Lee et al. integrate structural brain MRI with plasma proteomics to identify a three-region brain age model that predicts mortality more accurately than global measures and reveals shared immune and vascular mechanisms. These findings support regional brain aging as a scalable biomarker for precision geromedicine.

Wang et al. develop a standardized reaggregated glioblastoma organoid (rGBO) platform that enables scalable evaluation of patient-specific treatment responses. The platform links organoid radiosensitivity with patient survival, identifies response-related transcriptomic signatures, and reveals BET inhibition as a strategy to enhance radiotherapy efficacy in organoid and xenograft models.

Chen et al. establish a translational functional pipeline to reclassify OTOF variants of uncertain significance. This pipeline enables definitive molecular diagnosis and eligibility for gene therapy trials; it further reveals that K1992R drives pathogenicity in the E1700Q haplotype via disrupting otoferlin localization.

Zhao et al. investigate the role of the tongue microbiome in prediabetes and glycemic dysregulation. Rothia mucilaginosa and microbial nitrate metabolism are associated with lower prediabetes prevalence and improve the prediction of prediabetes progression, highlighting oral nitrate metabolism as a potential modifiable link between the oral microbiome and metabolic health.

Yang et al. demonstrate, in primates, that a fusion-loop-engineered Zika mRNA vaccine confers full protection with negligible dengue ADE. The response is dominated by convergent B cells orthologous to human IGHV5-10-1 whose antibodies target a distinct viral hotspot, with DENV envelope N67-linked glycan preventing cross-reactivity for safer flavivirus vaccines.

Chronic pain is a complex neurobiological problem whose solution is elusive. Powell et al. describe an approach to reduce chronic neuropathic pain in rodent models using a short lipidated peptide designed to inhibit the interaction between Nav1.8 and Ankyrin-3.

Xu et al. show that blocking the CD47-SIRPα phagocytic checkpoint paradoxically elevates tumor-derived PCSK9, which degrades MHC-I on macrophages and impairs antigen cross-presentation to CD8+ T cells. A bispecific fusion protein co-targeting CD47 and PCSK9 overcomes this resistance, restoring T cell priming and achieving tumor control with improved safety.

Cha and Kim review two decades of iPSC-based translation in neurodegenerative disease, highlighting disease-specific therapeutic logic and the emerging importance of transplantation biology. They propose a phase-resolved framework for the post-transplant “biological black box” linking graft survival, maturation, host interactions, and long-term therapeutic outcome.

Sheng et al. integrate spatial multi-omics, functional models, and clinical validation to show that fibrotic stroma suppresses epithelial cGAS-STING signaling and T cell recruitment in HCC. Their GCSS model links tumor architecture to response prediction for TACE plus immune checkpoint blockade.

Jo et al. show that transient OSKM induction generates two distinct liver progenitor-like cell populations with limited immune activation. Liver-targeted OSKM mRNA-LNPs induce hepatocyte dedifferentiation and enhance regeneration after acetaminophen-induced liver injury, supporting transient hepatic reprogramming as a strategy for inducing regenerative plasticity with therapeutic potential for acute injury.

Fu and Ma et al. develop DVH to edit DCs into CCR7+IL-7+ DCs, which target the T-zone within TDLNs and secrete IL-7 to promote Tscm differentiation. The Tscms can self-renew and generate effector T cells under antigen stimulation continuously, thereby killing tumor cells and reducing T cell exhaustion at the source.

German et al. use integrated multi-omics analysis to identify EZH2 as a central regulator of prostate cancer phenotypic plasticity. The study reveals TTP-associated pathways and adaptive PI3K/mTORC1 as mediators of response to EZH2 inhibition and demonstrates that co-targeting EZH2 and PI3K/mTORC1 is an effective strategy in aggressive prostate cancer models.

Guan et al. develop an IAA-assisted engineered bacterial therapy for pancreatic cancer. IAA suppresses neutrophil recruitment and synergizes with gemcitabine to eliminate neutrophils, boosting bacterial colonization and antitumor immune efficacy.

Van Renne, Agostinetto, et al. perform a multi-omics characterization of advanced TNBC to identify response predictors and treatment-induced dynamics during chemo-ICI. Poor outcomes are associated with fibrovascular and myeloid remodeling, highlighting coordinated resistance mechanisms, actionable therapeutic targets, and the value of microenvironment-based stratification for future ICI-based trials.

Handal et al. isolate a panel of naturally occurring human monoclonal antibodies against the measles fusion protein that potently neutralize in vitro and inhibit viral replication in vivo, demonstrating strong clinical potential. Two antibodies bind distinct portions of the F protein simultaneously with epitopes spanning across multiple F protomers.

Chen et al. identify two neutralizing antibodies, G4 and B9, targeting distinct epitopes on the mpox virus M1R protein (an L1R homolog). Despite targeting a conventional epitope, G4 overcomes Asp35-associated neutralization escape. Both antibodies protect against multiple orthopoxviruses in vitro and in vivo, supporting their potential as broad-spectrum antiviral candidates.

