗ · Free PDF ↗

Advances in the diagnosis and management of skin and soft tissue infections.

This review studied the diagnosis and management of skin and soft tissue infections (SSTIs) across clinical presentations in patients, focusing on non-purulent versus purulent disease. It found that non-purulent SSTI is most often linked to beta-haemolytic streptococci while purulent SSTI is typically associated with Staphylococcus aureus, and that point-of-care ultrasound can help distinguish cellulitis from abscess when laboratory testing is of limited value. These findings support more accurate bedside triage and targeted treatment decisions for common SSTIs, including cellulitis and necrotizing fasciitis.

Long B, Yadav K, Rech MA et al. · BMJ (Clinical research ed.) · (2026) · View on PubMed ↗

Mouse models of acute and chronic hepatitis E virus infection.

This study investigated whether laboratory mice can be infected with hepatitis E virus (HEV) and aimed to develop an inbred mouse model across HEV genotypes using AG129 and C57BL/6J mice. It found that HEV infection could be assessed using HEV RNA detection by RT-PCR and RNAscope along with liver function tests and histopathology, enabling characterization of acute and chronic infection parameters in these mouse strains. The resulting model is significant for mechanistic studies of host species range and for testing interventions against HEV infection.

Liu T, Yang X, Li B et al. · Journal of hepatology · (2026) · View on PubMed ↗

Levofloxacin-associated tendon disorders: Sex-, age-, and route-specific disproportionality analysis using FAERS and JADER.

This pharmacovigilance study used FAERS and JADER spontaneous adverse event databases to evaluate associations between individual fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin) and tendon disorders in Japan, with attention to sex-, age-, and route-specific patterns. While all fluoroquinolones showed positive signals in FAERS, levofloxacin demonstrated consistent and robust associations in the Japanese subset of FAERS and JADER, including strong signals for muscle, tendon, and ligament injuries. These findings support more targeted risk communication and monitoring for tendon toxicity with levofloxacin in real-world prescribing.

Nakashima T, Noguchi Y, Masuda R et al. · PloS one · (2026) · View on PubMed ↗ · Free PDF ↗

Out-of-Hospital Intensive Care in Germany - who´s out there? Key issues revealed by the clinical application of the new legislation in Baden Württemberg.

This German retrospective clinical application study evaluated out-of-hospital intensive care patients in Baden-Württemberg by examining 148 consecutive adults (Oct 2023–Feb 2026) for weaning potential under new legislation requiring intensive care prescription/optimization by experienced physicians. The key finding was that the first real-world cohort revealed practical issues in identifying and managing patients needing out-of-hospital intensive care and assessing weaning potential. Scientifically and clinically, it provides early implementation data to refine referral, staffing, and rehabilitation pathways for a vulnerable population at risk of poor outcomes.

Joves B, Kempa A, Rheinhold A et al. · Respiration; international review of thoracic diseases · (2026) · View on PubMed ↗

Pseudomonas Aeruginosa Abundotypes and Interactotypes Reflect Clinical Heterogeneity in Bronchiectasis.

This study analyzed sputum metagenomes from 600 individuals with bronchiectasis across 10 countries to define Pseudomonas aeruginosa abundance-based subgroups (abundotypes) and interaction-based subgroups (interactotypes) and to assess their longitudinal behavior during acute exacerbation and PA eradication. It identified four PA-abundotypes with comparable exacerbation risk and showed that transition probabilities differed across clinical scenarios, reflecting clinically meaningful heterogeneity. The significance is that PA “abundotypes/interactotypes” could enable more personalized risk stratification and treatment monitoring in bronchiectasis.

Narayana JK, Jaggi TK, Dimakou K et al. · American journal of respiratory and critical care medicine · (2026) · View on PubMed ↗ · Free PDF ↗

‘Leave no one behind’: cochlear implantation under regional anaesthesia in a humanitarian setting - a case series.

This case series evaluated feasibility, safety, and outcomes of cochlear implantation performed under regional anaesthesia (RA) in a humanitarian setting for patients with severe-to-profound hearing loss, including those with complex comorbidities who might be ineligible for general anaesthesia (GA). The key finding is that RA enabled cochlear implantation while avoiding GA-related logistical and safety risks, supporting the humanitarian principle of “leaving no one behind.” Clinically, this suggests RA can expand access to life-changing hearing restoration in low-resource emergency missions where GA is difficult or unsafe.

Aljazeeri I, Alzahrani MF, Halawani RT et al. · Journal of global health · (2026) · View on PubMed ↗ · Free PDF ↗

RNAi-mediated HBV antigen shutdown enhances the antiviral immune effects of PEGIFNα via T and B cell crosstalk remodeling.

This study investigated whether RNA interference–mediated hepatitis B virus (HBV) antigen shutdown using GalNac-conjugated siRNA (GalNac-siHBV) enhances the antiviral immune effects of PEGylated interferon-α (PEGIFNα) through T- and B-cell crosstalk remodeling in an extracellular humanized IFNAR (IFNAR-hEC) mouse model of chronic HBV infection. The key finding is that combining GalNac-siHBV with PEGIFNα improves antiviral immune responses beyond either approach alone, supported by flow cytometry, ELISpot, and single-cell RNA sequencing (scRNA-seq) analyses of immune phenotypes and functions. This provides mechanistic rationale for combination strategies that more effectively suppress HBV antigens to improve interferon responsiveness in chronic hepatitis B.

Zai W, Hu K, He M et al. · Clinical and molecular hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Bioengineered Extracellular Vesicles Mitigate Neuroinflammation by Neutralizing Pneumolysin and Delaying Disease Onset in Experimental Pneumococcal Meningitis.

This experimental study evaluated bioengineered extracellular vesicles (EVs) derived from human HEK293T cells that neutralize pneumolysin (Ply) to mitigate neuroinflammation and delay disease onset in a model of experimental pneumococcal meningitis caused by Streptococcus pneumoniae. The key finding is that Ply-neutralizing EVs reduced neuroinflammatory outcomes and postponed onset of disease compared with standard approaches, addressing the limitation that antibiotics poorly reach the brain and do not neutralize Ply. Scientifically, it suggests a toxin-targeting EV therapeutic could complement antibiotics and dexamethasone to reduce mortality and long-term neurological sequelae.

Farmen K, Mamand DR, Tofiño-Vian M et al. · Journal of extracellular vesicles · (2026) · View on PubMed ↗ · Free PDF ↗

Modeling reptile virus infection in vitro using Python regius airway organoids.

The study developed and characterized airway organoids derived from the reptile Python regius to model reptile virus infection in vitro. Using de novo assembly of a Python regius reference genome and single-cell resolution characterization, it identified diverse airway cell populations (including ionocytes and ciliated/secreto—cell types) to support infection modeling. This provides a scalable translational platform for studying reptile airway tropism and assessing zoonotic risk of reptile viruses.

Willemsen S, van Son G, Rissmann M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration and synaptic plasticity mechanisms

Gain-of-function suppressors restore microtubule dynamics and rescue dominant-negative tubulinopathies.

