PubMed Trending Research Digest — May 16, 2026

Automated digest · 94 articles · 17 research areas · May 16, 2026

Overview

This week’s digest is dominated by translational oncology and immune modulation themes, spanning next-generation targeted therapies (ADCs, PROTAC-mediated degradation) and multiple strategies to improve immunotherapy durability. Several studies converge on metabolic and immune coupling as a determinant of response or resistance—e.g., lactate-driven lactylation affecting angiogenesis and ferroptosis-linked pathways, mevalonate/isoprenoid control of Tfh differentiation, and NAD/NAMPT–IFN/PD-L1 coupling in melanoma. Complementing these mechanistic insights, CAR-T engineering papers emphasize safer and more scalable designs (reversible epigenetic control, humanized antigen-binding domains, and in vivo CAR-T generation), while tumor microenvironment work highlights specific neutrophil–T cell tolerance interactions that could be therapeutically disrupted.

Across non-oncology domains, a second major thread is neurobiology and neuroinflammation. Multiple ALS/AD-focused articles use spatially resolved immune profiling, genotype-specific neuropathology, and TDP-43 structural/biophysical frameworks to refine disease mechanisms and potential targets. In parallel, studies in acute spinal cord injury and Alzheimer’s disease emphasize immune program control and restoring autophagy/mitophagy (e.g., ULK1) as tractable intervention points. Aging and epigenetics also appear repeatedly—ranging from epigenetic noise as a driver of neuronal vulnerability to compartment-specific mTORC1 tools and reassessing biomarkers like whole-blood NAD+—highlighting a shift toward mechanistic readouts rather than single-marker assumptions.

Finally, the digest includes clinically oriented advances in radiation oncology (durable outcomes for shorter breast radiotherapy and MRI-guided adaptive glioblastoma treatment), cardiovascular prevention and intervention (new drug candidates, imaging-guided PCI consensus, and stroke selection frameworks), and infectious/inflammatory disease management. Microbiome-centered studies in IBD and related conditions (butyrate effects, microbiome-derived metabolic levers to improve anti-TNF response, and CDI management) reinforce the broader message that host metabolism, barrier function, and immune signaling are increasingly actionable—often via targeted, mechanism-based interventions rather than broad empiricism.

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Antibody-drug conjugates and targeted cytotoxic oncology

Navigating the clinical progress of antibody-drug conjugates: Emerging opportunities and remaining challenges.

This review studied the clinical progress of antibody-drug conjugates (ADCs) across hematologic and solid tumors, focusing on how their biology and emerging earlier-stage use affect patient selection and toxicity management. It found that ADCs can improve safety while delivering potent cytotoxic payloads directly to tumor cells, but that expanding indications and combination regimens increase the need for careful toxicity monitoring and stratification. The work is significant because it frames the key scientific and clinical challenges that must be addressed to optimize ADC efficacy and safety in broader patient populations.

Conilh L, Metrangolo V, Crescioli S et al. · Cell · (2026) · View on PubMed ↗

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Ferroptosis and lactylation-linked cell death/metabolic control

Targeting mitochondrial calcium homeostasis via novel S100A9 inhibitor B2 as a promising agent against AML.

This translational study investigated the role of S100A9 in relapsed/refractory acute myeloid leukemia (R/R AML) and tested a novel S100A9 inhibitor, B2, targeting mitochondrial calcium (Ca2+) homeostasis. Genetic perturbation of S100A9 and mitochondrial Ca2+ measurements supported a functional contribution to AML aggressiveness, and structure-guided virtual screening plus biochemical validation identified B2 as a direct S100A9 binder with anti-leukemic activity in AML cell lines and primary patient samples. The results position S100A9–mitochondrial Ca2+ control as a druggable vulnerability and B2 as a candidate therapeutic strategy for R/R AML.

Hu C, Wan J, Ma D et al. · Journal of translational medicine · (2026) · View on PubMed ↗

SPOCK1 acts as a negative regulator of ferroptosis in non-small cell lung cancer.

This study investigated the role of SPOCK1 as a negative regulator of ferroptosis in non-small cell lung cancer (NSCLC) and used a genome-wide association study in the Kunshan Elderly Cohort to identify genetic susceptibility loci. It reported that SPOCK1 emerged as a key candidate oncogene, with high SPOCK1 expression associated with poor prognosis, and linked SPOCK1 to ferroptosis suppression in NSCLC models. Clinically, SPOCK1 may serve as a prognostic biomarker and a potential therapeutic target to restore ferroptosis-mediated tumor control.

Liu N, Zhu XR, Liu Y et al. · NPJ precision oncology · (2026) · View on PubMed ↗

ZDHHC5-mediated BRAF palmitoylation activates the MAPK pathway and drives cholangiocarcinoma progression.

The study examined whether ZDHHC5, a palmitoyltransferase, drives cholangiocarcinoma progression by palmitoylating BRAF in cholangiocarcinoma models. ZDHHC5 expression and global protein palmitoylation were upregulated, and ZDHHC5 knockdown inhibited tumor growth by increasing MAPK pathway activity through BRAF palmitoylation at Cys194/195. These findings identify a ZDHHC5–BRAF palmitoylation axis as a potential therapeutic target to suppress MAPK signaling in cholangiocarcinoma.

Li C, Hu X, Zhang Z et al. · Cancer letters · (2026) · View on PubMed ↗

Piceatannol-3’-O-β-d-glucopyranoside mitigates myocardial ischemia-reperfusion injury by inhibiting ferroptosis through the regulation of NDUFS1 lactylation via metabolic reprogramming.

This study examined whether piceatannol-3’-O-β-d-glucopyranoside (PG) mitigates myocardial ischemia-reperfusion injury (MIRI) by inhibiting ferroptosis through regulation of NDUFS1 lactylation, using multi-omics approaches in a clinically oriented experimental setting. PG improved cardiac function (e.g., LVEF/LVFS), reduced injury biomarkers (cTnI, CK-MB), lowered ROS and lactate/LDH, and increased ATP expression, consistent with metabolic reprogramming that modulates NDUFS1 lactylation and ferroptosis. These findings are significant because they identify a lactylation-linked mitochondrial target (NDUFS1) as a potential mechanism and therapeutic axis for developing more specific MIRI treatments.

Fan G, Zhang C, Zhang W et al. · Redox biology · (2026) · View on PubMed ↗

ENO1 lactylation drives bevacizumab resistance through metabolic reprogramming and angiogenesis in ovarian cancer.

This study investigated how ENO1 lactylation drives resistance to bevacizumab in ovarian cancer by linking lactate-driven metabolic reprogramming to angiogenesis, using lactylation proteomics in patient samples plus functional validation in cell lines and patient-derived xenograft (PDX) models. It found that ENO1 lactylation is a key mediator of bevacizumab resistance and that targeting the lactylation/metabolic-angiogenic axis can modulate therapeutic response. The results are clinically significant because they provide a mechanistic biomarker/target (ENO1 lactylation) to help explain and potentially overcome bevacizumab resistance in ovarian cancer.

Zeng T, Wang Q, Li L et al. · Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · (2026) · View on PubMed ↗

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Cancer immunotherapy: CAR-T and immune checkpoint strategies

Approval of First PROTAC Opens New Era for Targeted Protein Degradation.

This article describes the regulatory approval of vepdegestrant, the first PROTAC (proteolysis-targeting chimera) drug, for ESR1-mutant advanced breast cancer after failure of standard hormone-based regimens. The key finding is that vepdegestrant’s approval establishes targeted protein degradation as a clinically validated therapeutic modality. Clinically, this supports PROTACs as an actionable platform for developing additional “protein-destroying” therapies beyond estrogen receptor–driven disease.

Cancer discovery · (2026) · View on PubMed ↗

Epigenetic editing balances TCR suppression and persistence in CAR T cells.

This study investigated an epigenetic editing strategy to suppress the CD3ε gene in CAR T cells to balance TCR (T-cell receptor) suppression with CAR T-cell persistence, avoiding permanent genome edits. The key finding is that epigenetic silencing of CD3ε can be efficient, specific, and reversible without altering the genome, thereby reducing graft-versus-host disease risk while preserving persistence. Scientifically, it provides a safer design principle for allogeneic/off-the-shelf CAR T therapies by replacing permanent DNA disruption (e.g., CRISPR-Cas9/base editing) with reversible epigenetic control.

Schönberg PY, Muñoz-Ovalle Á, Saleh HA et al. · Molecular therapy. Advances · (2026) · View on PubMed ↗

IL-12-engineered human PSMA-CAR T cells for the treatment of advanced prostate cancer.

This work engineered IL-12–expressing human PSMA-targeted CAR T cells for treatment of advanced prostate cancer, using a human scFv-based PSMA binder derived from the humanized murine mAb clone J591. The key finding (from the provided abstract) is that the authors optimized a human scFv-based PSMA CAR construct to improve safety and efficacy, motivated by prior toxicities such as macrophage activation syndrome. Clinically, IL-12–armed PSMA CAR T cells could enhance anti-tumor activity while more human-derived antigen-binding domains may reduce unwanted immune activation.