(Cell Reports Medicine 6, 102510; December 16, 2025)

Johnson et al. review how human induced pluripotent stem cells can model key stages of myocardial infarction, focusing on cell types involved across acute injury, repair, and remodeling. They examine current model strengths and limitations and discuss emerging applications in therapeutic discovery, patient-specific modeling, and regenerative cardiac repair.

Xiong et al. identify that punicalin broadly inhibits respiratory syncytial virus subtypes and clinical isolates by targeting the viral G and F proteins at sites outside known resistance hotspots. It retains potent activity against drug-resistant virus and, when delivered by nebulization, reduces pulmonary viral burden and inflammation in infected mice.

Wang et al. report that inhibition of EZH2 and, to lesser degree, other epigenetic modifiers promotes expression of ROR1 neoantigen on malignant cells. CART cells targeting ROR1 are able to detect the neoantigen at very low concentration and, in combination with EZH2 inhibition, highly effectively eliminate the ROR1-expressing cells.

Mandai et al. review iPSC-derived photoreceptor replacement therapy, contrasting cone precursor and retinal organoid transplantations. They highlight host-dependent cone integration, gene-edited organoids for enhanced integration, and synaptic rewiring in the adult primate retina, providing a framework to restore vision in patients with untreatable retinal degenerations.

Bernshtein et al. show that functional antibodies correlate with milder shigellosis at any age, yet only individuals over 5 years of age mount lasting responses to the surface O-specific polysaccharide that drives Shigella uptake by phagocytes and triggers IL-1β and IL-18 release.

Chen et al. apply multimodal cell-free DNA (cfDNA) profiling via TET-assisted pyridine borane sequencing to moyamoya disease. They identify cfDNA methylation signatures that distinguish moyamoya disease from atherosclerotic cerebrovascular disease and predict postoperative collateral formation, supporting minimally invasive diagnosis and preoperative assessment of moyamoya disease.

Grazda et al. show that defective inflammation resolution persists in autoimmune bone marrow failure, despite standard-of-care cyclosporine A therapy. Combining resolvin E1 with cyclosporine A restores immune homeostasis while reducing toxicity.

Irajizad et al. report a blood-based metabolite panel for earlier detection of lung cancer. The metabolite panel complements clinical risk models for lung cancer incidence and mortality. The panel provides a means for identifying ever-smoker individuals at elevated 1-year risk of lung cancer who would benefit from lung cancer screening.

Godinho et al. provide an overview of nucleic acid therapies, a new class of programmable drugs that enable disease-modifying treatments by acting at the gene transcript level. The authors summarize key advances in chemistry and delivery and offer a perspective on the advances expected in the near future.

Zhang et al. identify a key profibrotic function of FBXL6 in hepatic stellate cells through activation of the RPL4-YY1-PD-L1-PI3K-AKT-mTOR axis. Targeting RPL4 in combination with PD-L1 blockade achieves near-complete resolution of liver fibrosis.

Pan et al. combine single-cell lipidomics and graph deep learning to identify occult peritoneal metastasis in gastric cancer. The label-free platform detects rare free cancer cells, supports molecular stratification, and delivers patient-level diagnostic results within 30 min.

Duzagac et al. show that circulating tissue-surveillance neoantigen-specific T cells are detectable in Lynch syndrome carriers, even before cancer onset. Their metabolic states differ by disease stage, separating cancer-free carriers from survivors. Public TCRs spanning blood and tumor tissue open a non-invasive window for immunoprevention in mismatch repair-deficient cancers.

Gustav et al. introduce a concept-level explainability framework that exposes the morphology encoded by a pathology foundation model. The approach reveals prototypical histopathological features and maps the organization and overlap of tissue and cancer concepts, demonstrating that internal model representations reflect both task complexity and pathologist ambiguity.

Tignor et al. perform a comprehensive proteogenomic analysis of pediatric and AYA high-grade gliomas and identify age- and sex-dependent biology, candidate kinase targets, and proteins and immune signatures associated with poor survival outcomes.

Shen et al. map the evolutionary trajectory of multi-drug resistance (MDR) across cancers, revealing a biophysical spatial nexus formed by specific fibroblasts, macrophages, and tumor cells. They demonstrate that dismantling this multicellular barrier-like niche with an FAP/TREM2 bispecific antibody safely restores therapeutic sensitivity, highlighting a targeted strategy to resensitize MDR.

Zhou et al. identify ellagic acid (EA) as an allosteric inhibitor of YTHDF proteins that binds to a conserved site shared across YTHDF family members. By disrupting YTHDF2-mediated RNA decay, EA stabilizes PFKFB4 mRNA to prevent HIF-1α degradation and upregulates BNIP3 expression, thereby driving triple-negative breast cancer cell death.

