PubMed Trending Research Digest — September 24, 2026

Automated digest · 99 articles · 15 research areas · September 24, 2026

Overview

Across this week’s digest, a clear through-line is the move from “single-pathway” thinking toward systems-level, mechanism-informed stratification. In neurodegeneration, studies connect genetic risk (e.g., SORL1, ApoE4) and transmissible pathology (urine neuronal extracellular vesicles with RT-QuIC) to early synaptic dysfunction and potential noninvasive detection—while proteomic profiling around menopause links endocrine state to inflammatory and Alzheimer’s-related brain-aging signatures.

In oncology and immunotherapy, multiple papers emphasize context dependence: organ-specific metastatic niches (liver vs lung) shape secondary spread, and tumor transcriptional plasticity plus spatial architecture influence responses to immune checkpoint blockade and targeted BRAF/MEK therapy. Mechanistically, several studies highlight actionable vulnerabilities tied to cellular stress and genome maintenance—such as inflammation-linked DDR1 stability/AMPK control in KRAS-mutant PDAC, replication-stress response pathways (ATR/CHK1), and ecDNA maintenance via MMEJ. Complementing these, immune-biomarker work (cytokine dynamics during PD-1 blockade) and epigenetic brakes on T-cell exhaustion (ZMYND8–IL2R–STAT5) point toward more responsive, monitorable immunotherapy.

Finally, the digest repeatedly returns to “targetable biology” at the interface of metabolism, organelle function, and inflammation. Cardiovascular studies span RNA epitranscriptomics (ALKBH5–SLC38A3 glutamine aging), lysosome–mTORC1 and autophagy/mitochondrial homeostasis (LAPTM4A, Asb2–KIF11), and early post–heart failure pharmacologic timing (empagliflozin). In respiratory and inflammatory disease, sex-specific sphingolipid programs in COPD and neuron-intrinsic mTORC1 neuroimmune memory in allergic sensitization illustrate how host heterogeneity can guide future prevention and treatment strategies.

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Immuno-oncology & Cancer Immunotherapy (ICB, CAR-T, immune biomarkers)

Targeting ZMYND8 unleashes IL-2 signalling to override T cell exhaustion.

The study investigated how the chromatin reader ZMYND8 regulates IL-2 receptor (IL-2R)–STAT5 signaling to control CD8+ T cell exhaustion, using in vivo single-cell CRISPR screens in the context of chronic viral infection and cancer. ZMYND8 antagonized IL-2R–STAT5 signaling, and targeting ZMYND8 “unleashed” IL-2–STAT5 activity to override exhausted T cell states toward effector-like differentiation. This identifies ZMYND8 as a mechanistic epigenetic brake on IL-2–STAT5 that could be therapeutically targeted to improve T cell function in chronic infection and cancer.

Wang Y, Shi H, Chapman NM et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

Etuvetidigene Autotemcel for the Treatment of Wiskott-Aldrich Syndrome.

The study evaluated etuvetidigene autotemcel (etu-cel), an autologous lentiviral gene therapy delivering WAS complementary DNA, for Wiskott-Aldrich syndrome patients with variants in the WAS gene. Across integrated data from two prospective open-label studies (phase 1–2 and phase 3) plus expanded access, etu-cel was assessed for efficacy and safety in this patient population. This supports the clinical development of lentiviral WAS gene addition as a disease-modifying therapy for Wiskott-Aldrich syndrome.

Ferrua F, Cenciarelli S, Giannelli S et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Phase 1 Study of Anito-cel, a d-Domain BCMA CAR T Cell for Refractory or Recurrent Myeloma.

This phase 1 trial studied anitocabtagene autoleucel (anito-cel), an autologous BCMA-directed CAR T cell using a synthetic d-domain binder (ddBCMA), in patients with relapsed or refractory multiple myeloma who had received ≥3 prior lines or had triple-class refractory disease. The study evaluated safety and efficacy across dose levels of 100×10^6 and 300×10^6 CAR+ T cells, with primary endpoints focused on treatment-period adverse events and establishing the recommended phase 2 dose. If effective and tolerable, ddBCMA anito-cel could expand CAR T options for heavily pretreated, high-risk multiple myeloma populations.

Frigault MJ, Dhakal B, Jakubowiak AJ et al. · The New England journal of medicine · (2026) · 1 citations · View on PubMed ↗

Mechanism of GPR84 allosteric modulation at a helix 8-proximate site.

This work studied the mechanism of allosteric modulation of the immune-metabolic GPCR GPR84, focusing on a helix 8-proximate allosteric site and how it produces Gi-biased signaling. Using cryo-electron microscopy of GPR84–Gi complexes with the orthosteric agonist OX04539 alone or with the positive allosteric modulator PSB-16671, plus molecular dynamics simulations and mutagenesis, the authors identified a TM1–TM7 helix 8-proximate interaction network that underlies PSB-16671–driven biased signaling. These structural and mechanistic insights can guide the rational design of pathway-selective GPR84 allosteric drugs.

Zhang X, Guseinov AA, Jenkins L et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Structural basis of lenacapavir-induced HIV-1 capsid defects during virion maturation.

The study examined how the long-acting HIV capsid inhibitor lenacapavir (LEN) disrupts HIV-1 capsid structure during virion maturation using cryo-electron microscopy of mature capsid lattices assembled in virus-like particles. It found that LEN induces specific structural defects in the mature capsid lattice, altering interhexamer interactions required for proper maturation. These structural insights clarify LEN’s late-stage mechanism and can guide rational optimization of capsid-targeting antivirals.

Tanaka H, Morita R, Oka T et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Transcriptomic Plasticity and Its Spatial Architecture Shape Melanoma Response to Immunotherapy and Its Combination With BRAF/MEKi.

The study analyzed transcriptional states associated with resistance to immune checkpoint blockade (ICB) and response to ICB combined with BRAF/MEK inhibition in BRAF-mutant melanoma patients using integrated multi-omics datasets (including IMspire150, BRIM, and AVAST-M) and spatial transcriptomics. It found that tumor transcriptional plasticity and spatial architecture shape how melanomas respond to ICB and to ICB plus MAPK-targeted therapy, enabling identification of biomarkers linked to treatment outcomes. These results can help stratify patients and guide sequencing/combination strategies for BRAF/MEK inhibitors with ICB.

Shah K, Nguyen DAH, Gold M et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Circulating cytokines as potential dynamic biomarkers of PD-1 blockade response and prognosis in non-small cell lung cancer.

This study assessed whether circulating cytokines can serve as dynamic biomarkers of response and prognosis to PD-1 blockade in patients with non-small cell lung cancer (NSCLC). Serum levels and on-treatment changes in cytokines including TNF-α, IFN-γ, IL-6, IL-8, IL-17A, IL-1β, IL-2, IL-5, and IL-10 were associated with treatment response and outcomes. These findings support cytokine monitoring as a minimally invasive approach to predict and track PD-1 inhibitor efficacy and prognosis in NSCLC.

Peng B, Li Y, Li S et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer Biology & Tumor Microenvironment (mechanisms, metastasis, niches)

Hepatocytes promote liver metastasis of pancreatic cancer by providing serine.

The study examined how hepatocytes metabolically support pancreatic ductal adenocarcinoma (PDAC) liver metastasis, focusing on serine availability and the serine-biosynthesis dependency created by PHGDH loss. Hepatocyte-derived serine promoted colonization and growth of exogenous-serine–dependent PDAC cells, linking liver microenvironment metabolism to metastatic fitness. This suggests that disrupting serine supply or PHGDH/exSer metabolic coupling could be a strategy to limit PDAC liver metastases.

Ganguly K, Yamamoto K, Rodencal J et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

MMEJ repair of breaks at TA repeats maintains ecDNA and cancer fitness.

The study tested which DNA double-strand break repair pathway maintains extrachromosomal DNA (ecDNA) and cancer fitness, using inhibition of microhomology-mediated end joining (MMEJ) versus other repair pathways in ecDNA-dependent cancer models. Inhibiting MMEJ selectively depleted ecDNA, caused ecDNA-specific damage, and drove ecDNA into micronuclei, reducing fitness of tumors reliant on ecDNA-driven oncogene amplification. This establishes MMEJ as a therapeutic vulnerability for ecDNA maintenance and suggests pathway-targeted approaches to impair aggressive, therapy-resistant cancers.

Billing D, Selvaraj M, Kelley ME et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗

CD4 T cells convert transient responses to KRAS inhibition to durable remissions in pancreatic cancer.

The study investigated how CD4 T cells shape responses to KRAS inhibition in pancreatic cancer, using mouse models of KRAS inhibitor (KRASi) response and relapse and testing cytokine mimic therapy. An IL-21 cytokine mimic (21h10) induced durable remissions, and its efficacy depended on Th1-polarized CD4 T cells rather than CD8 T cells. This supports a strategy of combining KRASi with IL-21/Th1 CD4 programming to convert transient KRASi responses into long-term control in PDAC.

Qiang L, Hoffman MT, Chun JH et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

SCRMP-mediated SUMOylation of CSNK2B facilitates DNA damage repair to promote cisplatin resistance in small cell lung cancer.

This study investigated how SCRMP-mediated SUMOylation of CSNK2B (casein kinase 2 beta) promotes DNA damage repair and thereby drives cisplatin resistance in small cell lung cancer using multiomic analyses of cisplatin-resistant patient-derived xenograft (PDX) tissues and the IMpower133 cohort. The key finding was that SCRMP-dependent SUMOylation of CSNK2B facilitates DNA damage repair mechanisms that enable cisplatin-resistant tumor survival. Targeting the SCRMP–CSNK2B SUMOylation axis could provide a mechanistic strategy to overcome platinum resistance in SCLC.

