PubMed Trending Research Digest — June 14, 2026

Automated digest · 98 articles · 15 research areas · June 14, 2026

Overview

Across this week’s set of papers, a dominant theme is mechanism-driven intervention—researchers are moving from descriptive associations toward actionable pathways. In oncology and immunotherapy, multiple studies dissect how signaling and cellular states shape treatment response: examples include CNS-penetrant KRAS G12C inhibition for brain-metastatic NSCLC, structural/biochemical mechanisms for LRRK2 activation relevant to Parkinson’s, and cancer immune-evasion or activation circuits involving DDX6–ADAR1 dsRNA editing, STING1 control of mitophagy, and neutrophil secretory autophagy in sepsis-related lung injury. Several works also emphasize how the tumor microenvironment can be reprogrammed (e.g., BTK inhibition to modulate TLS in glioblastoma, nanoparticle strategies to convert macrophages into CAR effector cells, and micrometastasis-targeted delivery routes). Epigenetic and transcriptional control appears repeatedly, from PRC2 “brake” regulation via EZH2 phosphorylation to DNA G-quadruplex effects on homologous recombination and PARP inhibitor resistance, and RNA-driven reinforcement of oncogenic chromatin condensates.

A second major theme is circuit- and system-level biology informing disease trajectories and risk. Neurodegeneration papers connect pathology to functional impairment in sleep-wake circuitry (tauopathy affecting LH MCH neurons) and map cell-type-specific ALS mechanisms via single-nucleus multiomics, while other studies explore learned fear through neuroimmune pathways and prophylactic oxytocin effects on PTSD-like learning. In cardiopulmonary and metabolic domains, studies address remodeling and safety signals (post-MI fibrosis shaped by primary cilia; rare delayed ischemic/arrhythmic events after pulsed field ablation; early pulmonary fibrosis programs with spatial transcriptomics) alongside metabolic regulation through circadian/diet/temperature control of mitochondrial lipid cycling and nitrate sensing in adipose thermogenesis.

Finally, the digest includes a strong translational and clinical-evidence thread: pragmatic ICU trials (bicarbonate for metabolic acidosis; gastric residual volume monitoring in pediatric nutrition), registries and cohort studies for risk stratification (ICI-associated cardiac toxicity; early recurrence after hepatectomy for HCC; moyamoya phenotype outcomes), and multiple cancer therapy trials or safety evaluations (CD3 bispecific toxicity meta-analysis, CAR-T vs bispecific comparisons in myeloma, and PML risk assessment with bispecific antibodies). Together, these studies reflect a field increasingly focused on (1) identifying precise biological levers, (2) measuring outcomes with better granularity (including patient-reported and continuous digital monitoring), and (3) validating interventions through rigorous, mechanism-informed clinical testing.

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Cardiac remodeling & heart failure risk

Growth differentiation factor-15 and the incidence, bidirectional progression, and risk prediction of atherosclerotic cardiovascular disease and metabolic dysfunction-associated steatotic liver disease in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3.

This cohort study assessed whether circulating growth differentiation factor 15 (GDF-15) predicts incidence, bidirectional progression, and risk of atherosclerotic cardiovascular disease (ASCVD) and metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0–3. Using 29,697 UK Biobank participants and regression models (including Fine-Gray competing risk regression), it evaluated associations of GDF-15 with metabolic, inflammatory, and liver fibrosis markers as well as CKM stage. If confirmed, GDF-15 could serve as a practical biomarker for early risk stratification of combined cardiovascular and liver metabolic disease in CKM populations.

Chen X, Tang H, Xu Z et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Integrating inflammation, insulin resistance, and visceral adiposity: the C-reactive protein-triglyceride-glucose-Chinese visceral adiposity (CTI-CVAI) index is associated with cardiovascular disease risk across CKM stages 0-3 in a nationwide prospective cohort.

This nationwide prospective cohort study tested whether the composite C-reactive protein–triglyceride–glucose–Chinese visceral adiposity (CTI-CVAI) index predicts incident cardiovascular disease (CVD) in Chinese adults with CKM stages 0–3. In 6,728 CHARLS participants (2011–2020), the authors examined the association of CTI-CVAI with CVD risk to integrate inflammation, insulin resistance, and visceral adiposity into a single biomarker framework. If validated, CTI-CVAI could improve early CVD prevention targeting CKM stage 0–3 by capturing multiple interacting pathogenic pathways.

Wang Q, Li J, Qiao H et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Albuminuria and heart failure.

This article reviewed the clinical relationship between albuminuria (measured by urinary albumin-to-creatinine ratio) and heart failure risk and outcomes in patient populations. It reports that albuminuria is present in nearly half of heart failure patients and is an independent risk marker for incident heart failure and adverse outcomes even at low levels, while routine screening is not universally recommended in heart failure guidelines. The review argues that broader albuminuria testing could improve early detection, risk stratification, and opportunities for pharmacologic intervention.

Butler J, Jamil A, Cherney DZI et al. · European heart journal · (2026) · View on PubMed ↗

Life-Threatening Delayed Myocardial Ischemia, Ventricular Arrhythmias, and SCD After PFA of AF: An Extended Case Series.

This extended case series and systematic literature review characterized life-threatening delayed ischemic and ventricular arrhythmic adverse events occurring after pulsed field ablation (PFA) for atrial fibrillation (AF). The study included AF patients who developed delayed-onset or recurrent ST-segment elevation and/or ventricular arrhythmias after PFA delivered between March 2023 and January 2026. Scientifically and clinically, it highlights a rare but serious post-PFA safety signal that should inform monitoring, patient counseling, and refinement of procedural protocols.

Gunawardene MA, Schmidt B, Neuzil P et al. · JACC. Clinical electrophysiology · (2026) · View on PubMed ↗

Distinct Clinical Phenotypes in Moyamoya Disease: A Multicenter Comparison of Ischemic and Hemorrhagic Presentations.

This multicenter retrospective cohort study compared ischemic-type versus hemorrhagic-type moyamoya disease (MMD) in 485 patients undergoing revascularization surgery across 13 North American academic centers (2008–2022). It assessed differences in perioperative complications and long-term stroke risk between the two clinical phenotypes. The results are clinically important for risk stratification and surgical decision-making tailored to whether MMD presents with ischemia or hemorrhage.

Gabriel El-Hajj V, Musmar B, Roy JM et al. · Neurosurgery · (2026) · View on PubMed ↗

Early-Onset Obesity and Heart Failure Burden Independent of Cardiometabolic Risk Factors.

This study analyzed adults with obesity (BMI ≥30 kg/m2) in the NHANES 2017–2020 cohort, comparing early-onset obesity (obesity at ~age 25) versus adult-onset obesity (obesity at enrollment but not at age 25) in relation to cardiometabolic and cardiovascular outcomes. It found that the burden of heart failure and cardiovascular disease outcomes differed by obesity onset timing even after considering cardiometabolic risk factors. This is significant because it suggests that when obesity begins is an independent risk modifier for later heart failure, informing prevention and risk stratification strategies.

Sarfraz S, Cheema AH, Tayyab AZ et al. · Clinical obesity · (2026) · View on PubMed ↗

Primary cilia promote cardiac fibrosis and limit heart function after myocardial infarction.

The study investigated how primary cilia in cardiac cells influence post–myocardial infarction (MI) remodeling in mammalian models. Primary cilia promoted cardiac fibrosis and limited heart function after MI by shaping fibroblast/myofibroblast behavior and extracellular matrix deposition. These findings suggest that targeting primary cilia–dependent signaling could be a strategy to reduce post-MI fibrosis and preserve cardiac performance.

Liu X, Norris A, Appu A et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗ · Free PDF ↗

Asymptomatic and symptomatic cardiac toxicity associated with immune checkpoint inhibitors: insights from a Japanese registry.

This Japanese multicenter retrospective registry study characterized immune checkpoint inhibitor (ICI)-associated cardiac toxicity by comparing symptomatic versus asymptomatic cases and their clinical, biomarker, and pathological features. Across 90 patients (2020–2022), the registry approach enabled detailed comparison of mild/asymptomatic myocarditis and related cardiac injury patterns within ASCO guideline–defined categories. The results improve risk recognition and diagnostic interpretation of subclinical ICI cardiotoxicity, potentially guiding monitoring and management strategies.

Tamura Y, Tamura Y, Ohtsu H et al. · European heart journal open · (2026) · View on PubMed ↗ · Free PDF ↗

Standardized processing of explanted hearts after stereotactic arrhythmia radiotherapy (Bio-STAR): a STOPSTORM framework and first human findings.

The Bio-STAR study developed a standardized STOPSTORM framework for ex vivo assessment of stereotactic arrhythmia radiotherapy (STAR) effects and applied it to first human explanted heart samples. It standardized myocardial sampling into non-irradiated control, minimally fibrotic irradiated, and fibrotic irradiated zones using visual inspection, electroanatomical maps, and radiotherapy dose overlays, demonstrating feasibility for downstream analyses such as ex vivo MRI and histology. This provides a reproducible human tissue workflow to define STAR-induced myocardial changes underlying ventricular tachycardia treatment.

Nedios S, Hüttemeister J, Heil E et al. · European heart journal open · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration, neuroinflammation & brain circuits

Piriform cortex gates learned fear through a brain-spleen neuroimmune axis.