Jiao et al. develop an inhalable, single-dose rAAV/DJ-vectored mpox vaccine. The optimal formulation, MV-C, elicits durable mucosal and systemic immunity, inducing neutralizing antibodies and tissue-resident memory T cells, and confers protection against broad orthopoxvirus challenge.

Tavaglione and Loomba review the emerging role of GLP-1 mono, dual, and triple agonists in MASH-related fibrosis. These therapies target multiple metabolic and inflammatory pathways and show promising hepatic histological benefits, highlighting their potential to reshape MASH-related fibrosis treatment, while underscoring remaining challenges in treatment duration, tolerability, and individual response.

Feng et al. develop surface-engineered bacteria as the living therapeutic for tumor immunotherapy. Bacteria are genetically programmed to display surface-anchored B7H2 to provide co-stimulatory signal of T cells, and a Histag sequence. Coordinating zinc sulfide quantum dots with Histag images tumors and stimulates cGAS/STING pathway.

Shao et al. present LungGPT, a multimodal artificial intelligence system that fuses clinical features, lab tests and imaging to enhance respiratory healthcare. LungGPT enables accurate diagnoses, early warning of critical illness, and interpretable diagnostic reasoning and decision support, offering a powerful tool to streamline workflows and promote standardization in clinical practice.

Silva de Castro, Rahman, Bissa et al. show that an HIV vaccine candidate with an Env V1 deletion reduces SHIV acquisition risk by 81%, whereas an intact-V1 candidate is not efficacious. Protection is linked to mucosal Env IgG, V2-directed ADCC, CD73/ATP-adenosine signaling, and reduced mucosal inflammatory permissiveness to viral infection.

Olson et al. characterize multiple preclinical mechanisms associated with enfortumab vedotin activity, including direct and bystander cytotoxicity and induction of immunogenic cell death hallmarks. The findings provide mechanistic support for combining enfortumab vedotin with PD-1 inhibitors, such as pembrolizumab, in clinical settings.

Samarra et al. show that exclusive breastfeeding, through human milk oligosaccharides, shapes the infant gut resistome. Specific human milk oligosaccharides associate with reduced antibiotic resistance genes and modify delivery-related resistome differences, identifying human milk composition as a key regulator of early-life antimicrobial resistance.

Liu et al. developed a c-Met-targeting aptamer-drug conjugate (ApDC) that achieved robust anti-tumor efficacy across multiple c-Met-overexpressing tumor models through rapid tumor accumulation and payload release. Its maintained surface receptor expression and favorable pharmacokinetic properties contributed to greater efficacy than a benchmark c-Met-targeting ADC, highlighting its therapeutic promise.

Liu et al. demonstrate a cellular reprogramming strategy that directly transforms glioblastoma cells into functional dendritic cell-like cells. This in situ conversion remodels the tumor microenvironment and elicits robust, systemic antitumor immunity, offering a synergistic and promising approach for clinical cancer immunotherapy.

Saatci-Ulukan et al. show that lysyl oxidase (LOX) has non-canonical intracellular functions in promoting glucose metabolism, inhibiting mitophagy, and sustaining redox homeostasis and that inhibiting LOX creates a targetable vulnerability to DHODH-inhibition-mediated ferroptosis in chemo-free setting in triple-negative breast cancer, the deadliest subtype.

Sandholzer et al. track tumor-reactive T cells across TIL therapy in metastatic melanoma using single-cell RNA and TCR sequencing. They show how ex vivo expansion reshapes CD8+ and CD4+ T cell states and links type 17 T cell co-transfer and regulatory T cell expansion to treatment resistance.

Wang et al. report the efficacy of a preliminary cohort of patients who receive first-line fecal microbiota transplantation for the management of immune-mediated diarrhea and colitis with multi-omics characterization. Response is seen in 10 out of 13 patients, with an increase in alpha-diversity in a majority of patients who respond.

Yu et al. identify L013 as an NRF2-targeting agent that reduces NRF2 via UPS-associated degradation and A51-mediated suppression. L013 inhibits tumor growth in preclinical models, revealing therapeutic potential for NRFA-subtype ESCC.

Transition from ductal carcinoma in situ (DCIS) to invasive breast cancer remains a key step in disease progression that is poorly understood. Taifour et al. show that neutrophil elastase disrupts the myoepithelial barrier to promote invasive progression, identifying neutrophil elastase as a potential therapeutic target for high-risk DCIS.

Bennike et al. profile plasma proteins and cytokines/chemokines in 679 healthy newborns through mass spectrometry and immunoassays to characterize immune adaptation during the 48 h immediately after birth at bi-hourly resolution. They reveal non-linear trajectories and sex-specific differences especially during day-of-life one, providing a molecular framework for early-life immune development.

Esposito et al. develop a donor-optimized, mutation-agnostic AAV-HITI strategy for dominant rhodopsin-associated retinitis pigmentosa that simultaneously disrupts the mutant RHO P23H allele and restores rhodopsin expression through targeted integration at the human RHO locus, improving retinal structure, function, and vision in a semi-humanized mouse disease model, up to one year.