Early-life immune imprinting by a B. infantis-HMO synbiotic shapes infant immune signatures and protects against experimental respiratory disease

Rashid et al. report that an infant-type Bifidobacterium infantis-HMO synbiotic shapes immune signatures and reduces Th2 bias in formula-fed infants toward a breastfed-like profile. In experimental models, it protects against bronchiolitis and confers lasting immune effects into adulthood, associated with increased 12-HHT, a lipid mediator sufficient to promote disease tolerance.

dlvr.it

Targeting Gi/o-coupled GPCRs to inhibit nociceptors: Insights from the serotonin receptor Htr1b and triptans

Peng et al. develop a preclinical screening platform that identifies Gi/o-coupled and orphan GPCRs enriched in CGRP+ mouse and human DRG neurons. Using Htr1b and triptans as proof of principle, they show that activating Gi/o-coupled GPCRs attenuates nociceptor excitability and reduces specific pain-related behaviors in mice.

dlvr.it

Köhlmeier-Degos disease is an interferonopathy characterized by type I and II interferon-driven inflammatory vasculopathy

Cudrici et al. examine inflammatory vascular injury in Köhlmeier-Degos disease. Single-cell profiling of skin, blood, and cerebrospinal fluid reveals type I and II interferon activation and cytotoxic T cell involvement, while ruxolitinib treatment in one patient is associated with suppression of interferon programs.

dlvr.it

An antibody-PROTAC conjugate targets BRD4/c-Myc/PD-L1 to enhance immunotherapy efficacy in triple-negative breast cancer

Gu et al. develop ASA, an antibody-PROTAC conjugate for TNBC, that integrates tumor homing, hypoxia-responsive cleavage, and PROTAC-mediated degradation. This design enables targeted degradation within tumors and promotes robust antitumor immunity and long-term immune memory when combined with αPD-L1.

dlvr.it

Persistent cytolytic CD8+ T cells recognize SARS-CoV-2 and herpesvirus epitopes in long COVID

Ma et al. perform deep-phenotyping of CD8+ T cells specific for viruses implicated in LC pathogenesis: SARS-CoV-2, CMV, and EBV. These T cells from LC individuals share features of terminal differentiation, activation, exhaustion, and cytolysis. The inability to dampen acute-phase cytolytic viral-specific CD8+ T cell responses may be an LC feature.

dlvr.it

Tumor-induced dendritic cell deregulation perturbs T cell proliferation and predicts clinical outcome in acute lymphoblastic leukemia

Kumar et al. show that specialization of dendritic cells (DCs) into distinct functional subsets is disrupted in acute lymphoblastic leukemia (ALL). This disruption impairs the ability of DCs to prime T cells. DC phenotype in patient peripheral blood and bone marrow at ALL presentation is an indicator of their prognosis.

dlvr.it

Parent-of-origin effects in Alzheimer’s liability dissociate neurocognitive and cardiovascular traits in at-risk individuals

Savignac et al. show that parent-of-origin effects in Alzheimer’s disease extend beyond a classic gender-by-lineage model and instead reflect a complex, context-dependent genetic architecture. They identify and characterize three genetically anchored intermediate phenotypes, which display unique and spatially distributed gender and lineage biases across the brain and phenome.

dlvr.it

Real-time AR navigation with dynamic tracking for millimeter-level pulmonary nodule localization: A randomized clinical trial

Huang et al. compare real-time augmented-reality navigation with CT guidance for preoperative localization of small peripheral pulmonary nodules. In this randomized trial, AR guidance shows noninferior accuracy; reduces radiation exposure, procedure time, and needle adjustments; and maintains a safety profile comparable to CT guidance.

dlvr.it

DNA methylation profiling enables subclassification of mucinous ovarian carcinoma and distinguishes it from extraovarian mucinous metastases

Calina and Grafenhorst et al. using DNA methylation profiling of mucinous ovarian tumors characterize two mucinous ovarian carcinoma (MOC) subgroups with potential differing outcomes and describe epigenetic patterns consistent with the stepwise relationship between mucinous borderline ovarian tumor and MOC. An epigenetic classifier accurately distinguishes MOC from metastases, improving diagnosis.

dlvr.it

Therapeutic Gfral silencing via antisense oligonucleotides ameliorates cancer-associated cachexia and extends survival in tumor-bearing mice

Hong et al. demonstrate that silencing central GFRAL using an antisense oligonucleotide (ASO) reverses cancer-associated cachexia. In severe tumor models, a single central administration of the ASO mitigates muscle and adipose wasting, improves functional strength, and profoundly extends survival, highlighting receptor-targeted ASO therapy as a promising cachexia intervention.

