PubMed Trending Research Digest — August 08, 2026

Automated digest · 94 articles · 15 research areas · August 08, 2026

Overview

Across this week’s set of studies, a dominant theme is “precision beyond the usual boundaries”: extended time windows and better selection in stroke care (imaging- and trial-supported thrombolysis beyond 4.5 hours), more personalized risk stratification using noninvasive biomarkers (e.g., proteomics for OSA in MASLD; EV immune-checkpoint signatures for HCC immunotherapy resistance; and imaging-derived metrics like EPVS or PHISE/PHI-based approaches), and genomics/AI methods that refine diagnosis and treatment targeting (WGS implementation, variant curation frameworks, and deep-learning histology subtyping).

A second major thread is mechanistic immunology and microenvironment control—both for infection and for cancer. Multiple papers connect microbial metabolism and immune evasion to specific host pathways (e.g., S. aureus OhyA antagonizing TLR3–TRIF–IRF7; Candida auris persistence via IFNγ–keratinocyte signaling; and phage/bacterial antiviral systems). In oncology, studies converge on how stromal organization, cytokine signaling, and metabolic/ferroptosis pathways shape immunotherapy response or resistance (e.g., POSTN+CAF/APOE+TAM immune-exclusion niches in ccRCC; GEM–SERPINE1–LRP1 checkpoint resistance in ESCC; and PGF2α–FSP1 ferroptosis sensitization to improve immunotherapy efficacy). Engineered therapeutics (ADC/CD137 combinations, bispecific ADCs, intracranial CAR-T, and PSMA radioligands) reflect this same push toward rational combination strategies.

Finally, neurodegeneration and aging biology continue to be framed through actionable cellular mechanisms. Several studies dissect early subcellular toxicity processes in Parkinson’s disease and related proteinopathies (cholesterol-dependent lysosomal trafficking, α-synuclein/ER translocation disruption, and tau-driven mitochondrial RET/ROS/NAD+ imbalance), while others improve how pathology is detected or propagated (phosphorylation-independent TDP-43 staining; prion-like TAF15 seeding/spread). In parallel, evolutionary and systems-genetics work (sex-specific aging hypotheses, reproductive resilience, and long-term genomic mutation patterns) provides new conceptual scaffolding for why biology changes across the lifespan—suggesting that the next wave of interventions may increasingly combine mechanistic targets with better stratification of who will benefit.

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Extended-window Stroke Thrombolysis

Intravenous Thrombolysis Beyond the Conventional Time Window for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated intravenous thrombolysis (IVT) given at least 4.5 hours after acute ischemic stroke onset in adults, drawing on randomized clinical trials and imaging-selected extended-window studies. The key finding was that IVT in the extended time window (including imaging-selected patients) was associated with functional outcome benefits while maintaining an acceptable safety profile across included trials. Clinically, these results support considering IVT beyond the conventional 4.5-hour limit for appropriately selected patients when imaging and trial evidence indicate likely benefit.

Patel S, Nischal SA, Kale KM et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

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Diabetes Care & Physician Training

Type 2 diabetes mellitus limits the glucose-responsive β-like functionality but not pancreatic lineage commitment of induced human adipose-derived stem cells.

This in vitro study examined how a type 2 diabetes mellitus (T2DM) milieu affects pancreatic differentiation of human adipose-derived stem cells (ASCs), comparing ASCs from T2DM donors (dASCs) with non-diabetic ASCs. The abstract was truncated before the specific experimental results, but the study’s aim was to determine whether T2DM impairs glucose-responsive β-like functionality while preserving pancreatic lineage commitment. If confirmed, the findings would inform strategies to overcome diabetic microenvironment effects when generating insulin-producing cells for diabetes cell-replacement approaches.

Mohamed NA, Salem AMH, El-Erian AM et al. · The international journal of biochemistry & cell biology · (2026) · View on PubMed ↗

The Gain-of-Function GLP1R R131Q Variant Preserves β-Cell Function and Enhances Response to GLP-1 Receptor Agonists.

This study tested the functional impact of the GLP1R gain-of-function variant R131Q on pancreatic β-cell function and pharmacogenetic response to GLP-1 receptor agonists in a Korean community-based prospective cohort (n=6,373) using 20-year longitudinal 2-hour 75 g oral glucose tolerance tests and disposition index as a β-cell function surrogate. The key finding was that the GLP1R R131Q variant preserved β-cell function and enhanced response to GLP-1 receptor agonists compared with other genotypes. This provides a gene–drug interaction rationale for more personalized T2D treatment using GLP1R genotype to predict benefit from GLP-1RAs.

Lee H, Christie HE, Lee JS et al. · Diabetes care · (2026) · View on PubMed ↗

Role-Playing-Based Physician Training and Metabolic Outcomes Among Patients With Type 2 Diabetes: A Cluster Randomized Clinical Trial.

This cluster randomized clinical trial studied whether role-playing-based intensive physician training improves glycemic outcomes among patients with type 2 diabetes across 205 centers in China. The key finding was that the role-playing-based physician training intervention improved metabolic outcomes (glycemic control) compared with usual care over 12 months. Scientifically and clinically, the results suggest that structured, interactive physician training can help close guideline-to-practice gaps in diabetes management at scale.

Zhang Y, Peng Y, Chen Y et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

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Breast Cancer (CDK4/6) Therapeutics & Resistance

CDK4/6 Inhibitors in Breast Cancer Therapy: Mechanisms, Resistance, and Emerging Opportunities.

This narrative review examined cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in hormone-receptor-positive (HR+), HER2-negative (HER2-) breast cancer, focusing on mechanisms of action, resistance pathways, and emerging therapeutic opportunities. The key finding was that CDK4/6 inhibitors combined with endocrine therapy consistently improve progression-free survival and, in selected populations, overall survival, but resistance remains a major barrier requiring new strategies. The review’s significance is that it consolidates current mechanistic and resistance insights to guide next-generation combinations and biomarker-driven approaches for HR+/HER2- breast cancer.

Chinea L, Hauer C, Pal K et al. · Targeted oncology · (2026) · View on PubMed ↗

P-VERIFY: Real-World Comparative Overall Survival and Progression-Free Survival of CDK4/6 Inhibitors Plus an Aromatase Inhibitor in Patients with HR+/HER2- Metastatic Breast Cancer in the USA-A Vodcast.

This real-world comparative effectiveness report (P-VERIFY) summarized overall survival (OS) and real-world progression-free survival (rwPFS) for CDK4/6 inhibitors plus an aromatase inhibitor (AI) in patients with HR+/HER2- metastatic breast cancer treated in routine practice in the USA. The key finding was that P-VERIFY provided comparative OS and rwPFS outcomes for different CDK4/6 inhibitor–AI regimens using retrospective data with longer follow-up than many prior studies. Clinically, these findings help inform treatment selection among CDK4/6 inhibitor options in real-world HR+/HER2- metastatic breast cancer where head-to-head randomized data are limited.

Rugo HS, Ryan JC · Targeted oncology · (2026) · View on PubMed ↗ · Free PDF ↗

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Mitochondrial Trafficking & Organelle Transport Mechanisms

A molecular switch for coordinating kinesin and dynein transport of mitochondrial cargo.

This study investigated how the mitochondrial adaptor protein TRAK switches microtubule transport between kinesin and dynein using a cellular synthetic cargo transport assay combined with AlphaFold2-guided mutagenesis in human/engineered TRAK isoforms. It identified a regulatory helix in TRAK whose sequence differences explain why two near-identical TRAK isoforms drive predominantly opposite-polarity mitochondrial transport. These findings provide a mechanistic “molecular switch” for coordinating bidirectional mitochondrial trafficking, informing how stress-responsive organelle positioning could be therapeutically targeted.

Gladkova C, Paez-Segala MG, Grant WP et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

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Bacterial Immune Evasion & Host–Pathogen Signaling

Antiviral defence is a conserved function of diverse bacterial DNA glycosylases.

This study used structure-guided discovery to identify bacterial DNA glycosylase families (Dag1 and Dag2) and tested their antiviral activity against phages carrying modified guanine bases. It found that Dag1 and Dag2 act as conserved anti-phage DNA glycosylases that selectively target phages with specific modified guanine signatures, despite glycosylases being classically associated with DNA repair. Scientifically, the results expand the repertoire of bacterial antiviral defense mechanisms and provide a framework to discover additional defense-associated glycosylases.

Getz LJ, Qian AL, Vivian Liu Y et al. · Nature microbiology · (2026) · View on PubMed ↗

Influenza.

This Nature Reviews Disease Primers article synthesized current knowledge on influenza A and B, focusing on how antigenic drift and antigenic shift drive seasonal epidemics and pandemics. The key finding is that influenza’s public health impact is driven by viral evolution mechanisms—drift leading to predictable seasonal waves and reassortment enabling unpredictable cross-species pandemics—while clinical severity concentrates in high-risk groups. The review’s significance is to inform surveillance, risk assessment, and prevention strategies by linking viral adaptation to clinical outcomes.

Neumann G, Cowling BJ, Chen H et al. · Nature reviews. Disease primers · (2026) · View on PubMed ↗

Effectiveness of nirsevimab and maternal RSVpreF vaccination against infant hospitalisation across the island of Ireland.