The study performed suppressor screens in Caenorhabditis elegans to identify gain-of-function suppressors that restore microtubule dynamics and rescue dominant-negative tubulinopathies caused by missense mutations in α- and β-tubulin genes. It identified three classes of missense suppressors, including intergenic suppressors that restore microtubule architecture either by competitively excluding mutant tubulins (assembly-defective) or by modulating microtubule dynamics (assembly-competent), with conserved effects in human cells and murine oocytes. These results provide candidate genetic suppressors and mechanistic strategies for counteracting dominant-negative tubulin disorders.

Xu K, Guo Z, Ke J et al. · Nature cell biology · (2026) · View on PubMed ↗

Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.

This research examined how altered neuronal start codon stringency affects repeat-associated non-AUG (RAN) translation in the context of C9orf72 intronic GGGGCC repeat expansions relevant to ALS/FTD. It found that rodent neurons and human iNeurons favor cap-independent RAN translation from CGG and GGGGCC repeats across multiple reading frames, and that an eIF4E inhibitor (blocking cap-dependent translation) modulated this cap dependency. Scientifically, it clarifies cell-type–specific control of toxic RAN translation initiation and supports targeting translation pathways as a potential therapeutic approach.

Wieland CM, Wright SE, Willey S et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

Neuromodulatory Gating of Synaptic Plasticity: Mechanisms, Motivation, and Clinical Dysfunction Across Scales.

This article reviewed how synaptic plasticity is regulated across scales by a proposed four-layer hierarchy—energetic constraints, homeostatic stability, neuromodulatory gating (including dopamine and acetylcholine), and experience-dependent synaptic modification—in neural circuits. It argues that neuromodulators gate when and where plasticity can occur by integrating metabolic and stability constraints with ongoing experience. The framework is clinically relevant because dysfunction in these gating layers could contribute to disorders of learning and memory and provides mechanistic targets for future interventions.

Azimzadeh M, Azimzadeh M · Synapse (New York, N.Y.) · (2026) · View on PubMed ↗

Retromer-targeted therapy for neurodegenerative diseases.

This narrative review evaluated retromer-targeted therapeutic strategies in neurodegenerative diseases—Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—focusing on how retromer dysfunction intersects endosomal-lysosomal system (ELS) pathways. It concludes that retromer sits at a crossroads of shared mechanisms including proteostasis/protein misfolding, mitochondrial function, neurotransmission, and neuroinflammation that amplify neurodegeneration. The review is clinically important because it frames retromer as a tractable molecular target for disease-modifying therapies across multiple neurodegenerative disorders.

Persico M, Tuithung S, Lorenzo A et al. · Molecular neurodegeneration · (2026) · View on PubMed ↗ · Free PDF ↗

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Autoimmunity and inflammatory disease models/therapies (RA, SLE, pemphigus, mastocytosis)

Recognition and management of acute relapse of multiple sclerosis, neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease.

This review article synthesized current approaches for recognizing and managing acute relapses/attacks in multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Despite differences in target antigens and immune effector mechanisms, these disorders share a clinical pattern of acute neurological episodes and later relapses, and the review emphasizes challenges in distinguishing patient-reported symptoms from physician-confirmed attacks and managing confounding factors. Clinically, it supports more timely and accurate relapse recognition and management across the CNS autoimmune spectrum.

Li YJ, Jiang W, Zhang C et al. · Cell death and differentiation · (2026) · View on PubMed ↗

Treating Stage IV periodontitis: the UK adolopment of the EFP Stage IV Periodontitis Treatment Guidelines.

This article describes the UK adaptation (“adolopment”) of the European Federation of Periodontology (EFP) S3 Clinical Guideline for Stage IV Periodontitis, translating recommendations for rehabilitation of dentition in Stage IV (and sometimes Stage III) disease. It outlines the structure of an S3-level guideline and presents the adapted recommendations across case types for the UK context. The significance is providing standardized, guideline-based care to improve treatment consistency and outcomes for advanced periodontitis patients.

Raindi DS, Kebschull M, Chapple I · British dental journal · (2026) · View on PubMed ↗ · Free PDF ↗

Isolated perianal fistulizing Crohn’s disease in contemporary clinical practice: a multicenter ECCO-CONFER cohort study.

This multicenter ECCO-CONFER cohort study characterized isolated perianal fistulizing Crohn’s disease (IPFCD) in adults without luminal Crohn’s disease at baseline and assessed long-term outcomes. The primary endpoint was progression to luminal Crohn’s disease, with secondary outcomes including fistula response and patterns of medical and surgical management across 25 centers. Clinically, it aims to clarify natural history and contemporary diagnostic/therapeutic approaches for this uncommon Crohn’s presentation.

Basnayake K, Subhaharan D, Drobne D et al. · Journal of Crohn’s & colitis · (2026) · View on PubMed ↗ · Free PDF ↗

Glycocalyx-edited mesenchymal stem/stromal cell therapy in advanced osteoporosis.

This first-in-human clinical trial studied glycocalyx-edited autologous bone marrow-derived mesenchymal stem/stromal cells (MSCs) in ten women with advanced osteoporosis, using a strategy to enforce sialylated Lewis X (sLeX) expression to improve bone homing. It found that a single intravenous infusion of these MSCs was followed by a 2-year protocol-mandated evaluation including clinical assessments, radiographic studies, and bone turnover marker measurements. The significance is that glycocalyx editing may overcome poor osteotropism and provide a potentially effective cell-therapy platform for advanced osteoporosis.

Moraleda JM, Linares LF, García-Bernal D et al. · Cell · (2026) · 1 citations · View on PubMed ↗

Infantile Maculopapular Cutaneous Mastocytosis: A Case Report with an Integrative Unani Medicine Perspective.

This case report studied an infant with infantile maculopapular cutaneous mastocytosis using standard diagnostic work-up (serum tryptase, histopathology, immunohistochemistry) alongside an integrative Unani medicine perspective. The key finding was that the 9-month-old boy’s clinical presentation (multiple hyperpigmented macules with positive Darier’s sign) and laboratory/histologic testing confirmed maculopapular cutaneous mastocytosis while emphasizing the need to exclude systemic disease. The significance is improved clinical recognition and diagnostic rigor in pediatric mastocytosis, while documenting complementary care approaches.

Khanum S, Ilyas J, Eram F · Advances in mind-body medicine · (2026) · View on PubMed ↗

Macrophage activation syndrome in systemic lupus erythematosus and Still’s disease: distinct phenotypes shaped by the underlying diseases.

This retrospective multicenter cohort study compared macrophage activation syndrome (MAS) phenotypes in adults with systemic lupus erythematosus (SLE-MAS) versus Still’s disease (SD-MAS) using data from nine tertiary referral centers. The key finding was that SLE-MAS and SD-MAS show distinct clinical and laboratory profiles, with “inaugural MAS” defined as occurring within 6 months of underlying disease onset and exploratory profiling suggesting disease-specific features. The significance is improved phenotype-based understanding that may guide more tailored treatment strategies for these life-threatening complications.