The study investigated how the piriform cortex (Pir) regulates learned fear in a chronic acquired olfactory stress (CAOS) mouse model, mapping a brain-to-spleen neuroimmune pathway. It found that increased Pir excitability drives learned fear-avoidance via a functional tetrasynaptic circuit (Pir→vCA1→CeM→DVC→spleen) that depends on T helper 17 (Th17) cell responses. This identifies a neuroimmune mechanism linking stress circuitry to Th17-mediated fear, suggesting new targets for treating maladaptive learned fear in neuropsychiatric disorders.

Yao H, Qu MY, Du RH et al. · Neuron · (2026) · View on PubMed ↗

Ethyl acetate fraction of Chaidangbo prescription (EAFC) improves hippocampal neural plasticity in CUMS mice: involving glucocorticoid receptors and Akt-related signaling pathway.

The study tested whether the ethyl acetate fraction of the Chaidangbo prescription (EAFC) improves hippocampal neural plasticity in chronic unpredictable mild stress (CUMS) mice and explored underlying signaling mechanisms. It reported that EAFC enhances hippocampal plasticity through pathways involving glucocorticoid receptors and Akt-related signaling. This supports a mechanistic basis for EAFC’s antidepressant-like effects and identifies glucocorticoid/Akt signaling as potential therapeutic targets.

Zeng J, Tang Y, Zhao A et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

Oxytocin attenuates fear learning via enhancing somatostatin interneuron-mediated local GABAergic inhibition in the prelimbic cortex.

The authors tested whether prophylactic intranasal oxytocin modulates fear learning in relation to oxytocin receptor (OxtR/Oxtr) expression in the prelimbic cortex (PL), focusing on somatostatin (SST) interneurons. Oxytocin pretreatment produced prolonged but reversible attenuation of fear learning mediated by PL OxtRs, and local PL OxtR activation/infusion recapitulated the effect with SST interneurons showing higher Oxtr expression. This mechanistic circuit-level result supports oxytocin/Oxtr signaling as a potential prophylactic strategy to enhance resilience against PTSD-like fear learning.

Xu H, Li Y, Cui X et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Proximity labelling of D1-like dopamine receptors reveals distinct cellular environments and uncovers trafficking proteins that regulate DA mediated behaviors in Drosophila.

This preprint studied D1-like dopamine receptor biology in Drosophila (Dop1R1 and Dop1R2) by using proximity labelling proteomics to map receptor-specific proximal protein environments under basal versus dopamine-activated conditions. It found that both receptors recruit β-arrestin 2 upon dopamine activation, while Dop1R1 uniquely shows ligand-driven recruitment of GRK2/3 and proximity to clathrin-mediated endocytosis and the WASH complex, identifying trafficking proteins that regulate dopamine-mediated behaviors. This is significant because it connects receptor-specific trafficking microenvironments to functional dopamine behaviors, offering targets for modulating dopaminergic signaling.

Guhle DC, Kanagala B, Dust R et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗

Temporal coding expands the bandwidth of GPCR-mediated neuromodulation.

This work examined whether a single canonical Gs→cAMP signaling pathway can temporally encode information from multiple co-expressed neuromodulatory GPCRs in hippocampal pyramidal neurons. The authors report that temporal coding expands the effective bandwidth of GPCR-mediated neuromodulation, enabling distinct GPCR inputs to be discriminated despite shared downstream transduction. This provides a framework for how neural circuits overcome G-protein “bottlenecks” by using timing rather than pathway multiplicity to represent different neuromodulators.

He XJ, von Zastrow M · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗

Hypothalamic MCH neurons links tau pathology to sleep disruption.

The study examined how tau pathology affects sleep-wake circuitry by focusing on melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) in PS19 tauopathy mice. Longitudinal EEG/EMG showed progressive sleep architecture and homeostasis impairments, and histology plus in vivo fiber photometry indicated selective functional impairment and degeneration of LH MCH neurons (along with neighboring hypocretin/Hcrt neurons) at late stages. This identifies LH MCH neurons as a mechanistic link between tau pathology and sleep disruption, informing circuit-targeted approaches for Alzheimer’s disease sleep dysfunction.

Pang K, Guo S, Yang R et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗ · Free PDF ↗

Single-nucleus multiomic atlas of ALS primary motor cortex nominates neuroprotective WDR49-expressing astrocytes.

The study generated a single-nucleus multiomic atlas (single-nucleus RNA-seq and ATAC-seq) from primary motor cortex of 140 genetically characterized donors to define cell-type-specific ALS mechanisms. In ALS, astrocytes showed the most differentially expressed genes, and a WDR49-expressing astrocyte subpopulation was spatially associated with TDP-43 pathology, with genetic variants in WDR49 conferring ALS risk. These findings nominate WDR49-expressing astrocytes as neuroprotective and genetically implicated in ALS vulnerability, highlighting a potential therapeutic target.

Cooper-Knock J, Bonsall S, Kazu R et al. · Research square · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer therapeutics: targeted small molecules & mechanisms

Mutant KRAS-driven selective mRNA translation reveals mechanisms and therapeutic vulnerabilities in cancer.

The authors studied mutant KRAS–dependent control of mRNA translation programs and how these programs remodel upon KRAS inhibition, using cancer models with mutant KRAS. They found that mutant KRAS governs translation of specific mRNAs characterized by short, weakly folded 5′UTRs and low folding-energy consensus sequences, with ribosome accumulation on these selective targets. The work clarifies KRAS’s distinct role in translational regulation and suggests translational vulnerabilities that could be exploited therapeutically beyond mTOR or eIF4E–eIF4A pathways.

Shrivastava A, Pederson EN, Nguyen TU et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

The structural basis for LRRK2’s activation and autoinhibition.

This study investigated how the ROC GTPase domain regulates activation versus autoinhibition of the Parkinson’s disease kinase LRRK2 (including PD-linked mutations G2019S and R1441C/G/H) using cryo-EM, biochemical reconstitution, and cell-based assays. The authors found that GTP binding promotes LRRK2 activation while GDP binding enforces autoinhibition, and that the two mutation classes activate LRRK2 through distinct structural mechanisms. These mechanistic insights support more rational, structure-guided therapeutic strategies targeting LRRK2 kinase activity in autosomal-dominant and idiopathic Parkinson’s disease.

Villagran Suarez A, Hatch KS, Bodrug T et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗ · Free PDF ↗

Study of the blood-brain barrier-penetrating KRAS G12C inhibitor JMKX1899 in KRAS G12C-mutated NSCLC with brain metastases.

The study evaluated the blood-brain barrier penetration and antitumor activity of the selective KRAS G12C inhibitor JMKX1899 in KRAS G12C-mutated non-small cell lung cancer (NSCLC) models with brain metastases. JMKX1899 demonstrated preclinical antitumor efficacy alongside sufficient CNS penetration to support activity against brain metastatic disease. Clinically, this supports further development of JMKX1899 as a CNS-active KRAS G12C therapy for NSCLC patients with brain metastases.

He D, Zhu Y, Zhong J et al. · Journal of the National Cancer Center · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

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Cancer immunotherapy & tumor microenvironment

ERO1a fosters glioblastoma aggressiveness and metabolic flexibility by regulating mitochondria-associated membrane dynamics.

This study investigated how ERO1α regulates mitochondria-associated membrane (MAM) dynamics to drive glioblastoma (GBM) aggressiveness and metabolic flexibility, using patient association analyses and mechanistic cellular studies (details truncated). It identified ERO1α as a critical MAM protein controlling MAM structure, dynamics, and calcium-mediated functions, with expression/activity associated with poor GBM patient survival. The findings position ERO1α–MAM signaling as a potential therapeutic target to limit GBM plasticity and metabolic adaptation.

Bassot A, Violy L, Gorka L et al. · Nature cell biology · (2026) · View on PubMed ↗

Nanoparticles reach metastatic tumours via enhanced permeability of adjacent vessels.

This study investigated how nanoparticles deliver to early metastatic micrometastases in vivo using real-time intravital imaging in tumor-bearing models. The authors found that nanoparticles accumulate around avascular micrometastases via the enhanced permeability of vessels in adjacent non-malignant tissues, driven by micrometastasis-induced altered vessel mechanics and compressive stress that activates β1 integrins. This mechanism identifies a delivery route that could be exploited to improve nanoparticle targeting of micrometastatic disease before overt spread.

Wang Q, Zeng C, Chen Z et al. · Nature nanotechnology · (2026) · View on PubMed ↗

Cadonilimab plus chemotherapy as first-line treatment in PD-L1-negative advanced non-small cell lung cancer: a phase II clinical trial.

This phase II clinical trial studied cadonilimab, a PD-1/CTLA-4 bispecific antibody, combined with chemotherapy as first-line treatment in PD-L1-negative advanced non-small cell lung cancer (NSCLC) patients (ChiCTR2300071681). The trial reported that the 12-month progression-free survival (PFS) rate met the prespecified threshold (42.1%), with secondary outcomes including an objective response rate of 66.0% and median PFS of 9.7 months. These results support cadonilimab plus chemotherapy as a potentially effective immunotherapy strategy for PD-L1-negative advanced NSCLC.

Wang L, Rao C, Wang Q et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

In situ reprogramming of CAR-alveolar macrophages via liposomal nanomedicine for lung cancer immunotherapy.