This multicentre test-negative case-control study evaluated effectiveness of nirsevimab (in the Republic of Ireland) and RSVpreF vaccination (in Northern Ireland) against hospitalised RSV-associated acute lower respiratory infection (ALRI) in infants under 6 months during the 2024/25 season across five sites on the island of Ireland. The abstract provided objectives and methods but was truncated before reporting the estimated effectiveness results and comparative impact on emergency department bronchiolitis attendances. The findings are important for guiding RSV immunization policy by quantifying real-world protection against severe infant RSV outcomes under two different national strategies.

Treston B, O’Hagan S, Barrett M et al. · International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · (2026) · View on PubMed ↗ · Free PDF ↗

Virus-induced deconjugation of ISG15 dysregulates innate immunity and cellular metabolism.

This study investigated how SARS-CoV-2 disrupts interferon-stimulated gene 15 (ISG15) biology by genetically ablating the deISGylating activity of the viral papain-like protease (PLpro) in human cells and mice. It found that loss of PLpro deISGylation boosts innate immune activation, attenuates viral replication, and promotes viral clearance, with downstream effects on ISGylation-linked pathways and cellular metabolism assessed by metabolomics. The work is significant because it directly connects coronavirus deISGylation to ISG15-dependent immune control and metabolic rewiring, highlighting PLpro deISGylation as a potential antiviral vulnerability.

Zhu J, Liu G, Xu J et al. · Immunity · (2026) · View on PubMed ↗

Reverse transcriptases challenge the central dogma of biology, again.

This Cell commentary/review discusses a bacterial antiphage system reported by Wang et al. that uses two reverse transcriptases to challenge the central dogma by synthesizing double-stranded DNA. The key finding is that one reverse transcriptase uses a noncoding RNA template while the other uses its amino acid residues to template and prime DNA synthesis, enabling an unprecedented dsDNA production mechanism. Scientifically, it expands known reverse-transcription chemistry and suggests new molecular strategies bacteria use to counter phages.

Figiel M, Nowotny M · Cell · (2026) · View on PubMed ↗

A fungus makes itself at home on skin.

This Science commentary highlights how Candida auris establishes a skin niche by repressing host antifungal defenses. The central finding emphasized is that C. auris can modulate host immunity to persist on skin, enabling colonization despite antifungal pressures. This is significant for public health because it points to immune evasion mechanisms that could inform strategies to prevent or treat C. auris outbreaks.

Segre JA · Science (New York, N.Y.) · (2026) · View on PubMed ↗

The fungal pathogen Candida auris exposes chitin to trigger IFNγ and persist in hair follicles.

This study compared skin colonization by Candida auris versus Candida albicans in mice to define fungal-immune interactions, focusing on how C. auris exposes chitin to trigger IFNγ and persist in hair follicles. The key finding was that C. auris induced a type 1 IFNγ-driven response targeting hair follicles, where IFNγ enhanced colonization by signaling to keratinocytes and repressing epithelial antifungal defenses, unlike C. albicans which triggered a type 3/17-skewed sterilizing response. This is clinically important because it identifies an IFNγ–keratinocyte pathway that may be exploited to develop interventions that prevent C. auris persistence in skin and hair follicles.

Merrill ED, Prudent V, Basso P et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

A bacterial fatty acid enzyme hijacks nucleic acid-sensing Toll-like receptor signaling.

This study examined how the Staphylococcus aureus enzyme oleate hydratase (OhyA) manipulates host innate immune signaling in the context of Toll-like receptor (TLR) pathways. OhyA converts host fatty acids into hydroxylated lipids that antagonize the TLR3–TRIF–IRF7 axis activated by double-stranded RNA, and deletion of ohyA removes this immune evasion. The work links bacterial lipid metabolism to nucleic-acid-sensing TLR cross-talk, highlighting OhyA as a potential target to restore antiviral-like innate responses during S. aureus infection.

Lathram WA, Lages PC, Radka CD · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Host inflammation-derived citrate enhances Salmonella Typhimurium pathogenesis by fueling growth and activating virulence.

This study investigated how host inflammation alters the intestinal metabolite environment to promote Salmonella Typhimurium pathogenesis, focusing on luminal citrate and the bacterial CitAB two-component system. It found that STm-induced intestinal inflammation increases luminal citrate, which both fuels bacterial growth as an anaerobic fermentation substrate and activates virulence signaling. These results show that inflammation-derived metabolites can be co-opted by pathogens, identifying citrate/CitAB as a mechanistic lever for reducing Salmonella colonization.

Sun H, Ma S, Kang C et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗

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Metabolic Disease Biomarkers & Risk Prediction (Proteomics/EVs)

Prognostic Value of Psoas Muscle Index Improvement in Patients Undergoing Transjugular Intrahepatic Portosystemic Shunt.

This multicenter retrospective study evaluated whether early improvement in psoas muscle index (PMI), measured by CT before transjugular intrahepatic portosystemic shunt (TIPS) and about 1 month after, predicts outcomes in 390 cirrhosis patients with sarcopenia. Sarcopenia reversal (post-TIPS PMI above sex-specific cutoffs) was assessed for associations with overall survival and overt hepatic encephalopathy. If validated, PMI improvement could become a practical imaging-based prognostic marker to stratify cirrhosis patients undergoing TIPS.

Wang H, Zhang X, Zhu X et al. · Journal of vascular and interventional radiology : JVIR · (2026) · View on PubMed ↗

Prognostic relevance of the right ventricular fractional area change to pulmonary artery systolic pressure ratio in pulmonary arterial hypertension: Insights from the FOCUS-PAH registry.

Using the multicenter FOCUS-PAH registry, this study analyzed pulmonary arterial hypertension (PAH) patients with available echocardiographic fractional area change (FAC) and pulmonary artery systolic pressure (PASP) at diagnosis to test whether the FAC/PASP ratio predicts 1-year and 5-year all-cause mortality. The key finding was that the FAC/PASP ratio has prognostic value for mortality in PAH, supporting it as an alternative ventriculoarterial coupling metric to the commonly used TAPSE/PASP approach. Clinically, FAC/PASP could improve risk stratification and guide management intensity in PAH.

Bocchino PP, Pecoraro M, Pagliassotto I et al. · International journal of cardiology · (2026) · View on PubMed ↗

Association between placental microplastic burden and intrapartum fetal heart rate abnormalities.

This prospective cohort study in 2738 pregnant women in China examined whether placental microplastic (MP) accumulation is associated with intrapartum non-reassuring fetal heart rate (NRFHR) abnormalities. The key finding is the reported association between quantified placental MPs—measured using laser direct infrared (LD-IR) chemical imaging with focus on polyvinyl chloride (PVC) and other polymers (as described in the abstract)—and the occurrence of NRFHR during labor. This is significant because it links human placental microplastic exposure to fetal cardiac physiology, supporting potential environmental risk mechanisms in obstetric outcomes.

Teng X, Zhang X, Shen Y et al. · Ecotoxicology and environmental safety · (2026) · View on PubMed ↗ · Free PDF ↗

Association of Enlarged Perivascular Spaces and Total Small Vessel Disease Burden With Kidney Function.

This cross-sectional pooled individual patient data study examined associations between enlarged perivascular spaces in the basal ganglia (BG-EPVS) and centrum semiovale (CSO-EPVS) with kidney function outcomes—reduced eGFR and glomerular hyperfiltration—in patients with ischemic stroke or transient ischemic attack from the Microbleeds International Collaborative Network. The study found that greater cerebral small-vessel disease burden marked by EPVS was associated with worse kidney function metrics, including lower eGFR and altered hyperfiltration status. These findings support a shared vascular pathology linking cerebral small vessel disease (including EPVS relevant to cerebral amyloid angiopathy) with renal microvascular dysfunction, motivating integrated risk stratification across brain and kidney.

Nash PS, Ambler G, Best JG et al. · Neurology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Plasma Proteomic Profiles Predict Subsequent Obstructive Sleep Apnea Diagnosis in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease.

This study evaluated whether plasma proteomic profiles can predict subsequent obstructive sleep apnea (OSA) diagnosis in adults with metabolic dysfunction–associated steatotic liver disease (MASLD) using UK Biobank data. In 17,375 OSA-free MASLD participants with 2,911 quantified plasma proteins, Cox regression and LightGBM models identified predictive proteins and achieved diagnostic risk stratification in validation with AUC-based performance. Clinically, this supports a noninvasive proteomics-based approach for earlier OSA detection in a high-risk MASLD population.

Luo Y, Huang J, Chen R et al. · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · (2026) · View on PubMed ↗

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Neurodegeneration Mechanisms (α-synuclein, tau, TDP-43, prion-like spread)

α-Synuclein blocks endoplasmic reticulum co-translational protein translocation early in Parkinson’s disease.

This study used spatially and temporally resolved proteomics and transcriptomics in human iPSC-derived dopaminergic neurons exposed to increasing pathological α-synuclein burden, and it validated findings in post-mortem Parkinson’s disease brain tissue. It found that misfolded α-synuclein proteoforms form nanoscale intraneuronal puncta associated with impaired ER co-translational translocation, mediated by interaction with Sec61A that interferes with the Sec61 translocon. The results identify an early, subcellular mechanism of α-synuclein toxicity in Parkinson’s disease that could be targeted to preserve ER protein translocation.