Chen Y, Chen Q, Guo J et al. · Science translational medicine · (2026) · View on PubMed ↗

Metastasis enables immunogenicity through migrasome-mediated antigen release.

This Nature Immunology study investigated how metastasis promotes antitumor immunogenicity by using migrasome-mediated antigen release from circulating tumor cells during vascular migration. The authors found that migrasomes enriched for tumor-associated antigens are captured by antigen-presenting cells in secondary lymphoid organs, enabling cross-presentation that activates CD8+ T cell responses and constrains metastatic progression; genetic inhibition of migrasome formation increased metastasis. These results are significant because they identify migrasome formation as a metastasis-specific immunogenic mechanism and a potential therapeutic target to enhance antitumor immunity.

Jiang D, He J, Xie R et al. · Nature immunology · (2026) · View on PubMed ↗ · Free PDF ↗

Replication stress in cancer: origins, consequences and therapeutic opportunities.

This review studied the origins and downstream consequences of replication stress in cancer cells and how these vulnerabilities can be therapeutically exploited, focusing on replication fork stabilization/restart pathways. It concluded that replication stress arises from oncogene activation, transcription–replication conflicts, nucleotide metabolism changes, and DNA secondary structures, and that the ATR–CHK1 checkpoint pathway is essential for preventing excessive fork collapse, chromosomal instability, and mutagenesis. Clinically, it supports targeting replication-stress response mechanisms (notably ATR/CHK1-centered pathways) as a strategy to improve cancer treatment selectivity.

Chen J, Zou L · Nature reviews. Cancer · (2026) · View on PubMed ↗

The anion channel GPR89 is a tumor-specific dependency in breast cancer.

The study investigated the anion channel GPR89 as a tumor-specific dependency in breast cancer, focusing on its subcellular localization and role in ER pH regulation and stress signaling. It found that although GPR89 is normally Golgi-localized, tumor cells also localize GPR89 to the ER where it cooperates with vacuolar H+-ATPase to regulate ER pH and suppress ER stress through IRE1α–HSP47–XBP1s, ATF6, and ATP2A2 pathways, with key ER-function residues identified by modeling and mutagenesis. This establishes GPR89 as a breast cancer–specific vulnerability that could be targeted to disrupt ER homeostasis and reduce tumor survival.

Ferro R, Carroll A, Mendes-Pereira AM et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Integrative multi-omics landscape and diagnostic-therapeutic modelling of steatohepatitic hepatocellular carcinoma.

This integrative multi-omics study investigated steatohepatitic hepatocellular carcinoma (SH-HCC) by combining clinical and molecular datasets to define its diagnostic landscape and therapeutic targets. It found that multi-modal profiling across RNA-seq, spatial transcriptomics, spatial metabolomics, lipidomics, and serum proteomics enabled construction of non-invasive diagnostic models and identified FABP4 as a functionally validated candidate target (with validation in Sl [truncated in abstract]). This provides a framework for subtype-specific diagnosis and suggests FABP4-directed strategies for SH-HCC.

Zhang L, Chen C, Xu Y et al. · Gut · (2026) · View on PubMed ↗ · Free PDF ↗

WNT/β-catenin signaling: implications for homeostasis and tumorigenesis in the esophagus.

This review analyzed the roles of WNT/β-catenin signaling in esophageal epithelial homeostasis and tumorigenesis, focusing on how β-catenin activity is regulated during foregut development and how dysregulation affects adult esophageal progenitors. The key finding was that while WNT/β-catenin signaling is essential for lineage specification and epithelial transitions, its precise control of basal progenitor proliferation and differentiation in the adult esophagus remains incompletely defined and is implicated in cancer when WNT ligands are overexpressed or WNT inhibitors are downregulated. Clinically, clarifying these pathway mechanisms could inform targeted prevention or treatment strategies for esophageal cancer.

Chen Z, Guo X, Peppelenbosch MP et al. · Biochimica et biophysica acta. Reviews on cancer · (2026) · View on PubMed ↗

Modeling Liver Cancer Molecular and Histological Features by CRISPR Editing of Porcine Hepatocytes.

This study modeled hepatocellular carcinoma (HCC) by CRISPR editing of porcine hepatocytes, using pig hepatocytes (n=7) subjected to combinations of CRISPR knockouts of tumor suppressor genes (TP53, PTEN, CDKN2A, AXIN1) with or without c-Myc overexpression. The key finding was that specific gene-alteration combinations can drive hepatocyte transformation to create genetically defined HCC models that better recapitulate human molecular and histological features. This supports the use of CRISPR-engineered porcine systems for evaluating multimodal HCC therapies where human-like preclinical models are needed.

Elkhadragy L, David OG, Castillo CC et al. · JHEP reports : innovation in hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Mutant ASXL1 Cooperates with MECOM and BRD4 to Drive Transcriptional Dysregulation in Human Hematopoiesis.

The study tested how mutant ASXL1 cooperates with MECOM and BRD4 to drive transcriptional dysregulation in human hematopoiesis using a CRISPR-engineered human hematopoietic stem and progenitor cell model. Mutant ASXL1 reduced differentiation, increased clonogenicity in serial replating, and improved engraftment in immunodeficient mice, demonstrating functional oncogenic cooperation in a human HSPC context. These findings validate a mechanistic pathway for mutant ASXL1-driven myeloid malignancy and suggest that targeting cooperating factors such as MECOM/BRD4 could be therapeutically relevant.

Hall ML, Quintal A, Acharya SN et al. · Blood · (2026) · View on PubMed ↗ · Free PDF ↗

Inflammatory memory inactivates AMPK-stimulated DDR1 degradation to enable pancreatic cancer growth.

This study investigated how inflammatory memory regulates pancreatic ductal adenocarcinoma (PDAC) growth by controlling AMPK-stimulated degradation of the collagen receptor discoidin domain receptor 1 (DDR1) in PDAC cells. It found that defective type I collagen (Col-I) remodeling reduces the DDR1 ligand (the 3/4 Col-I fragment), lowering ATP and activating AMPK, which phosphorylates DDR1 at T519 to promote FBXW2-mediated proteasomal degradation—yet inflammatory memory inactivates this DDR1 degradation checkpoint to enable tumor growth. The work identifies an inflammation-linked DDR1 stability/AMPK axis as a mechanistic vulnerability for therapeutic targeting in KRAS-mutant PDAC biology.

Yang F, Lin B, Yuan Y et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting RAS for Pancreatic Cancer Interception.

This article reviewed strategies to target RAS in pancreatic cancer, emphasizing how therapies designed for KRAS-driven tumors may also enable cancer interception in pancreatic precancer stages. It highlights the translational rationale that pancreatic precancers commonly harbor KRAS mutations, making RAS-targeted approaches potentially applicable earlier in disease. The review is significant for guiding development and selection of RAS pathway interventions aimed at preventing progression to invasive pancreatic cancer.

Misale S, Zaidi N, Jaffee EM et al. · Cancer discovery · (2026) · View on PubMed ↗

The liver niche accelerates, while the lung niche restrains secondary spread of breast cancer.

This Cancer Discovery study investigated how organ-specific metastatic niches—liver versus lung—affect secondary spread and growth of breast cancer. Using patient data and rapid autopsy tissues, along with mouse models with barcode-mediated tracing, niche-labeling technology, and single-cell analysis, it found that the liver promotes metastasis-promoting properties and accelerates secondary spread, whereas the lung restrains these processes and favors local growth. These findings are clinically significant because they identify microenvironment-dependent mechanisms that could be exploited to prevent or limit visceral metastasis.

Sznurkowska MK, Castro-Giner F, D’Anna I et al. · Cancer discovery · (2026) · View on PubMed ↗ · Free PDF ↗

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Epitranscriptomics & RNA Regulation (m6A, epitranscriptomic control)

Lsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila.

The study investigated how the Drosophila protein Lsp2 connects mTORC1 signaling to translation of TOP (5′-terminal oligopyrimidine) motif mRNAs and to organismal lifespan. Lsp2 was required for physiologic tuning of TOP mRNA translation downstream of mTORC1, linking this translational control to lifespan regulation. This provides a mechanistic bridge between nutrient-sensing mTORC1, ribosome biogenesis programs, and aging.

Wang J, Cai Z, Gu J et al. · Nature · (2026) · 2 citations · View on PubMed ↗

Direct cell-to-cell transmission of retrotransposons.

The study investigated whether certain LTR retrotransposons can spread between cells, identifying a mechanism for retrotransposon transmission in the Drosophila ovary. It found that germline infection from somatic cells occurs without the canonical retroviral fusogenic Envelope protein, instead relying on a short transmembrane protein sORF2 that localizes to invasive somatic protrusions. This reveals a non-Envelope, cell-to-cell transmission route for retrotransposons that expands understanding of how mobile elements can propagate in multicellular organisms.

Voichek M, Bernhard A, Lauterjung L et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

The stability of m6A-marked transcripts is linked to cell identity in planarians.

This study investigated how N6-methyladenosine (m6A)–marked transcripts regulate cell identity in the planarian Schmidtea mediterranea by generating a high-confidence atlas of ~72,200 m6A sites using multiplexed direct RNA sequencing. The key finding was that m6A sites follow a DRAYW consensus motif and are enriched near stop codons while being largely excluded from coding sequences, linking m6A-marked transcript stability to cell-type-specific gene expression. These results are significant because they provide mechanistic insight into how epitranscriptomic regulation contributes to regeneration and cell identity in a highly regenerative organism.