dlvr.it

CRISPR-Cas9-producing probiotic bacteria for editing NOX2/gp91phox and treating inflammatory bowel disease

Zhang et al. prepare EcN-RNP hydrogel, aiming to treat IBD by inhibiting NOX2 expression via CRISPR-Cas9-mediated genome editing. The hydrogel enhances oxidative stress defense pathways and modulates glutamate and proline metabolism to reduce ROS.

dlvr.it

Combine antibody-drug conjugate with cmLumiOpto for triple-negative breast cancer treatment

Varadkar et al. show that combining a targeted antibody-drug conjugate with mitochondria-disrupting gene therapy shrinks tumors, halts metastasis, and activates the immune system in preclinical models with low toxicity, offering a promising therapeutic strategy for aggressive triple-negative breast cancer.

dlvr.it

Driving tumor-associated macrophages to a CXCL9Hi/SPP1Low phenotype eliminates pancreatic cancer

Immunosuppressive CXCL9Lo/SPP1Hi myeloid cells are highly abundant in PDAC, adding to the poor prognosis. Using the myeloid cell-targeting cyclodextrin nanoconstruct, Nguyen et al. found that simultaneously modulating CXCL9 and SPP1 through this single, systemically administered nanoformulation is highly effective in treating murine PDAC.

dlvr.it

A biomimetic hybrid membrane vesicle nanoplatform attenuates tendinopathy through neuroinflammation modulation and tendon regeneration

Li et al. develop an integrated nanoplatform for tendinopathy. The platform buffers inflammatory cytokines and pain-related neuropeptides, alleviates tendon stem/progenitor cell senescence, and improves tendon remodeling, pain behaviors, and function in rats.

dlvr.it

Self-sufficient killing of malignant tumors by an engineered cancer-selective gene circuit

Liu et al. present a synthetic cancer-selective promoter (PETS∗) that converts the aberrant expression profiles of ETS family transcription factors (e.g., amplification or gene fusion) into tumor-restricted gene expression in vivo, enabling self-sufficient elimination of malignant cells, while sparing fast-proliferating healthy tissues following adenovirus delivery.

dlvr.it

Combination of exosome vaccines, lenvatinib, and anti-PD-1 eradicates tumor in autochthonous hepatocellular carcinoma mice

Zuo et al. show that a dendritic cell-derived exosome vaccine combined with lenvatinib enhances intratumoral antigen presentation and T cell priming, while anti-PD-1 overcomes T cell exhaustion. This triple combination eradicates established autochthonous hepatocellular carcinoma in mice and generates durable antitumor immunity.

dlvr.it

A poly(I:C)/QS-21-based in situ vaccine synergizes with anti-PD-1 therapy to overcome tumor immunoresistance

Zhang et al. demonstrate that the combination of QS-21 and poly(I:C) facilitates the endosomal escape of poly(I:C) and enhances immunogenic cell death, thereby functioning as an in situ vaccine that potentiates CD8+T cell-mediated antitumor immunity and overcomes resistance to anti-PD-1 therapy.

dlvr.it

Efficacy and biomarker exploration of anlotinib plus penpulimab in second-line ES-SCLC: Results from the phase 2 ALTER-L041 trial

Zeng et al. show that combining penpulimab and anlotinib provides promising antitumor activity and a manageable safety profile in patients with platinum-resistant extensive-stage small cell lung cancer. This phase 2 trial suggests that this combination serves as a viable second-line treatment option.

dlvr.it

Fatty-acid-based antimiR-23b delivery in the DMSXL model: A potential therapeutic strategy for brain dysfunction in myotonic dystrophy type 1

Piqueras-Losilla et al. show that the fatty-acid-conjugated antimiR-23b X82108 reaches the brain after systemic administration in mice and non-human primates. X82108 increases MBNL1/2 levels, reduces toxic DMPK transcripts, corrects DM1-associated splicing defects, and improves behavioral abnormalities, resulting in broad correction of CNS defects in DMSXL mice.

dlvr.it

Nilotinib induces immunogenic cuproptosis to potentiate cancer immunotherapy

Yao et al. identify nilotinib, an FDA-approved anti-tumor drug, as a non-ionophore immunogenic cuproptosis inducer that potentiates anti-PD-1 immunotherapy. Mechanistically, nilotinib-copper represses ATP7A via ETV1 to drive mitochondrial copper accumulation and activates ERK2 phosphorylation to potentiate cuproptosis.