Tonutti A, Cavazzana I, Gerosa M et al. · Rheumatology (Oxford, England) · (2026) · View on PubMed ↗ · Free PDF ↗

Spatial Transcriptomics Identifies Characteristic Immunological Niches in Atopic Dermatitis.

This study used 10× Genomics Visium spatial transcriptomics on FFPE skin biopsies to map immune cell organization and interactions in atopic dermatitis (AD) compared with psoriasis and healthy controls. It identified characteristic immunological niches in human AD skin by integrating spatial transcriptomics with AD single-cell RNA-seq and validating with imaging mass cytometry and multiplex immunofluorescence. The results are clinically important because they provide a spatially resolved framework for understanding Type 2–driven AD pathology and for targeting pathogenic microenvironments.

Gross L, Bäriswyl L, Kupschke E et al. · Allergy · (2026) · View on PubMed ↗ · Free PDF ↗

Site-Specific Response and Psychosocial Outcomes in Head and Neck Atopic Dermatitis Treated with Tralokinumab: A Prospective Real-World Study.

This prospective real-world study evaluated site-specific response and psychosocial outcomes in adults with head and neck (H&N) atopic dermatitis treated with the IL-13 monoclonal antibody tralokinumab. In 100 patients followed up to 52 weeks, it assessed H&N involvement using H&N EASI and measured clinical endpoints (H&N EASI reduction and H&N EASI75 at weeks 16, 32, and 52) alongside patient-reported quality-of-life and psychological outcomes. The significance is that it connects H&N-specific clinical improvement with longitudinal psychosocial benefit, supporting patient-centered effectiveness of tralokinumab in this burdensome AD phenotype.

Mastorino L, Cangialosi L, Cavaliere G et al. · Dermatitis : contact, atopic, occupational, drug · (2026) · View on PubMed ↗

Efficacy and safety of subcutaneous efgartigimod with prednisone in moderate-to-severe pemphigus (ADDRESS): a global, phase III, randomised controlled, double-blind trial.

This global phase III randomized double-blind trial studied subcutaneous efgartigimod PH20 (an IgG1 Fc fragment co-formulated with recombinant human hyaluronidase PH20) given with prednisone in adult patients with newly diagnosed or relapsing moderate-to-severe pemphigus vulgaris or pemphigus foliaceus. The key finding reported in the abstract is that the trial was designed to evaluate efficacy and safety of this FcRn-blocking approach to reduce pathogenic IgG autoantibodies in combination with standard corticosteroid therapy. If effective and safe, this regimen could provide a steroid-sparing, targeted immunotherapy option for IgG-mediated pemphigus in real-world clinical practice.

Joly P, Murrell DF, Aoyama Y et al. · The British journal of dermatology · (2026) · View on PubMed ↗ · Free PDF ↗

Sequential disease activity assessment for predicting future treatment trajectories in patients with rheumatoid arthritis treated with JAK inhibitors: a group-based trajectory and landmark analysis.

The study analyzed rheumatoid arthritis (RA) patients treated with Janus kinase (JAK) inhibitors to identify disease activity trajectories and test whether early disease activity predicts longer-term treatment patterns. Using a multicentre registry of 843 patients, it applied group-based trajectory modeling of Clinical Disease Activity Index (CDAI) over 52 weeks and performed landmark analyses at weeks 4 and 12 with multivariate logistic regression. This supports a data-driven approach to forecasting future treatment trajectories from early disease activity measurements in JAK-treated RA.

Terabe K, Asai S, Yoshioka Y et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗

A new humanised TCR transgenic mouse model to study T cells reactive to citrullinated tenascin C, a relevant autoantigen in rheumatoid arthritis.

The study generated a humanised T-cell receptor (hTCR) transgenic mouse model to study T cells reactive to citrullinated tenascin C (citTNC), an autoantigen implicated in rheumatoid arthritis. It engineered a chimeric TCR with murine constant domains and human V(D)J sequences recognizing citrullinated tenascin C22 (citTNC22) in an HLA-DRB1*04:01 (HLA-DR4) restricted manner. This model enables functional experiments on rare citrullinated-antigen–reactive T cells and supports mechanistic studies of RA autoimmunity.

Schülein M, Afonso M, Sijbranda M et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗ · Free PDF ↗

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Immunotherapy and cellular therapies (CAR-T, TCEs, bispecifics, mRNA immunotherapy)

Prophylactic dexamethasone at the time of absolute lymphocyte expansion does not mitigate risk or event-free survival for immune effector cell associated delayed neurotoxicity.

This study evaluated whether prophylactic dexamethasone (DEX) given around the time of absolute lymphocyte count (ALC) expansion reduces immune effector cell–associated delayed neurotoxicity (IEC-DNT) in 57 patients with high-ALC after ciltacabtagene autoleucel (cilta-cel) CAR-T therapy. In a comparison with a historical high-ALC cohort (n=104), short-course DEX (10 mg twice daily for ≥3 days) did not mitigate IEC-DNT risk or improve event-free survival. These findings suggest that routine steroid prophylaxis at the ALC-expansion timepoint may not prevent cilta-cel–associated neurotoxicity, informing supportive-care strategies for CAR-T recipients.

Lim KJ, Tan M, Parrondo R et al. · Blood cancer journal · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochondrial ATP promotes T cell differentiation through chromatin accessibility.

This study investigated how mitochondrial ATP production influences cytotoxic CD8+ T cell differentiation, focusing on D-α-hydroxybutyrate (DAHB) as a signaling molecule. It found that DAHB increases mitochondrial ATP production by shifting ATP generation from glycolysis to oxidative phosphorylation supported by fatty acid oxidation, elevating phosphocreatine (PCr) and promoting conversion of proliferating T cells into cytotoxic effector cells. The scientific significance is that targeting mitochondrial bioenergetics via DAHB/ATP–PCr pathways could enhance immune effector differentiation for chronic infection or cancer.

Ng C, Fung TS, Li D et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting tumor-associated macrophages using mRNA lipid nanoparticles for cytotoxic T lymphocyte-mediated cancer immunotherapy.

This preclinical study developed an antibody-coated lipid nanoparticle (Ab-LNP) system delivering messenger RNA (mRNA) to target tumor-associated macrophages (TAMs) to enhance cytotoxic T lymphocyte (CTL)-mediated antitumor immunity. The key finding was that TAM-targeted mRNA delivery via Ab-LNPs can remodel the immunosuppressive tumor microenvironment to sustain CTL anticancer activity while addressing limitations of untargeted mRNA cytokine/chemokine approaches. If validated further, this platform could provide a more precise and potentially safer mRNA immunotherapy strategy for solid tumors.

Chen R, Xu L, Staudacher AH et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

The FAP × CD3 bispecific antibody OMTX305 induces T cell-mediated antitumor effects in patient-derived ex vivo models of solid tumors.