Höhn C, Pittroff A, Gribling-Burrer AS et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗

ALKBH5-Dependent m6A Demethylation Promotes Cardiac Aging Through SLC38A3 Reduction and Glutamine Metabolic Alteration.

This study examined whether the m6A demethylase ALKBH5 controls cardiac aging in physiologically aged and paraquat-induced mouse models and in senescent cardiomyocyte cultures. ALKBH5-dependent m6A demethylation reduced SLC38A3 expression and drove glutamine metabolic alterations that promoted cardiac aging. The work links ALKBH5–m6A regulation of SLC38A3 and glutamine metabolism to aging biology, suggesting potential RNA-epitranscriptomic targets for age-related cardiac decline.

Liu K, Liang CQ, Li HJ et al. · Circulation · (2026) · View on PubMed ↗

METTL3-Mediated N6-Methyladenosine Modification Activates the EGR1-ZBP1 Axis to Promote PANoptosis-Like Cardiomyocyte Death in Myocardial Ischemia-Reperfusion Injury.

This study investigated whether METTL3-mediated m6A modification activates the EGR1–ZBP1 axis to drive PANoptosis-like cardiomyocyte death during myocardial ischemia–reperfusion (I/R) injury. In mouse I/R and OGD/R models, METTL3 and global m6A levels increased, and METTL3-dependent m6A signaling promoted PANoptosis-like death via the EGR1–ZBP1 pathway. The results connect RNA epitranscriptomic regulation to a specific death program in I/R injury, suggesting METTL3/EGR1–ZBP1 as potential therapeutic targets.

Li L, Gao J, Zhang X et al. · MedComm · (2026) · View on PubMed ↗ · Free PDF ↗

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Diagnostics, Screening & Biomarkers (imaging, MRD, MCED, EVs, cytokines, AI models)

Pre-hospital time and risk of perforation in patients with acute appendicitis in 112 countries (AlliGatOr): an international, prospective, observational cohort study.

The study assessed whether pre-hospital time (symptom onset to first surgical assessment) is associated with perforation risk in patients with acute appendicitis across 112 countries using a prospective observational cohort (AlliGatOr). Longer pre-hospital time increased the risk of perforation, supporting delayed assessment/treatment as a clinically relevant risk factor. These findings can inform triage and referral strategies to reduce perforation and potentially avoid unnecessary negative appendicectomies.

Anyomih TTK, Aregawi AB, Calvache JA et al. · The Lancet. Global health · (2027) · View on PubMed ↗ · Free PDF ↗

Clinical Uses of Common Genetic Variants Associated with Common Diseases.

The article reviewed how common genetic variants from genome-wide association studies are used clinically, focusing on polygenic risk scores and their limited impact on most adult-onset common diseases. Despite thousands of small-effect variants enabling risk prediction, polygenic risk scores have had little effect on routine diagnosis or treatment, largely due to performance, utility, and implementation barriers. The review highlights where genomic risk information is currently actionable and what is needed to translate polygenic findings into clinical benefit.

Hunter DJ, Inouye M · The New England journal of medicine · (2026) · View on PubMed ↗

Effect of Screening with Multicancer Early-Detection Test on Late-Stage Cancer Diagnosis.

This randomized controlled trial studied whether screening with a blood-based multicancer early-detection test, in addition to usual care, reduces late-stage cancer diagnosis in adults aged 50 to 77 years in England. The key finding (as assessed by the primary endpoint of stage III or IV cancer across 12 prespecified cancer types) determined whether the intervention group had fewer late-stage diagnoses than the control group whose blood was stored. The results inform the clinical utility of population screening with blood-based multi-cancer tests beyond standard care.

Sasieni P, Johnson P, Round T et al. · The New England journal of medicine · (2026) · 2 citations · View on PubMed ↗

CRISPR-based functional genomic screening in neurodegeneration: mechanistic insights into AD, PD, and ALS.

This review summarized how CRISPR-based functional genomic screening is being applied to neurodegenerative disease models to generate mechanistic insights into Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). The key finding is that clustered regularly interspaced short palindromic repeats (CRISPR) screening enables large-scale genetic perturbation across cellular, organoid, and in vivo systems to systematically interrogate disease-relevant pathways despite biological heterogeneity. Scientifically, it highlights CRISPR screening as a route to identify actionable genes and pathways that could accelerate targeted therapy development.

Xue F, Bao L, He A et al. · Frontiers in aging neuroscience · (2026) · View on PubMed ↗ · Free PDF ↗

Imaging subtypes reveal distinct biological substrates and disability profiles in multiple sclerosis.

This study applied the unsupervised machine-learning framework Subtype and Stage Inference (SuStaIn) to multimodal 3T brain MRI data from 1,017 people with multiple sclerosis to derive biologically meaningful MRI subtypes. The key finding was that SuStaIn-identified MRI subtypes corresponded to distinct biological substrates and showed different disability profiles, including relationships with age at onset, cognitive measures, genetic susceptibility to severe disease, and relapse-independent progression. This is clinically significant because it moves beyond conventional MS phenotypes toward MRI-driven stratification that may better predict prognosis and guide personalized care.

Preziosa P, Storelli L, Clarelli F et al. · Brain : a journal of neurology · (2026) · View on PubMed ↗

Large-scale esophageal cancer screening through noncontrast computed tomography and artificial intelligence.

This Nature Medicine study developed and validated the Esophageal AI-Guided malignant Lesion Evaluation (EAGLE) model to detect precancerous lesions and esophageal cancer using noncontrast computed tomography (NC CT) from chest scans. The key finding was that EAGLE, trained on 6,813 patients from two centers and validated across 12 centers in three countries (80,612 patients total), could identify malignant lesions despite challenges from esophageal collapse and motion artifacts. This is significant because it offers a scalable, noninvasive screening approach that could improve early esophageal cancer detection where endoscopy-based screening is limited.

Zhou J, Guo G, Yao J et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial.

This Nature Medicine report analyzed prespecified secondary performance endpoints of a multi-cancer early detection (MCED) test in the randomized controlled NHS-Galleri trial. Among evaluable participants aged 50–77 years (N=142,250) randomized 1:1 to MCED plus usual care versus usual care, the authors reported descriptive (non–hypothesis-testing) performance across three annual screening rounds for intervention-arm participants with positive MCED results. The findings are significant for understanding real-world test performance characteristics that inform how MCED screening might be implemented and monitored in practice.

Neal RD, Dolly S, Johnson P et al. · Nature medicine · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Evaluating COVID-19 vaccine effectiveness across epidemiologic designs: test-negative case-control versus retrospective cohort analyses in a nationwide study.

This nationwide observational study compared two epidemiologic designs—test-negative case-control versus retrospective cohort analyses—to evaluate COVID-19 vaccine effectiveness in Qatar. Using harmonized analytic approaches across the 2021 period (1 Jan–18 Dec 2021) and focusing on BNT162b2 and mRNA-1273 primary series effectiveness against infection outcomes, it assessed how the two designs perform when applied to the same population and data sources. The results inform which study design is more reliable for real-world vaccine effectiveness estimates to guide public health policy.

Sukik L, Paul P, Ayoub HH et al. · International journal of epidemiology · (2026) · View on PubMed ↗

Large-scale organoid-derived cyst cultures as a drug discovery platform for polycystic kidney disease.

This protocol paper studied large-scale organoid-derived cyst cultures as a drug discovery platform for autosomal dominant polycystic kidney disease (ADPKD) using ureteric bud (UB) organoids derived from human induced pluripotent stem cells (hiPSCs), including wildtype and PKD2-deficient lines. The key finding was that day-12 nephron organoids can be dissociated into single cells and expanded under UB-propagating growth conditions in large-scale suspension culture to generate cyst cultures suitable for screening. This provides a scalable, genetically defined preclinical platform to accelerate identification and testing of ADPKD therapeutics.

Vanichapol T, Wangford R, Mishra S et al. · Kidney international · (2026) · View on PubMed ↗ · Free PDF ↗

Continuous versus intermittent non-invasive blood pressure monitoring and intraoperative hypotension: a systematic review and meta-analysis.

This systematic review and meta-analysis studied whether continuous versus intermittent non-invasive blood pressure monitoring affects intraoperative hypotension and perioperative outcomes. The key finding was that continuous non-invasive monitoring (e.g., beat-to-beat finger-cuff approaches) is designed to better detect short-lived hypotensive episodes between intermittent measurements, potentially reducing cumulative hypotension exposure compared with standard intermittent oscillometric monitoring. If supported by pooled results, this would have practical implications for intraoperative monitoring strategies to reduce hypotension-related morbidity.

Rinaldi P, Di Folco M, Fotticchia V · Anaesthesia, critical care & pain medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Causes of death across the life course in the Association of Southeast Asian Nations (ASEAN): a systematic analysis for the Global Burden of Disease Study 2023.

This systematic analysis used Global Burden of Disease Study 2023 data to examine causes of death across the life course in ASEAN countries, estimating life expectancy and age-specific probability of death from birth to age 70 (70q0) from 1990–2023. The key finding was that mortality drivers and associated risk factors shift across age and sex over the life course, reflecting changing epidemiology over time. This is important for designing age-appropriate, equitable health interventions tailored to evolving risk profiles across ASEAN populations.

The Lancet. Public health · (2026) · View on PubMed ↗ · Free PDF ↗

Proteome-wide Mendelian randomization and transcriptome analysis of a novel osteoarthritis blood-targeting USP8, single-cell model and experimental validation.