Lam CL, Gatford NJF, Aragón-González A et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

C9orf72-associated and sporadic FTD patient iPSC-microglia show differences in phagocytosis and gene expression.

This study generated induced pluripotent stem cell-derived microglia (iMG) from sporadic FTD patients and from C9orf72 hexanucleotide repeat expansion (C9-HRE) behavioral variant FTD (bvFTD) patients and compared them with healthy controls. It found that C9-HRE iMG show C9-HRE-associated RNA foci and dipeptide repeat proteins, have fewer LAMP2-A-positive vesicles than control iMG, and exhibit increased LC3BII/I conversion, indicating altered lysosomal/autophagy-related phenotypes and phagocytosis-related differences. The findings are significant because they define subtype-specific microglial dysfunction mechanisms in C9orf72-associated versus sporadic FTD, supporting more targeted therapeutic hypotheses.

Rostalski H, Hietanen T, Hoffmann D et al. · Stem cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

Tau-induced mitochondrial reverse electron transport drives neurodegeneration.

This study tested whether TATA-binding protein-associated factor 15 (TAF15) amyloid fibrils propagate in a prion-like manner and drive neurodegeneration. It found that TAF15 forms self-propagating amyloid fibrils and that a single injection of synthetic TAF15 pre-formed fibrils into the prefrontal cortex of wild-type mice triggers aggregation of endogenous TAF15 and promotes cell-to-cell spread. The findings are significant because they establish TAF15 as a propagating pathogenic protein species, strengthening prion-like mechanisms for frontotemporal lobar degeneration and informing therapeutic strategies to block seeding/spread.

Li W, Rimal S, Bhurtel S et al. · Neuron · (2026) · View on PubMed ↗

Aggregation and propagation of TAF15 trigger neurodegeneration.

This study investigated how tau regulates mitochondrial reverse electron transport (RET) and how this contributes to neurodegeneration across model systems. It found that tau controls RET to generate excess reactive oxygen species (ROS), lowers the NAD+/NADH ratio, and that tau depletion eliminates stress-induced RET and confers resilience in flies, mice, and human iPSC-derived neurons. The work is significant because it links tau pathology to a specific mitochondrial bioenergetic mechanism (RET/ROS/NAD+ imbalance), offering a mechanistic target for tauopathies.

Meng L, Liu C, Gong H et al. · Neuron · (2026) · View on PubMed ↗

Cholesterol enhances lysosome-autophagosome fusion for better α-synuclein clearance in GBA L444P-mutated Parkinson disease.

This study investigated how cholesterol affects lysosome–autophagosome fusion to improve α-synuclein clearance in Parkinson disease driven by the GBA L444P mutation using human patient data and human α-synuclein knock-in L444P-mutated mice. It found that GBA L444P-mutated PD is associated with lower serum cholesterol and that cholesterol loss disrupts lysosome–cytoplasmic vesicle interactions and cholesterol-containing lipid microdomains, impairing autophagic flux and α-synuclein clearance. The findings suggest that restoring cholesterol-dependent lysosomal trafficking could be a therapeutic strategy for GBA-associated PD.

Chen M, Liu F, Yang Y et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer Signaling & Target Discovery (mTOR/TFEB, METTL3, PTMs, ferroptosis)

Neuroligin-3-CSPG4 interaction maintains oligodendrocyte precursor cell progenitor state and promotes glioma proliferation through mechanotransduction.

This mechanistic study investigated how neuroligin-3 (NLGN3) signaling regulates glioma growth by using NLGN3–chondroitin sulfate proteoglycan 4 (CSPG4/NG2) interactions to drive mechanotransduction in glioma and oligodendrocyte precursor cells (OPCs). It found that shed NLGN3 binds CSPG4 on glioma and OPCs, promotes CSPG4 shedding via ADAM10, alters membrane tension, and activates mechanotransducers—primarily PIEZO1—to promote glioma proliferation while maintaining the OPC progenitor state. Scientifically, this defines a neuron-to-glia adhesion/mechanotransduction axis as a potential therapeutic target in glioma.

Kim YS, Gillespie SM, Geraghty AC et al. · Nature neuroscience · (2026) · View on PubMed ↗ · Free PDF ↗

Stromal cell senescence augments haematopoietic cell fitness in clonal haematopoiesis.

This study used single-cell RNA-sequencing of the bone-marrow microenvironment in a mouse model of DNMT3A-mutant clonal haematopoiesis (CH) to determine how stromal cell senescence affects pre-malignant clonal fitness, and it validated relevance in humans with CH. It found that mesenchymal stromal cells enter a senescent state in CH, driven by mutant haematopoietic cells via soluble TNF-α and IL-6 that activate a Stat3-driven pathway. The work identifies a senescence–cytokine–Stat3 axis in the microenvironment that can enhance haematopoietic fitness and may represent a therapeutic target to limit CH progression.

Mistry JJ, Young KA, Navarro Figueredo A et al. · Nature cell biology · (2026) · View on PubMed ↗

RNA methyltransferase 3 drives pancreatic acinar cell carcinoma growth and is a therapeutic target.

This study examined the role of METTL3, an m6A RNA methyltransferase, in pancreatic acinar cell carcinoma (ACC) using transgenic mouse models overexpressing Mettl3 and SV40 large T antigen under the pancreatic elastase I promoter. It found that METTL3-mediated m6A RNA methylation drives ACC growth and that pharmacologic inhibition with the METTL3 inhibitor STM2457 suppresses tumor progression. The work positions METTL3 as a therapeutic target in ACC and provides mechanistic and translational rationale for m6A-directed therapies.

Tatekawa S, Hara T, Meng S et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.

This article is a mechanistic review that synthesizes evidence on how post-translational modifications (PTMs) regulate metabolic reprogramming in cancer and how this can be leveraged for metabolic therapy and immunotherapy. The key finding is a proposed three-tiered PTM logic—PTMs interpret oncogenic/environmental signals, control metabolic flux, and stabilize malignant phenotypes via epigenetic and feedback mechanisms—across glucose, lipid, amino acid, and nucleotide utilization. Its significance is to unify PTM-driven control of cancer metabolism into actionable concepts for designing metabolic and immunotherapeutic strategies.

Chen SJ, Yue SW, Zhang YP et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: 52-week results from the randomised, double-blind, placebo-controlled phase 3 POETYK PsA-1 trial.

This phase 3, randomized, double-blind, placebo-controlled POETYK PsA-1 trial evaluated the efficacy and safety of the oral selective TYK2 inhibitor deucravacitinib in adults with active psoriatic arthritis who were naïve to biologic DMARDs. Over 52 weeks, deucravacitinib demonstrated improved clinical outcomes versus placebo with an acceptable safety/tolerability profile (with the abstract reporting the 52-week results following earlier 16-week randomization and continuation/switch design). These findings support deucravacitinib as an effective long-term targeted therapy option for biologic-naïve patients with active psoriatic arthritis.

van der Heijde D, Mease PJ, Paul C et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗

A phase 2a, double-blind, randomised, placebo-controlled trial of the myeloperoxidase inhibitor, mitiperstat, in participants with chronic obstructive pulmonary disease.

This phase 2a, double-blind, randomized, placebo-controlled trial evaluated the myeloperoxidase (MPO) inhibitor mitiperstat (5 mg daily up to 24 weeks) in adults with moderate-to-severe COPD at high risk of exacerbation who were receiving dual or triple inhaled therapy. The study tested whether mitiperstat could delay exacerbations using a primary endpoint of time to first composite COPD exacerbation endpoint (COPDCompEx) and assessed additional secondary exacerbation and inflammatory outcomes. If positive, targeting neutrophil MPO with mitiperstat would represent a disease-modifying anti-inflammatory approach for COPD beyond bronchodilation and inhaled corticosteroids.

Saralaya D, Mustapa MN, Ferreira J et al. · The European respiratory journal · (2026) · View on PubMed ↗

Preclinical models of COPD: a state of the art.

This article is a state-of-the-art review summarizing preclinical COPD models and how they incorporate key disease features such as emphysema, small airway disease, chronic bronchitis, and exacerbations. It synthesizes evidence from in vivo (genetic and injury models, environmental exposures), ex vivo (precision-cut lung slices), and multi-omics/single-cell-informed approaches to improve translational relevance for testing candidate disease-modifying therapies. The review highlights which model types best capture COPD heterogeneity and where gaps remain, guiding future experimental design for more predictive COPD drug development.

Polverino F, Benam KH, Cloonan SM et al. · The European respiratory journal · (2026) · View on PubMed ↗

Targeting GRP75 by natural compound polyphyllin II triggers mitochondrial calcium overload and pyroptosis to potentiate cancer immunotherapy.

This study tested whether the natural compound polyphyllin II (PPII) targets GRP75 (mortalin/HSPA9) to induce mitochondrial calcium overload and pyroptosis, thereby enhancing cancer immunotherapy. Using a high-throughput screen to identify immunogenic cell death (ICD) inducers, the authors found that PPII triggered ICD markers, promoted tumor growth inhibition, and increased immune activation, with GRP75 targeting as a mechanistic driver. The work supports combining GRP75-directed ICD induction with immune checkpoint blockade as a strategy to overcome resistance to ICB therapy.