This translational preclinical study evaluated the FAP×CD3 bispecific antibody OMTX305 (a trivalent Fab-eIg T cell engager) in patient-derived ex vivo models of solid tumors, including precision-cut tumor slices (PCTSs) of lung and ovarian cancers co-cultured with autologous PBMCs. The key finding was that OMTX305 induces T cell-mediated antitumor effects in these patient-derived systems by targeting fibroblast activation protein (FAP)-positive tumor-supportive cancer-associated fibroblasts. Scientifically and clinically, the data support OMTX305 as a strategy to overcome stromal barriers and immune exclusion by reprogramming the tumor microenvironment to improve T cell function.

Thiel J, Schlegel JA, Liang C et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

T-cell engagers in small cell lung cancer.

This review article examined the role of T-cell engagers (TCEs) in small cell lung cancer (SCLC), focusing on the predominant target delta-like ligand 3 (DLL3) and the DLL3xCD3 TCE tarlatamab. The key finding is that DLL3-directed TCEs can bypass the immunosuppressive SCLC tumor microenvironment by directly engaging CD3+ T cells to mediate tumor cell lysis, while introducing distinct toxicity-management and implementation challenges. Scientifically and clinically, it frames how DLL3xCD3 therapy has reshaped SCLC treatment and highlights future directions for improving safety and real-world effectiveness.

Cooper AJ, Sands J · Cancer · (2026) · View on PubMed ↗

The evolving role of immunotherapy in ovarian cancer.

This narrative review summarized the evolving role of immunotherapy in ovarian cancer, emphasizing why immune checkpoint inhibitors have shown limited activity due to tumor heterogeneity, an immunosuppressive tumor microenvironment, and insufficient predictive biomarkers. The key finding is that current research is shifting toward combination and precision approaches—including dual-checkpoint blockade, integration with chemotherapy or antiangiogenic therapy, PARP inhibitors, and emerging modalities such as adoptive cell therapies, vaccines, and oncolytic viruses. Clinically, it supports a strategy of tailoring immunotherapy combinations and biomarker-driven selection to overcome ovarian cancer immune resistance.

Veneziani AC, Venegas L, Oza AM · Cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Combination Of Bispecific Antibodies Enable Targeted TNFRSF Agonism and Effective Antitumor Activity.

This preclinical study investigated how combining bispecific antibodies enables targeted TNFRSF agonism of 4-1BB (CD137) in a HER2-dependent manner to achieve effective antitumor activity while limiting systemic toxicity. The key finding is that 4-1BB activation was assessed using 4-1BB-GFP and reporter cells, and the bispecific strategy produced cytokine induction and tumoricidal activity in primary T cells with strong in vivo antitumor efficacy in PBMC-xenograft and syngeneic h4-1BB/h4-1BBL transgenic models. Clinically, this supports a safer therapeutic design principle for 4-1BB agonism by restricting receptor clustering/activation to HER2+ contexts.

Diby L, Malinge P, Moine V et al. · Molecular therapy : the journal of the American Society of Gene Therapy · (2026) · View on PubMed ↗ · Free PDF ↗

A bispecific CD3×CD19 antibody for systemic lupus erythematosus: a phase 1 trial.

This phase 1 trial evaluated A-319, a next-generation bispecific CD3×CD19 T cell engager, in 12 patients with systemic lupus erythematosus receiving intravenous treatment. The key finding reported is that A-319 enables deep B cell depletion via CD19 targeting while engaging CD3+ T cells, demonstrating early clinical activity in this first-in-disease setting. This is significant because it offers an off-the-shelf alternative to CD19 CAR T approaches that typically require lymphodepletion and complex manufacturing infrastructure.

Xu J, Mei C, Guan X et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Configurational diversity of metabotropic glutamate receptor complexes with beta-arrestins.

This study investigated how perioperative remodeling of myeloid cells affects chimeric antigen receptor (CAR)-T cell efficacy in glioblastoma (GBM) using mouse models and human GBM ex vivo systems. Surgical resection induced rapid, sustained tumor microenvironment remodeling with upregulation of TREM2 in myeloid cells and subsequent emergence of T cell exhaustion-like phenotypes, and targeting TREM2 reshaped the perioperative TME to enhance antigen-specific CAR-T persistence, proliferation, effector differentiation, and survival in male mice. These results support timing- and myeloid-targeted strategies to improve CAR-T performance in the immunosuppressive perioperative GBM setting.

Marx DC, Gonzalez-Hernandez AJ, Lee J et al. · Nature communications · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

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Clinical oncology trials and treatment safety (drugs, ADCs, targeted therapy)

Deubiquitinases in mitophagy: therapeutic control of mitochondrial quality.

This long-term safety analysis of the phase 3 FLAURA2 trial studied first-line osimertinib plus platinum-pemetrexed versus osimertinib monotherapy in patients with EGFR-mutated advanced non-small-cell lung cancer (NSCLC). The study reports incidence and temporal patterns of treatment-emergent adverse events (AEs) across the combination arm’s exposure to platinum-pemetrexed for four cycles followed by osimertinib plus pemetrexed maintenance. The results are clinically significant for balancing the survival benefit of osimertinib-based combination therapy against long-term tolerability in EGFR-mutated advanced NSCLC.

Xu Y, Behrouz B, Lee A et al. · Trends in pharmacological sciences · (2026) · View on PubMed ↗

Safety and antitumor activity of the first-in-class EGFR-HER3 bispecific antibody-drug conjugate iza-bren (BL-B01D1) in patients with pretreated locally advanced or metastatic breast cancer: a phase 1b study.

This phase 1b clinical trial studied iza-bren (BL-B01D1), a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, in heavily pretreated patients with locally advanced or metastatic breast cancer. It found that the study enrolled 162 patients across HER2-positive, HR+/HER2-, and triple-negative breast cancer cohorts and evaluated safety as the primary endpoint after intravenous dosing (2.5 mg/kg on days 1 and 8 of 21-day cycles). The significance is that this EGFR-HER3 bispecific ADC approach may offer a new therapeutic option for multiple breast cancer subtypes after prior treatments.

Zhang J, Meng Y, Du Y et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗

Increased risk of early recurrence after gross-total resection in males with a WHO grade II meningioma: the impact of sex on recurrence and death in 5441 meningioma patients.

This retrospective cohort study analyzed 5441 patients with intracranial meningiomas (WHO grade I–III) from the international Personalized Neurosurgery database to determine whether sex affects recurrence and death after gross-total resection (GTR), with secondary analyses after subtotal resection. The study found sex-specific differences in early recurrence and survival following GTR, indicating that male sex was associated with increased risk of early recurrence. Clinically, these results suggest sex should be incorporated into prognostic counseling and risk stratification after meningioma surgery.

Broechner A, Rehné Jensen L, Juratli TA et al. · Journal of neurosurgery · (2026) · View on PubMed ↗

Trastuzumab Botidotin Versus Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Phase III, Open-Label, Randomized Controlled Trial.