This study investigated lung cancer immunotherapy by developing a precision-engineered cascade-targeted liposomal nanomedicine (pCAR-P3/LNP) to reprogram alveolar macrophages in situ. Using intrapulmonary nebulization and promoter-driven activation, the approach generated functionally optimized chimeric antigen receptor (CAR)-expressing alveolar macrophages that overcome tumor microenvironment–mediated immunotherapy resistance. This provides a nanomedicine platform for converting endogenous macrophages into CAR effector cells directly within the lung tumor niche.

Li H, Lyu C, Cai X et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

SPP1+ macrophages facilitate the differentiation and maturation of regulatory T cells in tumour-draining lymph nodes of colorectal cancer.

This study mapped the immune microenvironment of colorectal cancer tumor-draining lymph nodes (TDLNs) using single-cell RNA sequencing across matched patient samples to identify macrophage subsets linked to regulatory T cell (Treg) maturation. The authors found that SPP1+ macrophages facilitate differentiation and maturation of Tregs in tumor-draining lymph nodes, indicating an immunomodulatory axis within the CRC lymph node niche. This highlights SPP1+ macrophages as a potential therapeutic target to modulate Treg-driven immune suppression in colorectal cancer.

Wang J, Zhou M, Tan B et al. · Gut · (2026) · View on PubMed ↗

A DPHV-liver module recapitulates AML infiltration and chemotherapy-induced hepatotoxicity with translational utility.

A dynamic perfusable human vascularized liver module was developed to model acute myeloid leukemia (AML) liver infiltration and chemotherapy-induced hepatotoxicity in a translationally relevant setting. The system recapitulated AML infiltration and reproduced chemotherapy-driven hepatotoxic injury in a way intended to mirror in vivo drug responses while remaining clinically useful. This provides a vascularized in vitro platform for mechanistic studies and drug discovery that can better predict patient-relevant liver toxicity and disease progression.

Deng B, Ma Y, Huang W et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting TMED4 enhances CD8+ T cell function and CAR T cell efficacy in solid tumors through the IRE1α-autophagy axis.

The study examined how the ER-stress–linked transmembrane protein TMED4 (Tmed4) regulates CD8+ T cell antitumor immunity and CAR T cell efficacy in solid tumor models. T cell–specific Tmed4 deletion enhanced CD8+ T proliferation, tumor infiltration, and killing while reducing terminal exhaustion via hyperactivation of the IRE1α–XBP1 pathway and increased autophagy flux in an IRE1α-dependent manner. These findings identify TMED4 as a therapeutic target to improve T cell function and CAR T performance in solid tumors through the IRE1α-autophagy axis.

Wang H, Shi L, Jiang K et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Serplulimab Plus Chemotherapy, with or without HLX04, versus Chemotherapy as First-Line Treatment for Nonsquamous NSCLC: Final Survival Analysis of the Phase III ASTRUM-002 Study.

This phase III randomized clinical trial (ASTRUM-002) studied first-line treatment in 636 treatment-naïve, locally advanced or metastatic nonsquamous non-small cell lung cancer (nsq-NSCLC) patients without EGFR or ALK/ROS1 alterations, comparing serplulimab plus HLX04 (bevacizumab biosimilar) with chemotherapy versus serplulimab plus HLX04 placebo with chemotherapy versus double placebo plus chemotherapy. It found that the final survival analysis supported the efficacy of the serplulimab plus HLX04 plus chemotherapy regimen relative to the control arms. This is significant because it extends evidence for adding serplulimab (an immunotherapy) and HLX04 (anti-VEGF biosimilar) to standard chemotherapy as a survival-improving first-line option for this molecularly selected NSCLC population.

Hao X, Wang L, Hao Y et al. · Cancer communications (London, England) · (2026) · View on PubMed ↗ · Free PDF ↗

BTK inhibition enhances immunovirotherapy in glioblastoma via tertiary lymphoid structure modulation.

This study tested whether Bruton’s tyrosine kinase (BTK) inhibition can enhance oncolytic herpes simplex virus type 1 (oHSV-1) immunovirotherapy in glioblastoma by modulating tertiary lymphoid structures (TLS). The authors found that BTK inhibition improves immunovirotherapy efficacy in GBM and is associated with changes in the tumor microenvironment consistent with TLS modulation. Clinically, this suggests a combinatorial strategy—BTK inhibition plus oHSV-1—to overcome GBM immunotherapy resistance.

Kyritsi K, Zhu D, Ding H et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗ · Free PDF ↗

An Itch Receptor Drives Melanoma.

This study investigated the role of the itch receptor MRGPRX4 (Mas-Related GPCR X4) in melanoma progression and therapy resistance using human tumor analyses and mouse functional experiments. The authors found that MRGPRX4 is upregulated in invasive neural-crest-like/pre-EMT melanoma states and that ectopic MRGPRX4 expression in mouse melanocytes drives highly metastatic, ligand-independent PI3K–AKT–MAPK–activated melanoma. This is significant because it identifies MRGPRX4 as an actionable melanoma driver linked to a distinct invasive niche and potential therapeutic vulnerability.

Gour N, Atakkatan A, Akbarzadeh M et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗ · Free PDF ↗

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CAR-T and bispecific antibody therapies (safety, efficacy, sequencing)

Dual-target CAR-T cell therapy: latest updates from the 2025 ASH annual meeting.

This article summarized updates from the 2025 ASH annual meeting on dual-target chimeric antigen receptor T (CAR-T) cell therapies across preclinical and clinical development. It reports that dual-target engineering strategies—using diverse receptor architectures, logic-gated designs, and novel manufacturing platforms—can improve disease control and reduce antigen-negative escape across B-cell malignancies, acute myeloid leukemia, and autoimmune disease models. These advances support dual-target CAR-T as a next-generation approach to overcome limitations of single-target CAR-T in heterogeneous antigen settings.

Feng S, Kong R, Xiao L et al. · Experimental hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Impact of Bridging Response on Outcomes After CD19 CAR T-Cell Therapy in Large B-Cell Lymphoma.

This retrospective multicenter study assessed whether response to bridging therapy (BT) during CD19 CAR T-cell manufacturing predicts outcomes in patients with relapsed/refractory large B-cell lymphoma (LBCL). The key finding was that bridging response had prognostic relevance for progression-free survival (PFS) and overall survival (OS) after CD19 CAR T-cell therapy, independent of the BT modality. Clinically, this supports using BT response status to refine risk stratification and potentially guide BT selection or intensity before CAR T infusion.

Wills B, Samorodnitsky S, Brown S et al. · Transplantation and cellular therapy · (2026) · View on PubMed ↗

Treatment-related adverse events of CD3-based T cell-engaging bispecific antibodies in patients with cancer: a meta-analysis of clinical trials.

This meta-analysis synthesized treatment-related adverse events from clinical trials of CD3-based T cell-engaging bispecific antibodies across cancer indications. By searching major databases through July 31, 2025, the study characterized the overall incidence and spectrum of key toxicities associated with CD3 engagement, summarizing patterns across trials. These pooled safety estimates are important for clinical management and for designing future trials by anticipating common and serious adverse-event risks of CD3-based bispecific therapies.

Zhu Y, Liu K, Rosen ST et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Real-world patient-reported symptomatic adverse events and concordance with physician assessments after CAR T-cell therapy in patients with aggressive B-cell lymphomas: a prospective study.

This prospective multicenter study measured real-world patient-reported symptomatic adverse events and compared them with physician assessments after CAR T-cell therapy in adults with aggressive B-cell lymphomas. The key finding was that patient-reported symptom burden showed varying concordance with physician-rated assessments and that specific factors predicted the overall short-term burden of therapy. This supports incorporating patient-reported outcomes into CAR T toxicity monitoring to better capture clinically meaningful symptoms that may be under- or over-estimated by clinicians.

Efficace F, Zinzani PL, Bonifazi F et al. · The Lancet. Haematology · (2026) · View on PubMed ↗

Epcoritamab monotherapy or epcoritamab with lenalidomide as first-line therapy for patients with diffuse large B-cell lymphoma (EPCORE DLBCL-3): primary analysis of an open-label, multicentre, randomised, phase 2 trial.

This open-label, multicenter randomized phase 2 trial compared first-line epcoritamab monotherapy versus epcoritamab plus lenalidomide in older adults with diffuse large B-cell lymphoma (DLBCL) who were ineligible for anthracycline-based chemoimmunotherapy (EPCORE DLBCL-3). The primary analysis evaluated efficacy and safety of these fixed-duration regimens in CD20-positive large B-cell lymphoma patients aged ≥80 or ≥75 with comorbidities. The trial informs anthracycline-free treatment options for frail/elderly patients by directly testing whether adding lenalidomide improves outcomes over epcoritamab alone.

Vitolo U, Burgues JMB, Duell J et al. · The Lancet. Haematology · (2026) · View on PubMed ↗

Bispecific antibody therapy in multiple myeloma and risk of progressive multifocal leukoencephalopathy.

The study assessed whether bispecific antibody therapies for multiple myeloma (MM) are associated with progressive multifocal leukoencephalopathy (PML) risk by analyzing cases from the French prospective registry of JC polyomavirus CNS infections and the French pharmacovigilance database, plus a systematic review. It evaluated whether a disproportionality signal for PML reporting exists among MM patients treated with bispecific antibodies. Establishing or refuting this safety signal is clinically important for monitoring and risk mitigation in the rapidly expanding bispecific antibody MM treatment landscape.