Lopez LS, Cui Z, Yamaguchi Y et al. · Molecular therapy. Advances · (2026) · View on PubMed ↗

Betrixaban activates cGAS-STING to promote antitumor immunity without pathological inflammation.

This study tested whether betrixaban, an FDA-approved Factor Xa inhibitor, can activate cGAS–STING signaling to enhance antitumor immunity while avoiding pathological inflammation in preclinical cancer models. Betrixaban increased innate tumor sensing and adaptive immune responses, including greater infiltration of activated CD8+ T cells, and it suppressed hyperinflammation, with epigenetic modulation contributing to the effect. The findings are significant because they position betrixaban as a single-agent immunomodulator that can synergize with immune checkpoint blockade without triggering excessive inflammatory toxicity.

Zhao Y, Chen X, Tang L et al. · EMBO molecular medicine · (2026) · View on PubMed ↗

Targeting CD74 may mitigate immune-escape features and enhance BCMA CAR-T activity in preclinical models of relapsed/refractory multiple myeloma.

This preclinical study investigated whether targeting CD74 can mitigate immune-escape features and enhance BCMA CAR-T activity in relapsed/refractory multiple myeloma (R/R MM). Using single-cell RNA sequencing of paired bone marrow samples before and after BCMA CAR-T, along with in vitro co-culture assays, genetic perturbation, and in vivo xenograft models, the authors found that CD74 inhibition reduces immune-escape programs in treatment-persistent myeloma cells and improves CAR-T antitumor function. These results provide a mechanistic rationale for combining CD74-targeting strategies with BCMA CAR-T to overcome resistance in R/R MM.

Chen X, Zhang J, Chen H et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗

In Vivo Generation of CAR-T Cells: Current Obstacles, Strategic Solutions, and Clinical Translation.

This critical review evaluated in vivo CAR-T cell generation as an alternative to conventional ex vivo manufacturing for hematologic malignancies. It identifies key obstacles—such as inefficient systemic delivery, off-target transduction, the balance between transfection efficiency and biosafety, and limited persistence of CAR expression—and summarizes emerging engineering solutions including targeted vector systems. The review’s significance lies in guiding clinical translation by outlining how to overcome delivery and safety barriers to make in vivo CAR-T more scalable and accessible.

Jiang Z, Xu S, Li W et al. · Critical reviews in oncology/hematology · (2026) · View on PubMed ↗

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Tumor microenvironment and immune evasion mechanisms

CD300ld on pathologically activated neutrophils promotes tumor immune suppression by binding phosphatidylserine on CD8+ T cells.

This study examined how CD300ld on pathologically activated neutrophils (PMN-MDSCs) suppresses cytotoxic CD8+ T cells in the tumor microenvironment. CD300ld promoted tumor immune suppression by binding phosphatidylserine on CD8+ T cells, enabling contact-dependent T cell tolerance. These findings identify a specific neutrophil–T cell interaction axis (CD300ld–phosphatidylserine) that could be targeted to improve anti-tumor immunotherapy efficacy.

Wang C, Zheng P, Wang A et al. · Nature cancer · (2026) · View on PubMed ↗

Bi-directional regulation between NAD/NAMPT and IFN-γ/PD-L1 axes via BRD4/IRF1 and mitochondrial respiration in metastatic cutaneous melanoma.

This study examined how the NAD/NAMPT metabolic axis and the IFN-γ/PD-L1 immune axis interact in metastatic cutaneous melanoma, focusing on BRD4/IRF1 signaling and mitochondrial respiration. The authors found bidirectional regulation between NAD/NAMPT and IFN-γ/PD-L1 mediated by BRD4/IRF1, with altered mitochondrial respiration contributing to therapeutic resistance. These findings suggest targeting NAD metabolism–IFN signaling coupling (via BRD4/IRF1 and respiratory rewiring) could improve durability of BRAF/MEK inhibitor and immune checkpoint inhibitor responses in metastatic melanoma.

Fiorilla I, Ghezzi B, Ponzano A et al. · Journal of experimental & clinical cancer research : CR · (2026) · View on PubMed ↗

Modulation of the mevalonate pathway by TCR engagement regulates T follicular helper cell generation in homeostasis and autoimmunity.

This Immunity study examined how T-cell receptor (TCR) engagement modulates the mevalonate pathway to regulate T follicular helper (Tfh) cell generation in homeostasis and autoimmunity. It showed that geranylgeranyl diphosphate (GGPP) is required for Tfh cell generation, with pharmacologic inhibition or genetic depletion of geranylgeranyl diphosphate synthase (GGPS1) impairing Tfh development via reduced geranylgeranylation of RAB GTPases (including RAB35) and consequent surface protein expression. These mechanistic insights suggest that targeting mevalonate/isoprenoid metabolism could modulate pathogenic Tfh responses in autoimmune disease.

Wang L, Jiang J, Yin H et al. · Immunity · (2026) · View on PubMed ↗

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Radiation oncology: hypofractionation, adaptive radiotherapy, and imaging guidance

Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 10-year efficacy and late normal tissue effects from a multicentre, open-label, non-inferiority, phase 3, randomised controlled trial and 5-year efficacy results from a randomised axillary substudy.

This multicentre, open-label, non-inferiority phase 3 randomized trial evaluated long-term (10-year) efficacy and late normal tissue effects of FAST-Forward hypofractionated breast radiotherapy schedules in early-stage breast cancer, including an axillary-treatment substudy. The 1-week regimen (26 Gy in 5 fractions) was previously shown non-inferior to the standard 3-week regimen (40 Gy in 15 fractions) for 5-year ipsilateral breast recurrence and had similar normal tissue effects, and this report extends those outcomes to 10 years. The significance is that it provides durable evidence supporting shorter-course adjuvant radiotherapy to maintain cancer control while limiting treatment burden and toxicity.

Brunt AM, Cafferty FH, Kirby AM et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

MRI-guided adaptive radiotherapy for high grade glioma (UNITED): a single-centre, single-arm, non-inferiority, phase 2 trial.

This single-centre, single-arm, non-inferiority phase 2 trial studied MRI-guided adaptive radiotherapy with small margins for adults with pathologically confirmed glioblastoma receiving concurrent daily chemoradiotherapy at Sunnybrook Health Sciences Centre, Toronto. The approach aimed to reduce irradiated brain volume by adapting treatment using daily MRI guidance while delivering standard long-course or short-course fractionation to 60 Gy/30 fractions or 40 Gy/15 fractions. Scientifically and clinically, it tests whether adaptive MRI-guided planning can improve safety by limiting normal tissue exposure without compromising efficacy in glioblastoma.

Detsky JS, Chan AW, Moore-Palhares D et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

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Clinical oncology guidelines and treatment sequencing

Atezolizumab + Chemotherapy in Older Patients With Lung Cancer in Japan.

This prospective observational Japanese study (J-TAIL-2) evaluated atezolizumab plus chemotherapy regimens in advanced non-small cell lung cancer and extensive-stage small cell lung cancer patients who were treated in routine practice, including older and trial-ineligible populations. The key finding was that real-world outcomes and safety could be assessed across age, ECOG performance status, G8 score, and creatinine clearance subgroups for patients receiving atezolizumab-based therapy under Japanese labeling. Clinically, the study supports evidence for how atezolizumab–chemotherapy performs in older, less strictly selected patients, informing treatment decisions beyond global phase 3 eligibility criteria.

Shimizu J, Nishio M, Ohashi K et al. · Cancer science · (2026) · View on PubMed ↗

HILL: the efficacy and safety of hepatic arterial infusion chemotherapy with the FOLFOX regimen combined with lenvatinib and the PD-L1 inhibitor durvalumab in unresectable hepatocellular carcinoma: a prospective, single-arm, phase 2 clinical trial.

This prospective, single-arm phase 2 trial evaluated hepatic arterial infusion chemotherapy with the FOLFOX regimen (FOLFOX-HAIC) combined with lenvatinib and the PD-L1 inhibitor durvalumab as initial therapy in unresectable hepatocellular carcinoma (uHCC). In 40 enrolled patients (Aug 2021–Sep 2023), the primary endpoint was progression-free survival (PFS) with secondary endpoints including objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The clinical significance is that it tests a triple-combination strategy aimed at improving outcomes for patients with uHCC, a population with poor prognosis.

Li SH, Zuo ZJ, Lu LH et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗

Comparative and Critical Analysis of Immune-based Combinations for First-line Treatment of Metastatic Renal Cell Carcinoma.

This comparative analysis studied the relative efficacy and statistical robustness of four first-line immune-based combination regimens versus sunitinib in metastatic renal cell carcinoma using patient-level progression-free survival (PFS) and overall survival (OS) data from phase 3 randomized controlled trials. It compared nivolumab + ipilimumab (CheckMate-214), nivolumab + cabozantinib (CheckMate-9ER), pembrolizumab + axitinib (KEYNOTE-426), and pembrolizumab + lenvatinib (CLEAR) with attention to censoring patterns. The significance is that it provides an evidence-based framework for interpreting and comparing immunotherapy combinations when head-to-head RCTs are lacking.

Meirson T, Mutti L, Goldstein DA et al. · Clinical genitourinary cancer · (2026) · View on PubMed ↗

To Treat or Not to Treat: Navigating Early-Stage CLL in the Era of Targeted Therapy.