The study used genome-wide association meta-analysis, proteome-wide Mendelian randomization (PWMR), and summary-data-based Mendelian randomization (SMR) to identify and validate blood protein targets for osteoarthritis (OA), focusing on the blood-targeting drug target USP8. It reported a proteome-wide MR framework to prioritize causal blood proteins for OA and included a single-cell model plus experimental validation for the novel USP8 target. This work advances causal target discovery for OA and supports USP8 as a candidate therapeutic direction grounded in genetic evidence.

He Q, Liu Y, Liu X et al. · International immunopharmacology · (2026) · View on PubMed ↗ · Free PDF ↗

Soluble BCMA Defines Spatial Phenotypes and Prognosis in Newly Diagnosed Multiple Myeloma.

The article reviewed how measurable residual disease (MRD) testing can personalize allogeneic hematopoietic cell transplantation (allo-HCT) for adults with acute myeloid leukemia (AML). It highlighted MRD-driven use cases including selecting patients for transplant, tailoring conditioning intensity, post-transplant relapse surveillance, and potentially guiding maintenance or pre-emptive interventions. This provides a clinical framework for using MRD as a biomarker to improve allo-HCT outcomes through individualized risk management.

Toho M, Tabata R, Ikeda D et al. · Blood · (2026) · View on PubMed ↗

How I Treat: MRD testing to personalize allogeneic HCT for adults with AML.

The study examined soluble B-cell maturation antigen (sBCMA) as a biomarker to define spatial tumor phenotypes and prognosis in newly diagnosed multiple myeloma (MM). In 352 patients, it combined bone marrow plasma cell percentage (BMPC) from whole-slide imaging with MRI diffusion volume (TDV), PET metabolic tumor volume (TMTV), and serum sBCMA, using principal component analysis and unsupervised clustering to classify four phenotypes in which sBCMA showed the strongest and most consistent prognostic association. This supports sBCMA as a practical marker for stratifying MM tumor burden patterns and predicting outcomes at diagnosis.

Ellaithy HA, Chen YB, Hourigan CS · Blood · (2026) · View on PubMed ↗

Phase III trial of sodium dichloroacetate for pyruvate dehydrogenase complex deficiency in children.

This phase III multicenter randomized trial evaluated oral sodium dichloroacetate (DCA) versus placebo in 34 children with pyruvate dehydrogenase complex deficiency (PDCD), followed by washout and crossover, with dosing guided by pharmacogenomic analysis of GSTZ1. The key finding was that DCA treatment produced measurable improvements on the primary observer-reported motor domain outcome (ObsROmotor score) compared with placebo during the randomized phase. This is significant because it provides high-level evidence for DCA efficacy in pediatric PDCD and demonstrates a pharmacogenomic approach (GSTZ1) to optimize dosing.

Stacpoole PW, Abdenur JE, Bedoyan JK et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗

Adjuvanted RSVPreF3 vaccine impact over three respiratory syncytial virus seasons in older adults with comorbidities.

This post hoc analysis assessed the impact of one dose of AS01E-adjuvanted RSVPreF3 vaccine across three RSV seasons in older adults (≥60 years) with comorbidities enrolled in the AReSVi-006 phase 3 trial. The vaccine showed efficacy against RSV-related lower respiratory tract disease within medically stable subgroups defined by conditions such as COPD, asthma, diabetes, and obesity. These findings extend real-world relevance by characterizing how adjuvanted RSV vaccination performs in higher-risk older populations.

Papi A, Halpin DMG, Feldman RG et al. · ERJ open research · (2026) · View on PubMed ↗ · Free PDF ↗

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Cell Death & Inflammation Mechanisms (pyroptosis, necroptosis, inflammatory memory)

Lactate couples metabolic state to necroptosis across pathological and physiological conditions.

The study examined how lactate regulates necroptosis decisions across pathological and physiological settings, focusing on post-translational modification of RIPK3. Lactate directly promoted necroptosis by PCAF-mediated K63 lactylation of RIPK3, enhancing RIPK3 kinase activity and stabilizing the RIPK3–MLKL complex, with suppression observed in K63R RIPK3 or PCAF loss. This identifies a lactate–RIPK3 lactylation axis as a metabolic control point for necroptosis that may be targetable in diseases with dysregulated cell death.

Zhang N, Huang X, Lu S et al. · Cell metabolism · (2026) · View on PubMed ↗

An iron-regulated methionine redox axis governs adipose browning and cancer cachexia.

The study investigated an iron-dependent methionine redox pathway in human adipose specimens and mouse models to determine how it drives adipose browning and cancer cachexia. It found that adrenergic stimulation drives iron influx, which activates methionine sulfoxide reductase A (MSRA) via iron coordination of an EXXH motif that dimerizes/stabilizes MSRA and restores oxidized methionine residues, initiating browning in both physiological and cachectic contexts. This mechanistic iron–MSRA axis identifies a potential therapeutic target to prevent or mitigate adipose wasting and metabolic deterioration in cancer cachexia.

Nam JS, Ahn SS, Shin Y et al. · Nature cancer · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Switching of transcriptional control from interferon regulatory factor 2 to interferon regulatory factor 1 drives innate immune cell activation.

The study investigated how interferon regulatory factor 2 (IRF2) and interferon regulatory factor 1 (IRF1) control innate immune activation in skin inflammation and pyroptosis in Irf2-deficient mice. It found that skin inflammation in Irf2-deficient mice is driven by IRF1 activation of interferon-stimulated genes (ISGs), with chromatin profiling showing IRF1 and IRF2 occupy the same ISG regulatory sites but IRF2 limits ISG transcription by acting as a weaker activator, while Toll-like receptor (TLR) signaling favors IRF1-driven transcription via induction of Irf1. This clarifies a transcriptional “switch” mechanism (IRF2 to IRF1) that can reconcile IRF2’s paradoxical roles and informs strategies to modulate TLR-driven inflammatory programs.

Cadena C, Reja R, Bolech E et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular Disease & Heart Failure (including arrhythmia, cardiomyopathy, PAH)

Tenecteplase Before Thrombectomy at 4.5 to 24 Hours for Basilar Artery Occlusion: The ATTENTION LATE Randomized Clinical Trial.

The ATTENTION LATE randomized clinical trial evaluated whether intravenous tenecteplase given before endovascular thrombectomy (EVT) improves outcomes in patients with moderate-to-severe basilar artery occlusion presenting 4.5 to 24 hours after stroke onset. The trial compared tenecteplase plus EVT versus EVT alone in 330 participants across 40 stroke centers in China, assessing efficacy and safety with blinded end point evaluation. If tenecteplase improves functional outcomes without unacceptable hemorrhagic risk, it could change late-window management for basilar artery occlusion.

Li R, Yao X, Nogueira RG et al. · JAMA · (2026) · View on PubMed ↗

Programmed Ventricular Stimulation for Risk Stratification in Nonischemic Cardiomyopathy With Preserved or Mildly Reduced LVEF.

This study evaluated programmed ventricular stimulation (PVS) as an arrhythmic risk stratification tool in nonischemic cardiomyopathy (NICM) patients with cardiac magnetic resonance-confirmed myocardial scar and left ventricular ejection fraction (LVEF) ≥40%. The key finding was the performance of PVS for identifying higher-risk patients among NICM patients who do not meet current implantable cardioverter-defibrillator (ICD) criteria, using a cohort enriched for frequent PVCs (>5%) or nonsustained ventricular tachycardia. If validated, PVS could refine ICD decision-making and reduce sudden cardiac death risk in this LVEF range.

Gardziejczyk P, Sagawa Y, Afzalian A et al. · JACC. Clinical electrophysiology · (2026) · View on PubMed ↗ · Free PDF ↗

Different Substitutions at the Same β-Myosin Residue Underlie Divergent Molecular Phenotypes and Distinct Cardiomyopathies.

This study investigated how two missense mutations at the same β-myosin heavy chain (MYH7) residue produce divergent cardiomyopathies by comparing molecular effects of HCM-associated I467V versus LVNC-associated I467T using recombinant human MYH7 subfragment-1 (S1) in vitro assays. The key finding was that despite similar mechanochemical behavior in some assays (e.g., unchanged actin-activated maximal ATPase), the mutations yield distinct molecular phenotypes that can explain different disease outcomes. These results support a residue-specific but mutation-dependent mechanism for MYH7 cardiomyopathy and may guide more precise genotype-to-phenotype interpretation.

Lehman SJ, Meller A, Solieva SO et al. · The Journal of biological chemistry · (2026) · View on PubMed ↗ · Free PDF ↗

Specific treatment of ATTR-CM in Germany-expert consensus of the German Society of Amyloid Diseases (DGAK) and German Cardiac Society (DGK).

This expert consensus article reviewed and synthesized evidence for specific disease-modifying treatment choices in transthyretin amyloid cardiomyopathy (ATTR-CM) for patients in Germany, focusing on the approved agents tafamidis and acoramidis (TTR stabilizers) and vutrisiran (TTR gene silencer). It provided practical guidance for individual treatment decisions in the absence of head-to-head randomized trials by integrating pivotal trial data, extension studies, and real-world evidence. The consensus is clinically significant because it standardizes how clinicians select among TTR-targeted therapies to manage ATTR-CM progression and outcomes.

Aus dem Siepen F, Trenkwalder T, Aßmus B et al. · Clinical research in cardiology : official journal of the German Cardiac Society · (2026) · View on PubMed ↗ · Free PDF ↗

Early versus delayed or no empagliflozin initiation after hospitalisation for heart failure in the United States: A target trial emulation.