dlvr.it

Discovery of a peripherally restricted α2AAR agonist as a safe and broad-spectrum oral analgesic

Cheng et al. describe CC10137, an orally bioavailable, peripherally restricted α2AAR agonist. Unlike conventional analgesics, CC10137 achieves broad-spectrum pain relief across eight rodent models without CNS side effects, preserves protective nociceptive reflexes and synergizes with opioids, offering a promising non-opioid strategy for chronic pain.

dlvr.it

Targeted antibody-drug conjugates for rhabdomyosarcoma and other FGFR4-expressing cancers

Tian et al. develop FGFR4-targeted antibody-drug conjugates that selectively kill rhabdomyosarcoma and other FGFR4-expressing cancers. Their findings show that FGFR4 can be exploited to deliver potent cytotoxic payloads selectively to tumors, with an exatecan-based ADC producing durable tumor control in several aggressive preclinical models.

dlvr.it

Tryptophan degradation by intestinal Bacteroides induces anti-tumor immunity and limits melanoma growth

Diaz-Olea et al. identify indoles as tryptophan breakdown products that induce anti-tumor immunity and inhibit melanoma growth. Indoles, produced upon tryptophan breakdown by Bacteroides uniformis- (human) or Bacteroides rodentium- (mouse) encoded enzymes, induce anti-tumor immunity independent of AhR signaling. Patients who respond to ICB exhibit higher expression of these enzymes.

dlvr.it

Repurposed ethoxzolamide reprograms antitumor immunity through β-TrCP-dependent PD-L1 ubiquitination

Lin et al. reveal that the drug ethoxzolamide triggers the degradation of PD-L1, an immune-suppressing protein on cancer cells. This reprogramming of the tumor environment overcomes resistance to immunotherapy, suggesting a potential strategy for treating solid tumors.

dlvr.it

Preventative semaglutide and tirzepatide treatment does not alter disease progression in the 5xFAD mouse model of Alzheimer's disease

Vear et al. report that chronic semaglutide or tirzepatide treatment does not slow the progression of Alzheimer's disease neuropathology in two distinct mouse models, the 5xFAD mouse or lipopolysaccharide-treated mice. This guides the design of future preclinical investigations testing next-generation incretin mimetics for brain diseases.

dlvr.it

Core gastric microbiota linked to pathogenesis and preserved across age-stratified cohorts

Huang et al. identify a core gastric microbial network established in early childhood. They show that imbalance within this antagonistic network is associated with pediatric peptic ulcer and is exacerbated by Helicobacter pylori. This ecological framework predicts gastric disease risk across age groups, providing potential targets for precision microbiome medicine.

dlvr.it

Differential T cell clonal dynamics underlie outcomes to frontline chemoimmunotherapy in advanced gastric cancer

Wright et al. use serial single-cell RNA/TCR sequencing to show that durable benefit from gastric cancer chemo-immunotherapy associates with persistence of putative tumor-reactive progenitor-exhausted T cells, circulating TCR clones that infiltrate tumors after immunotherapy, increased B cell abundance after chemotherapy, and B cell interactions that support T cell persistence.

dlvr.it

Targeting cytokine-like protein FAM3D alleviates atherosclerosis

Shirong Zhu et al. found that elevated circulating FAM3D levels are associated with the incidence of atherosclerosis in humans. FAM3D exacerbates atherosclerosis through both lipid-dependent and lipid-independent mechanisms. Treatment with FAM3D antibodies significantly alleviates atherosclerosis in mice, highlighting FAM3D as a promising therapeutic target for combating atherosclerosis.

dlvr.it

Metabolomic and lifestyle profiles refine BMI-metabolic phenotypes in older adults

Chen et al. apply large-scale metabolomics to develop machine learning models that accurately classify metabolic dysfunction within each BMI category, derive a BMHS that independently predicts mortality beyond BMI-metabolic phenotypes, and, when combined with lifestyle factors, further refine metabolic risk stratification, offering scalable precision management for older adults.

dlvr.it

High-dose furmonertinib as first-line treatment for untreated EGFR-mutated advanced NSCLC with central nervous system metastases: A phase 2 trial

Yan et al. demonstrate that high-dose furmonertinib delivers promising intracranial efficacy for untreated EGFR-mutated NSCLC patients with CNS metastases. This phase II study reports a median progression-free survival of 16.59 months, significant early molecular clearance in plasma and cerebrospinal fluid, and manageable safety.

dlvr.it