This review studied how to decide whether to treat versus observe early-stage chronic lymphocytic leukemia (CLL) in the era of targeted therapies, contrasting the historical watch-and-wait standard with modern risk stratification. It found that genomic profiling (e.g., IGHV mutational status, TP53 disruption, recurrent mutations, and complex karyotype) reveals heterogeneity in progression risk, challenging one-size-fits-all early treatment decisions. The clinical significance is guiding individualized management of early-stage CLL by integrating molecular risk markers with targeted therapy considerations.

Martino EA, Caserta S, Vigna E et al. · European journal of haematology · (2026) · View on PubMed ↗

Development and validation of a novel prognostic index for mantle cell lymphoma integrating TP53 mutations (MIPI53).

This study developed and validated a prognostic index for mantle cell lymphoma (MCL) called MIPI53 by integrating TP53 mutation status with clinical variables in 143 newly diagnosed patients from a real-world cohort. The authors found that adding TP53 mutations to the existing MIPI framework (incorporating TP53, LDH, ECOG status, and age) improved prognostic stratification, with internal validation by bootstrapping and external validation using an independent dataset. Scientifically and clinically, MIPI53 may better predict outcomes and guide risk-adapted management in MCL patients.

Bastos-Boente M, Medina-Herrera A, Navarro-Bailón A et al. · British journal of haematology · (2026) · View on PubMed ↗

Prostate-specific antigen (PSA) test for prostate cancer screening.

This Cochrane systematic review studied the effects of prostate-specific antigen (PSA)–based prostate cancer screening versus no screening in men without prior prostate cancer diagnosis. It updates prior evidence by incorporating results from two new large trials and extended follow-up through November 2025, assessing impacts on prostate cancer–specific and overall mortality and related outcomes. The review is significant for informing guideline decisions on whether PSA screening reduces mortality and how screening programs should be implemented or avoided.

Franco JV, Hwang EC, Jung JH et al. · The Cochrane database of systematic reviews · (2026) · View on PubMed ↗

NCCN Guidelines® Insights: Prostate Cancer, Version 5.2026.

This article summarized the 2026 NCCN Guidelines Insights for prostate cancer, focusing on updates for staging/risk assessment and management of nonmetastatic disease in clinical practice. Key updates included elimination of the very-low-risk group, revisions to active surveillance principles, and caution regarding focal therapy in newly diagnosed patients. The significance is that it translates guideline panel deliberations into actionable changes that can affect treatment selection and surveillance strategies for patients with nonmetastatic prostate cancer.

Spratt DE, Srinivas S, Adra N et al. · Journal of the National Comprehensive Cancer Network : JNCCN · (2026) · View on PubMed ↗

Perioperative Systemic Treatment Options for Muscle-Invasive Bladder Cancer.

This review assessed perioperative systemic treatment options for muscle-invasive bladder cancer (MIBC) in the context of radical cystectomy, including neoadjuvant, adjuvant, and “sandwich” approaches. It highlights cisplatin-based chemotherapy as the mainstay for eligible patients and notes that immune checkpoint inhibition has shown promise in neoadjuvant settings with evidence of improved disease outcomes. Clinically, it supports selecting systemic therapy timing and modality around cystectomy to improve survival and reduce recurrence risk in MIBC.

Brown JR, Parikh M · Journal of the National Comprehensive Cancer Network : JNCCN · (2026) · View on PubMed ↗

Addition of autologous stem-cell transplantation to an ibrutinib-containing first-line treatment in patients aged 18-65 years with mantle cell lymphoma (TRIANGLE): 4·5-year follow-up of a three-arm, randomised, open-label, phase 3 superiority trial of the European MCL Network.

The TRIANGLE phase 3 trial studied whether adding autologous stem-cell transplantation (ASCT) to a first-line regimen containing ibrutinib improves outcomes in adults aged 18–65 years with mantle cell lymphoma (165 patients across 3 arms). With 4.5-year follow-up, the trial evaluated failure-free survival and overall survival to determine whether the ASCT addition provides incremental benefit over ibrutinib-containing immunochemotherapy alone. If ASCT meaningfully improves failure-free survival without unacceptable toxicity, it would refine first-line treatment sequencing for mantle cell lymphoma in transplant-eligible patients.

Dreyling M, Doorduijn J, Giné E et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Neoadjuvant mFOLFOXIRI with or without cadonilimab versus mFOLFOX6 in locally advanced colorectal cancer: A randomized phase 2 trial (OPTICAL-2).

The OPTICAL-2 open-label randomized phase 2 trial studied neoadjuvant mFOLFOXIRI with or without the PD-1/immune checkpoint inhibitor cadonilimab versus mFOLFOX6 in patients with locally advanced colorectal cancer stratified by pMMR/MSS status. The primary endpoint was pathological complete response (pCR), with secondary outcomes including major pathological response (MPR), safety, and locoregional recurrence. If cadonilimab plus mFOLFOXIRI improves pCR/MPR with manageable toxicity, it would support adding dual immune checkpoint blockade to standard neoadjuvant chemotherapy for pMMR/MSS LACRC.

Zhang J, Qi S, Hu H et al. · Med (New York, N.Y.) · (2026) · View on PubMed ↗

Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes.

This article studied sickle cell disease-associated pulmonary hypertension (SCD-PH) by proposing an integrated framework that links five interacting pathophysiologic axes—anaemia/high-output, haemolysis/haem/iron toxicity, hypoxia, inflammation, and thrombosis—to clinically defined hemodynamic phenotypes. It found that these axes map onto distinct phenotype categories (post-capillary, pre-capillary, combined, chronic thromboembolic PH [CTEPH], and acute cor pulmonale), with chronic anaemia driving high-output physiology and post-capillary PH features. The framework is significant because it aims to improve classification, trial design, and treatment selection despite the mechanistic and hemodynamic heterogeneity of SCD-PH.

Vallelian F, Schaer DJ, Lechartier B et al. · EBioMedicine · (2026) · View on PubMed ↗

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Neurodegeneration (ALS/FTD/AD) mechanisms and biomarkers

Heterogenous Neuropathology in a Pedigree with RAB39B-Related Parkinson’s Disease.

This study characterized neuropathology in a family with RAB39B-related Parkinson’s disease carrying the RAB39B p.G192R (c.574G>A) variant and assessed RAB39B protein distribution and effects on α-synuclein and tau. Using autopsy findings and induced pluripotent stem cell (iPSC)-derived dopaminergic neurons plus Western blotting for RAB39B, α-synuclein, phospho-α-synuclein, and phospho-tau, it documented heterogeneous neuropathological features across affected siblings. The work refines genotype–phenotype understanding for RAB39B Parkinson’s disease and clarifies how the variant may influence key neurodegeneration proteins.

Latimer C, Lorenzo-Betancor O, Chen DH et al. · Movement disorders : official journal of the Movement Disorder Society · (2026) · View on PubMed ↗

TDP-43: [GU]-ardian of the transcriptome.

This review examined the biology of the RNA/DNA-binding protein TDP-43—its structure, regulation, nuclear depletion, and cytoplasmic aggregation—and how these processes drive neurodegenerative disease mechanisms in ALS, frontotemporal dementia (FTD), and Alzheimer’s disease (AD). It highlights splicing repression of cryptic exons (nonconserved RNA sequences) as a central disease-relevant function affected by TDP-43 dysfunction. Scientifically, the synthesis strengthens cryptic-exon dysregulation as a mechanistic framework and potential therapeutic direction for TDP-43 proteinopathies.

Sinha IR, Atkinson AL, Irwin KE et al. · Molecular neurodegeneration · (2026) · View on PubMed ↗

Cellular state heterogeneity underlying sex differences in Alzheimer’s disease based on single-cell transcriptome.

This study analyzed sex differences in Alzheimer’s disease (AD) using single-cell/single-nucleus transcriptomic data, curating 3,302,741 profiles from 603 samples (296 female, 307 male; 339 AD, 264 normal) across 10 cohorts. Using non-negative matrix factorization to derive cell-type-specific meta-programs, the authors identified cellular state heterogeneity patterns that differ by sex in AD brains. These results provide a molecular basis for sex-biased AD vulnerability and suggest that sex-specific cell-state programs could guide tailored biomarker or therapeutic strategies.

Wu Z, Tan Q, Xue F et al. · Alzheimer’s research & therapy · (2026) · View on PubMed ↗

Maintenance and disruption of the physiological dimer structure of TDP-43 in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

This review analyzed evidence that the earliest pathogenic event in ALS and frontotemporal lobar degeneration involves disruption of the physiological TDP-43 N-terminal homodimer (“Molecular Zipper”) rather than only later cytoplasmic aggregation. It synthesizes data supporting that loss of the physiological dimer impairs nuclear solubility and cooperative RNA binding, promoting downstream neurodegenerative mechanisms. The proposed molecular framework is significant because it reframes TDP-43 as a targetable structural/biophysical defect, potentially guiding therapies aimed at restoring dimerization or preventing its disruption.

Tamaki Y, Kaneko S, Urushitani M · BMC medicine · (2026) · View on PubMed ↗

Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer’s disease pathology.