In a phase III, open-label randomized controlled trial (NCT06968585) in adults with HER2-positive unresectable/metastatic breast cancer who had received prior trastuzumab and a taxane, trastuzumab botidotin was compared with trastuzumab emtansine. The trial’s primary endpoint was progression-free survival (PFS) assessed by blinded independent central review, and the study evaluated safety and efficacy between the two HER2-directed antibody-drug conjugates. If efficacy and tolerability are favorable, trastuzumab botidotin could become an additional HER2-targeted treatment option for this previously treated metastatic population.

Zhang J, Ouyang Q, Zhang Q et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Natural Course and Clinical Outcomes of Patients With Hemorrhagic Moyamoya Disease: A Large Cohort Study.

This retrospective large cohort study assessed the natural course and outcomes of hemorrhagic moyamoya disease (hMMD) in patients admitted to the Chinese PLA General Hospital (April 2002–March 2022), including evaluation of rebleeding and prognostic factors and the role of indirect revascularization. The analysis used logistic and Cox regression models to identify risk factors for poor outcomes and rebleeding during natural history and compared outcomes after indirect revascularization using overlap weighting. Scientifically and clinically, the work clarifies long-term risk trajectories in hMMD and informs which patients may benefit most from indirect revascularization strategies.

Chen C, Gao G, Wang H et al. · Neurology · (2026) · View on PubMed ↗

Impact of safe-anastomosis digital training on 30-day anastomotic leak after right colectomy: international prospective cohort study (EAGLE-2).

This international prospective cohort study (EAGLE-2) evaluated whether open-access digital safe-anastomosis training reduces 30-day anastomotic leak after right colectomy in consecutive adults undergoing primary anastomosis. The key finding was the real-world effectiveness (or lack thereof) of the EAGLE safe-anastomosis digital training package outside a randomized trial setting, assessed by 30-day anastomotic leak rates. Clinically, it informs whether scalable digital surgical training can translate into lower postoperative morbidity for right colectomy patients.

The British journal of surgery · (2026) · View on PubMed ↗ · Free PDF ↗

Treatment patterns after first-line abemaciclib therapy in patients with HR+, HER2- metastatic breast cancer in Japan.

This retrospective observational study analyzed Japanese administrative claims to characterize real-world treatment patterns after first-line abemaciclib in patients with HR+, HER2− metastatic breast cancer. Among 3057 patients receiving first-line abemaciclib, 520 proceeded to second-line therapy, and the study estimated time to treatment discontinuation (TTD) using Kaplan–Meier methods. The findings are significant for understanding sequencing and durability of care in abemaciclib-treated patients in Japan, informing clinical decision-making and future comparative studies.

Naito Y, Aruga T, Tanizawa Y et al. · Future oncology (London, England) · (2026) · View on PubMed ↗ · Free PDF ↗

COVID-19 vaccination around immune checkpoint inhibitor start and survival in a nationwide cohort of patients with cancer.

This nationwide French cohort study assessed whether COVID-19 mRNA vaccination around immune checkpoint inhibitor (ICI) initiation affects survival in 95,015 adults starting ICI therapy between December 2020 and March 2023. Using inverse probability of treatment weighting and cloning-censoring-weighting target-trial emulation, it found vaccination timing relative to ICI start was associated with differences in all-cause mortality and secondary cancer-specific and non-COVID-19 mortality outcomes. The results are clinically important for optimizing vaccination strategies in patients receiving ICIs without compromising cancer outcomes.

Salem JE, Curmin R, Ajrouche A et al. · Nature medicine · (2026) · View on PubMed ↗

Phenomic profiles and disease patterns of 1.9 million participants from Our Future Health.

This Nature Medicine report characterized phenomic profiles and disease patterns in 1.9 million participants from the Our Future Health prospective UK cohort, comparing self-reported behaviors, geolocation, diagnoses, and medication with national estimates and UK Biobank. It found that sociodemographic and lifestyle/health characteristics largely mirrored UK population patterns and that observed disease patterns aligned broadly with external benchmarks. The study is significant because it validates a large-scale resource for future discovery and translation of prevention, detection, and treatment approaches.

Straub VJ, Benonisdottir S, Bentivoglio GS et al. · Nature medicine · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

PTEN homozygous deletion is a negative prognostic factor in tumor treating fields-treated glioblastoma, IDH wildtype patients.

The study evaluated whether PTEN homozygous deletion predicts outcomes in glioblastoma, IDH wildtype patients treated with tumor treating fields (TTFields). Using molecular profiling from DNA methylation and a TSO500 DNA/RNA panel across TTFields-treated cohorts, it identified PTEN homozygous deletion as a negative prognostic factor for survival. This suggests PTEN status could help stratify GBM patients for TTFields initiation and guide precision treatment decisions.

Nückles J, Jelgersma C, Siewert C et al. · Brain pathology (Zurich, Switzerland) · (2026) · View on PubMed ↗ · Free PDF ↗

Evaluating AI-assisted detection of fetal intracranial malformations in prenatal ultrasound practice: a multicentre, self-crossover, randomised controlled trial in China.

The trial assessed whether an AI-assisted system for prenatal ultrasound (PAICS) improves detection of AI-recognisable fetal intracranial malformations and affects identification of anomalies outside its recognition scope in high-risk pregnancies. In a multicentre, self-crossover, randomized controlled design across five Chinese centers, sonographers examined singleton pregnancies at 11–32 weeks using PAICS support. The results are intended to determine real-world diagnostic performance and clinical impact of AI decision support in prenatal screening.

Lei T, Shang N, Xie B et al. · The Lancet. Digital health · (2026) · View on PubMed ↗ · Free PDF ↗

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Mitochondrial dynamics, bioenergetics, and mitophagy

Association Between Castration-resistant Prostate Cancer Progression Patterns and Survival Outcomes in Metastatic Castration-sensitive Prostate Cancer: A Post Hoc Analysis of the TITAN Trial.

This review article examined how mitochondrial deubiquitinases (DUBs) regulate mitophagy, focusing on ubiquitin-dependent signaling at damaged mitochondria. It highlights that DUBs modulate ubiquitin tag dynamics and thereby influence the efficiency and selectivity of mitochondrial turnover, with implications for diseases including neurodegeneration, cardiovascular disease, cancer, and inherited mitochondrial disorders. Scientifically, it frames mitochondrial DUBs as potential therapeutic control points for mitochondrial quality and mitophagy-related pathology.

Hori T, Iwamoto H, Inaba T et al. · European urology focus · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochondrial homeostasis in musculoskeletal diseases: From pathogenic mechanisms to precision therapies.

This review studied mitochondrial homeostasis as a unifying pathogenic mechanism in musculoskeletal diseases, including osteoporosis, osteoarthritis, and rheumatoid arthritis. It found that mitochondrial dysfunction contributes to disease progression across key cell types (osteoblasts, osteocytes, osteoclasts, chondrocytes, and skeletal muscle cells) and that this supports a shift toward mechanism-based precision therapies. The scientific significance is that mitochondrial pathways may provide actionable targets for developing more tailored treatments for multiple musculoskeletal disorders.