Wang Y, Dong J, Long Y et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Coordination of ALT telomere maintenance across the cell cycle.

This review studied how alternative lengthening of telomeres (ALT)—a recombination-based telomere maintenance pathway active in ~10–15% of human cancers—coordinates telomere-associated DNA synthesis and replication stress across the cell cycle. It finds that ALT-associated telomere synthesis is initiated in S phase but becomes prominent in G2, can extend into mitosis via mitotic DNA synthesis (MiDAS), and can continue into the next G1 through post-MiDAS DNA synthesis, with persistent telomeric replication stress and elevated DNA damage driving ALT activity. Mechanistically mapping ALT timing across S/G2/M/G1 is significant because it identifies when telomere recombination stress is highest, informing strategies to target ALT in cancer cells.

Vornberger J, Altmeyer M · Molecular cell · (2026) · View on PubMed ↗ · Free PDF ↗

Zhigancao decoction ameliorates ischemic heart failure-related ventricular arrhythmias through attenuation of transforming growth factor-β/Smad-associated myocardial fibrosis.

This Journal of Ethnopharmacology study investigated Zhigancao Decoction (ZGCT/Fumai Decoction) for ischemic heart failure-related ventricular arrhythmias by targeting myocardial fibrosis pathways. The key finding is that ZGCT ameliorated ventricular arrhythmias through attenuation of transforming growth factor-β (TGF-β)/Smad-associated myocardial fibrosis. Scientifically and therapeutically, it supports a mechanistic basis for a traditional Chinese medicine formula as a potential anti-fibrotic anti-arrhythmic strategy in ischemic heart failure.

Wang X, Zhou L, Ding H et al. · Journal of ethnopharmacology · (2026) · View on PubMed ↗

Coixol attenuates Ulcerative Colitis by modulating the ILC3 response via the Wnt/β-catenin pathway.

This Journal of Ethnopharmacology study evaluated Coixol in ulcerative colitis (UC) and focused on how it modulates innate lymphoid cell 3 (ILC3) responses. The key finding is that Coixol attenuated UC by modulating the ILC3 response via the Wnt/β-catenin signaling pathway. This is significant because it identifies a specific immune pathway mechanism that could be leveraged for targeted UC therapies.

Ma J, Yin Q, Zhou Y et al. · Journal of ethnopharmacology · (2026) · View on PubMed ↗

Systemic Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: ASCO Living Guideline, Version 2026.1.4.

This ASCO Living Guideline (Version 2026.1.4) systematically reviews and updates evidence on systemic therapy choices for patients with metastatic castration-resistant prostate cancer (mCRPC). The key finding is the guideline’s continuously revised, evidence-based recommendations for systemic treatment sequencing and selection as new trials emerge. Clinically, it provides an up-to-date decision framework for oncologists managing mCRPC, while emphasizing that recommendations do not replace individualized clinical judgment.

Taplin ME, Parikh RA, Rumble RB et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Endocardial transcription factor HAND2 orchestrates hypoxic and TGF-β signaling to modulate coronary artery formation.

This mechanistic mouse study investigated how the endocardial transcription factor HAND2 regulates hypoxic and TGF-β signaling to control coronary artery formation. Endocardial deletion of Hand2 disrupted arterial–venous network development and stunted coronary arteries, with RNA-seq showing enhanced hypoxic metabolic activation alongside reduced TGF-β/p38MAPK-dependent endothelial signaling, leading to excessive tip cells with impaired movement. These findings identify HAND2 as a key transcriptional orchestrator of coronary vascular morphogenesis and suggest molecular targets within hypoxia/TGF-β pathways for congenital coronary development disorders.

Wang H, Zhang H, Zheng L et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

Microenvironmental Prostaglandin F2α Antagonizes FSP1 in Cancer Cells to Sensitize Tumors to Ferroptosis and Immunotherapy.

This cancer biology study integrated single-cell and bulk transcriptomics from immunotherapy cohorts to identify microenvironmental pathways linked to ferroptosis sensitivity, then focused on prostaglandin F2α (PGF2α) as a ferroptosis sensitizer. The key finding was that microenvironmental PGF2α antagonizes FSP1 (ferroptosis suppressor protein 1) by binding at alanine 295 (A295), thereby sensitizing tumors to ferroptosis and improving immunotherapy efficacy. Scientifically and therapeutically, it highlights a prostaglandin–FSP1 axis as a potential target to boost ferroptosis-based cancer treatment and immunotherapy responses.

Meng Y, Zhou Q, Zhao D et al. · Cancer research · (2026) · View on PubMed ↗

Non-canonical mTORC1-TFEB activation promotes hepatocyte plasticity and high-grade malignancy in hepatocellular carcinoma.

This study examined how non-canonical mTORC1–TFEB activation drives hepatocyte plasticity and high-grade malignancy in hepatocellular carcinoma (HCC), with emphasis on TSC1-mutant disease. Using human tissue arrays and bulk/single-cell RNA-seq plus biochemical, histological, metabolomic, and transcriptomic analyses in liver-specific Tsc1 knockout (L-Tsc1 KO) and L-Tsc1,Tfeb double knockout (DKO) mice, it defined TFEB-associated transcriptional programs linked to aggressive tumor behavior. The work clarifies a signaling route (mTORC1–TFEB) that could be exploited to stratify or target high-grade TSC1-associated HCC.

Zhang C, Chao X, Williams SN et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer Microenvironment, Immunotherapy Resistance & Biomarkers

An oxidative stress - and immunotherapy-related six-gene signature defines immune subtypes and predicts prognosis and immunotherapy response in hepatocellular carcinoma.

This bioinformatics study integrated transcriptomic and clinical data from TCGA and GEO to derive an oxidative stress- and immunotherapy-related six-gene signature (OSIRDEGs) for hepatocellular carcinoma (HCC). It used WGCNA and LASSO-Cox regression to build a prognostic model, then applied consensus clustering, TIDE, CIBERSORT, and ssGSEA to define immune subtypes and predict immunotherapy response. The resulting gene signature links oxidative stress biology with tumor immune microenvironment features and may help select HCC patients likely to benefit from immunotherapy.

Liang Y, Chen X, Su Y et al. · Gene · (2026) · View on PubMed ↗

APOE+ macrophages and POSTN+CAFs form immune-exclusion niche driving immunotherapy resistance in clear-cell renal carcinoma.

This study mapped tumor immune barriers in clear-cell renal cell carcinoma (ccRCC) and identified a peritumoral immune-exclusion niche composed of POSTN+ cancer-associated fibroblasts (CAFs) interlaced with APOE+ tumor-associated macrophages (TAMs). Spatial transcriptomics and single-cell profiling showed that this POSTN+CAF/APOE+TAM niche enriched extracellular-matrix remodeling, immunosuppressive ligand-receptor circuits, and metabolic reprogramming, excluding CD8+ T cells from tumor cores and correlating with poor prognosis and immune-checkpoint blockade (ICB) refractoriness. Mechanistically, the niche provides a targetable explanation for ICB resistance in ccRCC by defining how stromal-immune organization prevents T-cell infiltration.

Ge Q, Ge S, Wang Z et al. · Science advances · (2026) · View on PubMed ↗

Circulating extracellular vesicles carrying PD-1, PD-L1 and CTLA-4 inform resistance to anti-PD-L1-based therapy in HCC.

This study profiled circulating extracellular vesicles (EVs) carrying immune checkpoint proteins PD-1, PD-L1, and CTLA-4 to predict resistance to anti-PD-L1 therapy in hepatocellular carcinoma (HCC). Across three cohorts (including an HCC explorer cohort of n=40 and additional early-stage/treated cohorts), EV immune checkpoint signatures were associated with treatment response and resistance, offering a liquid-biopsy alternative to tissue sampling. These results suggest that EV-based checkpoint profiling could improve biomarker-driven selection for anti-PD-L1-based therapy in HCC.

Gorgulho J, Masood R, Buescher G et al. · Gut · (2026) · View on PubMed ↗ · Free PDF ↗

Superior Effectiveness of Upadacitinib Over Tofacitinib and Ustekinumab in Bio-Exposed Ulcerative Colitis: The TRIDENT-UC Study.

The TRIDENT-UC retrospective multicenter study compared real-world effectiveness of upadacitinib versus tofacitinib versus ustekinumab in bio-exposed ulcerative colitis (UC) patients who failed at least one advanced therapy (AT), assessing outcomes at weeks 16 and 52. The abstract indicates the study’s conclusion that upadacitinib was superior, with primary outcome steroid-free clinical remission (SFCR) and secondary biochemical/endoscopic remission measures. This supports evidence-based selection of second-line therapy in UC after prior AT failure, potentially improving remission rates while reducing steroid dependence.

Camões Neves J, Costa D, Cristiano M et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · (2026) · View on PubMed ↗

Responders vs. non-responders to mesenchymal stromal cells in knee osteoarthritis: Mechanistic correlates of donor cell and patient features.