This study assessed ULK1 (Atg1) levels and function in aging and Alzheimer’s disease using human cohorts (COGNORM and NorCog) and AD mouse models, focusing on autophagy/mitophagy pathways. It found reduced ULK1 in serum and cerebrospinal fluid during aging and in AD patients, while ULK1 overexpression enhanced autophagic flux, improved mitochondrial quality, reduced amyloid-β and tau pathology, and delayed cognitive decline. The significance is that restoring ULK1-driven autophagy/mitophagy may be a therapeutic strategy to slow AD progression by improving neuronal clearance and mitochondrial homeostasis.

Pan JP, Wang PJ, Zhang J et al. · Nature aging · (2026) · View on PubMed ↗

Integrated single-cell and spatial transcriptomic profiling in ALS uncovers peripheral-to-central immune infiltration and reprogramming.

The study used integrated single-cell and spatial transcriptomic profiling plus spatial proteogenomics to map immune programs in peripheral blood and spinal cord tissues from patients with sporadic ALS and C9orf72 repeat-expansion ALS. It found broad immune remodeling in C9orf72 ALS, including peripheral-to-central immune infiltration and immune reprogramming linked to ALS subtype-specific programs. These results identify spatially resolved immune pathways that could be targeted to modify neuroinflammation and motor neuron degeneration in C9orf72-driven ALS.

Zhang Z, van Olst L, Alessandrini F et al. · Nature neuroscience · (2026) · View on PubMed ↗

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Neuroinflammation and immune programs in CNS injury/disease

Multi-omics mapping identifies a C/EBPβ-S100a4⁺ macrophage axis as a therapeutic target in acute spinal cord injury.

This multi-omics study mapped immune regulatory circuits after acute spinal cord injury (SCI) by integrating high-temporal-resolution single-cell RNA sequencing, bulk transcriptomics, histology, and network modeling across uninjured and early post-injury time points. It identified a C/EBPβ-driven S100a4+ macrophage axis as an upstream determinant of early neuroinflammation and proposed it as a therapeutic target. Scientifically, the work links early macrophage transcriptional control (C/EBPβ) to downstream inflammatory programs, enabling more mechanistically grounded intervention strategies for acute SCI.

Wang H, Wu H, Li Z et al. · Journal of translational medicine · (2026) · View on PubMed ↗

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Developmental biology and mechanobiology

Early Clinical, Imaging, and Pathological Characteristics of SRPK3/TTN-Digenic Myopathy.

This study characterized early clinical, imaging, and histopathological features of SRPK3/TTN digenic myopathy in one previously reported and seven newly identified pediatric patients using next-generation sequencing and deep phenotyping. The key finding is that among eight male patients (ages 5–19 at last evaluation), five had prenatal onset with reduced fetal movements, and at birth five had hypotonia with additional findings including contractures and respiratory distress. Clinically, these early phenotype patterns can support earlier recognition and diagnostic workup for SRPK3/TTN digenic myopathy in children presenting with congenital hypotonia and respiratory involvement.

Orbach R, Donkervoort S, Hedberg-Oldfors C et al. · Annals of clinical and translational neurology · (2026) · View on PubMed ↗

Tissue rigidity phase transition shapes morphogen gradients.

The authors investigated how a tissue-scale rigidity phase transition regulates morphogen patterning in zebrafish embryos by combining rigidity percolation theory, reaction–diffusion modeling, quantitative imaging, and optogenetics. They found that global rigidity dynamics tune the length scales and timescales of morphogen signaling, actively reshaping the Nodal gradient by locally changing its concentration and accelerating its spread. This provides a mechanistic framework for how mechanical state transitions can instruct developmental fate decisions through morphogen control.

Autorino C, Khoromskaia D, Harari L et al. · Nature cell biology · (2026) · View on PubMed ↗

SphK1/mitophagy axis in cementocytes drives orthodontic root resorption via mitochondrial transfer to osteoclasts.

The study investigated how sphingosine kinase 1 (SphK1) in cementocytes mediates orthodontic root resorption by driving mitophagy-dependent mitochondrial transfer to osteoclasts in models of orthodontically induced inflammatory root resorption (OIIRR). Heavy orthodontic force increased mitophagy markers in cementocytes in vivo and, in IDG-CM6 cementocytes, compression induced SphK1-dependent mitophagy with mitochondrial transfer toward osteoclast activation. This mechanistic SphK1/mitophagy axis links mechanotransduction to osteoclastogenesis and suggests a potential therapeutic target to prevent orthodontic root resorption.

Wang H, Chen S, Chen S et al. · Bone research · (2026) · View on PubMed ↗

Cilia beating of ependymal cells regulates adult neural stem cell quiescence via mechanical forces mediated by PKD1/2-TRPM3.

This Neuron study investigated how mechanical forces from beating cilia in ependymal cells regulate adult neural stem cell (NSC) quiescence. By transiently inhibiting ependymal cilia beating using magnetic bead–coupled antibodies and a magnetic field, the authors found that cilia beating enforces NSC quiescence via PKD1/2- and TRPM3-mediated Ca2+ transients. These results define a mechanotransduction pathway controlling stem cell state, informing how niche mechanics could be manipulated in regenerative or disease contexts.

Bressan C, Gengatharan A, Rodriguez-Aller R et al. · Neuron · (2026) · View on PubMed ↗

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Plant intercellular transport and cell wall/plasmodesmata

In situ architecture of plasmodesmata in Physcomitrium patens resolved by cryo-electron tomography.

This work used cryo-electron tomography to resolve the in situ ultrastructure of plasmodesmata in the moss Physcomitrium patens across tissues and physiological states. The study showed that callose-related cell wall remodeling shapes plasmodesmatal pore architecture, including a previously undescribed fully sealed state, and resolved helical protein assemblies that scaffold the ER-derived desmotubule. These findings clarify how plant cell wall chemistry and protein architecture regulate intercellular permeability.

Dickmanns M, Pöge M, Xu P et al. · Nature plants · (2026) · View on PubMed ↗

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Microbial pathogenesis and host–pathogen immune evasion

African swine fever virus I10L protein inhibits autolysosome formation by disrupting RAB7-HOPS complex-dependent SNARE complex assembly.

This study investigated how African swine fever virus (ASFV) I10L protein affects host autophagy in infected cells. I10L inhibited autolysosome formation by directly interacting with the endolysosomal GTPase RAB7, competitively preventing RAB7 binding to VPS39 and thereby disrupting RAB7–HOPS complex-dependent SNARE assembly. Scientifically, it reveals a precise viral mechanism to block autophagy flux, informing antiviral strategies targeting RAB7/HOPS/SNARE trafficking.

Chen M, Sunkang Y, Cheng T et al. · Autophagy · (2026) · View on PubMed ↗

Mpox virus D8L protein binds to STAT1 and inhibits its phosphorylation to antagonize IFN-induced signaling.

This study characterized how mpox virus (MPXV) immune evasion occurs in host cells by focusing on the MPXV D8L protein and its effects on interferon (IFN)-induced signaling. D8L bound STAT1 and inhibited STAT1 phosphorylation, suppressing transcription and protein expression of multiple IFN-stimulated genes (including CIG5, MX2, ISG56, IFITM1, OAS1, and ISG15). These findings clarify a specific viral–host interaction mechanism that antagonizes innate antiviral responses and can inform antiviral target discovery.

Zhou H, Yang Z, Jiang Q et al. · Cell communication and signaling : CCS · (2026) · View on PubMed ↗

Concepts of RNA virus evolution for the design of better antiviral countermeasures.

This article reviewed concepts from molecular virology and evolutionary biology to explain how RNA virus evolution—driven by mutation, recombination, reassortment, and constrained fitness landscapes—affects host switching and immune escape. It highlights that understanding mutation biases, genome organization, and epistasis can inform the design of more robust antiviral countermeasures. The significance is that evolutionary-informed strategies may better prevent resistance and improve long-term antiviral effectiveness against rapidly evolving RNA viruses.

Tran QD, Vignuzzi M · Nature reviews. Microbiology · (2026) · View on PubMed ↗

The apical polar ring is essential during the blood stage of Plasmodium falciparum.

The study examined the apical polar ring (APR) in the malaria parasite Plasmodium falciparum by identifying PfAPR3 as an APR-resident protein and using conditional knockout genetics. PfAPR3 knockout parasites underwent asexual replication defects and, while contacting host red blood cells, failed to form a tight junction, causing a complete block in invasion; PfAPR3 was also used as bait to identify PfAPR4, PfCHAKRA, and PfAPR5 and to define APR biogenesis using ultrastructure expansion microscopy. This establishes PfAPR3 and associated APR components as essential invasion machinery and provides targets for antimalarial intervention.

Gurung P, Back PS, Ali I et al. · Nature microbiology · (2026) · View on PubMed ↗

A fungal pathobiont promotes Streptococcus vaginal persistence and pathogenesis through physical and metabolic interactions.