Le Henaff JR, Le Guennec L, Schiro P et al. · Blood advances · (2026) · View on PubMed ↗ · Free PDF ↗

Outcomes of CAR-T Cell Therapy and Bispecific Antibodies as Single-Modality and Sequential Strategies in Relapsed/Refractory Multiple Myeloma.

The study compared outcomes of CAR-T cell therapy and bispecific antibodies (BsAbs) in relapsed/refractory multiple myeloma (RRMM) using a retrospective multicenter cohort of 640 patients and bias-correction analysis. It found that sequential therapy using both modalities produced the most favorable survival trajectories, with CAR-T initiation (ide-cel, cilta-cel, cesni-cel) associated with longer remission, while early progression mortality was similar across initial modalities. These findings support rational sequencing strategies and suggest that product-level effects (notably cilta-cel and cesni-cel) may drive CAR-T benefit in RRMM.

Merz M, Jelinek T, Pabst T et al. · Blood cancer discovery · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer genomics, epigenetics & transcriptional regulation

Integrated proteogenomic and metabolomic profiling of acute myeloid leukemias to identify molecular subtypes and associated therapy targets.

This study applied integrated proteogenomic and metabolomic profiling across 13 modalities to analyze 173 treatment-naive acute myeloid leukemia (AML) patients to define molecular subtypes and therapy targets. Multi-omics integration revealed distinct AML subtypes and extensive metabolomic/lipidomic reprogramming driven by divergent MYC and mTOR activity, including links to mitochondrial protein hyperacetylation in CEBPA-mutant contexts (truncated). These findings provide subtype-resolved biomarkers and mechanistic metabolic vulnerabilities that could guide targeted AML therapies.

Chu SA, Hsiao Y, Wang C et al. · Nature cancer · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Recurrent COPA mutation drives R-spondin-independent Wnt activation in intestinal tumors.

This study examined intestinal tumorigenesis in small intestinal adenoma/adenocarcinoma by identifying recurrent in-frame COPA deletions and testing them in patient-derived and CRISPR-engineered intestinal organoids. COPA in-frame deletion produced R-spondin-independent but Wnt ligand-dependent growth by stabilizing the Frizzled coreceptor LRP6 and maintaining LGR5 expression despite the absence of canonical Wnt pathway drivers. These findings define a COPA-driven alternative Wnt activation mechanism that may inform stratified therapies for intestinal cancers lacking APC and other canonical Wnt alterations.

Fujii M, Abeto N, Kishimoto S et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

RNA reinforces condensate nucleation on chromatin to amplify oncogenic transcription.

This study examined how RNA influences chromatin-associated condensate formation driven by oncogenic mutant ENL (a YEATS-domain chromatin reader) in cells and in vitro systems. The authors found that locally produced transcripts reinforce mutant ENL condensate nucleation and chromatin engagement, enhancing oncogenic transcriptional activity, with RNA binding mediated in part by a basic patch in ENL’s YEATS domain. Scientifically, it reveals an extrinsic RNA mechanism that amplifies chromatin condensates, suggesting new intervention points for transcriptional dysregulation in ENL-driven cancers.

Budinich KA, Yao X, Gong C et al. · Molecular cell · (2026) · View on PubMed ↗

Mechanism of lipid transfer by bridge-like protein VPS13A and the scramblase XK.

The study examined how the bridge-like lipid-transfer protein VPS13A cooperates with the plasma-membrane scramblase XK to mediate lipid transfer between organelles. Using cryo-electron microscopy, it visualized a near-atomic complex in which VPS13A binds XK via its pleckstrin homology domain to prime VPS13A’s lipid-transfer bridge for direct lipid delivery to the cytosolic side. This mechanistic structural insight clarifies a core step in vesicle-independent lipid trafficking and may inform therapeutic strategies for diseases involving VPS13A/XK dysfunction.

Hu B, Álvarez D, Rocha-Roa C et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

DDX6 induces immunosuppression in cancer by disrupting structural stability of endogenous double-stranded RNAs.

The study examined how the RNA helicase DDX6 modulates immune activation by altering endogenous double-stranded RNA (dsRNA) structure and ADAR1-mediated A-to-I RNA editing in cancer. DDX6 interacted with ADAR1 to repress editing of A:C mismatches, disrupted dsRNA structural stability, and suppressed interferon signaling and immune responses, acting as an immune protector under normal conditions but an immunosuppressor in cancer. This identifies DDX6–ADAR1–dsRNA structural control as a mechanism of tumor immune evasion and a potential therapeutic vulnerability.

Ng L, Tano V, Pitcheshwar P et al. · Science immunology · (2026) · View on PubMed ↗

Single-Cell Studies Advance Understanding of the Genetic and Molecular Basis of Atherosclerosis.

This review summarized how single-cell and spatial genomics approaches (e.g., single-cell RNA sequencing and single-cell epigenome sequencing) have been used to dissect the cellular and genetic basis of atherosclerosis in human arterial plaques. It found that these techniques reveal dynamic, genetically linked transcriptional programs in specific vascular and immune/stromal cell states that are obscured by bulk assays. This is significant because it provides a framework to connect genetic risk to cell-type-specific phenotypes, potentially enabling more precise therapeutic targeting of atherosclerosis.

Li DY, Monteiro JP, Zhao Q et al. · Circulation research · (2026) · View on PubMed ↗

G quadruplex DNA facilitates a pervasive path to homologous recombination.

This work investigated how G-quadruplex (G4) DNA structures influence homologous recombination (HR) template strand invasion and how the G4 helicase DHX36 regulates this process. The authors found that G4 DNA is a pervasive facilitator of template strand invasion, while DHX36 loss stabilizes G4s, enhances HR, and accelerates repair of replication-associated DNA breaks. This is significant because it connects G4 biology to HR efficiency and partially restores HR and PARP inhibitor resistance in BRCA1-deficient cells, suggesting potential combinatorial therapeutic implications.

Thakur BL, Basak P, Khurana S et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗

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Infectious disease: vaccines & antimicrobial therapy

mRNA-based tuberculosis vaccines BNT164a1 and BNT164b1 are immunogenic, well tolerated and efficacious in rodent models.

The study evaluated two mRNA-lipid nanoparticle tuberculosis vaccine candidates, BNT164a1 (nucleoside-unmodified mRNA) and BNT164b1 (N1-methylpseudouridine-modified mRNA), encoding eight Mycobacterium tuberculosis antigens (Ag85A, Hrp1, ESAT-6, RpfD, RpfA, HbhA, M72, VapB47) in multiple mouse strains including C57BL/6, BALB/c, and HLA-A2.1/DR1 humanized mice. Prime-boost immunization induced antigen-specific antibody and/or T cell responses across all antigens and showed favorable safety in a rat toxicity study while significantly reducing tuberculosis burden (details truncated in the abstract). These findings support mRNA vaccine platform feasibility and antigen design for TB and suggest that mRNA modification (unmodified vs N1-methylpseudouridine) can be leveraged without compromising immunogenicity or tolerability in preclinical models.

Agrawal N, Ates LS, Schille SA et al. · Nature immunology · (2026) · 3 citations · View on PubMed ↗ · Free PDF ↗

Human vaccine responses regulated by parallel cytokine pathways.

This study analyzed 66 cytokines in 581 participants across four cohorts receiving inactivated influenza vaccine (IIV) over five seasons to identify correlates of day 28 antibody responses, and then tested cytokine causality in human tonsil and spleen organoids. Baseline serum IL-18 and IFN-β correlated with day 28 antibody responses, while organoid experiments showed that type I IFNs, IL-21, and IL-12 enhanced antibody production and that adding IFNβ to IIV recapitulated key features of the live-vaccine cytokine program. The work defines parallel cytokine pathways—IL-12 inducing IL-21 independent of type I IFNs—providing mechanistic targets for improving human vaccine responses.

Chen G, Guo J, Heath J et al. · Nature immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Bacterial cell division protein FtsZ complexes with a phage protein to activate bacterial immunity.

This study examined how the antiphage defence protein CapRelEbc (from the fused toxin–antitoxin system in Enterobacter chengduensis) detects a T7 phage protein in the context of bacterial host factors. It found that CapRelEbc senses the T7-encoded protein Gp0.4 only when Gp0.4 is complexed with the essential bacterial cell division protein FtsZ, and that this Gp0.4–FtsZ complex triggers immune activation whereas either protein alone does not. The work reveals a host-factor-dependent molecular trigger for bacterial immunity and clarifies how phage-mediated disruption of FtsZ polymerization can activate defence systems.

Zhang T, Nadieina A, Soderstrom CBW et al. · Nature microbiology · (2026) · View on PubMed ↗ · Free PDF ↗

Analysis of monoclonal antibodies against the malaria invasion complex protein RIPR reveals the structural basis for synergistic antibody protection.