This clinical translational study analyzed knee osteoarthritis (KOA) responders versus non-responders to autologous bone marrow-derived mesenchymal stromal cell (MSC(M)) injection using clinical trial data from NCT02351011 and correlated outcomes with donor batch attributes and patient baseline features. It found that MSC(M) donors with increased immunomodulatory potency were more efficacious, with multivariable MSC(M) gene signatures strongly associated with responder status and 12- and 24-month improvements in Knee Injury and Osteoarthritis Outcome Scores, and that responder batches had distinct microRNA expression and monocyte-polarizing capacity (CD14+ monocytes). These mechanistic correlates are significant because they suggest biomarkers and potency-linked donor selection criteria to improve MSC therapy response rates in KOA.

Robb KP, Rabani R, Vohra S et al. · Stem cell reports · (2026) · View on PubMed ↗ · Free PDF ↗

Group 2 innate lymphoid cells activate myelin-reactive T cells to augment neuroinflammation.

This study examined the role of group 2 innate lymphoid cells (ILC2s) in experimental autoimmune encephalomyelitis (EAE) and their interaction with myelin-reactive T cells in the dura. Using single-cell RNA sequencing and flow cytometry, it found that ILC2s accumulate during EAE progression, express MHC class II, and act as antigen-presenting cells to activate and expand myelin-reactive T cells in an MHC class II-dependent manner. The results are significant because they identify an ILC2–T cell antigen-presentation axis that can amplify neuroinflammation, suggesting new immunomodulatory targets for CNS autoimmunity.

Huang H, Liu G, Han Y et al. · Immunity · (2026) · View on PubMed ↗

Single-cell analysis of the human retina reveals stage-linked microglial states and neural-immune circuit rewiring in diabetic retinopathy.

This Genomics study performed single-cell RNA sequencing on 20 human retina samples spanning non-diabetic, diabetic, and diabetic retinopathy (DR) states to map neural-immune changes. The key finding is identification of stage-linked microglial states—homeostatic and inflammatory—along a functional continuum, plus a neutrophil cluster within C1QA+ myeloid cells with dynamic transitions across disease progression, indicating neural-immune circuit rewiring. This is significant because it provides a cellular transcriptomic atlas that may reveal therapeutic targets and biomarkers for diabetic retinopathy.

Yang L, Lin S, Tao Y et al. · Genomics · (2026) · View on PubMed ↗ · Free PDF ↗

Targeting GEM Reprograms Macrophages and Overcomes Immunotherapy Resistance in Esophageal Squamous Cell Carcinoma.

This study examined the tumor-intrinsic role of GEM (GTP-binding protein overexpressed in skeletal muscle) in esophageal squamous cell carcinoma (ESCC) and how it drives resistance to anti–PD-L1 immunotherapy. GEM expression promoted tumor-associated macrophage (TAM)–mediated immunosuppression via SERPINE1 secretion acting on macrophage LRP1, resulting in reduced CD8+ T-cell infiltration and impaired cytotoxic function. These findings identify a GEM–SERPINE1–LRP1 axis as a mechanistic driver of checkpoint resistance and a potential therapeutic target to restore immunotherapy responsiveness in ESCC.

Wu L, Ren C, Zhang Y et al. · Cancer research · (2026) · View on PubMed ↗

Deep learning-based histologic classifiers enable molecular subtyping of metastatic prostate cancer.

This study developed deep learning-based histologic classifiers to molecularly subtype metastatic prostate cancer from H&E-stained slides, targeting clinically relevant neuroendocrine prostate cancer (NEPC) under androgen receptor (AR) therapy pressure. The model used interpretable cellular features to improve feature extraction and enable molecular subtyping of metastatic disease, addressing the diagnostic challenge posed by NEPC histologic and molecular heterogeneity. This approach could support earlier, more accurate identification of resistant/lineage-plastic NEPC phenotypes and guide treatment decisions.

Chen Z, Sayar E, Guevara D et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗

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Engineered Immunotherapies (CAR-T/ADCs/Bispecifics/Radioligands)

DECIDER-2: Prospective randomized multicenter phase III trial of decitabine and venetoclax administered in combination with all-trans retinoic acid or placebo in patients with acute myeloid leukemia who are ineligible for induction chemotherapy.

DECIDER-2 was a prospective randomized multicenter phase III trial in older, induction-ineligible acute myeloid leukemia (AML) patients testing decitabine plus venetoclax (DAC+VEN) combined with all-trans retinoic acid (ATRA) versus placebo. The trial evaluated overall survival and other clinical endpoints to determine whether adding ATRA improves outcomes beyond the DAC+VEN backbone. If positive, this would establish a new combination strategy for medically unfit AML patients; if negative, it would refine evidence on ATRA’s role in venetoclax-based regimens.

Grishina O, Schmoor C, Sellner C et al. · BMC cancer · (2026) · View on PubMed ↗ · Free PDF ↗

Intracranial delivery of B7-H3-targeting CAR-T cells for recurrent glioblastoma: a phase 1 trial.

This phase 1, open-label 3+3 dose-escalation trial evaluated autologous B7-H3-targeting CAR-T cells (TX103) delivered by intracranial infusion for recurrent glioblastoma (rGBM) in adults aged 18–75 years with B7-H3-positive tumors (≥30%). The study’s primary endpoints were safety, maximum tolerated dose, and recommended phase 2 dose, with secondary endpoints including survival, pharmacokinetics, and immunologic responses. If the safety and efficacy signals support further development, intracranial B7-H3 CAR-T could become a targeted treatment option for patients with recurrent glioblastoma.

Zhang Y, Chi X, Feng R et al. · Nature medicine · (2026) · View on PubMed ↗

Real-World Outcomes of [177Lu]Lu-PSMA-617 in the French Early-Access Program for Patients with Metastatic Castration-Resistant Prostate Cancer.

This real-world French early-access program study assessed outcomes of radioligand therapy with [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed after standard treatments. The program reported clinical effectiveness consistent with PSMA-targeted radiopharmaceutical benefit in a routine-care setting, aligning with prior evidence from the VISION trial regarding survival and radiographic progression-free survival improvements. These data help inform feasibility, effectiveness, and potential patient selection for [177Lu]Lu-PSMA-617 implementation in early-access clinical practice.

Bailly C, Vija L, Somme F et al. · Journal of nuclear medicine : official publication, Society of Nuclear Medicine · (2026) · View on PubMed ↗ · Free PDF ↗

SKYSCRAPER-03: A Phase III Study of Tiragolumab Plus Atezolizumab Versus Durvalumab in Locally Advanced, Unresectable, Stage III NSCLC After Platinum-Based Concurrent Chemoradiation.

This phase III, open-label randomized trial (SKYSCRAPER-03; NCT04513925) studied consolidation therapy with tiragolumab plus atezolizumab versus durvalumab in patients with locally advanced, unresectable stage III non-small cell lung cancer (NSCLC) after platinum-based concurrent chemoradiation. The abstract provided only the trial design and dosing details, without reporting the primary efficacy or safety results. Clinically, the study is intended to determine whether adding tiragolumab to atezolizumab improves outcomes compared with standard durvalumab consolidation in this post-chemoradiation setting.

Wakelee HA, Ahn MJ, Bradley J et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗

[177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial.

The PSMAddition phase 3 randomized controlled trial studied [177Lu]Lu-PSMA-617 combined with androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) in PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (APMN/S). The abstract provided the trial rationale, design, and scope (169 sites in 20 countries) but was truncated before reporting efficacy endpoints and safety outcomes. The results are clinically significant because they test whether adding PSMA-targeted radioligand therapy improves outcomes beyond ADT+ARPI in hormone-sensitive metastatic prostate cancer.

Tagawa ST, Sartor O, Piulats JM et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Dual Targeting of EGFR and HER2 by a Bispecific Antibody-Drug Conjugate Demonstrates Broad Antitumor Activity in Multiple Solid Tumors.

This preclinical study developed GenSci139, an EGFR×HER2 bispecific antibody-drug conjugate (BsADC), and evaluated its antitumor activity across multiple solid tumor models where EGFR and HER2 are co-expressed. The key finding was that dual targeting of EGFR and HER2 by GenSci139 produced broad antitumor efficacy and was designed to improve binding/internalization and address resistance limitations seen with HER2-only ADCs such as ENHERTU (DS-8201). This supports a therapeutic strategy for tumors with low or heterogeneous HER2 expression by expanding target coverage through bispecific ADC engineering.

Chai X, Li F, Xie H et al. · Molecular cancer therapeutics · (2026) · View on PubMed ↗ · Free PDF ↗

Talquetamab in patients with relapsed/refractory multiple myeloma: 3-year follow-up of the phase 1/2 MonumenTAL-1 study.

This report evaluated 3-year efficacy and safety outcomes of the GPRC5D-targeting bispecific antibody talquetamab in adults with relapsed/refractory multiple myeloma in the phase 1/2 MonumenTAL-1 study, including cohorts with and without prior T-cell redirection therapy (TCR). Talquetamab produced sustained overall response rates (~67–74%) across dosing schedules (0.4 mg/kg weekly and 0.8 mg/kg every other week) with continued safety follow-up over median follow-up of ~30–38 months. These long-term data strengthen the clinical evidence for talquetamab’s durability of response and ongoing tolerability in a real-world relapsed/refractory setting.

Rasche L, Schinke C, Touzeau C et al. · Blood · (2026) · View on PubMed ↗ · Free PDF ↗

Antibody-Drug Conjugates Synergize with Agonist Anti-CD137 Monoclonal Antibodies in Solid Tumors.