This study investigated how the fungal pathobiont Candida albicans affects Group B Streptococcus (GBS) persistence and disease using an adapted murine model of vaginal colonization and co-colonization. C. albicans supported GBS fitness, promoted ascension to the uterus, increased persistence across vaginal/cervical/uterine sites, and contributed to antibiotic evasion through physical and metabolic interactions. These findings identify a microbial interaction mechanism that could be targeted to reduce pregnancy-associated GBS colonization and neonatal invasive infection risk.

Cohen S, Crossen AJ, Jensen O et al. · Cell host & microbe · (2026) · View on PubMed ↗

Coronavirus protein interaction mapping in bat and human cells reveals network rewiring governing immune evasion and zoonotic potential.

Using affinity purification mass spectrometry (AP-MS), this study mapped coronavirus protein–protein interactions in bat and human cells for SARS-CoV-2 and its bat progenitor RaTG13 to understand immune evasion and zoonotic potential. It found conserved and host-/virus-specific interaction differences and highlighted that a nonsynonymous nucleocapsid mutation is required for SARS-CoV-2 replication in bat cells expressing human ACE2 and TMPRSS2. The work links specific interaction network rewiring to host adaptation, supporting mechanistic prediction of zoonotic risk.

Batra J, Rutkowska M, Zhou Y et al. · Cell host & microbe · (2026) · View on PubMed ↗

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Microbiome and metabolic immunology in inflammatory disease

AGA Clinical Practice Update on Management of Clostridioides difficile Infection in Inflammatory Bowel Disease: Expert Review.

This expert review studied evidence and management strategies for Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD). It found that IBD patients have higher CDI risk, severity, and recurrence, creating clinical dilemmas around antibiotic choice and timing/intensity of IBD therapy adjustments, with emerging microbiota-based options including donor-derived fecal microbiota therapies. Clinically, the update provides guidance to reduce flares, hospitalization, treatment failure, and surgery in the IBD–CDI population.

Khanna S, Allegretti JR, Hashash JG et al. · Gastroenterology · (2026) · View on PubMed ↗

Human Colitis-on-Chip Model Reveals Dual Roles of Butyrate in Epithelial and Macrophage Defense Against Candida albicans Tissue Invasion.

This study used a human immunocompetent colitis-on-chip model to test how microbiota-derived butyrate affects epithelial and macrophage defenses against Candida albicans tissue invasion under DSS-induced inflammation. Butyrate showed dual protective roles by stabilizing epithelial adherens junctions and promoting epithelial renewal while also modulating macrophage function to enhance antifungal activity and limit fungal invasion. These results support butyrate restoration as a mechanistic therapeutic approach to reduce opportunistic fungal complications in inflammatory bowel disease.

Allwang M, Wipplinger M, Akbarimoghaddam P et al. · Small (Weinheim an der Bergstrasse, Germany) · (2026) · View on PubMed ↗

Sirtuin 1 Activation Mitigates Murine Vasculitis Severity by Promoting Mitophagy.

This study investigated whether sirtuin 1 (SIRT1) activation mitigates vasculitis severity in Kawasaki disease using the Lactobacillus casei cell wall extract (LCWE) murine model. It found that SIRT1 activation reduced murine vasculitis severity by promoting mitophagy, consistent with SIRT1’s role in regulating cardiovascular inflammation and mitochondrial quality control. These findings suggest SIRT1–mitophagy as a potential therapeutic pathway to lessen Kawasaki disease vascular injury.

Atici AE, Jena PK, Carvalho TT et al. · Circulation research · (2026) · View on PubMed ↗

Type-2-Inflammatory-Diseases Share Comorbidities, Molecular Signatures, IL4/IL13 Genetics, and Response to IL4/IL13 Blockade.

This study analyzed shared comorbidities, molecular signatures, IL4/IL13 genetic architecture, and clinical response to IL4/IL13 blockade—especially dupilumab—in individuals with type-2 inflammatory diseases (including asthma, atopic dermatitis, and eosinophilic esophagitis). The authors found that many T2IDs share overlapping IL4/IL13-driven molecular programs and that IL4/IL13 genetics and pathway activation help explain why disease manifests in different tissues and predicts response to dupilumab. These findings support a pathway-based, genetics-informed approach to selecting and anticipating benefit from IL4/IL13-targeted therapy across multiple atopic conditions.

Hamilton JD, Ferreira MAR, Lim WK et al. · Allergy · (2026) · View on PubMed ↗

Stiffness-dependent CMOT hydrogels promote mucosal repair in ulcerative colitis through YAP‑mediated mechanosensing in intestinal epithelial cells.

This preclinical study developed stiffness-tunable CMOT hydrogels for colon-targeted delivery and tested their ability to promote mucosal repair in a DSS-induced ulcerative colitis model using intestinal epithelial cells. The moderately stiff CMOT-M hydrogel reduced colitis severity, restored tight-junction proteins (ZO-1 and occludin), and lowered inflammatory cytokines (TNF-α, IL-6, IL-1β) by activating YAP-mediated mechanosensing through Hippo pathway modulation via integrin–cytoskeletal tension transmission. The work supports mechanobiology-based biomaterials as a therapeutic route to restore epithelial barrier function in inflammatory bowel disease.

Chen G, Fang Z, Feng M et al. · Journal of nanobiotechnology · (2026) · View on PubMed ↗

The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and the risk of cancer, cardiovascular diseases, hypertension, all-cause, and cardiovascular diseases mortality: a systematic review and meta-analysis of observational studies.

This systematic review and meta-analysis synthesized observational studies to assess whether adherence to the MIND diet score is associated with cancer, cardiovascular disease (CVD), hypertension, and all-cause/CVD mortality. Across included studies, the authors extracted hazard ratios and odds ratios to quantify the relationship between MIND diet adherence and these chronic disease outcomes. The results summarize current epidemiologic evidence and help clarify whether MIND diet patterns may confer cardiometabolic and cancer/mortality benefits.

Ahmadirad H, Pasdar Y, Moludi J et al. · Nutrition & metabolism · (2026) · View on PubMed ↗

Targeted enzymatic therapy for coeliac disease.

This translational study developed celiacase (Clc), a recombinant prolyl endopeptidase engineered from pitcher plant neprosin, to enzymatically degrade gluten immunogenic peptides in coeliac disease. Clc showed gastric pH–optimal activity, resisted pepsin, efficiently cleaved key immunogenic GIPs (including the 33-mer), and reduced GIP levels by up to 99% in a dynamic human gastrointestinal simulator. The clinical significance is that Clc provides a rational targeted enzymatic approach that could reduce gluten-triggered immune activation in coeliac disease without requiring complete gluten elimination.

Girbal-González M, Rodríguez-Banqueri A, Swaid H et al. · EMBO molecular medicine · (2026) · View on PubMed ↗

m6A modification suppresses innate anti-tumour immunity in colorectal cancer by limiting alu-derived dsRNA accumulation.

The study tested how m6A RNA methylation regulates innate anti-tumor immunity in colorectal cancer by focusing on the m6A methyltransferase METTL3 and its control of alu-derived double-stranded RNA (dsRNA) accumulation. It found that METTL3 suppresses innate immune activation by limiting dsRNA buildup, whereas targeting METTL3 increased alu-derived dsRNA from endogenous retroelement transcripts, amplified immunostimulatory signaling, and activated cell-intrinsic anti-tumor immunity. This suggests that METTL3 inhibition could enhance endogenous viral mimicry to boost anti-tumor immune responses in CRC.

Wang Y, Daddi AA, Hosseini A et al. · Nature communications · (2026) · View on PubMed ↗

Breaking the therapeutic ceiling in inflammatory bowel disease: myth or reality?

This Viewpoint article evaluated whether the observed “therapeutic ceiling” in inflammatory bowel disease (IBD) remission rates reflects a true biological limit or is driven by modifiable constraints in therapy and trial methodology. It argues that plateauing (often 30–50% at 1 year) is more likely due to factors such as late intervention, reliance on monotherapy, inadequate capture of disease complexity, and endpoint limitations. The significance is a strategic framework to overcome current limits via prevention, early interception, and more sustainable innovation in IBD treatment development.

Solitano V, Jairath V, Magro F et al. · The lancet. Gastroenterology & hepatology · (2026) · View on PubMed ↗

Microbial phosphoketolase promotes histone lactylation to improve anti-TNF therapy efficacy in inflammatory bowel disease.

This Cell Metabolism study tested whether a microbial phosphoketolase pathway can enhance anti-TNF therapy efficacy in inflammatory bowel disease by improving response to anti-TNF antibodies. The key finding was that bacterial phosphoketolase increased primary anti-TNF response by enhancing Treg-mediated immunosuppression and maintaining higher serum drug concentrations, mediated through macrophage lactate production that drives histone H4K12 lactylation and downstream serotonin transporter upregulation. Clinically, this suggests a microbiome-derived metabolic lever that could be exploited to improve anti-TNF effectiveness and reduce non-response.

Jiang Y, Ma Y, Ning L et al. · Cell metabolism · (2026) · View on PubMed ↗

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Cardiovascular therapeutics and clinical trials (incl. arrhythmia/HTN/PCI)

Laroprovstat, the First Oral Small-Molecule PCSK9 Inhibitor for the Treatment of Hypercholesterolemia: Results From a Randomized, Single-Blind, Placebo-Controlled Phase 1 Trial in Treatment-Naive Patients.