This structural immunology study analyzed 83 human IgG monoclonal antibodies against the malaria invasion complex protein RIPR (from RIPR-vaccinated Kymouse platform mice) to determine why antibody combinations act synergistically. Single antibodies showed limited neutralization, but pools targeting the RIPR-tail region produced strong synergistic inhibition, and structural/molecular dynamics analyses mapped this effect to antibodies binding RIPR EGF-like domains 6–8 (RIPREGF(6–8)). The work provides a mechanistic structural basis for designing more effective RIPR-targeting antibody vaccines or combination antibody therapies against blood-stage Plasmodium falciparum.

Williams BG, Barrett JR, Scott JB et al. · Immunity · (2026) · View on PubMed ↗ · Free PDF ↗

Emerging Trends in Targeted Molecular Therapies for Inflammatory Bowel Disease: Biologics and Small Molecules.

This review studied emerging targeted molecular therapies for inflammatory bowel disease (Crohn’s disease and ulcerative colitis) across recent clinical and preclinical evidence in human populations. It found that newer biologics and small molecules—along with emerging delivery technologies—are increasingly designed to more precisely modulate immune dysregulation and improve efficacy/safety compared with conventional therapies. These advances are clinically significant because they expand mechanism-based treatment options for IBD patients who often have limited response and adverse effects with standard regimens.

Borra PK, Chandra P, Raghav A et al. · Current pharmaceutical design · (2026) · View on PubMed ↗

Cellular nucleic acid-binding protein (CNBP) dependent cytokine programming shapes host defense against Plasmodium infection.

This preprint studied how the zinc-finger transcriptional regulator cellular nucleic acid-binding protein (CNBP) shapes cytokine programming and host defense during blood-stage Plasmodium infection, focusing on the IL12β–IFN-γ axis in vivo. It found that CNBP contributes to transcriptional tuning of IL12β production in myeloid cells, thereby influencing downstream IFN-γ–mediated control of infection. This is significant because it identifies CNBP as a regulator of protective cytokine responses, potentially informing strategies to enhance immunity against malaria.

Rashid R, de Souza Silva L, Banday S et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗ · Free PDF ↗

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CNS infections & antimicrobial penetration

Real-World Data on the Use of Intravenous Fosfomycin for the Treatment of Central Nervous System Infections: a Subgroup Analysis from the FORTRESS Study.

This subgroup analysis of the prospective, multicenter FORTRESS study evaluated real-world use, effectiveness, and safety of intravenous fosfomycin (FOS) for central nervous system (CNS) infections. It focused on patients with CNS infections where FOS is used because of broad-spectrum activity and reliable cerebrospinal fluid (CSF) penetration, addressing antimicrobial resistance and limited CSF penetration of many alternatives. The results aim to inform clinical decision-making on FOS as a combination-therapy partner for severe CNS infections.

Jarczak D, Kluge S, Kieninger M et al. · Infectious diseases and therapy · (2026) · View on PubMed ↗ · Free PDF ↗

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Virology & surrogate virus/vaccine platforms

Host-virus determinants of Ebola virus persistence in a human cerebral organoid model.

This study investigated host and viral determinants of Ebola virus (EBOV) persistence using a human cerebral organoid model, focusing on persistence defined as ongoing EBOV genome replication beyond the acute phase. In the organoid system, EBOV persistence for 120 days was sustained by continuous infection of (cell type/details truncated in the abstract), implicating specific host-virus interactions in CNS persistence. The model provides a platform to identify mechanisms that enable EBOV recrudescence and could inform interventions to prevent persistent infection after EVD.

Widerspick L, Vidal Freire S, Steffen JF et al. · Nature microbiology · (2026) · View on PubMed ↗

Targeted cleavage site mutations in the Gn precursor enable efficient generation of replication-competent rVSV-based surrogates for emerging nairoviruses.

The study engineered targeted cleavage-site mutations in the nairovirus glycoprotein precursor (Gn precursor) to enable efficient generation of replication-competent recombinant vesicular stomatitis virus (rVSV)-based surrogates for emerging nairoviruses. By optimizing precursor processing, the authors improved rescue efficiency of rVSV surrogates expressing nairovirus glycoproteins, facilitating neutralization studies under lower containment than authentic high-risk pathogens. This advances surrogate virus platforms for emerging nairoviruses such as Yezo virus and supports safer, more accessible vaccine/antibody evaluation.

Jain S, Marot S, Karaaslan E et al. · Emerging microbes & infections · (2026) · View on PubMed ↗ · Free PDF ↗

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Respiratory disease (COPD, asthma/CRSwNP, pulmonary fibrosis, lung injury)

Indirect Treatment Comparison of Tezepelumab Versus Other Biologics in Severe Chronic Rhinosinusitis with Nasal Polyps: A Systematic Literature Review and Network Meta-analysis.

This systematic literature review and network meta-analysis compared tezepelumab with other approved biologics and endoscopic sinus surgery (ESS) in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP). Across synthesized randomized controlled trials, tezepelumab showed comparative effects on nasal polyp score and related patient-reported and clinician-assessed outcomes versus comparators in the network. These indirect comparative results support evidence-based positioning of tezepelumab among biologic options and ESS for CRSwNP management.

Han JK, Mullol J, Hopkins C et al. · Advances in therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Heme orchestrates a tissue stress response to proteolytic damage.

This preprint studied tissue-level responses to proteolytic damage in lung models using diverse proteases to define a conserved injury signature. It found that proteolytic stress causes vascular disruption, red blood cell extravasation, and heme release that triggers oxidative stress, with alveolar macrophages acting as primary sensors that activate an NRF2-dependent heme detoxification program. This is significant because it links protease-driven injury to a unified heme–NRF2 stress pathway that could be targeted to mitigate diseases involving excessive proteolysis.

Agaronyan K, Greaney AM, Yu S et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗

Early Pulmonary Fibrosis is Defined by Niche- and Cell-Specific Molecular Programs.

This study defined early pulmonary fibrosis programs by profiling spatially preserved and remodeled lung tissue from subjects with preclinical familial pulmonary fibrosis (FPF), idiopathic pulmonary fibrosis (IPF), and controls. Using spatial transcriptomics, single-nucleus RNA sequencing (snRNAseq), and blood proteomics, the authors identified niche- and cell-specific molecular programs associated with early fibrotic remodeling and proposed tissue-informed circulating biomarker signatures. The significance lies in improving early detection and mechanistic understanding of the compartmentalized events that precede overt fibrosis.

Waich A, Ochsner SA, Villalba JA et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗

Defining disease stability in COPD: Evidence from Phase 3 clinical trials.

This post hoc analysis assessed whether COPD “disease stability” defined as no moderate/severe exacerbations and no worsening in CAT and FEV1 at Week 28 predicts later outcomes in Phase 3 trials. Using data from IMPACT and FULFIL (and additional trials including MATINEE/METREX/METREO with mepolizumab added to triple therapy), the study evaluated prognostic value for time to first on-treatment moderate/severe exacerbation and all-cause mortality after Week 28. The work supports COPD stability as a clinically meaningful composite endpoint that could guide treatment targets and stratification in future trials.

Singh D, Stacey R, Halpin DMG et al. · American journal of respiratory and critical care medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Kidney disease & renal regeneration

Bioelectric Reawakening by a Self-Powered Thermoelectric Hydrogel Accelerates Diabetic Ulcer Repair.

This preclinical study examined a self-powered ionic thermoelectric dual-network hydrogel for diabetic foot ulcer (DFU) repair in a diabetic ulcer wound setting. The hydrogel generated wound-relevant microcurrents under physiological skin–air temperature gradients and simultaneously reconstructed wound bioelectric cues while remodeling the DFU microenvironment (including infection/inflammation/oxidative stress), with luteolin incorporated as part of the therapeutic design. By restoring bioelectricity without external power, this approach could offer a clinically practical strategy to accelerate DFU healing and improve outcomes in patients with hard-to-treat wounds.

Luo W, Zhang S, Sun H et al. · Advanced materials (Deerfield Beach, Fla.) · (2026) · View on PubMed ↗

Keratin 18 functions as a lactyltransferase to trigger necroptosis in diabetic kidney disease by modulating Fas transcription.

This study investigated diabetic kidney disease (DKD) mechanisms by testing how lactate-induced histone lactylation regulates necroptosis and Fas transcription, focusing on keratin 18 (KRT18) as a lactyltransferase. The authors found that lactate-driven H3K18la and H3K27la modulate Fas transcription to promote necroptosis and DKD progression, and that KRT18 regulates these lactylation marks to induce Fas-mediated necroptotic signaling. This links KRT18-dependent histone lactylation to necroptosis in DKD, suggesting potential epigenetic/necrotic pathway targets for intervention.

Zhao Q, Liu X, Yang Y et al. · Experimental & molecular medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Human CD24+ dental papilla cells are competent seed cells for dentin-pulp regeneration via BMP2/SIRT1 axis.

This study investigated regenerative capacity of human CD24+ dental papilla cells (hDPCs) for dentin-pulp repair using ectopic murine and preclinical in situ minipig models. The authors found that CD24+ hDPCs robustly drive coordinated, well-vascularized pulp regeneration and structurally integrated dentin formation, outperforming conventional dental pulp stem cells, via a BMP2/SIRT1 axis in which elevated BMP signaling sustains SIRT1 expression. This identifies a specific cell subset and signaling pathway that could improve stem-cell–based strategies for tooth regeneration.

Liang C, Liu Z, Li J et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Regenerative macrophages enhance stem cell-derived β cell function and engraftment.