This study tested whether antibody-drug conjugates (ADCs) synergize with agonist anti-CD137 (4-1BB) monoclonal antibodies in solid tumor models, focusing on ADCs delivering MMAE or deruxtecan against NECTIN-4 or HER2. The key finding was that combining CD137 agonism with MMAE- or deruxtecan-conjugated ADCs enhanced antitumor effects beyond ADCs alone, with ADC-induced changes in tumor stroma and immune activation contributing to improved efficacy. Clinically, this supports a rationale for combination strategies pairing ADCs with CD137 agonists to potentiate immune-mediated tumor killing in solid cancers.

Gomis G, Herrero C, Arrieta-Aranzueque S et al. · Cancer research · (2026) · View on PubMed ↗

Generative design of bacteriophages with genome language models.

This study used genome language models to generatively design complete bacteriophage genomes, using phage ΦX174 as a template to target specific host tropism. The authors generated viable phages with diverse fitness profiles and confirmed structural features by cryo-electron microscopy, including use of an evolutionarily distant DNA packaging protein in the capsid. A cocktail of these AI-designed phages rapidly overcame ΦX174-resistant Escherichia coli strains, demonstrating a practical route toward engineered phage therapies.

King SH, Driscoll CL, Li DB et al. · Science (New York, N.Y.) · (2026) · 1 citations · View on PubMed ↗

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Clinical Trials & Evidence Synthesis in Neurology (PD, MG, Stroke rehab, sleep)

Bilateral transcutaneous auricular nerve stimulation promotes motor function recovery after stroke: A randomized controlled trial.

In a randomized controlled trial, this study tested whether bilateral transcutaneous auricular nerve stimulation (BtaNS) improves motor recovery after stroke compared with conventional approaches, focusing on comprehensive post-stroke limb motor rehabilitation. The key finding was that bilateral taNS promoted motor function recovery, supporting greater neuromodulatory benefit than unilateral taNS approaches. This suggests a noninvasive, safer rehabilitation strategy that could broaden neuromodulation options for post-stroke motor impairment.

Wang J, Liu Q, Zhou Y et al. · Therapeutic advances in neurological disorders · (2026) · View on PubMed ↗ · Free PDF ↗

SSRI/SNRI and long COVID in children and adolescents with neuropsychiatric conditions: a cohort study from the RECOVER Initiative.

This retrospective cohort study from the RECOVER Initiative examined 110,955 children and adolescents with pre-existing neuropsychiatric conditions across 37 US health systems to determine whether SSRI or SNRI use is associated with long COVID outcomes. It found associations between SSRI/SNRI exposure and long COVID-related outcomes in this pediatric population. Clinically, these results inform risk-benefit considerations for commonly used antidepressant classes in children and adolescents who develop COVID.

Zhou T, Zhang B, Lu Y et al. · Nature. Mental health · (2026) · View on PubMed ↗ · Free PDF ↗

Prehospital Injury Severity Estimate (PHISE) matches in-hospital trauma scores when embedded in AI models.

This study developed and externally validated the Prehospital Injury Severity Estimate (PHISE), a scene-based prehospital trauma severity score, and compared its performance to in-hospital Injury Severity Score (ISS) and New Injury Severity Score (NISS) when embedded in AI models using National Trauma Data Bank (NTDB) data. The key finding was that PHISE matches in-hospital trauma scores and can be used effectively in AI-based prediction despite lacking imaging in the prehospital setting. This supports broader deployment of trauma risk stratification and benchmarking in real-world emergency care where imaging is unavailable.

Sigle M, Goldschmied A, Gawaz M et al. · NPJ digital medicine · (2026) · View on PubMed ↗ · Free PDF ↗

A phosphorylation‑independent monoclonal antibody improves detection of TDP‑43 pathology across frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and limbic predominant age related TDP‑43 encephalopathy neuropathological change.

The study compared a phosphorylation-independent monoclonal antibody against a C-terminal TDP-43 epitope (MAb No. 9) with a phospho-specific pSer409/410 antibody to detect TDP-43 pathology across post-mortem brain tissue from a multicenter autopsy cohort spanning FTLD-TDP types A–C, ALS-TDP, and limbic predominant age-related TDP-43 encephalopathy (LATE-NC). MAb No. 9 improved in situ detection of TDP-43 pathology relative to the phospho-specific antibody, indicating that epitope accessibility is constrained by phosphorylation state and aggregate architecture across subtypes. This supports using phosphorylation-independent C-terminal TDP-43 immunostaining to more reliably map TDP-43 proteinopathy burden for diagnosis, research stratification, and biomarker development across the TDP-43 disease spectrum.

Zheng X, Zhang N, Wang L et al. · Journal of neuropathology and experimental neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Precise nanodelivery of screened compounds alleviates sepsis-associated encephalopathy by targeting microglial ANXA2.

The study developed a translational nanodelivery pipeline to treat sepsis-associated encephalopathy (SAE) by targeting microglial Annexin A2 (ANXA2) using screened small compounds and targeted nanodelivery in cecal ligation and puncture (CLP) mice, supported by transcriptomic analyses of septic patient brain tissue (GSE135838) and WGCNA. ANXA2 was identified as a microglia-associated candidate linked to SAE, and targeted nanodelivery of the screened compound(s) alleviated SAE phenotypes in vivo while mechanistically implicating microglial neuroinflammation. This provides a gene-targeted (ANXA2) and delivery-engineered preclinical strategy that could enable more specific SAE therapeutics beyond current non-targeted supportive care.

Lin D, Huang Y, Wu S et al. · Science bulletin · (2026) · View on PubMed ↗ · Free PDF ↗

Integrating GLP-1 Receptor Agonists Into Dermatology Practice: Safety and Monitoring Strategies.

This article reviewed how glucagon-like peptide-1 receptor agonists (GLP-1RAs)—including oral semaglutide, oral orforglipron, and next-generation agents such as retatrutide—are being integrated into dermatology practice. It highlights the expanding dermatologic relevance of GLP-1RAs and focuses on safety and monitoring strategies as patient numbers increase. Scientifically and clinically, it supports safer prescribing and surveillance for dermatology patients receiving GLP-1RAs, including those on oral formulations and emerging multi-agonist therapies.

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

Efficacy of citicoline as an add-on therapy in Parkinson’s disease: a randomized, double-blind trial.

This randomized, double-blind, multicenter trial (CITIPARK) studied citicoline add-on therapy in Parkinson’s disease patients receiving stable dopaminergic medications. The key finding is that citicoline was tested at 1000 mg/day intramuscularly in two 6-week cycles versus placebo over 24 weeks with the primary endpoint being change in MDS-UPDRS total score (with motor and non-motor/QOL secondary outcomes). Clinically, the study directly evaluates whether citicoline improves motor and non-motor symptoms and quality of life beyond standard levodopa-based treatment.

Marano M, Pilotto A, Logroscino G et al. · Parkinsonism & related disorders · (2026) · View on PubMed ↗ · Free PDF ↗

Lithium for the prevention of suicide in US veterans: a target trial emulation.

This BMJ Mental Health study used target trial emulation with US veterans’ electronic health records and administrative claims (2010–2022) to evaluate lithium initiation and continuation for suicide prevention in adults with bipolar disorder or major depressive disorder. The key finding is an estimated effect of lithium on suicide deaths and non-lethal suicidal behaviors over 1 year, benchmarked against the CSP-590 randomized trial approach (details truncated in the abstract). Scientifically and clinically, it strengthens real-world evidence for whether lithium reduces suicidal outcomes in large routine-care populations.

Szmulewicz AG, Gerlovin H, Rezaee N et al. · BMJ mental health · (2026) · View on PubMed ↗ · Free PDF ↗

Responsiveness of muscle mass gain to different load intensities of resistance training in older women: A randomized crossover study.

This randomized crossover study in 27 older women (mean age ~68 years) tested whether resistance training load intensity affects skeletal muscle mass (SMM) gain responsiveness. The key finding is that two 8-week training schemes—15RM versus 10RM—were compared for estimated SMM adaptations and responsiveness, with a 12-week detraining period between interventions. Clinically, it informs how to prescribe resistance training intensity to maximize hypertrophic response in older adults.

Ribeiro AS, Sansone G, Cunha PM et al. · Experimental gerontology · (2026) · View on PubMed ↗ · Free PDF ↗

Prospective study of efgartigimod in severe myasthenia gravis exacerbations requiring ventilatory or enteral support.

This prospective, single-arm, open-label study evaluated efgartigimod in 16 adults with severe generalized myasthenia gravis (AChR- or MuSK-antibody positive) experiencing exacerbations requiring ventilatory or enteral support. The key finding is clinically meaningful improvement (CMI) in MG Activities of Daily Living (MG-ADL) as the primary endpoint, assessed in patients meeting criteria for impending myasthenic crisis (MGFA Class IIIb/IIIa/IVb). Clinically, it tests whether the FcRn antagonist efgartigimod can improve function and safety in a high-acuity MG population needing life-support-level care.