This phase 1 randomized, single-blind, placebo-controlled trial studied laroprovstat (AZD0780), a novel oral small-molecule PCSK9 inhibitor, in treatment-naive patients with hypercholesterolemia. Laroprovstat bound the PCSK9 C-terminal domain and was evaluated for effects on LDL receptor expression and LDL-C lowering, alongside safety and tolerability outcomes. The trial supports clinical development of an oral alternative to injectable PCSK9 inhibitors for reducing cardiovascular risk.

Vega RB, O’Mahony G, Barbour AM et al. · Circulation · (2026) · View on PubMed ↗

Calcium Channel Blockade Versus Beta-Blockade for Hypertension in Heart Failure With Preserved Ejection Fraction: A Randomized Crossover Trial.

This randomized double-blind crossover trial studied whether calcium channel blockade with amlodipine (5–10 mg) versus beta-blockade with metoprolol succinate (100–200 mg) better controls blood pressure in adults with heart failure with preserved ejection fraction (HFpEF) and hypertension. The key comparison was the difference in mean home systolic blood pressure over 4 weeks between the two drug strategies. The results are intended to guide antihypertensive selection in HFpEF, where evidence has been limited.

Cohen JB, Hossain A, Chittams J et al. · Hypertension (Dallas, Tex. : 1979) · (2026) · View on PubMed ↗

Single Cell Analysis of Human Heart Failure With Preserved Ejection Fraction.

This study used single-nucleus RNA sequencing to define cellular and molecular differences in human heart failure with preserved ejection fraction (HFpEF) myocardium versus nonfailing controls. In septal biopsies from 19 HFpEF patients and 24 controls analyzed on the 10× Genomics Chromium platform with souporcell demultiplexing and CellRanger/CellBender processing, it identified HFpEF-associated gene expression patterns across annotated cardiac cell types. The work provides a high-resolution atlas of HFpEF pathobiology that can highlight candidate pathways and cell populations for targeted therapies.

Hahn VS, Chaffin M, Simonson B et al. · Circulation research · (2026) · View on PubMed ↗

Glucocorticoids to reduce permanent pacemaker implantation after TAVI: the GLUCO-TAVI randomised trial.

This pilot PROBE-design randomized trial studied whether peri-procedural glucocorticoids (methylprednisolone) could reduce permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) in 100 TAVI patients. The key finding reported in the abstract is that the trial was designed to test feasibility, safety, and preliminary efficacy for preventing post-TAVI cardiac conduction disturbances that often require PPI, with results pending due to truncation. If effective, methylprednisolone could provide a practical anti-inflammatory strategy to lower PPI rates and associated morbidity and costs after TAVI.

Fuertes-Kenneally L, Torres-Mezcua F, Herrero-Brocal M et al. · EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology · (2026) · View on PubMed ↗

Periprostatic adipose tissue-derived adipokine profile in prostate cancer patients reveals two distinct molecular phenotypes linked to obesity-related comorbidities: multifaceted role of lipocalin-2.

This multi-omic study profiled periprostatic adipose tissue (PPAT) adipokines and related secretome/circulating/urinary signals in prostate cancer patients, focusing on lipocalin-2 (LCN/LCN2) and obesity-linked comorbidities. The work identified two distinct PPAT molecular phenotypes associated with obesity-related comorbidity patterns and implicated LCN2 as a multifaceted mediator within the tumor–adipose communication network. Clinically, the LCN2-linked PPAT phenotypes may help stratify prostate cancer risk and reveal metabolic microenvironment targets for intervention.

Pérez-Gómez JM, Prats-Escribano A, Gil-Duque I et al. · Cell communication and signaling : CCS · (2026) · View on PubMed ↗

Perivascular adipose single-cell atlas identifies CD55+ adipose-derived stem cells as vascular remodeling regulators in atherosclerosis.

This study created a perivascular adipose (PVAT) single-cell atlas using single-cell RNA sequencing and flow cytometry across 169 clinical samples to identify PVAT cell populations linked to atherosclerotic plaque instability. It found two adipose-derived stem cell (ADSC) subsets and identified CD55+ ADSCs as elevated in patients with symptomatic carotid stenosis or prior stroke, with evidence that these cells migrate into plaques. The significance is that CD55+ ADSCs may be key regulators of vascular remodeling and could represent a cellular target to stabilize atherosclerotic disease.

Chen J, Li K, Shao J et al. · Nature communications · (2026) · View on PubMed ↗

Intracoronary imaging for left main percutaneous coronary intervention: a clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC and the European Bifurcation Club (EBC).

This clinical consensus statement studied the role of intracoronary imaging in guiding left main percutaneous coronary intervention (PCI), focusing on complex left main bifurcation stenting in acute and chronic coronary syndromes. It concluded that patient benefit depends on interventional adoption of imaging-guided planning, lesion assessment, and stent optimization, aligning with recent guideline endorsements. The significance is standardized recommendations to improve safety and outcomes in a high-risk PCI subset.

Johnson TW, Gonzalo N, de la Torre Hernandez JM et al. · European heart journal · (2026) · View on PubMed ↗

Preventing sudden cardiac death among football athletes in Cameroon: 22-year follow-up to the tragic death of Marc-Vivien Foé - supported by the BJSM Global Research Grant Programme.

This cross-sectional survey studied cardiovascular (CV) screening practices and emergency response planning for sudden cardiac arrest (SCA) among football clubs’ technical/medical staff in Cameroon’s domestic professional and amateur leagues and national teams (surveyed June–August 2024). The study found substantial gaps in how clubs perform CV screening and prepare for SCA, indicating that current club-level prevention and emergency readiness are not consistently aligned with the needs highlighted by the 2003 death of Marc-Vivien Foé. These findings support targeted improvements in standardized CV screening and SCA response infrastructure for football athletes in Cameroon to reduce sudden cardiac death risk.

Douryang M, Borjesson M, Ngo Bilong VA et al. · British journal of sports medicine · (2026) · View on PubMed ↗

Elevated Tmax >4 Seconds Volume Predicts Worse Functional Outcome Following Endovascular Treatment in M2 Middle Cerebral Artery Occlusion.

This retrospective multinational study evaluated whether the perfusion deficit volume with Tmax >4 seconds predicts functional outcome after endovascular treatment (EVT) in patients with M2 middle cerebral artery (MCA) occlusion. Patients with larger Tmax >4 s volumes had worse functional outcomes, suggesting that extensive hemodynamic compromise (including potentially at-risk tissue) reduces the likelihood of benefit from EVT. Clinically, Tmax >4 s volumetry could help refine EVT patient selection and prognostication in M2 stroke.

Kiani I, Kooshki A, Salim HA et al. · AJNR. American journal of neuroradiology · (2026) · View on PubMed ↗

ASFNR Current State of Practice in Neuroimaging of Distal Medium Vessel Occlusion Stroke.

This article summarizes the current state of practice and evidence for neuroimaging detection and workflow in distal medium vessel occlusion (DMVO) stroke, focusing on how radiologists identify these lesions despite challenges of vessel caliber, tortuosity, and limited sensitivity of standard CT angiography. It highlights that recent randomized trials of mechanical thrombectomy (MT) for DMVO (e.g., DISTAL, ESCAPE-MeVO, DISCOUNT, ORIENTAL-MeVO, DISTALS) have shown heterogeneous outcomes and higher symptomatic intracranial hemorrhage rates in the MT arm. The review’s practical guidance is intended to improve imaging-based diagnosis and triage workflows to better match patients to appropriate treatment pathways.

Sriwastwa A, Allen JW, Jain R et al. · AJNR. American journal of neuroradiology · (2026) · View on PubMed ↗

Long-Term Outcomes of Paroxysmal and Persistent Atrial Fibrillation Management Strategy During Non-Emergent Coronary Artery Bypass Surgery.

This study analyzed long-term outcomes of atrial fibrillation (AF) management strategies during non-emergent coronary artery bypass grafting (CABG) in patients with paroxysmal or persistent AF. Using the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2011–2022) linked to Medicare claims, it compared no AF treatment versus left atrial appendage occlusion (LAAO) only, epicardial ablation (EA), or intracardiac ablation (IA) and assessed all-cause mortality and other endpoints. The results are clinically important because they evaluate which intraoperative AF strategies during CABG may improve survival and reduce downstream complications over the long term.

Hawkins RB, Kubi B, Strobel RJ et al. · The Annals of thoracic surgery · (2026) · View on PubMed ↗

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Aging, epigenetics, and metabolic biomarkers

UNG-RPA interaction governs the choice between high-fidelity and mutagenic uracil repair.

This study examined how the UNG–RPA interaction determines whether uracil repair proceeds via high-fidelity versus mutagenic pathways in mammalian DNA repair contexts. It found that UNG’s engagement with RPA governs repair outcomes, and that a viral UNG homolog from B cell–tropic murine gammaherpesvirus 68 (MHV68UNG) could process AID-induced uracils but did not support hypermutation. These mechanistic insights explain how cells (and viral homologs) bias uracil repair fidelity, informing understanding of immunoglobulin diversification and genome stability.