Wen P, Bai Y, Yang Z · Pharmacological research · (2026) · View on PubMed ↗ · Free PDF ↗

Direct activation of SARM1 by dsDNA is not supported by biochemical and cellular evidence.

This study tested whether cytosolic double-stranded DNA (dsDNA) directly activates the axon-degeneration enzyme SARM1 by using purified SARM1, biochemical/biophysical assays, primary neurons, and cellular pharmacology. Across multiple experimental platforms, dsDNA did not stimulate SARM1 NADase activity, did not promote SARM1 higher-order assembly, and did not produce the metabolic signature of activated SARM1. The significance is that it refutes a proposed dsDNA–SARM1 activation mechanism and reinforces the canonical model in which SARM1 activation depends on NMN/NAD+ changes.

Kao AH, Mishra BP, Sorbello M et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Palmitoyl Acyltransferase Zdhhc17 Promotes Functional Recovery After Spinal Cord Injury by Targeting the Nuclear Transport Factors Kpna2 and Ipo9.

This study investigated the palmitoyl acyltransferase Zdhhc17 in adult mammals to determine whether it improves functional recovery after spinal cord injury (SCI) by modulating nuclear transport factors. Neuron-specific Zdhhc17 overexpression enhanced axon regeneration and functional recovery in a palmitoyl-transferase activity-dependent manner, identifying the karyopherins Kpna2 and Ipo9 as Zdhhc17 substrates whose SCI-associated protein loss was linked to reduced palmitoylation. Scientifically, it implicates Zdhhc17-mediated palmitoylation of Kpna2/Ipo9 as a mechanistic driver of post-SCI neuroprotection and a potential therapeutic target.

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

InsP3R signaling and actomyosin-dependent mitochondrial dynamics play essential roles in mitochondrial stress-induced longevity.

The study examined how inositol 1,4,5-trisphosphate receptor (InsP3R) ER Ca2+ signaling and actomyosin-dependent mitochondrial dynamics regulate mitochondrial stress-induced longevity in C. elegans carrying a Complex I/nuo-6 mutation. It found that longevity from the nuo-6 mitochondrial Complex I mutation requires InsP3R, while mitochondrial calcium uniporter (MCU)-dependent respiration stimulation is dispensable and mitochondrial dynamics are instead essential. This links ER Ca2+ release via InsP3R to actomyosin-driven mitochondrial remodeling as a mechanistic determinant of beneficial mitochondrial stress responses.

Feng G, Ruark EM, Mulligan AG et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular disease and vascular risk prediction

Simultaneous derivation, validation, and comparison of predictor hazard ratios for cardiovascular risk prediction equations in patients with diabetes from high versus non-high income countries: cohort study.

This population-based cohort study compared cardiovascular risk prediction equations across countries by deriving and validating predictor hazard ratios for first cardiovascular events in adults with diabetes aged 30–74 years in New Zealand (high income) versus China (non-high income). Using electronic health records, it tested generalisability of CVD risk predictors and sought more effective cross-population prediction strategies by generating country-specific five-year equations. The scientific significance is improving the transferability and calibration of diabetes CVD risk models between healthcare systems and populations.

Liang J, Choi Y, Shen P et al. · BMJ (Clinical research ed.) · (2026) · View on PubMed ↗ · Free PDF ↗

VALVE DISEASES IN CARDIAC AMYLOIDOSIS: WHAT WE HAVE TO KNOW.

This review studied valvular manifestations in patients with cardiac amyloidosis, emphasizing how amyloid type (AL versus transthyretin [ATTR]) relates to aortic stenosis (AS). It found that AS is the most prevalent valvular manifestation, especially in wild-type ATTR, and that concomitant cardiac amyloidosis and AS interact synergistically to worsen ventricular outcomes. Clinically, recognizing this overlap is important for risk stratification and management of patients with ATTR-related cardiac disease and coexisting AS.

Lisi DD, Salvo FD, Castro F et al. · Current problems in cardiology · (2026) · View on PubMed ↗ · Free PDF ↗

In-Hospital Cardiac Arrest in Impella-Supported Cardiogenic Shock: Insights From the J-PVAD Registry.

This registry-based study examined in-hospital cardiac arrest (IHCA) presentations among patients with Impella-supported cardiogenic shock in the J-PVAD registry. It found that 8,577 patients treated with Impella could be stratified into IHCA, no arrest, out-of-hospital cardiac arrest with ROSC, and out-of-hospital cardiac arrest without ROSC, and it identified factors associated with mortality in IHCA occurring before Impella implantation. Clinically, these insights help refine prognostication and management strategies for arrest timing and hemodynamic collapse in Impella-treated cardiogenic shock.

Arai R, Kojima K, Fukamachi D et al. · Resuscitation · (2026) · View on PubMed ↗

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Neural circuits for stress, sleep, itch, and feeding

A hypothalamic-vagal pathway mediates stress-induced feeding suppression and gastric dysfunction.

This neuroscience study investigated how hypothalamic paraventricular nucleus (PVN) neurons coordinate stress-induced feeding suppression and gastric dysfunction. It found that PVN neurons expressing neuropeptide Y receptor Y1 (NPY1R) are rapidly activated by acute stress, and that activating PVN NPY1R neurons projecting to the dorsal vagal complex suppresses feeding while inhibiting the pathway reverses stress-induced hypophagia. These circuit-level findings are significant for understanding neural control of stress-related appetite and gut dysfunction.

Dai D, Zhang B, Zhang X et al. · Neuron · (2026) · View on PubMed ↗

Microglia stabilize sleep homeostasis via adenosine A3 receptor signaling.

This study investigated how microglia regulate sleep homeostasis in freely behaving mice, focusing on adenosine A3 receptor (A3R) signaling and microglial calcium (Ca2+) dynamics. Using miniaturized two-photon microscopy, the authors showed that microglial Ca2+ activity rapidly changes with brain-state transitions and that A3R-dependent signaling stabilizes sleep homeostasis. The results identify a mechanistic link between sleep pressure sensing and microglial A3R signaling, suggesting new targets for disorders of sleep-wake regulation.

Zhao Z, Gu X, Yu J et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Kappa opioids suppress histaminergic itch by inhibiting mediodorsal thalamus-projecting claustrum glutamatergic neurons.

This neurocircuit study examined how kappa opioid receptor (KOR) signaling suppresses histaminergic itch by identifying a claustrum-to-mediodorsal thalamus pathway. Chemogenetic inhibition of glutamatergic claustrum neurons projecting to the mediodorsal thalamus (CLA^Glu→MD) reduced histamine-induced scratching, while activation increased scratching, and optogenetic pathway manipulation supported this circuit’s role in itch modulation. Mechanistically, the work links KOR-mediated antipruritic effects to specific glutamatergic neurons and a defined CLA–MD pathway, informing circuit-based targets for itch therapeutics.