Shelly S, Rosenberg A, Zoabi M et al. · Journal of neuromuscular diseases · (2026) · View on PubMed ↗ · Free PDF ↗

Cognitive and Biomarker Signatures of Late-Onset Temporal Lobe Epilepsy: Toward Non-Alzheimer Neurodegenerative Mechanisms.

This Italian cross-sectional cohort study characterized cognitive profiles and cerebrospinal fluid (CSF) biomarker phenotypes in late-onset temporal lobe epilepsy (LO-TLE) patients with normal CSF β-amyloid (Aβ), comparing them with age- and sex-matched healthy controls and with mild cognitive impairment due to Alzheimer disease (MCI-AD). The key finding was that LO-TLE with normal CSF Aβ shows a distinct cognitive/CSF signature that differs from MCI-AD, supporting non-Alzheimer neurodegenerative mechanisms and biological heterogeneity within late-onset epilepsy. Clinically, this helps refine biomarker-based stratification of LO-TLE and guides more targeted diagnostic and mechanistic research beyond an Alzheimer-only framework.

Casarini A, Ballerini A, Maramotti R et al. · Neurology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Migraine and headache in children and adolescents: A 2026 evidence-based factsheet.

This 2026 evidence-based factsheet synthesized research on migraine and other headache disorders in children and adolescents using population-based studies, systematic reviews, clinical cohorts, and Global Burden of Disease (GBD) 2023 estimates. It summarizes the global burden, developmental considerations, and key clinical domains relevant to pediatric headache recognition and management. Scientifically and clinically, it provides an accessible, policy-relevant framework to improve under-recognized pediatric headache care worldwide.

Uludüz D, Abu-Arafeh I, Orr SL et al. · Cephalalgia : an international journal of headache · (2026) · View on PubMed ↗ · Free PDF ↗

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Sleep & Circadian/Neurophysiology

Psilocybin-assisted therapy for treatment-resistant major depressive disorder in a public healthcare setting: a randomized controlled trial.

This randomized, double-blind, placebo-controlled feasibility trial studied whether a single 25-mg dose of psilocybin with psychological support is feasible and potentially beneficial for treatment-resistant major depressive disorder in adults meeting DSM-5 criteria at one NHS site in England. The key finding was that administering the 25-mg psilocybin dose with structured psychological support in this public healthcare setting was feasible within the trial framework over 6 weeks of follow-up. These results support the clinical implementability of psilocybin-assisted therapy as a next-step option to test efficacy more broadly in treatment-resistant depression.

Rucker JJ, Mantingh T, Kerr-Gaffney J et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Melatonin Use and Polysomnographic Sleep Architecture in Children.

This cross-sectional, propensity score-matched study assessed whether outpatient melatonin use is associated with differences in objective sleep architecture measured by polysomnography (PSG) in children. Using the Nationwide Children’s Hospital Sleep DataBank (2017–2019) and linked electronic health record data, it compared PSG-derived sleep parameters between melatonin users and matched non-users in a pediatric sleep clinic population. The results inform whether melatonin, widely used as a pediatric sleep aid, meaningfully alters clinically measurable sleep architecture.

Juginovic A, Rodman L · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

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Genetic & Genomic Methods for Diagnosis/Variant Curation

SLF2 and SMC5 dysfunction drives HSC aging and predisposes to MDS, defining a new inherited bone marrow failure syndrome.

This work investigated the mechanism by which inherited bone marrow failure syndrome genes SLF2 and SMC5 contribute to hematopoietic dysfunction and early myelodysplastic syndrome (MDS) by analyzing hematopoietic progenitor cells (HPCs) from affected patients with longitudinal follow-up. The key finding was that SLF2 and SMC5 dysfunction drives HSC aging and predisposes patients to develop MDS at a young age. Clinically, defining this pathway clarifies disease biology in Atelis syndrome–related IBMFS and supports risk stratification and mechanism-informed interventions for early MDS prevention.

Shibata S, Chonabayashi K, Nakamura H et al. · Leukemia · (2026) · View on PubMed ↗

Development of an arabinose-inducible gene expression system for nontuberculous mycobacteria.

The study developed an arabinose-inducible gene expression system using a modified pBAD24 vector for nontuberculous mycobacteria, with experiments in Mycobacterium abscessus (Mycobacteroides abscessus). Arabinose produced dose-dependent induction of target gene expression (including increased antibiotic resistance and quantitative RT-PCR readouts), with tunable expression despite detectable basal activity without arabinose. This provides a practical genetic tool for controlled gene expression in NTM, enabling more precise functional studies and potential therapeutic target validation.

Yanagita Y, Maruhashi M, Sawai K et al. · Journal of microbiological methods · (2026) · View on PubMed ↗

BRD4 binds the nucleosome via both histone and DNA interactions.

This structural biology study used cryo-electron microscopy (cryo-EM) to determine how the BET family chromatin reader BRD4 short isoform (BRD4-S) binds a nucleosome diacetylated on histone H4. The key finding was that BRD4 BD1 engages both the H4 tail and nucleosomal DNA, providing a full-length nucleosome-binding mechanism beyond acetylated-peptide-only models. Scientifically, this clarifies BRD4–nucleosome recognition and can inform the design and interpretation of BET inhibitors that disrupt chromatin binding.

Zhu J, Leith EM, O’Donnell EN et al. · Molecular cell · (2026) · View on PubMed ↗

Haplotype-resolved DiMeLo-seq maps centromeric chromatin in a complete diploid human genome.

This study mapped centromeric chromatin in the complete diploid human T2T-HG002 genome by generating haplotype-resolved satellite DNA annotations and using directed methylation with long-read sequencing (DiMeLo-seq) to profile CENP-A, H3K9me3, and CpG methylation on ultra-long nanopore reads. It found that CENP-A occupies multiple discrete subdomains within hypomethylated centromere dip regions (CDRs) with constrained total size and balanced CENP-A dosage between homologous chromosomes despite extensive alpha-satellite variation. The approach is significant for resolving centromere organization within repetitive DNA and for enabling allele-specific centromere epigenetic benchmarking in personalized genomics.

Xu Y, Loucks H, Menendez J et al. · Cell genomics · (2026) · View on PubMed ↗ · Free PDF ↗

Complex subtelomeric architectures in a complete rhesus macaque reference genome.

This study produced a near-perfect telomere-to-telomere (T2T) assembly of the rhesus macaque (Macaca mulatta) genome (T2T-MMU8v2.0) to resolve subtelomeric satellite-rich regions. It found that subtelomeric satellite arrays (~8 Mbp) are the main bottleneck due to long-read biases and hybrid assembly limitations, and it resolved four distinct SATR satellite architectures with unique satellite composition, segmental duplication organization, and epigenetic signatures. The assembly is significant because it provides a high-accuracy primate reference that enables comparative and mechanistic studies of subtelomeric genome structure and evolution.

Zhang S, Xu N, Lu Y et al. · Cell · (2026) · View on PubMed ↗

A complete diploid human genome benchmark for personalized genomics.

This study created a telomere-to-telomere genome benchmark for personalized genomics by generating near-perfect accuracy mapping across 99.4% of the diploid HG002 genome. It found that the benchmark adds 701.4 Mb of autosomal sequence plus both sex chromosomes (216.8 Mb), annotates genes and repeats on both haplotypes (19,956 maternal and 19,190 paternal protein-coding genes), and includes new methods to measure read accuracy without relying on a single reference-mapping paradigm. The benchmark is significant because it reduces reference bias—especially in duplicated and structurally polymorphic regions—improving variant calling and accuracy for individualized genomes.

Hansen NF, Dwarshuis N, Ji HJ et al. · Cell · (2026) · View on PubMed ↗

Clinical genome sequencing in neurodegenerative diseases-outcome in the first 500 patients.

This clinical implementation study evaluated diagnostic performance of clinical whole genome sequencing (WGS) in the first 500 patients with neurodegenerative diseases (NDDs) spanning a wide spectrum of phenotypes. The key finding was that WGS enabled comprehensive variant detection—including single-nucleotide variants, copy-number variants, structural variants, and repeat expansions—using flexible gene lists tailored to clinical presentation, supporting improved diagnostic yield compared with narrower testing approaches. Clinically, it supports broader adoption of WGS for definitive molecular diagnosis, genetic counseling, and potential eligibility for genotype-informed clinical trials in heterogeneous NDDs.

Ehn E, Thonberg H, Nennesmo I et al. · Human molecular genetics · (2026) · View on PubMed ↗ · Free PDF ↗

A quantitative definition of the clinical manifestations of GATA2 deficiency in adults.

This study analyzed adult clinical phenotype data to quantitatively define germline GATA2 deficiency for variant curation in the context of the Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP). The authors used statistical comparison of phenotype patterns to derive well-defined criteria for what constitutes GATA2 deficiency manifestations in adults, rather than relying on qualitative descriptions. This improves the scientific rigor and clinical consistency of interpreting GATA2 variants, supporting more accurate diagnosis and risk assessment for patients with suspected GATA2 deficiency.

Mohan S, Carlelycke TE, Koppayi AL et al. · Blood · (2026) · View on PubMed ↗

Expansion of functional human long-term HSCs through restraining excessive cell cycle activation.