Mu Y, Chen Z, Plummer JB et al. · Nucleic acids research · (2026) · View on PubMed ↗

Drug targets for lipid modification and risk of type 2 diabetes: a cis-Mendelian randomization study.

This cis-Mendelian randomization study used individual-level genetic data from UK Biobank and Lifelines plus external GWAS to evaluate whether genetically proxied targets of lipid-modifying drugs (and their gene products) influence risk of type 2 diabetes (T2D). The analysis systematically assessed drug-target pathways for T2D-related side effects, leveraging genetic instruments for lipid-modifying targets to infer causal risk. The findings provide a genetics-based prioritization framework for anticipating T2D risk across existing and pipeline lipid-modifying therapies.

Chen Z, Triatin RD, Luo L et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗

Glutamine-driven reductive TCA cycle metabolism supports aged muscle stem cell function via de novo lipogenesis.

This work investigated how glutamine-driven reductive TCA cycle metabolism regulates aged muscle stem cell (MuSC) function in mice, linking metabolic control to de novo lipogenesis. The authors found that glutamine-dependent reductive TCA flux supports aged MuSC regenerative capacity by enabling de novo lipid synthesis during activation. Scientifically and clinically, the results identify a metabolic bottleneck in aged MuSCs that could be targeted to counter sarcopenia and improve muscle regeneration.

Lee DE, McKay LK, Bareja A et al. · Nature aging · (2026) · View on PubMed ↗

Human whole-blood NAD+ levels do not vary with age or lifestyle interventions.

This study measured human whole-blood NAD+ levels across seven independent cohorts to test whether NAD+ declines with age or changes with lifestyle interventions, using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry with rigorous analytical controls. The key finding was that whole-blood NAD+ levels were stable across age and lifestyle interventions, while responding to nicotinamide riboside supplementation as expected. Scientifically, it challenges the use of blood NAD+ as a biomarker of aging or lifestyle effects, emphasizing the need for careful validation of NAD+ readouts.

Trętowicz MM, Scantlebery AML, Schomakers BV et al. · Nature metabolism · (2026) · View on PubMed ↗

Genetically targeted mTORC1 inhibitor reveals transcriptional control by nuclear mTORC1.

This study developed TerminaTOR, a genetically encodable, subcellularly targetable mTORC1 inhibitor, to determine how nuclear versus lysosomal mTORC1 pools control transcription. When TerminaTOR was directed to specific compartments, the authors found that nuclear mTORC1 signaling governs transcriptional programs distinct from classical lysosomal activation. The scientific significance is that it provides a tool and mechanistic evidence for compartment-specific mTORC1 functions, informing how to selectively modulate mTORC1-driven gene expression in disease.

Zhong Y, Sahan AZ, Shao Z et al. · Nature chemical biology · (2026) · View on PubMed ↗

Retatrutide And Lipid And Metabolite Profiles In Participants With Obesity With Or Without Type 2 Diabetes.

The study analyzed plasma metabolome and lipidome changes associated with retatrutide treatment in participants with obesity with and without type 2 diabetes using fasting samples from two randomized, placebo-controlled phase 2 trials. Retatrutide (1, 4, 8, 12 mg) produced measurable shifts in lipid and metabolite profiles over 36 weeks (obesity trial) and 48 weeks (obesity with T2D trial), compared with placebo. These findings are clinically relevant because they connect retatrutide’s metabolic effects to specific lipidomic/metabolomic signatures that may help refine biomarkers of response and mechanistic understanding.

Pearson MJ, Willency JA, Lin Y et al. · The Journal of clinical endocrinology and metabolism · (2026) · View on PubMed ↗

Epigenetic noise in the aging brain: tuning neuronal vulnerability to neurodegeneration.

This review studied how aging-related increases in epigenetic noise—across DNA methylation, histone modifications, and chromatin accessibility—affect neuronal vulnerability to neurodegeneration. It concluded that age-associated epigenetic dysregulation can actively destabilize transcriptional precision and neuronal identity, with single-cell and spatial epigenomics suggesting region- and cell-type-specific vulnerability. The scientific significance is that targeting epigenetic noise mechanisms may represent a strategy to modulate neurodegenerative risk.

Yin X, Zhang H, Zhang R et al. · Trends in neurosciences · (2026) · View on PubMed ↗

Structure and function of IWS1 in transcription elongation.

This mechanistic study examined the structure and function of IWS1 (Interacts with SPT6) in RNA polymerase II transcription elongation. Using cryo-electron microscopy to map short linear motifs (SLiMs) in the intrinsically disordered IWS1 C-terminal region that engage Pol II subunits (RPB1, RPB2, RPB5) and elongation factors (DSIF, SPT6, ELOF1), the authors showed that distinct IWS1 SLiMs specify recruitment and IWS1-dependent transcriptional elongation. These findings clarify how IWS1 coordinates the elongation machinery, advancing understanding of transcription regulation at the molecular level.

Syau D, Steinruecke F, Roth S et al. · Nucleic acids research · (2026) · View on PubMed ↗

Cellular Senescence as a Systems-Level Driver of Cardiovascular Ageing.

This review article synthesized evidence on how cellular senescence acts as a systems-level driver of cardiovascular ageing across interacting endothelial, vascular smooth muscle, immune, and stromal cell networks. It emphasizes that cardiovascular senescence is heterogeneous and emerges from network interactions shaped by metabolic stress, immune dysregulation, and chromatin reorganization rather than being purely cell-autonomous. The translational significance is that targeting senescence-related pathways may require network-aware strategies to more effectively mitigate age-associated cardiovascular decline.

Wang MM, Liu T, Xu CQ et al. · Ageing research reviews · (2026) · View on PubMed ↗

Is weight cycling clinically harmful?

This Personal view reviewed evidence from human and animal studies on whether weight cycling (repeated weight loss and regain) is clinically harmful. It discusses the hypothesis that weight cycling may worsen fat-mass rebounds, reduce lean-mass regain, promote sarcopenia, lower metabolic rate, and exacerbate metabolic complications such as glucose intolerance. The significance is that it frames current evidence quality and mechanistic concerns to inform clinical counseling and future research on weight-cycling risk.

Magkos F, Stefan N · The lancet. Diabetes & endocrinology · (2026) · View on PubMed ↗

A comparison of deep multiomics profiles across ethnicity, geography, and age.

This Cell study performed comprehensive multiomics profiling across ethnicity, geography, and age in 322 healthy individuals of European, East Asian, and South Asian ancestry. It identified ethnicity-associated molecular features and ancestry/geography-related changes affecting metabolism, immune function, microbiome composition, and pathways relevant to autoimmune disease risk, drug metabolism, and neurodegeneration. The findings support more precise, population-aware interpretation of biomarkers and therapeutic responses in precision medicine.

Barapour N, Cao JZ, Wu Y et al. · Cell · (2026) · View on PubMed ↗

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Psychiatry, neuropsychiatric epidemiology, and mental health outcomes

Risk of all-cause and cause-specific mortality, and suicide attempt in people with anxiety and stress-related disorders: a systematic review, meta-analysis and meta-regression analysis of 165 studies.

This systematic review and meta-analysis (with meta-regression) quantified all-cause and cause-specific mortality and suicide attempt risk in people with anxiety and stress-related disorders across 165 studies totaling 7,395,722 participants. The key finding is that the authors calculated risk ratios for mortality outcomes and suicide-related mortality/attempts, with sensitivity and meta-regression analyses to explore heterogeneity (full numeric results are truncated). Clinically, it provides a quantitative evidence base to inform risk stratification and mental-health–integrated mortality prevention strategies.

Wagner E, Mortazavi M, Poddighe L et al. · World psychiatry : official journal of the World Psychiatric Association (WPA) · (2026) · View on PubMed ↗

Child and adolescent psychiatry: challenges, solutions, opportunities, and future directions.

This narrative review outlined challenges, solutions, opportunities, and future directions in child and adolescent psychiatry, motivated by the high global prevalence of diagnosable mental disorders in youth and early onset of major mental disorders. The key finding is that child and adolescent psychiatry remains a relatively young discipline with ongoing gaps in services, training, and research translation (details are truncated). Scientifically and clinically, it frames priorities to improve early identification, care delivery, and long-term outcomes for affected children and adolescents.

Cortese S, Arango C, Aymerich C et al. · World psychiatry : official journal of the World Psychiatric Association (WPA) · (2026) · View on PubMed ↗

How muscle talks to brain: apelin protein mediates exercise-induced antidepressant effects.

This study investigated muscle-to-brain signaling by testing whether exercise-induced increases in skeletal muscle–derived apelin mediate antidepressant effects via apelin and its receptor APJ in mice. Voluntary running for 4 weeks increased serum and muscle apelin levels and alleviated depression-like behaviors, while muscle-specific apelin knockout abolished the exercise-induced antidepressant effects. The significance is that apelin–APJ signaling is identified as a mechanistic mediator of exercise benefits, suggesting a potential therapeutic target for depression.

Yu J, Cheng T, Guo H et al. · Molecular psychiatry · (2026) · View on PubMed ↗

Post-traumatic stress disorder.