This target trial emulation used Optum de-identified Clinformatics Data Mart data to compare early versus delayed or no initiation of empagliflozin after hospitalization for heart failure (HHF) in U.S. adults. The key finding was that initiating empagliflozin during HHF or within 0–7 days post-discharge was associated with better outcomes than initiation delayed to 8–91 days or not initiated. Clinically, it supports earlier empagliflozin start after HHF to improve real-world post-discharge prognosis.

Greene SJ, Tskhvarashvili G, Tran P et al. · ESC heart failure · (2026) · View on PubMed ↗ · Free PDF ↗

Mechanistic diversity within RLC-dependent myosin ATPase inhibitors differentiates EDG-7500, a diastolic-selective cardiac sarcomere modulator.

This mechanistic preclinical study characterized EDG-7500, a diastolic-selective cardiac sarcomere modulator, by examining how diverse RLC-dependent myosin ATPase inhibition profiles affect relaxation and contraction in engineered human tissue, human hypertrophic cardiomyopathy (HCM) cardiac strips, and an R403Q mutation swine model. The key finding was that EDG-7500 preferentially inhibited myofibril ATPase activity and force at diastolic calcium levels, preserved length-dependent activation, accelerated relaxation, and showed a shallow, self-limiting inhibitory-exposure response. This is significant because it supports EDG-7500’s mechanism as a diastolic-targeted therapy for HCM with potentially favorable functional selectivity.

Emter CA, Henze M, DuVall M et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗

Sotatercept Improves Right Heart Mechanics Despite Reduced Myocardial Contractility in Pulmonary Arterial Hypertension: A Prospective Exercise Hemodynamic Study.

This prospective exercise hemodynamic study assessed sotatercept’s effects on right heart mechanics in patients with pulmonary arterial hypertension (PAH) by combining echocardiography with invasive pressure measurements at rest and during exercise. The key finding was that sotatercept improved right ventricular (RV) mechanics and RV-PA coupling/load-independent contractility measures despite reduced myocardial contractility, indicating beneficial changes in RV performance during exertion. Clinically, this helps reconcile prior inconsistent RV findings and supports sotatercept’s mechanistic benefit in PAH.

Reddy YNV, Kazui S, Miranda WR et al. · Circulation · (2026) · View on PubMed ↗

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Metabolic Disease & Obesity/Diabetes (GLP-1, tirzepatide, SGLT2, UPF)

AGA Clinical Practice Update on the Evaluation and Management of Metabolic Dysfunction- and Alcohol-Associated Liver Disease: Expert Review.

This AGA Clinical Practice Update reviewed evidence and provided best-practice recommendations for evaluating and managing metabolic dysfunction- and alcohol-associated liver disease (MetALD), a steatotic liver disease (SLD) category defined by the 2023 multisociety nomenclature. The key contribution is an expert synthesis focused on diagnosis, staging, and treatment strategies for MetALD rather than reporting new experimental results. Clinically, it aims to standardize care for patients with MetALD and improve consistency in how this increasingly recognized SLD phenotype is managed.

Arab JP, Malhi H, Winder GS et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · (2026) · View on PubMed ↗

Ultra-processed food consumption and risk of multiple chronic diseases among 8,819,894 adults from 51 prospective cohorts: a dose-response meta-analysis.

This dose-response meta-analysis studied associations between ultra-processed food (UPF) intake and multiple chronic disease outcomes in 8,819,894 adults across 51 prospective cohorts. It found that higher UPF consumption was associated with increased risk of cardiovascular events and other chronic diseases (with effect estimates synthesized across cohorts using dietary assessment methods such as FFQs and 24-hour recalls). The large prospective evidence base supports UPF reduction as a potentially actionable public health strategy to lower chronic disease burden.

Liu X, Luo S, Zeng Y et al. · Family medicine and community health · (2026) · View on PubMed ↗

Prevalence of liver fibrosis and steatotic liver disease in community-dwelling adults in China (the CHESS-LiverHealth project): cross-sectional baseline data from a prospective cohort study.

This cross-sectional baseline analysis from the CHESS-LiverHealth prospective cohort studied the prevalence of liver fibrosis and steatotic liver disease in community-dwelling adults across China and identified associated factors. The key finding was the quantification of population-level burden of fibrosis and steatotic liver disease and the characterization of risk associations in a large, community-based Chinese sample. These findings are significant for public health planning and for targeting prevention and screening efforts for chronic liver disease in China.

Liu S, Liu X, Song J et al. · The lancet. Gastroenterology & hepatology · (2026) · View on PubMed ↗

A liver-cartilage selenium axis underlies metabolic comorbidity in osteoarthritis.

This study investigated a liver–cartilage selenium axis in osteoarthritis (OA), combining nationwide human cohorts with mouse models of acute/chronic liver injury and metabolic dysfunction-associated steatohepatitis (MASH). The key finding was that hepatic dysfunction disrupts the SELENOP–ApoER2 axis, impairing selenium delivery to cartilage and thereby promoting OA, with mechanistic evidence that hepatic stress reduces hepatocyte SELENOP output. These results identify a liver-driven micronutrient pathway as a mechanistic link to OA comorbidity and suggest selenium/SELENOP–ApoER2 pathway modulation as a potential therapeutic direction.

Yong S, Jo H, Yook G et al. · Cell metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Vitamins and Chronic Wounds: How Altered Pharmacokinetics and Comorbidities Contribute to Vitamin Deficiencies.

This review summarized evidence on how altered pharmacokinetics, comorbidities, and wound-related physiology contribute to vitamin deficiencies in patients with chronic wounds. It focused on why vitamin supplementation trials have produced inconsistent outcomes, arguing that suboptimal study designs and dosing may fail to account for changes in vitamin kinetics during wound repair. The review is significant because it frames how future supplementation studies should determine appropriate vitamin dosing and timing based on chronic-wound-specific pharmacokinetic requirements.

Balvers MGJ, de Smit TL, Slotegraaf AI et al. · Basic & clinical pharmacology & toxicology · (2026) · View on PubMed ↗ · Free PDF ↗

Long-Term Clinical Outcomes and Real-World Effectiveness of Tirzepatide in Adults With Overweight or Obesity: A Systematic Review.

This systematic review evaluated long-term clinical outcomes and real-world effectiveness of tirzepatide in adults with overweight or obesity. Across included real-world studies and longer follow-up reports, tirzepatide was associated with sustained weight loss and clinically meaningful improvements in obesity-related outcomes over extended periods. The synthesis supports tirzepatide’s effectiveness beyond trial settings and informs expectations for long-term management of obesity.

Olaniyi AO, Gogineni KK, Olaniyi H et al. · Cureus · (2026) · View on PubMed ↗ · Free PDF ↗

Trends in GLP-1 Receptor Agonist Prescribing Without an Apparent FDA-Approved Indication.

This retrospective cohort study examined temporal trends and patient characteristics of GLP-1 receptor agonist prescribing among US adults without an apparent FDA-approved indication using Cosmos electronic health records (01/2021–12/2025). The key finding was not fully available in the provided abstract text because the results were truncated before reporting the magnitude of off-label prescribing trends and associated patient profiles. Scientifically and clinically, quantifying off-label use of liraglutide, semaglutide, and tirzepatide can inform safety monitoring and policy around indication-appropriate prescribing.

Orandi BJ, Yan L, Levan ML et al. · Obesity (Silver Spring, Md.) · (2026) · View on PubMed ↗

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Oncology Therapeutics & Drug Safety/Attribution (toxicity, PK/PD, monitoring)

Model-based clinical pharmacology profiling of subcutaneous nivolumab in renal cell carcinoma: Bridging to alternative dosing regimens and indications.

This paper used model-informed drug development (MIDD) and population pharmacokinetic (popPK) modeling to profile subcutaneous (SC) nivolumab in renal cell carcinoma and bridge dosing regimens and indications. The key finding was that the derived exposure metrics supported pharmacokinetic noninferiority of nivolumab 1200 mg SC every 4 weeks (Q4W) versus nivolumab 3 mg/kg intravenous (IV) every 2 weeks (Q2W), using coprimary endpoints including time-averaged concentration over 28 days (Cavgd28) and minimum steady-state concentration (Cminss) from the phase III CheckMate 67T study. This supports SC nivolumab as a dosing alternative with comparable systemic exposure for RCC treatment strategies.

Zhao Y, Hu Z, Gibson E et al. · Clinical pharmacology and therapeutics · (2026) · View on PubMed ↗ · Free PDF ↗

Microfluidics-mediated spatial control of mRNA lipid nanoparticles primes translation and enhances vaccine potency.

The study developed a microfluidics-based platform (MIMAC) to spatially control mRNA lipid nanoparticle (LNP) architecture in order to prime translation and enhance vaccine potency. It found that shear-mediated reorganization inserts a metabolic-enhancing RNA into a peripheral compartment and relocates the therapeutic mRNA to the core, enabling early cytosolic release of the metabolic RNA to boost ATP (up to 4.2-fold) and thereby increase subsequent therapeutic translation. This provides a design principle for next-generation mRNA-LNP vaccines that improves intracellular expression by controlling encapsulation/release kinetics.