Liu Z, Shu X, Wang Z et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Corticotropin-releasing hormone neurons in the bed nucleus of the stria terminalis control wakefulness in physiological and stressful conditions in mice.

This study investigated how corticotropin-releasing hormone (CRH) neurons in the bed nucleus of the stria terminalis (BNST) regulate wakefulness in mice under physiological and stressful conditions using optogenetic activation. Optogenetic activation of BNST CRH-expressing neurons increased wakefulness, whereas activation of BNST cholecystokinin- or somatostatin-expressing neurons did not. These findings identify a specific CRH neuronal subpopulation as a mechanistic driver of stress-linked arousal, informing circuit-level targets for insomnia and related sleep disorders.

Zhang KL, Xu W, Sun P et al. · Molecular psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗

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Microbiome and host–microbe immune axes (bacteria/virome)

The role of viral infections and other microbial factors in the pathogenesis of multiple sclerosis: a systematic review.

This systematic review evaluated evidence from 2020–2025 studies on how microbial agents—especially viral infections such as Epstein-Barr virus (EBV)—may influence multiple sclerosis (MS) risk, disease activity, and progression. Across 61 included studies, the reviewed data support a contributory role for specific microorganisms (with EBV highlighted in the results) in MS pathogenesis. These findings reinforce the scientific rationale for investigating infection-driven immune mechanisms and for considering microbiome/viral-targeted strategies as potential MS risk-modifying approaches.

Morawiec N, Adamczyk B, Adamczyk-Sowa M · Multiple sclerosis and related disorders · (2026) · View on PubMed ↗ · Free PDF ↗

Virobiome-mediated regulation of microbiota-gut-brain axis signaling and neuroimmune homeostasis.

This review synthesized evidence on how the virome—bacteriophages and eukaryotic viruses—mediates microbiota-gut-brain axis signaling and neuroimmune homeostasis. It reports that viral components can influence microbial community function and immune regulation, thereby modulating downstream neuroimmune signaling along the gut-brain axis. The work is significant because it highlights the virome as a potential therapeutic lever for neuroinflammatory and neuropsychiatric conditions beyond bacteria-focused approaches.

Afkhamian A, Saffari Natanzi A, Jafaridarabjerdi M et al. · Cell communication and signaling : CCS · (2026) · View on PubMed ↗ · Free PDF ↗

Commensal bacteria inhibit viral infections via a tryptophan metabolite.

The study investigated how specific commensal bacteria inhibit viral infection using HIV as a model system and focused on tryptophan catabolism. It found that aromatic amino acid aminotransferase (ArAT) metabolizes tryptophan into 3-indolelactic acid, which activates the aryl hydrocarbon receptor (AhR) to suppress viral replication. This identifies a defined microbiome–tryptophan–AhR axis as a potential therapeutic strategy to enhance antiviral protection.

Jiang D, Soo N, Tan CY et al. · Nature communications · (2026) · View on PubMed ↗

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Neurodevelopmental genetics and brain organoid models

Elucidating the role of DEAF1 in neurodevelopment and shared molecular pathways in high-risk autism genes using cortical organoids.

This study used human cortical organoids to model neurodevelopmental effects of a DEAF1 mutation, aiming to connect DEAF1 biology to shared molecular pathways in high-risk autism genes. The authors found that a DEAF1 mutation in human embryonic stem cells disrupts chromatin accessibility at neuronal gene loci, producing substantial transcriptional changes in organoids. These results strengthen the causal role of DEAF1 in human neurodevelopment and highlight chromatin dysregulation as a convergent pathway relevant to autism-spectrum and intellectual disability risk.

Kim J, Choe MS, Yang WS et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Formin-1 maintains cochlear microtubule architecture required for hearing in humans and mice.

This work studied the role of formin-1 (FMN1) in hearing by combining genetic analysis of an extended Palestinian kindred with autosomal recessive congenital hearing loss and functional studies in human-deficient and Fmn1 knockout mice. The key finding was that the FMN1 splice-site variant c.2162-2A>G caused aberrant splicing, nonsense-mediated decay, and absence of detectable formin-1 protein, and that Fmn1 loss disrupts cochlear microtubule architecture required for hearing. The significance is that it establishes FMN1 as a human hearing gene and links microtubule organization to congenital deafness, informing diagnosis and potential future molecular therapies.

Kamal L, Aburayyan A, Hahn R 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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Kidney disease: AKI/CKD mechanisms and clinical risk/therapies

Protein mediators of chronic kidney disease in Type 2 diabetes: A mendelian randomization study.

This study used two-sample Mendelian randomization to identify circulating protein mediators of chronic kidney disease in people with type 2 diabetes, leveraging deCODE proteomic GWAS (35,559 individuals) and T2D GWAS (80,154 cases). It identified 71 proteins genetically associated with T2D and then implicated specific proteins as mediators linking T2D predisposition to kidney disorders. These findings prioritize candidate drug targets and biomarkers for preventing or treating diabetic CKD by moving from genetic risk to mechanistic protein pathways.

Liang KYH, Zheng TM, Tan D et al. · PLoS medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Complement in Kidney Disease: Core Curriculum 2026.

This Core Curriculum review examined how the complement cascade contributes to kidney inflammation and summarized FDA-approved complement inhibitory drugs for renal diseases in clinical practice. It reports that complement inhibitors are approved for atypical hemolytic uremic syndrome, C3 glomerulopathy, immune-complex membranoproliferative glomerulonephritis, ANCA-associated vasculitis, and IgA nephropathy, with ongoing trials expanding to new drugs and indications. Clinically, it supports complement-targeted therapy as an evidence-based strategy across multiple immune-mediated kidney disorders and highlights the pipeline for broader renal use.

Thurman JM, Poppelaars F · American journal of kidney diseases : the official journal of the National Kidney Foundation · (2026) · View on PubMed ↗

Mechanisms of regeneration and maladaptive repair in acute kidney injury.

This review examined how acute kidney injury (AKI) repair is orchestrated by tubular epithelial cells (TECs), immune cells, and fibroblasts, and how these interactions can lead to regeneration versus maladaptive repair that progresses to chronic kidney disease (CKD). It highlights that TECs can trigger regulated cell death programs and then diverge into states that either restore tubular structure through proliferation/expansion or promote maladaptive repair. Understanding these TEC–immune–fibroblast trajectories is clinically important for designing interventions that improve AKI-to-CKD outcomes by steering repair toward regeneration.

Seibt T, Hoeft K, Schaefer GJL et al. · Nature reviews. Nephrology · (2026) · View on PubMed ↗

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Aging, frailty, and cognitive decline

Are Comparable Short-term Outcomes Between Hamstring and Quadriceps Tendon Autografts for ACL Reconstruction Statistically Robust? A Reverse Continuous Fragility Index Analysis of Randomized Controlled Trials.