This study investigated how to expand functional human long-term hematopoietic stem cells (HSCs) while restraining excessive cell-cycle activation during ex vivo culture, using single-cell multiome sequencing (scMultiome-seq) of human umbilical cord blood CD34+ cells. The authors identified transcriptional and epigenetic adaptations associated with maintaining HSC identity under culture conditions that limit excessive cell-cycle activation, linking these molecular states to improved functional long-term HSC expansion. This provides mechanistic guidance for optimizing HSC culture protocols to reduce myeloid bias and preserve self-renewal for potential regenerative medicine applications.

Mao X, Zhang N, He X et al. · Blood · (2026) · View on PubMed ↗

AI-designed viral genomes.

This article discusses the concept and implications of AI-designed viral genomes, focusing on the generation of functional viral genome sequences and the associated biosafety/biosecurity risks. The key point is that computational design approaches can produce viable viral genomes, raising urgent concerns about misuse and the need for governance. Scientifically and clinically, it frames how genome design capabilities must be paired with risk assessment, safeguards, and policy to prevent harmful applications.

Inglesby TV, Hanke MS · Science (New York, N.Y.) · (2026) · View on PubMed ↗

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Rare Disease Care Models & Clinical Pathways

Developing consensus on rare disease care pathways and ERN integration across Europe: insights from stakeholder workshops and a Delphi study.

This exploratory study used stakeholder workshops and a Delphi consensus process to develop agreement on rare disease care pathways and how to integrate them with European Reference Networks (ERNs) across Europe. It gathered input from stakeholders across 16 European countries (within the JARDIN project), aiming to produce a shared consensus-based framework for coordinated care. The work is significant for standardizing cross-border rare disease service delivery and improving implementation of ERN-aligned pathways for genetic diagnosis and multidisciplinary management.

Juozapavičiūtė-Dvinelė A, Tsang-A-Sjoe MWP, Auzenbaha M et al. · European journal of medical genetics · (2026) · View on PubMed ↗ · Free PDF ↗

How I treat autoimmune neutropenia in adults.

This review article summarizes current approaches to diagnosing and managing autoimmune neutropenia (AiN) in adults, contrasting it with pediatric disease. The key clinical points are that adult AiN is typically chronic, occurs predominantly in females and often alongside other autoimmune conditions, anti-neutrophil antibodies are detected in about half of cases, and many patients remain asymptomatic even with persistently low absolute neutrophil counts (ANC <500/µL). The significance is practical: it consolidates evidence-based management strategies for a rare adult hematologic disorder and highlights the need to consider both antibody-mediated and cell-mediated mechanisms.

Leaf RK, Sykes DB · Blood · (2026) · View on PubMed ↗ · Free PDF ↗

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Evolution, Aging & Reproductive Biology

Large-scale whole-genome sequencing reveals the landscape and health implications of de novo mutations.

This study used large-scale whole-genome sequencing of 24,030 individuals from 7,851 parent-offspring families to characterize de novo single-nucleotide variants (dnSNVs) and assess how parental age and assisted reproductive technology (ART) relate to de novo mutation patterns and offspring health. It found distinct paternal versus maternal mutational patterns, with maternal de novo mutation accumulation accelerating at advanced ages and paternal dnSNVs partially explaining the link between advanced parental age and shorter gestation. These findings improve scientific understanding of how reproductive factors shape germline mutation burden and may help refine risk assessment for congenital disease and adverse pregnancy outcomes.

Qin N, Dai J, Jiang Y et al. · Nature medicine · (2026) · View on PubMed ↗

Cell size reduction distinctly scales spindle elongation and chromosome segregation in C. elegans.

This study used high-resolution lattice light-sheet fluorescence microscopy with automated image analysis to quantify mitotic spindle and chromosome segregation dynamics across 2- to 64-cell Caenorhabditis elegans embryos under wild-type and size-perturbed conditions. It found that reducing cell size scales spindle elongation with cell size but leaves chromosome segregation dynamics largely invariant, indicating distinct mechanisms for these mitotic processes. The combination of femtosecond laser ablation and electron tomography further supports a mechanistic separation that helps explain how embryos maintain accurate chromosome segregation during developmental scaling.

Okafornta CW, Farhadifar R, Fabig G et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Neuronal expression of bromodomain proteins alters neuronal health and peripheral protein homeostasis to promote longevity.

The study investigated how neuronal overexpression of the C. elegans bromodomain protein bet-1 affects organismal longevity and stress resilience, focusing on cell-nonautonomous signaling to peripheral tissues. Neuronal bet-1 promoted longevity via a neurotransmitter-dependent pathway that activated the intestinal stress-responsive transcription factor HSF-1, improving proteostasis, oxidative stress resistance, metabolic remodeling, and immune defense, with lifespan extension requiring hsf-1 and daf-16 in neurons but only hsf-1 in peripheral tissues. These findings connect chromatin-reader function (bet-1) to systemic proteostasis and stress programs, suggesting conserved mechanisms that could be leveraged for longevity and resilience interventions.

Dutta N, Hicks D, Esparza E et al. · Genes & development · (2026) · View on PubMed ↗ · Free PDF ↗

Revisiting the Links Between Asthma and the Psychosis Spectrum: shared molecular mechanisms.

This study examined shared molecular mechanisms linking asthma to the psychosis spectrum using observational cohort data, polygenic risk scores, and Mendelian randomization (MR), with genetic colocalisation to assess shared genetic architecture. It reported that asthma at age 7 and polygenic risk for asthma were associated with psychotic experiences in early adulthood in a UK prospective birth cohort, supporting a potential causal or shared-genetic relationship. Clarifying these links could inform risk stratification and mechanistic research into neuropsychiatric outcomes in people with asthma.

Dardani C, Robinson JW, Havdahl A et al. · Biological psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗

Lactobacillus gasseri postbiotics ameliorate age-related decline in endometrial receptivity.

This study investigated how age-related changes in the endometrial microbiome affect endometrial receptivity, using a cross-sectional human cohort with clinical follow-up and functional screening of reproductive tract isolates. It identified an age-associated shift away from Lactobacillus-enriched states toward increased Lactobacillus iners, linked to impaired receptivity and worse embryo transfer outcomes, and highlighted Lactobacillus gasseri as a candidate strain with antioxidant activity. These findings suggest microbiome-targeted interventions (e.g., L. gasseri postbiotics) could mitigate age-related fertility decline by improving endometrial receptivity.

Li M, Li S, Zheng D et al. · Cell host & microbe · (2026) · View on PubMed ↗ · Free PDF ↗

Why studying females reveals more about aging: The reproductive resilience hypothesis for the evolution of sex-specific aging.

This Cell article proposes the reproductive resilience hypothesis to explain sex-specific aging patterns by integrating how female reproductive strategies (including prolonged survival and caregiving) shape selection pressures on survival. The key finding is the hypothesis that when reproductive success depends on extended survival, natural selection favors mechanisms that slow aging in females, helping explain why females often outlive males and why eusocial queens can show both extreme fecundity and longevity. This provides a new evolutionary framework for studying sex differences in aging and for generating testable predictions about how reproductive ecology drives longevity biology.

Singh P, Tanwar V, Xiang Y et al. · Cell · (2026) · View on PubMed ↗

Does Toxoplasma gondii infection have a causal impact on human psychopathology? A Mendelian randomization analysis.

This two-sample Mendelian randomization analysis used genome-wide association study (GWAS) data from European populations to test whether genetically predicted Toxoplasma gondii exposure—instrumented by 25 SNPs for anti-T. gondii IgG seropositivity and 76 SNPs for anti-T. gondii IgG levels—causally affects human psychopathology and risk-taking behaviors. The analysis did not support causal effects of T. gondii exposure on outcomes including addiction, bipolar disorder, obsessive-compulsive disorder, schizophrenia, or risk-taking behavior, contrary to prior observational associations. Scientifically, the results weaken the case for a direct causal role of T. gondii in these psychiatric phenotypes and illustrate how genetic instruments can clarify confounding in infection–mental health hypotheses.

Pang J, Valente MJ, Kim K et al. · PLoS pathogens · (2026) · View on PubMed ↗

A central role for dietary sugars in human evolution.

This study modeled human evolution of macronutrient distribution over ~4 million years to test the role of dietary sugars in meeting glucose demands for brain enlargement and reproduction. The key finding is that before cooking made starch readily digestible, sugars from fruit and honey likely provided >25% of dietary energy and specifically supplied obligatory glucose, with pounding/cooking releasing glucose. This is significant because it reframes early hominin dietary evolution as glucose-driven rather than primarily animal-food-driven, linking metabolism to brain evolution.

Brand-Miller J, Hardy K, Raubenheimer D et al. · Science (New York, N.Y.) · (2026) · 1 citations · View on PubMed ↗

Systems genetics approaches model the heritable architecture of polyendocrine metabolic ovarian syndrome.

This study used systems genetics to model the heritable architecture of polyendocrine metabolic ovarian syndrome (PMOS/PCOS) across mice and humans. By integrating genetic diversity and environmental factors, it identified conserved drivers of PMOS and its comorbidities, pinpointed susceptible cell types and organs, and proposed mechanisms connecting PMOS to downstream disease risk. These insights provide a framework for prioritizing causal pathways and potential interventions for PMOS-associated metabolic and cardiovascular complications.

Nguyen CM, Velez LM, Cheon Y et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on August 08, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.