The study investigated whether regenerative-state stem cell–derived macrophages (SC-MReg) improve differentiation, insulin function, and engraftment of stem cell–derived β cells (SC-β cells) for type 1 diabetes. Coaggregation with SC-MReg during stage 7 of SC-β cell differentiation enhanced β cell function and engraftment compared with unpolarized or inflammatory macrophage states. This suggests that macrophage polarization can be used as a cell-engineering strategy to generate more mature, therapeutically effective SC-β cells.

Freitas BFA, Fox SA, Orban PC et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Collecting Duct-Targeted Lipid Nanoparticles Deliver Pkd2 mRNA to Restore Polycystin-2 and Attenuate ADPKD.

This study developed collecting duct–targeted lipid nanoparticles delivering PKD2 mRNA to restore polycystin-2 (PC2) expression in a model of autosomal dominant polycystic kidney disease (ADPKD). The key finding is that CD-targeted LNPs achieved functional PKD2 mRNA delivery to cyst-lining renal epithelia, restoring PC2 and attenuating ADPKD cyst progression. This is significant because it demonstrates a gene-replacement approach that directly targets the PKD2 genetic defect rather than only downstream signaling.

Giblin J, Lambaren K, LaMastro R et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗ · Free PDF ↗

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Metabolism, obesity & thermogenesis

Adipose tissue as a humoral-neuronal hub in metabolic regulation.

This Nature Reviews Endocrinology article reviewed how adipose tissue regulates systemic metabolism through both humoral and neuronal pathways. It highlights that adipose depots secrete peptide hormones, lipid mediators, metabolites, chemokines, and exosomal microRNAs, while sympathetic efferents control lipolysis and thermogenesis and sensory afferents detect chemical/thermal/mechanical cues to tune sympathetic output. The synthesis underscores adipose tissue as a therapeutic target for cardiometabolic disease by linking endocrine signaling and neural circuit control.

Tsuji T, Tseng YH · Nature reviews. Endocrinology · (2026) · View on PubMed ↗

Nitrate-Sialin2 axis couples ER-mitochondrial calcium signaling with fatty acid metabolism to drive white adipose browning.

This study investigated how dietary inorganic anions regulate adipose thermogenesis by identifying Sialin2 as a nitrate sensor and mapping its intracellular signaling in models of white adipose browning. The authors found that Sialin2 couples ER–mitochondrial Ca2+ transfer to fatty acid metabolism by strengthening ER–mitochondria contacts and engaging an IP3R1–VDAC1–MCU1 calcium conduit, thereby promoting mitochondrial oxidation and a spatially confined thermogenic program. This mechanistic nitrate–Sialin2 axis suggests a targetable pathway to induce browning and improve metabolic health.

Jiang O, Cao Z, Kong S et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of interorganellar lipid cycling.

This study investigated how circadian clock, diet, and environmental temperature signals are integrated to control mitochondrial lipid cycling via the orphan transporter SLC25A34. The authors found that sleep suppresses Slc25a34 transcription through REV-ERBα, while waking, lipid-rich diets, or cold exposure relieve repression and allow PPARα-driven induction; SLC25A34 then imports oxaloacetate to accelerate mitochondrial substrate export for acetyl-CoA production. This is significant because it links specific transcriptional regulators (REV-ERBα and PPARα) to a defined mitochondrial carrier that coordinates thermogenic lipid metabolism.

Karavaeva I, Basse AL, Trammell SAJ et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗ · Free PDF ↗

A genetic tool targeting brain GPR75.

This study created and validated a genetic mouse tool to target the brain G-protein-coupled receptor GPR75. The authors generated a GPR75-GFP-Ires-Cre knock-in line in which Cre is driven by the endogenous GPR75 promoter and GFP is fused to the GPR75 C-terminus, confirming colocalization with endogenous GPR75 expression and preserved function with normal susceptibility to diet-induced obesity (DIO). This is significant because it enables anatomically precise, cell-type–specific interrogation of GPR75 biology for anti-obesity drug development.

Wheeler EC, Yang R, Farmer SM et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗

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Epigenetics & chromatin regulation (general mechanisms)

Developing WNT-derived bone anabolic peptides for skeletal aging and fracture by reconstructing thumb and index domains of WNT7B.

This study developed WNT-derived bone anabolic peptides by reconstructing the thumb and index domains of WNT7B (WNT7BRTID) using AlphaFold-empowered sequence prediction and in silico docking screening, then tested the peptide in aged mouse and pig osteoporosis models. WNT7BRTID improved osteogenic potential of mesenchymal stromal/stem cells (MSCs) and enhanced bone regeneration, supported by single-cell sequencing, transgenic lineage tracking, and biochemical assays (truncated). These preclinical results suggest a more tractable WNT-based anabolic therapeutic strategy for skeletal aging and fracture repair.

Yu F, Li F, Yu P et al. · Nature biomedical engineering · (2026) · View on PubMed ↗ · Free PDF ↗

A progeria syndrome links DNA hypermethylation to age-related pathology.

This study investigated whether DNA hypermethylation can causally drive age-related pathology by analyzing an epigenetically driven accelerated aging syndrome caused by DNMT3A gain-of-function mutations in Heyn-Sproul-Jackson syndrome. The authors showed that DNMT3A GOF recapitulates age-related increases in DNA methylation across multiple lineages and leads to multilineage age-associated pathology. This provides genetic evidence that DNMT3A-mediated hypermethylation is not merely correlative but can be mechanistically causal for age-like disease features.

Sarni D, Neary G, Carroll PL et al. · Nature genetics · (2026) · View on PubMed ↗ · Free PDF ↗

Mechanical Activation of Piezo1 Drives Osteoarthritis Through Kdm5c-Mediated Epigenetic Silencing.

The study examined how mechanical stress drives osteoarthritis (OA) through Piezo1 activation and Kdm5c-mediated epigenetic silencing in mice. Using Piezo1 conditional knockout mice (Col2a1CreERT; Piezo1flox/flox), it found that excessive mechanical stress activates Piezo1, triggering cytoskeletal force–dependent chromatin remodeling that promotes Kdm5c erasure of H3K4me3 at promoters of cartilage-anabolic genes Col2a1 and Runx3. This identifies the Piezo1→Kdm5c epigenetic axis as a mechanistic target for preventing or slowing OA progression.

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

Transcription factor Tono mediates histone H3K4 trimethylation to regulate endoreplication through transcriptional reprogramming.

The authors studied how the transcription factor Tono regulates endoreplication by controlling histone H3K4 trimethylation during the mitotic-to-endoreplication transition using Bombyx silk gland and Drosophila salivary gland models. They found that H3K4me3 levels increase upon endoreplication entry and that Tono mediates H3K4 trimethylation to drive transcriptional reprogramming required for endoreplication. This links a specific epigenetic regulator (Tono → H3K4me3) to the transcriptional control of cell cycle remodeling in endoreplicating tissues.

Li H, Song Y, Guo M et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.

This review synthesized evidence from human genomic studies and neurobiology to argue that microtubule motor proteins are essential for neuronal longevity. It links mutations affecting microtubule transport machinery to disrupted neurodevelopmental processes and, in mature neurons, to impaired axon integrity and synaptic proteostasis. The work is significant because it frames neuronal aging and degeneration as mechanistically tied to long-range intracellular transport, guiding future therapeutic target discovery.

Turner ED, Twelvetrees AE · Journal of neurochemistry · (2026) · View on PubMed ↗ · Free PDF ↗

Piezo1-activated mesenchymal stem cells-derived extracellular matrix hydrogel promotes the repair of osteoporotic bone defects through osteogenic and angiogenic coupling.

This preclinical study developed a mesenchymal stem cell–derived extracellular matrix hydrogel preconditioned with Yoda1 (Y-ECM-gel) to activate the Piezo1 mechanosensory channel in order to repair osteoporotic bone defects. It found that Piezo1-activated MSC-derived ECM hydrogel promotes osteogenic and angiogenic coupling, improving healing of osteoporotic bone defects. This is clinically significant because it suggests a biomaterial strategy that addresses both impaired bone formation and vascularization—key limitations in current osteoporotic defect therapies.

Yin H, Zhang W, Wei D et al. · Regenerative biomaterials · (2026) · View on PubMed ↗ · Free PDF ↗

EZH2 Serine 21 Phosphorylation Restrains Compact-State PRC2 Activation and H3K27me3 Propagation.

This study examined how phosphorylation of EZH2 at serine 21 regulates Polycomb Repressive Complex 2 (PRC2) activation and propagation of H3K27me3. Using cryo-EM classification of wild-type versus phospho-null EZH2 S21A PRC2 complexes, the authors found that EZH2 S21 phosphorylation restrains PRC2 compact-state activation and reduces the extent of H3K27me3 propagation. Scientifically, this clarifies a post-translational “brake” on PRC2 positive feedback, informing how cells tune epigenetic silencing magnitude.

Rashoff AQ, Matyas M, Porter EG et al. · bioRxiv : the preprint server for biology · (2026) · View on PubMed ↗ · Free PDF ↗

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Immunology & cytokine signaling (general)

STING1 senses mitochondrial damage to promote mitophagy.