This systematic review evaluated the statistical robustness of nonsignificant short-term outcomes comparing hamstring tendon (HT) versus quadriceps tendon (QT) autografts for anterior cruciate ligament reconstruction (ACLR) using a reverse continuous fragility index (rCFI) across randomized controlled trials. It tested whether the lack of significant differences in continuous outcomes was robust to threshold changes in trial events/outcomes. The clinical significance is that it strengthens or challenges confidence in the equivalence of HT and QT autografts for short-term ACLR outcomes based on statistical sensitivity.

Tseng TH, Fu SH, Lo YC et al. · Orthopaedic journal of sports medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Developmental regulation of progenitor aging shapes long-term intestinal homeostasis in Drosophila.

This Drosophila study examined how developmental regulation of aging-associated pathways in larval adult midgut progenitors (AMPs) shapes long-term intestinal homeostasis in adult flies. The key finding is that genetically inducing aging-associated pathways in AMPs causes aberrant proliferation, skewed differentiation, barrier dysfunction, and genomic instability, whereas reversing these aging-associated effects improves homeostasis and normalizes age-related molecular signatures. This mechanistically links progenitor “aging trajectory” programming during development to adult tissue maintenance, informing how early-life pathway modulation can influence later-life degeneration.

Malik S, Mahajan AA, Pillai SJ et al. · FEBS letters · (2026) · View on PubMed ↗ · Free PDF ↗

Dynamic frailty exposure and cognitive aging trajectories: A multicohort study.

This multicohort longitudinal study examined how baseline frailty status, two-wave frailty change, and mean frailty burden relate to annual cognitive change and cognitive aging trajectories in 19,586 participants from the China Health and Retirement Longitudinal Study, English Longitudinal Study of Ageing, and Health and Retirement Study. It found that dynamic frailty exposure patterns were associated with differences in the rate of cognitive decline and shaped distinct cognitive aging trajectories over time. These results support frailty as a modifiable, time-varying risk marker for cognitive deterioration and can inform stratified prevention strategies in aging populations.

Wang X, Hao H, Jiang T et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Effects of different training modalities on lower-limb explosive power, acceleration, 20-m sprint performance, and change-of-direction ability in youth soccer players: a systematic review and network meta-analysis.

This systematic review and network meta-analysis compared structured physical-conditioning training modalities (e.g., plyometric, strength/resistance, sprint/acceleration, neuromuscular, multicomponent, and combined programs) on lower-limb explosive power, acceleration, 20-m sprint performance, and change-of-direction ability in healthy youth soccer players. It synthesized randomized controlled trial evidence to rank which training types most effectively improve these performance outcomes. The findings are significant for evidence-based youth soccer conditioning program design to target explosive and multidirectional capabilities.

Wang K, He J, Zhu A et al. · BMC sports science, medicine & rehabilitation · (2026) · View on PubMed ↗ · Free PDF ↗

Implementing an exercise intervention for sarcopenia in oldest-old nursing home residents: protocol for a pragmatic cluster-randomized controlled trial (SCOPE Study).

This protocol paper describes the SCOPE study, a pragmatic cluster-randomized controlled trial implementing caregiver-led modified Baduanjin, resistance training, and combined exercise to treat sarcopenia in oldest-old nursing home residents. It aims to test feasibility and effectiveness of these exercise modalities in a real-world long-term care setting where prior evidence has been limited. The trial is clinically significant because it targets an underserved, high-prevalence population and could establish scalable non-pharmacologic interventions for sarcopenia.

Xiang C, Li L, Zhao J et al. · BMC geriatrics · (2026) · View on PubMed ↗ · Free PDF ↗

Hypothalamic Inflammaging: A Central Driver of Type 2 Diabetes Mellitus and Metabolic Disease in Aging.

The review examined age-associated “inflammaging” in the hypothalamus and how glial senescence (microglia, astrocytes, tanycytes, and neural stem cells) contributes to type 2 diabetes mellitus and metabolic disease. It reports that hypothalamic inflammatory remodeling disrupts neuronal circuits controlling glucose sensing, energy balance, and insulin responsiveness, thereby promoting metabolic dysfunction. This frames hypothalamic inflammaging as a central mechanistic driver and potential target for interventions in aging-related metabolic disease.

Lyoo SH, Kim KH, Kim KW · Diabetes & metabolism journal · (2026) · View on PubMed ↗ · Free PDF ↗

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GPCR structure, signaling bias, and receptor–arrestin mechanisms

Pharmacological modulation of GPR84 revealed by dual states structures and immune functional assays.

This work studied the orphan immune GPCR GPR84 in human systems to define how pharmacological modulation works, combining cryo-electron microscopy (cryo-EM) with immune functional assays. It reported cryo-EM structures of human GPR84 in inactive and active states, including a 3.5 Å inactive conformation bound to the antagonist GLPG1205, revealing conformational changes in extracellular loop 2 and Arg172 that explain inactivation/antagonism. The structural mechanism supports rational design of pathway-selective GPR84 modulators for metabolic inflammation and fibrotic diseases.

Choi MK, Park DJ, Kim P et al. · Experimental & molecular medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins.

This study examined how metabotropic glutamate receptor 8 (mGluR8) couples to β-arrestins during activation/desensitization using an integrative biophysical and structural approach. Negative-stain EM and cryo-EM defined mGluR8/β-arrestin complex orientations and stoichiometries, and structures of mGluR8 alone or bound to G proteins or β-arrestin 1 (β-arr1) revealed how active-state coupling is organized. These mechanistic insights clarify β-arrestin engagement by a family C GPCR and can guide development of drugs that bias mGluR8 signaling toward desired desensitization/endocytic outcomes.

Marx DC, Huynh K, Gonzalez-Hernandez AJ et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Cancer-driver-agnostic targeting of amplified surface proteins identifies MPZL1 for selective CAR-T cell therapy.

This study developed a single molecule pulldown (SiMPull) assay to quantify GPCR–β-arrestin interaction strength and stoichiometry for neuromodulatory metabotropic glutamate receptors (mGluRs). It found that mGluRs couple to β-arrestins with variable apparent interaction strength and with either 2:1 or 2:2 GPCR:β-arrestin stoichiometry, demonstrating configurational diversity beyond monomeric family A GPCR paradigms. This provides a quantitative framework for understanding how different receptor–β-arrestin assemblies can produce distinct signaling and desensitization behaviors.

Jiménez-Vázquez S, Berthel A, Patsis C et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Spatial control of parathyroid hormone receptor-1 signaling dictates ligand-specific biological outcomes.

This study investigated how spatial control of parathyroid hormone receptor-1 (PTH1R) signaling determines ligand-specific outcomes by using the Eiken syndrome mutant R485X-PTH1R, which truncates the C-tail and removes key β-arrestin docking sites. It identified β-arrestins as critical modulators of compartmentalized PTH1R signaling, supporting that distinct receptor locations (e.g., plasma membrane versus internalized compartments) encode different biological responses to PTH versus PTHrP. These findings are significant for understanding and potentially targeting subcellular GPCR signaling to influence mineral ion homeostasis and skeletal development.

Höppner J, Jüppner H, Reyes M et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on September 13, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.