This Nature Reviews Disease Primer summarized what is known about post-traumatic stress disorder (PTSD) in humans, including its symptom clusters (intrusive re-experiencing, avoidance, negative cognition/mood, and altered arousal) and epidemiology. It emphasizes that PTSD affects tens of millions in the USA and has a global lifetime prevalence of roughly 4–6%, with higher rates after severe trauma, and notes substantial comorbidity with depression and anxiety disorders. The significance is a consolidated clinical framework for diagnosis, risk understanding, and treatment development for a highly prevalent, debilitating psychiatric condition.

Ressler KJ, Rothbaum BO, Schnurr PP et al. · Nature reviews. Disease primers · (2026) · View on PubMed ↗

Paracetamol in Pregnancy: Uncertain Evidence, Certain Consequences.

This article critically appraised a September 2025 claim and underlying systematic review about paracetamol (acetaminophen) use in pregnancy and autism risk, focusing on the evidence base and methodological limitations. It found that the cited review relied on observational studies without causal evidence and used selective reporting and flawed frameworks, which amplified public uncertainty about paracetamol safety in pregnancy. The significance is that it highlights how scientific uncertainty can be manipulated in public health messaging, with implications for interpreting pregnancy medication risk claims.

Tunnicliffe DJ, Cumpston M, Kennedy D et al. · The Medical journal of Australia · (2026) · View on PubMed ↗

Positive body image is a pathway between nature contact and life satisfaction across 58 nations.

This study examined whether positive body image mediates the relationship between nature contact and life satisfaction across 58 nations using the Body Image in Nature Survey (BINS; N=50,363). It found that nature contact was associated with greater self-compassion and perceived restoration in nature, which in turn were linked to higher life satisfaction through positive body image pathways. The significance is identifying a cross-national psychological mechanism that can explain how nature exposure translates into well-being outcomes.

Swami V, Voracek M, Stieger S et al. · Environment international · (2026) · View on PubMed ↗

Pharmacological interventions for ADHD: a systematic review and dose-effect network meta-analysis.

This systematic review and dose-effect network meta-analysis synthesized double-blind randomized controlled trials to estimate dose–response curves for efficacy and tolerability of oral ADHD medications (stimulants and non-stimulants) across age groups. It aimed to address gaps in guideline dosing information and concerns about subtherapeutic prescribing by comparing dose-dependent outcomes across medications. The significance is that it can support more evidence-based dosing strategies to improve ADHD symptom control while managing adverse effects.

Nourredine M, Jurek L, Hamza T et al. · The lancet. Psychiatry · (2026) · View on PubMed ↗

Maternal and paternal antidepressant use before and during pregnancy and offspring risk of neurodevelopmental disorders: a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated offspring risk of neurodevelopmental disorders (including ADHD and autism spectrum disorder) associated with maternal and paternal antidepressant use before and during pregnancy. It synthesized evidence while accounting for antidepressant classes/agents/dose and addressing confounding by treatment indication. The significance is that it provides a more comprehensive, confounding-aware estimate of prenatal antidepressant exposure risk for neurodevelopmental outcomes.

Chan JKN, Zhong AHF, Lam JYH et al. · The lancet. Psychiatry · (2026) · View on PubMed ↗

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Infectious disease therapeutics and antimicrobial development

Hepatocellular carcinoma attributable to hepatitis B, hepatitis C and other risk factors at global, regional and national levels: an updated systematic review and meta-analysis.

This updated systematic review and meta-analysis studied the global, regional, and national burden of hepatocellular carcinoma (HCC) attributable to hepatitis B virus (HBV), hepatitis C virus (HCV), and other risk factors by estimating attributable fractions and age-standardized incidence rates. Using studies published between 2014-10-01 and 2023-12-31 that reported HBV/HCV prevalence among at least 20 HCC patients, it pooled prevalence to derive HBV- and HCV-attributable fractions by country and region. The significance is informing hepatitis elimination strategies by quantifying how much HCC burden is attributable to HBV and HCV across geographies.

Cao M, Wei F, Georges D et al. · Gut · (2026) · View on PubMed ↗

Encephalitis.

This Seminar reviewed encephalitis as an urgent global emergency, focusing on distinguishing infectious versus autoimmune causes in clinical practice. It emphasizes pragmatic diagnostic approaches using pre-test impressions plus targeted “simple investigations,” particularly serum and cerebrospinal fluid nucleic acid testing and autoantibody testing, to identify the causative agent early. The significance is improved diagnostic accuracy and earlier, cause-directed treatment to reduce encephalitis morbidity and mortality.

Binks SNM, Saylor D, Easton A et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Quantifying relative health impact across Gavi, the Vaccine Alliance’s portfolio in 117 countries at the subregional level: a modelling study.

This modelling study quantified relative vaccine health impact across Gavi’s portfolio in 117 low- and middle-income countries using multiple models for 14 vaccine-preventable diseases. The key output was vaccine impact ratios at the subregional level to enable cross-vaccine comparisons under global health resource constraints. These estimates can directly inform Gavi allocation and immunisation strategy decisions by standardising how different vaccines’ health benefits are compared.

Gaythorpe KAM, Li X, Shankar M et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Efficacy and safety of cefepime-nacubactam and aztreonam-nacubactam compared with imipenem-cilastatin for complicated urinary tract infection or acute uncomplicated pyelonephritis (Integral-1): a double-blind, randomised phase 3 trial.

The Integral-1 double-blind phase 3 trial compared intravenous cefepime-nacubactam and aztreonam-nacubactam versus imipenem-cilastatin in adults (≥18 years) with complicated urinary tract infection or acute uncomplicated pyelonephritis. The study’s key finding was the relative efficacy and safety of these nacubactam-containing β-lactamase inhibitor combinations against the carbapenem comparator. If non-inferior or superior with acceptable safety, these regimens could expand effective options for cUTI/pyelonephritis while targeting β-lactamase–mediated resistance.

Takahashi S, Tateda K, Yanagihara K et al. · Lancet (London, England) · (2026) · View on PubMed ↗

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Autoimmunity diagnostics, consensus, and pharmacovigilance

Potential risk of neoplasms with fezolinetant: clinical evidence, mechanisms, and post-marketing implications.

This review evaluated clinical evidence, proposed mechanisms, and post-marketing implications for neoplasm risk associated with fezolinetant, a neurokinin 3 receptor (NK3R) antagonist approved for moderate-to-severe menopausal vasomotor symptoms. The key finding is that while initial regulatory assessments dismissed a neoplasm signal, emerging meta-analyses and pooled analyses consistently reported an increased risk of non-benign neoplasms. Scientifically and clinically, it highlights the need for ongoing pharmacovigilance and risk–benefit reassessment for fezolinetant in treated populations.

Boretti E, Dogné JM, Douxfils J · Journal of the Endocrine Society · (2026) · View on PubMed ↗

Meningococcal prophylaxis in neurological diseases treated with complement inhibitors: an expert consensus for Germany, Austria, and Switzerland.

This expert consensus article addressed meningococcal prophylaxis and vaccination management for patients with neurological diseases treated with terminal complement inhibitors, focusing on acetylcholine receptor antibody-positive generalized myasthenia gravis (gMG) and aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (NMOSD). The key finding is that vaccination against meningococcal serogroups A, C, W, Y, and B is recommended as mandatory for all patients receiving complement inhibitors, with guidance on timing and procedures. Clinically, it aims to reduce the increased risk of invasive meningococcal infection inherent to complement blockade in these patient groups.

Berthele A, Aktas O, Ayzenberg I et al. · Therapeutic advances in neurological disorders · (2026) · View on PubMed ↗

Vitamins and Cancer Risk: A Comprehensive Review of Epidemiologic and Clinical Evidence.

This scoping review synthesized epidemiologic and clinical evidence on vitamins A, D, E, K, C, and B-complex regarding cancer prevention, treatment response, and toxicity. The key finding is that the evidence base is heterogeneous and includes both mechanistic effects (e.g., immune activation, ferroptosis modulation) and epidemiologic/clinical signals that can be protective, neutral, or potentially tumor-promoting depending on context. Scientifically, it underscores that universal vitamin supplementation in oncology may have complex, sometimes paradoxical effects, supporting more targeted, evidence-based use.

El Halabi L, AlBayeh A, Khoury A et al. · Kansas journal of medicine · (2026) · View on PubMed ↗

International expert consensus recommendations on standardised nomenclature of SSA/Ro (TROVE2/Ro60 and TRIM21/Ro52) autoantibodies in autoimmune diseases.

This work studied the need for standardized nomenclature of SSA/Ro autoantibodies, specifically TROVE2/Ro60 and TRIM21/Ro52 (and TRIM21/Ro52), by conducting a systematic literature review to inform a Delphi consensus process in systemic lupus erythematosus (SLE) and Sjögren disease (SjD). It found that despite improved separate testing, TROVE2/Ro60 and TRIM21/Ro52 antibodies remain frequently confused in the literature, motivating harmonized naming rules. The significance is improved clarity and precision for autoantibody reporting and interpretation across autoimmune disease research and diagnostics.

Nikolic RPA, Ben-Chetrit E, Fritzler MJ et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗

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Generated automatically on May 16, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.