Zheng Z, Jiang Y, Gong Y et al. · Nature biomedical engineering · (2026) · View on PubMed ↗

DNL343 and Disease Progression in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

This randomized clinical trial studied the safety and efficacy of DNL343, a brain-penetrant eIF2B activator designed to inhibit the integrated stress response, in individuals with amyotrophic lateral sclerosis (ALS) within the HEALEY ALS Platform Trial. The trial evaluated a 200-mg once-daily formulation and used integrated stress response biomarkers for target engagement, building on prior phase 1B evidence of CNS penetrance and favorable safety. If efficacy signals are supported, DNL343 would represent a mechanism-based therapeutic approach targeting the eIF2α–eIF2B integrated stress response pathway in ALS.

Paganoni S, Chibnik LB, Quintana M et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Selinexor plus lenalidomide versus lenalidomide alone as maintenance therapy after autologous haematopoietic stem cell transplantation in newly diagnosed multiple myeloma: Results of the phase 3 ALLG MM23 (SeaLAND) trial.

This phase 3 randomized open-label trial compared low-dose weekly selinexor (40 mg) plus lenalidomide versus lenalidomide alone as maintenance therapy after autologous hematopoietic stem cell transplantation in newly diagnosed, transplant-eligible multiple myeloma patients. The study found that complete response rates were numerically higher with selinexor-R than with lenalidomide alone (67% vs 53%) but not significantly, and progression-free survival was not significantly different at 24 months median follow-up (HR 1.22). These results indicate that adding selinexor to lenalidomide maintenance did not demonstrate clear efficacy benefit despite target engagement rationale, informing future maintenance strategy development in multiple myeloma.

Rees MJ, Lasica M, Kalff A et al. · British journal of haematology · (2026) · View on PubMed ↗

Oral Toxicities Secondary to TROP2 and HER2-directed Antibody Drug Conjugates. A Multicenter Retrospective Cohort Study.

This multicenter retrospective cohort study characterized oral toxicities associated with TROP2- and HER2-directed antibody-drug conjugates in advanced-stage cancer patients. It reviewed 207 patients treated with datopotamab deruxtecan and sacituzumab govitecan (TROP2) and trastuzumab deruxtecan (HER2), but the specific incidence/timing/severity findings were truncated in the abstract. Clinically, defining the oral toxicity phenotype and management for these ADCs can improve supportive care and treatment continuity.

Fantozzi PJ, Sonis S, Botticelli A et al. · The oncologist · (2026) · View on PubMed ↗ · Free PDF ↗

Toxicity Attribution During Enfortumab Vedotin Plus Pembrolizumab Therapy in Urothelial Carcinoma: A Practical Framework.

This practical framework article synthesized evidence on toxicity attribution during enfortumab vedotin plus pembrolizumab therapy in advanced urothelial carcinoma. It focused on distinguishing adverse events attributable to the antibody-drug conjugate (enfortumab vedotin) versus immune-mediated toxicities from pembrolizumab, including scenarios where both may contribute. This helps clinicians manage EV/P treatment safely by guiding mechanism-informed monitoring and intervention.

Zarka J, Childs DS, Muniz Rincon M et al. · The oncologist · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration & Dementia (including AD/PD/MSA/α-synuclein)

Differential Remodeling of the Macular Neovascular Network under Different Anti-VEGF Agents in Age-Related Macular Degeneration.

This multicenter retrospective observational cohort study compared how different anti-VEGF agents remodel the macular neovascular (MNV) network in neovascular age-related macular degeneration (nAMD) using OCT B-scan and OCT angiography (OCTA) at baseline and 1 year. The key finding was differential changes in OCTA/OCT-derived MNV network characteristics among eyes treated with ranibizumab 0.5 mg Q4W, aflibercept 2.0 mg Q4W, aflibercept 8.0 mg Q12W, or faricimab 6.0 mg Q8W in a treat-and-extend regimen. Clinically, these imaging-based differences may help tailor anti-VEGF selection and dosing intervals to optimize vascular remodeling outcomes.

Crincoli E, Borrelli E, Savastano MC et al. · Ophthalmology science · (2026) · View on PubMed ↗ · Free PDF ↗

Blood proteomics of menopause map to brain aging and dementia risk.

This Nature Medicine study used blood proteomics (NULISAseq) from 80 rigorously staged (STRAW+10) pre-, peri-, and postmenopausal women (ages 43–58) to map menopause-associated protein changes to brain aging and dementia risk. The key finding was that spontaneous menopause was characterized by dysregulation of inflammatory, synaptic, metabolic, and Alzheimer’s disease–related biological processes that tracked more strongly with hormone status than with chronological age. This is clinically significant because it links menopausal biology to measurable systemic proteomic signatures relevant to later neurodegenerative risk.

Wood Alexander M, Rabin JS, Caunca M et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Lipophagy and lipid droplets in neurodegeneration.

This review studied lipid droplet biology in neurodegeneration, focusing on lipophagy as a selective autophagic pathway for lipid droplet clearance in Alzheimer’s disease, Parkinson’s disease, and ALS. It concluded that lipid droplet accumulation in neurons and glia is linked to oxidative stress and neuroinflammation, and that emerging work is mapping noncanonical regulators of lipophagy beyond the classic nutrient-deprivation context studied in hepatocytes. Scientifically, it frames lipophagy/lipid droplet clearance as a promising mechanistic axis for developing therapies that complement protein-targeted approaches.

McKee NW, Jing Y, Serdah R et al. · Trends in pharmacological sciences · (2026) · View on PubMed ↗ · Free PDF ↗

Anterior zona incerta to ventral tegmental area circuit controls compulsive eating in a binge-eating-disorder mouse model.

The study examined tyrosine hydroxylase (TH)-BAC-Cre–labeled GABAergic neurons in the anterior zona incerta (aZIT) and their projections to the ventral tegmental area (VTA) in a mouse model of binge-eating disorder (BED). Intermittent high-fat-diet training increased aZIT neuronal excitability and this was required for the development of compulsive binge intake, with aZIT→VTA signaling promoting aversion-resistant food seeking and consumption. These findings identify an aZIT–VTA circuit as a mechanistic driver of compulsive eating and suggest a neurocircuit target for BED interventions.

Chen Z, Wang M, Xue J et al. · Neuron · (2026) · View on PubMed ↗ · Free PDF ↗

Probiotics as Functional Dietary Interventions for Gut Health, Immune Modulation, and Overall Well-Being: A Systematic Review.

This systematic review evaluated strain-specific probiotic interventions in children (search 2006–2024; PRISMA 2020) with outcomes spanning gut health, immune modulation, and overall well-being, focusing on specific strains such as Lactobacillus rhamnosus GG and Saccharomyces boulardii. The review found strong evidence supporting Lactobacillus rhamnosus GG and Saccharomyces boulardii for acute diarrhea, while strain-specific efficacy across other pediatric conditions remained inconsistent. These findings support more targeted probiotic selection in pediatric care rather than “one-strain-fits-all” use, while highlighting the need for better mechanistic and clinical evidence by strain.

Mishra S, Saxena S · Clinical pediatrics · (2026) · View on PubMed ↗

ApoE4 as a Therapeutic Target in Epilepsy: From Pathogenic Mechanisms to Precision Medicine.

This narrative review examined apolipoprotein E4 (ApoE4) as a therapeutic target in epilepsy by synthesizing evidence on molecular mechanisms, clinical implications, and precision-medicine strategies. The review concluded that ApoE4 can modify epilepsy susceptibility, progression, and treatment response through multiple pathways, making it a plausible biomarker/target for stratified therapy. Scientifically, it frames ApoE4-driven biology as a route toward more individualized epilepsy treatments.

Pan K, Zhu K, E Y et al. · CNS neuroscience & therapeutics · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochonic acid 5 alleviates amyotrophic lateral sclerosis phenotypes via mitochondrial augmentation.

This study tested mitochonic acid 5 (MA-5), a mitochondria-targeted compound, for therapeutic effects in amyotrophic lateral sclerosis (ALS) using a Drosophila ALS model expressing mutant human SOD1 (G85R) and human cellular systems including ALS patient skin fibroblasts and induced pluripotent stem cell–derived motor neurons. The key finding was that MA-5 ameliorated ALS phenotypes by enhancing mitochondrial function, including restoration of ATP-related measures and improved locomotor performance in the SOD1(G85R) model. Scientifically and clinically, it positions MA-5 as a mitochondria-augmenting candidate therapy for ALS.

Oikawa Y, Luo Y, Suzuki N et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗

Dementia progression with GLP-1 receptor agonists in people with mild cognitive impairment and type 2 diabetes: target-trial emulation study.

This target-trial emulation study used TriNetX data to evaluate whether GLP-1 receptor agonists affect dementia progression in people with type 2 diabetes (T2D) and mild cognitive impairment (MCI). The key finding was not fully available in the provided abstract text, which was truncated before results were reported. If GLP-1 RAs reduce progression from MCI to dementia specifically in T2D, it would support a diabetes-stratified prevention strategy for Alzheimer’s disease risk.

Schechter M, Sehtman-Shachar DR, Fishkin A et al. · Alzheimer’s & dementia (New York, N. Y.) · (2026) · View on PubMed ↗ · Free PDF ↗

The Alzheimer’s disease risk gene SORL1 is a regulator of excitatory neuronal function.

This study investigated how the Alzheimer’s disease risk gene SORL1 regulates excitatory neuronal function in human excitatory cortical neurons. Using mesoscale proteomics to map synaptic protein interactions and immunocytochemistry for AMPA receptor subunits, it found that SORL1 influences synaptic protein composition and neuronal activity. These mechanistic results strengthen SORL1’s causal role in early synaptic dysfunction relevant to Alzheimer’s disease.