This mechanistic study investigated how the innate immune adaptor STING1 regulates PINK1-PRKN-dependent mitophagy in cells exposed to mitochondrial damage. The authors found that mitochondrial injury recruits STING1 to damaged mitochondria via a process requiring PINK1- and VCP/p97-mediated degradation of outer mitochondrial membrane proteins, positioning STING1 as an upstream controller of selective mitophagy. These findings expand cGAS–STING1 biology beyond immune activation and suggest STING1 as a potential target to modulate mitochondrial quality control in disease.

Huang ZB, Lin JY, Cheng LJ et al. · Autophagy · (2026) · View on PubMed ↗

Recent advances and clinical relevance of microbiome dynamics in health and disease.

This review summarized evidence on microbiome dynamics across health and disease, covering microbial communities in multiple human niches (gut, skin, oral cavity, respiratory tract, and urogenital system). It emphasizes that microbiomes are dynamic ecosystems whose interactions with host physiology influence digestion, vitamin biosynthesis, immune development, and metabolism over the lifespan. The synthesis supports the clinical relevance of tracking microbiome changes for diagnosis, prognosis, and understanding mechanisms of disease.

Gavanji S, Suhail M, Bencurova E et al. · Gut microbes · (2026) · View on PubMed ↗ · Free PDF ↗

Exploring the organismal role of UFMylation in development, stress resilience and neurological function in C. elegans.

This study examined the organismal role of UFMylation (UFM1 conjugation) in the nematode Caenorhabditis elegans, focusing on UFM-1 expression and its regulation during development and stress. UFM-1 expression increased from larval stages to adulthood with predominant intestinal localization and was upregulated during ER stress and autophagy induction, linking UFMylation to stress-resilience and neurological function pathways. These findings support UFMylation as a conserved, developmentally regulated stress-response system and provide a viable in vivo model to dissect UFMylation biology relevant to human disease where UFMylation loss-of-function is lethal.

Kaiser CS, Kahl J, Kouekem EJ et al. · The Journal of biological chemistry · (2026) · View on PubMed ↗ · Free PDF ↗

Coordinated IFN-γ/TNF Axis Drives Selective Loss of Activated Enteric Glia in Inflammatory Bowel Diseases.

This study investigated how an IFN-γ/TNF cytokine axis affects enteric glial cell (EGC) activation and survival in inflammatory bowel diseases (IBD) using human intestinal samples and mouse gut inflammation models. Using bulk and single-nucleus RNA sequencing of 390 patient samples (validated in datasets totaling >1,160 patients and ~19,000 EGC transcriptomes), the authors found that coordinated IFN-γ/TNF signaling drives selective loss of activated EGCs. This mechanistic insight identifies a cytokine-driven vulnerability of activated EGCs that may contribute to impaired gut homeostasis in IBD and suggests potential targets to preserve EGC function during inflammation.

Bubeck M, Penkert KA, Limberger H et al. · Cellular and molecular gastroenterology and hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Interleukin 23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid receptor activity.

This study investigated how interleukin-23 (IL-23) promotes a pro-inflammatory Th17 state by stabilizing RORγt while suppressing glucocorticoid receptor (GR) activity. Integrating phosphoproteomics and transcriptomics downstream of IL-23R and IL-12R, the authors identified CHD1 as an epigenetic mediator that promotes IL-23R signaling via STAT3 and co-binding at the RORγt locus while concurrently suppressing GR activity. These findings clarify a molecular switch controlling Th17 differentiation and may inform targeted therapies for IL-23/Th17-driven autoimmune inflammation.

Yang D, Huang L, Yang J et al. · Immunity · (2026) · View on PubMed ↗ · Free PDF ↗

Simiao Yongan decoction alleviates sepsis-induced liver injury by modulating macrophage polarization via gut-derived ursodeoxycholic acid.

The study investigated how Simiao Yongan (SMYA) Decoction alleviates sepsis-induced liver injury (SLI) by modulating macrophage polarization through gut-derived ursodeoxycholic acid (UDCA). Using an integrated multi-omics approach including metabolomics, transcriptomics, 16S rRNA sequencing, and mass spectrometry, it linked sepsis-associated metabolic and microbial changes to macrophage polarization shifts that were reversed by SMYA treatment. This provides a gut–liver immunometabolic mechanism that could support development of adjunct therapies for SLI.

Yu T, Liu Z, Liu Y et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

The tissue-specific regulation of immunobiology by IL-17 signaling.

This review summarized evidence on how IL-17 signaling regulates immunobiology in a tissue- and cell-specific manner, focusing on IL-17 receptor (IL-17R) complex signaling and downstream pathways. It highlights how intersecting transcriptional and posttranscriptional mechanisms shape IL-17–driven responses across tissues and discusses roles in immunometabolism, neuroimmune interactions, and cancer. The synthesis supports more precise, targeted therapeutic strategies by accounting for tissue-specific IL-17 pathway biology.

Li Y, Vyas SP, Draber P et al. · Science immunology · (2026) · View on PubMed ↗

H3K18la- driven neutrophil secretory autophagy promotes pulmonary endothelial dysfunction in sepsis-induced lung injury.

This mechanistic study investigated how H3K18la (lactylation of histone H3 at lysine 18) driven neutrophil secretory autophagy contributes to pulmonary endothelial dysfunction in sepsis-induced lung injury. In septic patients and experimental models, elevated neutrophil lactate promoted H3K18 lactylation, which enhanced ATG7/GSA7 transcription and initiated a non-degradative secretory autophagy program that impaired endothelial function. These findings identify an epigenetic–metabolic pathway (lactate–H3K18la–ATG7) as a potential therapeutic target to mitigate sepsis-associated lung injury.

Li Y, Li R, Zhu D et al. · Autophagy · (2026) · View on PubMed ↗

Cell stress and death liberate the autophagy-inhibitory tissue stress hormone DBI/ACBP into the circulation.

This mechanistic study investigated how cell stress and regulated cell death influence secretion of the autophagy-inhibitory tissue hormone DBI/ACBP into circulation. It found that DBI/ACBP release is driven by stress-associated pathways and that extracellular DBI/ACBP functions as a feedback inhibitor of autophagy, promoting metabolic and inflammatory alterations. The findings are significant because they identify a systemic signaling mechanism linking cellular stress/death to organism-level metabolic and inflammatory outcomes.

Rong Y, Lambertucci F, Yang Y et al. · Autophagy · (2026) · View on PubMed ↗ · Free PDF ↗

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Clinical trials, registries & health services research (including AI/publishing)

Mesenchymal Stem Cells Therapy for Intrauterine Adhesions and Endometriosis: Potential, Mechanisms, and Future Directions.

This review evaluated the potential mechanisms and future directions of mesenchymal stem cell (MSC) therapy for intrauterine adhesions (IUA) and endometriosis in patients with these gynecologic disorders. It highlights that MSCs may counter key drivers of disease—aberrant fibrosis, inflammatory cascades, and impaired tissue regeneration—more directly than current approaches such as surgical adhesiolysis for IUA and hormonal suppression for endometriosis. If validated in rigorous clinical trials, MSC-based regenerative and immunomodulatory strategies could improve fertility outcomes by targeting underlying pathophysiology in IUA and endometriosis.

Liu SH, He SY, Ji BQ et al. · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · (2026) · View on PubMed ↗

Clinical Phenomenology of Bipolar Disorder With Substance Use Disorders: A Systematic Review.

This systematic review synthesized clinical studies on bipolar disorder (BD) phenotypes in people with comorbid substance use disorders (SUDs), including alcohol, cannabis, tobacco, stimulants, and opioids. It reports that comorbid SUDs are associated with worse BD clinical presentation—such as more severe mood episodes, rapid cycling, and poorer recovery—while emphasizing that substance-specific effects on BD course and prognosis remain insufficiently characterized. Clarifying how different SUDs shape BD symptomatology could improve risk stratification and guide more tailored, substance-specific management strategies.

Garvie S, Sorkhou M, George TP · Bipolar disorders · (2026) · View on PubMed ↗

Rethinking EDSS-based ambulation assessment in multiple sclerosis using continuous variable monitoring.

This prospective observational study evaluated whether continuous variable monitoring can improve ambulation assessment in relapsing-remitting multiple sclerosis (RRMS) compared with the Expanded Disability Status Scale (EDSS) in patients at two German centers. It found that digital health technology enables more objective, continuous measurement of real-world walking performance than single, discrete EDSS-based patient-estimated assessments. If implemented clinically, continuous monitoring could refine disability tracking and better capture progression-related changes in MS ambulation.

Werner NM, Schuette M, Hagler R et al. · Neurological research and practice · (2026) · View on PubMed ↗ · Free PDF ↗

General-purpose large language models outperform specialized clinical AI tools on medical benchmarks.

This study evaluated whether general-purpose large language models (LLMs) outperform specialized clinical AI tools by benchmarking OpenEvidence and UpToDate Expert AI against frontier LLMs (GPT-5.2, Gemini 3.1 Pro, Claude Opus 4.6) using MedQA (500 questions), HealthBench (500 items), and the real clinical queries (RCQ) benchmark built from 100 de-identified physician queries in a live US clinical environment. Across stages, general-purpose LLMs outperformed the specialized clinical AI tools on medical benchmarks (with RCQ performance assessed by clinician interaction, truncated). The results suggest that broadly trained LLMs may provide more reliable clinical decision support than narrow, tool-specific systems, motivating independent evaluation and deployment strategies.