Williams CA, Rose SE, Stamenkovic V et al. · Alzheimer’s & dementia : the journal of the Alzheimer’s Association · (2026) · View on PubMed ↗ · Free PDF ↗

Urine-Derived Neuronal Extracellular Vesicle α-Synuclein Seed Amplification Assay for Synucleinopathies: A Non-Invasive Biomarker Study.

This non-invasive biomarker study evaluated whether urine-derived neuronal extracellular vesicles (NEVs) can detect pathogenic α-synuclein seeds using an RT-QuIC seed amplification assay in synucleinopathies. It tested samples from patients with Parkinson’s disease (PD) and multiple system atrophy (MSA) and used L1CAM-conjugated magnetic beads for NEV enrichment, but the diagnostic performance results were truncated in the provided text. If validated, this approach could enable repeated, large-scale α-synuclein seeding detection without cerebrospinal fluid collection.

Tran HBT, Nguyen HD, Nguyen TT et al. · Movement disorders : official journal of the Movement Disorder Society · (2026) · View on PubMed ↗

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Musculoskeletal Health, Exercise & Rehabilitation (TKA, sarcopenia, musculoskeletal aging)

Exploring the Impact of Urolithins A and B on Muscle Health: A Transcriptomic Analysis in Human Myotubes.

This study used RNA sequencing to compare the transcriptomic effects of the gut microbiota metabolites urolithin A (UA) and urolithin B (UB) in primary human CD56+ satellite cell–derived myotubes from 9 older adult donors (age 55–96). UA and UB produced distinct, drug-specific changes in gene expression related to mitochondrial function, inflammation, and muscle metabolism after 24-hour exposure to 5 μM. These findings support UA/UB as mechanistically active candidates for modulating muscle health and provide molecular targets for future interventions in sarcopenia or age-related muscle decline.

Henrotin Y, Florin A, Sanchez C et al. · Journal of cachexia, sarcopenia and muscle · (2026) · View on PubMed ↗ · Free PDF ↗

A High-Fat, High-Protein, Carbohydrate-Restricted Dietary Interventions in Pompe Disease: A Case Series with Long-Term Follow-Up.

This case series studied high-fat, high-protein, carbohydrate-restricted dietary interventions as an adjunct to enzyme replacement therapy (ERT) in patients with Pompe disease (PD). The long-term follow-up reported clinical utility of the diet, with detailed outcomes including treatment duration, caloric intake, and macronutrient distribution used to characterize the intervention. These findings support further investigation of carbohydrate restriction as a potential adjunct strategy to address persistent skeletal muscle pathology in PD patients receiving ERT.

Teke Kisa P, Dogan BB, Zubarioglu T et al. · Annals of nutrition & metabolism · (2026) · View on PubMed ↗

The Role of Eccentric Contraction Training in the Postoperative Rehabilitation of Patients With Total Knee Arthroplasty.

This randomized controlled trial studied whether adding eccentric contraction training to standard rehabilitation improves early postoperative outcomes after primary total knee arthroplasty (TKA) in 44 patients, comparing an eccentric-concentric (ECC-CON) group versus a concentric-only (CON) group. The key finding was that the ECC-CON program produced superior early functional recovery outcomes (including pain and range-of-motion and patient-reported measures) compared with concentric-only rehabilitation. Clinically, this supports incorporating supervised eccentric quadriceps training into early post-TKA rehab protocols to enhance recovery.

Fan Z, Zhang Y, Du X et al. · Physiotherapy research international : the journal for researchers and clinicians in physical therapy · (2026) · View on PubMed ↗

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Reproductive Health & Fertility (PCOS/PMOS, endometriosis, vaccines in older adults)

Prenatal exposure to paracetamol and the risk of autism and attention-deficit/hyperactivity disorder: An umbrella review and meta-meta-analysis.

This umbrella review and meta-meta-analysis evaluated whether prenatal exposure to paracetamol (acetaminophen) is associated with autism and/or attention-deficit/hyperactivity disorder (ADHD) in offspring by synthesizing systematic reviews and meta-analyses. Across included evidence up to November 2025, the authors assessed pooled associations while accounting for methodological quality (AMSTAR-2) and overlap of primary studies. The results are clinically important because they inform risk-benefit considerations for prenatal paracetamol use and highlight where stronger causal evidence is needed.

Tayebi-Hillali H, Blanco-Suárez M, Rivas-Mundiña B et al. · Developmental medicine and child neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Evaluating the impact of cannabinoid extracts on chronic pain and quality of life in endometriosis patients - a pilot study.

The study evaluated standardized oral cannabinoid-based medicinal products (CBMPs) in a prospective single-center pilot cohort of women with endometriosis and chronic pelvic pain (n=30 enrolled, 27 completing 3 months). It assessed changes in pain and quality of life after 3-month CBMP treatment, aiming to determine whether cannabinoid extracts improve chronic pain outcomes in this population. If confirmed in larger trials, these data would support cannabinoids as symptom-relieving options for endometriosis-associated pain and quality-of-life impairment.

Kratz JW, Velho RV, Bock S et al. · PloS one · (2026) · View on PubMed ↗ · Free PDF ↗

Evaluating the Therapeutic Potential of Antioxidants in Polyendocrine Metabolic Ovarian Syndrome (PMOS)-Associated Infertility.

This structured narrative review evaluated clinical evidence for antioxidant adjunct therapy to improve PMOS (polyendocrine metabolic ovarian syndrome/PCOS)-associated infertility in women of reproductive age. Across included studies, antioxidants were reported to modulate the ovarian microenvironment and support folliculogenesis and oocyte competence, potentially improving fertility outcomes. The review highlights antioxidant supplementation as a plausible adjunct in PMOS-related infertility while emphasizing the need for more rigorous, standardized trials.

Mahapatra PD, Bhat VV, Vyas NA et al. · International journal of women’s health · (2026) · View on PubMed ↗ · Free PDF ↗

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Microbiome, Probiotics & Diet–Microbiome Axes

Effects of anti-aging diets and exercise on age-related musculoskeletal diseases via gut microbiota modulation.

This narrative review summarized evidence on how anti-aging dietary strategies (e.g., caloric restriction variants such as ketogenic diet, fasting-mimicking diet, intermittent fasting, and time-restricted feeding) combined with exercise influence age-related musculoskeletal diseases through gut microbiota modulation. The key finding is that diet–exercise synergy can reshape gut–joint, gut–bone, and gut–muscle axes, linking microbial changes to downstream tissue outcomes relevant to musculoskeletal aging. This synthesis is significant for guiding mechanistically informed prevention strategies targeting microbiome-mediated pathways in older adults.

Yu M, Guo P, Liu Q et al. · Annals of medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Biologic outcomes in severe asthma patients by smoking status: evidence from SHARP.

This retrospective real-world analysis used the ERS SHARP registry (OMOP Common Data Model) to evaluate biologic treatment outcomes in 3,876 adults with severe asthma stratified by smoking status across 16 European countries. The study found that biologic response and/or observed clinical outcomes varied by smoking exposure category (never-smokers, ex-smokers with <10 pack-years, and ≥10 pack-years). These findings are significant for tailoring biologic selection and management strategies in severe asthma patients with different smoking histories.

Caminati M, Charriot J, Bansal AT et al. · American journal of respiratory and critical care medicine · (2026) · View on PubMed ↗ · Free PDF ↗

The Gut Microbiota-Muscle Axis: Lactobacillus as a Potential Modulator of Skeletal Muscle Health.

This narrative review assessed evidence for the gut microbiota–muscle axis, focusing on Lactobacillus species as potential modulators of skeletal muscle health in humans and relevant experimental contexts. It concludes that Lactobacillus-derived effects on host metabolism and protein turnover may help counter muscle deterioration such as sarcopenia and atrophy, particularly in metabolic disease settings. The synthesis supports Lactobacillus-based probiotic strategies as candidate adjuncts for preserving skeletal muscle function, though clinical evidence remains heterogeneous.

Janet B, Jena R, Rao BSS et al. · BioMed research international · (2026) · View on PubMed ↗ · Free PDF ↗

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Respiratory Disease (ARDS, COPD, optic neuropathy NAION, lung inflammation)

Updates in COPD Management: From Inflammatory Pathways to Targeted Therapies.

This narrative review synthesized advances in COPD management, focusing on how understanding inflammatory pathways has enabled phenotype-directed and targeted therapies. The key finding is that modern COPD care increasingly integrates biomarkers and emerging targeted treatments to address heterogeneity driven by neutrophilic and eosinophilic inflammation, structural changes, and airflow limitation. This review is significant because it frames how clinicians can translate mechanistic and biomarker evidence into more precise COPD treatment selection.

Raman S, Rahman S, Polverino F et al. · European journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

Sphingolipid metabolism contributes to sex dimorphism in COPD pathogenesis.

This study examined whether sphingolipid metabolism differs by sex and contributes to chronic obstructive pulmonary disease (COPD) pathogenesis using lung tissue and paired plasma from never-smoking and ever-smoking controls and COPD subjects, plus mouse bronchial smooth muscle and human bronchial smooth muscle cell experiments. It found sex-dependent regulation of sphingolipid enzyme expression and metabolite levels in COPD, and that estradiol and cigarette smoke extract (CSE) modulate sphingolipid pathways relevant to airway epithelial integrity, inflammation, and bronchial smooth muscle tone. These results suggest that targeting sex-specific sphingolipid metabolic programs could improve mechanistic understanding and potentially stratify COPD therapies.

Granato E, Wang X, Zhang Y et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗

Inhaled granulocyte-macrophage colony-stimulating factor (molgramostim) as host-directed therapy for pneumonia-related acute respiratory distress syndrome: a multicentre, randomised, placebo-controlled phase 2a trial (GI-HOPE).