Vishwanath K, Alyakin A, Ghosh M et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Atomic-level protein-ligand recognition with PBCNet2.0 for probe discovery.

This study introduced PBCNet2.0, a Cartesian tensor-based Siamese neural network for protein–ligand relative binding affinity prediction, trained on 8.6 million protein–ligand complex pairs. PBCNet2.0 achieved zero-shot accuracy comparable to physics-based simulations while being computationally efficient, and retrospective prioritization showed a 7.18-fold improvement in optimization efficiency with 41% lower resource use (truncated). The method can accelerate probe discovery and lead optimization by improving binding affinity prediction without the cost of intensive molecular simulations.

Yu J, Sheng X, Fan Z et al. · Nature chemical biology · (2026) · View on PubMed ↗

Enhancing screening, early diagnosis and treatment initiation of oral, breast and cervical cancer in selected districts of India: an implementation research protocol.

This study describes an implementation research protocol to improve screening, early diagnosis, and timely treatment initiation for oral, breast, and cervical cancers in selected districts of India within the NP-NCD framework. The intervention is planned as a multisite, phased model co-developed across seven districts, aiming to raise screening coverage and address screening quality and diagnostic/treatment delays. If successful, it will provide evidence-based operational strategies for strengthening district-level cancer control programs in low-coverage settings.

Kankaria A, Shukla P, Vijayakumar M et al. · BMJ open · (2026) · View on PubMed ↗ · Free PDF ↗

Safety and feasibility of an endoscopic retrograde cholangiopancreatography robotic system in common bile duct stone: a propensity score matched observational study.

This propensity score matched observational study evaluated the safety, feasibility, and learning curve of a robotic endoscopic retrograde cholangiopancreatography (ERCP) system for common bile duct stones in 26 patients. Compared with conventional ERCP performed by the same operator (1:1 propensity matching for 20 stone-extraction cases), robotic-assisted ERCP showed acceptable adverse-event safety and demonstrated technical success with measurable procedural-time and operator-radiation learning-curve effects. The results support robotic ERCP as a feasible approach that may reduce occupational hazards while maintaining procedural performance.

Tang D, Yan R, Zhou L et al. · Endoscopy · (2026) · View on PubMed ↗

National- and state-level burdens of substance use disorders in the USA, 1990-2023, with forecasts up to 2050: Global Burden of Disease Study 2023.

The study quantified national- and state-level burdens of substance use disorders (SUDs) in the USA from 1990–2023 and projected trends to 2050 using Global Burden of Disease Study 2023 estimates for alcohol use disorders (AUDs) and drug use disorders (DUDs). It found that in 2023 the USA had the highest age-standardized SUD prevalence globally and reported increasing trends in age-standardized prevalence over time (with state-level variation and future forecasts to 2050). These results provide evidence for targeting prevention and treatment resources by geography and time horizon.

Med (New York, N.Y.) · (2026) · View on PubMed ↗

Myelodysplastic Syndromes in VEXAS.

This article reviewed myelodysplastic syndromes in the context of VEXAS syndrome, a clonal hemato-inflammatory disorder caused by somatic mutations in the X-linked UBA1 gene. It highlighted that loss-of-function UBA1 variants (commonly M41 missense) reduce UBA1b expression, leading to misfolded protein accumulation and endoplasmic reticulum stress, with systemic inflammation and progressive bone marrow failure often requiring chronic glucocorticoids and immunosuppressive therapy. Understanding how VEXAS-related biology presents as myelodysplastic syndromes can improve diagnosis and guide targeted management of older male patients with refractory inflammatory cytopenias.

Patel BA, Calvo KR, Reichard KK et al. · Blood advances · (2026) · View on PubMed ↗ · Free PDF ↗

Angioarchitecture and classification of adult intracranial pial arteriovenous fistulas: a multicenter study.

The study characterized adult intracranial pial arteriovenous fistulas (AVFs) by analyzing their angioarchitecture and proposing a classification, and it assessed treatment outcomes. In a nationwide multicenter retrospective cohort of adult pial AVFs in Japan (2013–2024) with centrally reviewed imaging, it aimed to define clinical/radiological features and relate angioarchitectural categories to outcomes. A standardized classification and outcome assessment can improve diagnosis, procedural planning, and prognostication for this rare cerebrovascular condition.

Yamada H, Kaku Y, Mizutani K et al. · Journal of neurosurgery · (2026) · View on PubMed ↗

Artificial Intelligence in Biomedical Scientific Publishing.

This commentary assessed how artificial intelligence (AI) is being used across biomedical scientific publishing, including discovery, analysis, knowledge translation, authorship, peer review, and editorial workflows. It emphasizes that AI can increase efficiency and consistency while introducing risks such as bias, reduced transparency, data integrity concerns, and challenges to authorship responsibility. The discussion highlights the need for governance and safeguards to maintain trust in the scientific record as generative AI becomes more embedded in publishing.

Guzik TJ, Aboyans V, Agewall S et al. · European heart journal · (2026) · View on PubMed ↗

Identifying a biologically high-risk subgroup of anatomically resectable hepatocellular carcinoma.

This multicenter retrospective cohort study examined preoperative predictors of early recurrence (within 2 years) after curative-intent hepatectomy in patients with anatomically resectable hepatocellular carcinoma (HCC). It identified a biologically high-risk subgroup and used independent predictors to build a simple preoperative biology-based risk score for early recurrence. Clinically, this score could help stratify anatomically resectable HCC patients for closer surveillance and/or consideration of additional perioperative strategies to reduce early relapse.

Tanaka K, Tsuji K, Hiraoka A et al. · Hepatology international · (2026) · View on PubMed ↗

Three-monthly gonadotropin-releasing hormone agonist for ovarian function suppression in premenopausal breast cancer: a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated whether 3-monthly versus monthly dosing of gonadotropin-releasing hormone agonists (GnRHa) provides equivalent ovarian suppression and clinical outcomes in premenopausal women with hormone receptor-positive (HR+) breast cancer receiving endocrine therapy. The analysis compared ovarian escape rates, estradiol (E2) levels, disease-free survival (DFS), progression-free survival (PFS), and adverse events between 3-monthly and 1-monthly regimens. If equivalence is supported, a 3-monthly schedule could improve treatment convenience and adherence without sacrificing efficacy or safety.

de Liz CD, Reis PCA, Blanchard-Cavagis ER et al. · Breast cancer research and treatment · (2026) · View on PubMed ↗ · Free PDF ↗

The impact of age on efficacy and safety of disease modifying treatment-insights from the Austrian Multiple Sclerosis Treatment Registry.

Using prospectively collected real-world data from the Austrian Multiple Sclerosis Treatment Registry (AMSTR), this study assessed how age modifies efficacy and safety of multiple disease-modifying therapies in people with multiple sclerosis (MS). It evaluated outcomes across age groups for treatments including alemtuzumab, cladribine, dimethyl fumarate, fingolimod, natalizumab, ocrelizumab, ofatumumab, ozanimod, ponesimod, siponimod, and teriflunomide. The findings are significant for tailoring MS therapy selection and risk–benefit decisions as immunosenescence and comorbidities increase with age.

Guger M, Enzinger C, Heschl B et al. · Journal of neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Sodium Bicarbonate for Critically Ill Adults with Metabolic Acidosis and Shock.

In a pragmatic, adaptive, double-blind randomized trial, critically ill adults with metabolic acidosis receiving vasopressors in the ICU were assigned to sodium bicarbonate versus placebo. The study tested whether bicarbonate improves outcomes in this high-risk setting where acidemia correction benefit is uncertain. If effective, sodium bicarbonate could become a targeted intervention for vasopressor-dependent shock patients with metabolic acidosis; if not, it would support avoiding routine bicarbonate use.

Serpa Neto A, McNamara M, White K et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Gastric Residual Volume Assessment in Critically Ill Children: The GASTRIC-PICU Randomized Clinical Trial.

This pragmatic, multicenter randomized noninferiority trial evaluated whether not routinely assessing gastric residual volume (GRV) versus checking GRV at least every 6 hours affects outcomes in critically ill mechanically ventilated children. In 4700 pediatric ICU patients across 23 UK PICUs and 1 Swiss PICU, the intervention targeted improvements in nutrition delivery by reducing feed withholding driven by perceived high GRV. The findings are significant for establishing evidence-based enteral feeding protocols in pediatric critical care.

Tume LN, Mouncey PR, Broomhall JM et al. · JAMA · (2026) · View on PubMed ↗

What Is a Clinically Meaningful Change in Diabetes Distress? Findings for Diabetes Care and Research From the SFDT1 Cohort.

This cohort analysis studied diabetes distress (DD) trajectories over 1 year in people with type 1 diabetes (PwT1D) from the SFDT1 cohort, estimating minimal clinically important differences (MCIDs) for the Problem Areas in Diabetes (PAID) scale and its sub-dimensions. It found MCID-based thresholds that define clinically meaningful worsening/stability/improvement of DD over 1 year and identified predictors of PAID worsening using logistic regression. This is important scientifically and clinically because it provides interpretable DD change metrics and risk factors to guide patient monitoring and intervention targeting in type 1 diabetes.

Canha D, Riveline JP, Kazanlieva F et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on June 14, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.