This multicentre, randomized, placebo-controlled phase 2a trial tested nebulised recombinant human GM-CSF (molgramostim) as host-directed therapy in pneumonia-related ARDS. Patients receiving molgramostim (150 μg or 450 μg) underwent bronchoalveolar lavage before and after dosing, and the study evaluated safety/feasibility and efficacy endpoints over 3 days of treatment. The trial informs whether inhaled GM-CSF can improve pulmonary host defense and alveolar barrier recovery in pneumonia-associated ARDS.

Herold S, Welte T, Zacharowski K et al. · ERJ open research · (2026) · View on PubMed ↗ · Free PDF ↗

Lipid droplet-mitochondria contact sites as druggable spatial-pharmacology targets in respiratory disease: cross-cell-type mechanisms and translational strategies.

This 2026 review studied lipid droplet–mitochondria contact sites as druggable spatial-pharmacology targets across liver, muscle, adipose, and respiratory disease contexts. It concluded that the lipid droplet–mitochondria contact site is an emerging, tractable target in respiratory medicine, organizing evidence for translational strategies (with graded emphasis on direct versus indirect mechanisms). Clinically, this framework could guide development of therapies that modulate organelle contact-site biology to treat lung disorders driven by lipid handling and remodeling.

Li S, Bai R · Frontiers in cell and developmental biology · (2026) · View on PubMed ↗ · Free PDF ↗

Comparative Risk of Nonarteritic Anterior Ischemic Optic Neuropathy Among Glucagon-Like Peptide-1 Receptor Agonists: An Integrated Safety and Mechanistic Analysis.

This integrated safety and mechanistic analysis compared the risk of nonarteritic anterior ischemic optic neuropathy (NAION) across GLP-1 receptor agonists and explored underlying mechanisms. It used a network meta-analysis for comparative risk and validated findings with real-world pharmacovigilance from the FDA Adverse Event Reporting System (FAERS), but the specific comparative results were not included in the truncated abstract. Determining agent-specific NAION risk could improve prescribing decisions and mechanistic understanding of this rare but serious adverse event.

Sun H, Xin X, Yan J et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗

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Autoimmune/Inflammatory Diseases (Crohn’s, atopic dermatitis, uveitis, allergy)

Revisiting the role of lymphatics in Crohn’s disease.

This narrative review studied the evidence linking intestinal lymphatic dysfunction to Crohn’s disease (CD) pathogenesis and evaluated therapeutic implications. It concluded that lymphatic obstruction, lymphangitis, and lymphangiectasia are early and widespread features of CD, with structural remodeling occurring alongside compensatory lymphatic changes. The review highlights lymphatic pathways as underappreciated contributors and potential targets for future CD therapies.

Le Berre C, Rezazadeh Ardabili A, Czepielewski R et al. · Inflammatory bowel diseases · (2026) · View on PubMed ↗

Immunosenescence in Uveitis: From Mechanistic Insights to Therapeutic Implications.

This review examined how immunosenescence—age-associated immune remodeling—contributes to chronicity, refractoriness, and treatment heterogeneity in uveitis, integrating mechanistic pathways linked to immune aging. The key finding was that features such as thymic involution, reduced naïve T cells, accumulation of memory/terminally differentiated T cells, and inflammaging can drive persistent ocular inflammation and influence therapeutic response variability. Scientifically and clinically, framing uveitis through immunosenescence highlights potential age-tailored immunomodulatory targets and stratification approaches.

Wu Y, Zou Y, Yang M et al. · Ageing research reviews · (2026) · View on PubMed ↗ · Free PDF ↗

Sensory neuronal mTORC1 kinase signaling establishes neuroimmune memory that initiates allergic immunity.

The study examined how cutaneous sensory neurons use intrinsic mTORC1 signaling to form neuroimmune memory that initiates allergic immunity after protease allergen exposure. Protease allergen exposure induced sustained mTORC1 kinase signaling and PGC-1α–associated transcriptional programs in sensory neurons, supporting cumulative sensitization rather than only acute responses. This provides a neuron-intrinsic mechanism linking repeated allergen encounters to Th2-skewing immune initiation, highlighting mTORC1/PGC-1α as potential targets for preventing allergic sensitization.

Zhu X, Yang H, Zhan H et al. · Immunity · (2026) · View on PubMed ↗ · Free PDF ↗

Development of a Conceptual Disease Model of Atopic Dermatitis Using Data from the Phase 3 ARCADIA 1 Trial.

This study developed a conceptual disease model (CDM) of atopic dermatitis (AD) using baseline data from the phase 3 ARCADIA 1 trial of nemolizumab in adults with moderate-to-severe AD. Using validated clinical outcome assessments and structural equation modeling, it defined latent constructs for skin severity, itch severity, sleep disturbance, and quality of life/health status to create a clinically credible, data-driven framework. The resulting model is scientifically significant because it can support interpretation of treatment effects and guide future trial design and endpoint selection in AD.

Silverberg JI, Daniele P, Rodriguez D et al. · Dermatology and therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Adrenal insufficiency in individuals with Duchenne muscular dystrophy treated with glucocorticoids: Insights from the past, current challenges, and future directions.

This review analyzed adrenal insufficiency risk in individuals with Duchenne muscular dystrophy (DMD) treated with long-term high-dose glucocorticoids, integrating evidence from past experience, current challenges, and future directions. The key finding was that glucocorticoid-induced adrenal suppression is a common and potentially life-threatening complication in DMD patients on chronic steroids, requiring proactive monitoring and management. This is clinically significant because it emphasizes prevention and early detection strategies to reduce morbidity and mortality from iatrogenic adrenal insufficiency.

Weber DR, Ahmet A, Kinnett K et al. · Journal of neuromuscular diseases · (2026) · View on PubMed ↗ · Free PDF ↗

Upadacitinib treatment in pediatric Crohn’s disease: 52-week outcomes of an international multicenter retrospective cohort study from the pediatric IBD Porto Group of ESPGHAN.

This retrospective multicenter cohort study evaluated 52-week effectiveness and safety of upadacitinib maintenance therapy in pediatric Crohn’s disease patients from the Porto Group of ESPGHAN (35 centers). The key finding was not fully available in the provided abstract text because the results section was truncated before reporting outcomes and adverse events. If confirmed, these data would inform dosing and risk–benefit decisions for upadacitinib maintenance in children with Crohn’s disease.

Spencer EA, Cohen S, Dubinsky MC et al. · Journal of Crohn’s & colitis · (2026) · View on PubMed ↗

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Organellar/Autophagy/Lysosome & Cellular Homeostasis

Restoration of aged liver regeneration by youthful systemic factors via LTβ-driven hepatocyte reprogramming.

This study investigated systemic youthful factors and the cellular mediator LTβ in restoring regenerative capacity of aged liver, using a split liver transplantation (SLT) cohort in humans and heterochronic parabiosis in young (2-month) versus aged (18-month) mice. The key finding was that youthful systemic signals promote hepatocyte reprogramming in aged livers through an LTβ-driven mechanism, improving regeneration after age-associated decline. These results suggest LTβ-mediated hepatocyte reprogramming as a potential therapeutic strategy to enhance liver regeneration and expand surgical options for elderly patients.

Chenhao J, Lu H, Yasong L et al. · Journal of hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Dishevelled drives disassembly of primary cilia through an unusual PDZ domain-mediated binding mode with Girdin-L.

The study investigated how the Wnt pathway scaffold protein Dishevelled (DVL2) uses its PDZ domain to bind Girdin-L and drive disassembly of primary cilia, focusing on a PDZ domain–mediated binding mode. Using proximity labeling along with structural and biophysical analyses, it identified DVL2 PDZ-binding partners and characterized functional relevance for β-catenin-independent Wnt responses, including effects on primary cilia. This mechanistic work links Dishevelled PDZ interactions to ciliary remodeling, informing how noncanonical Wnt signaling controls cell fate and polarity.

Renko M, Beitia GJ, Rutherford TJ et al. · Science signaling · (2026) · View on PubMed ↗

Novel mTORC1 Booster LAPTM4A Potentiates Pathological Cardiac Hypertrophy.

This study investigated how the lysosomal transmembrane protein LAPTM4A regulates mTORC1-dependent protein homeostasis in rat cardiomyocytes and mouse models of pathological cardiac hypertrophy. LAPTM4A acted as an mTORC1 booster, potentiating pathological hypertrophy by promoting maladaptive lysosome–mTORC1 signaling and cardiomyocyte protein accumulation. These findings identify LAPTM4A–mTORC1 as a mechanistic target for therapeutic strategies aimed at limiting pathological cardiac hypertrophy.

Hu Y, Li W, Hu M et al. · Circulation · (2026) · View on PubMed ↗

Asb2-KIF11 Axis Protects Against Heart Failure by Restoring Lysosomal Distribution and Mitochondrial Homeostasis.

This study evaluated the role of the Asb2–KIF11 axis in adult heart failure using inducible mouse models and mechanistic analyses of lysosomal positioning and mitochondrial homeostasis. Asb2 protected against heart failure by restoring lysosomal distribution and improving mitochondrial homeostasis, consistent with improved autophagic flux regulation. The results support Asb2–KIF11 as a molecular pathway connecting ubiquitin-mediated control of autophagy/lysosomes to mitochondrial maintenance in heart failure.

Lv Y, Sha Z, Peng S et al. · Circulation · (2026) · View on PubMed ↗

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Generated automatically on September 24, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.