Results 151 to 160 of about 7,145 (238)

High‐Fidelity Synthetic Data Replicates Clinical Prediction Performance in a Million‐Patient Diabetes Cohort

open access: yesAdvanced Science, EarlyView.
This study generates high‐fidelity synthetic longitudinal records for a million‐patient diabetes cohort, successfully replicating clinical predictive performance. However, deeper analysis reveals algorithmic biases and trajectory inconsistencies that escape standard quality metrics. These findings challenge current validation norms, demonstrating why a
Francisco Ortuño   +5 more
wiley   +1 more source

F‐Box and Leucine‐Rich Repeat Protein 4 (FBXL4) Maintains Sarcomere Integrity and Cardiac Function by Enhancing K48‐Linked Ubiquitinated Degradation of Profilin‐1 (PFN1)

open access: yesAdvanced Science, EarlyView.
Schematic diagram depicting the proposed signaling mechanisms underlying the effects of FBXL4 in the setting of cardiac hypertrophy. Under hypertrophic stimulation, cardiomyocytes‐specific overexpression FBXL4 maintains sarcomere integrity and cardiac function by enhancing K48‐linked ubiquitinated degradation of PFN1 at the K70 site.
Xingda Li   +11 more
wiley   +1 more source

Single‐Cell Atlas of Subchondral Bone Marrow Lesions Reveals Proteostasis Dysfunction as a Druggable Mechanism for Early Osteoarthritis

open access: yesAdvanced Science, EarlyView.
This study reveals that abnormal mechanical stress downregulates the expression of HSP70 and impairs proteasome function in osteoarthritic bone cells, leading to misfolded collagen I accumulation and ER stress. When intracellular proteostasis capacity is exceeded, USP19 mediates the secretion of misfolded proteins into the extracellular space ...
Hailun Xu   +20 more
wiley   +1 more source

β‐Adrenergic Signaling Promotes Anti‐Tumor Immunity in TP53‐mutant Oral Squamous Cell Carcinoma

open access: yesAdvanced Science, EarlyView.
β‐adrenergic stimulation enhances anti‐tumor immunity in TP53‐deficient oral squamous cell carcinoma by inducing tumor‐derived secretion of CXCL10, which attracts and activates cytotoxic CD8+ T cells. The findings demonstrate that β‐adrenergic signaling alters tumor–immune interactions via CXCL10‐mediated paracrine activation, revealing a neuro‐immune ...
Frederico O. Gleber‐Netto   +20 more
wiley   +1 more source

Mapping Genetic Regulation of Transcription to Identify Functional Variants and Genes Associated with Pancreatic Cancer Risk

open access: yesAdvanced Science, EarlyView.
Integration of a pancreatic eQTL map with a GWAS meta‐analysis identifies 82 putative functional variants and 15 genes. The association between rs11102484 and pancreatic cancer risk is observed in a total of 5699 cases and 8467 controls. The G allele of rs11102484 weakens ZNF263 binding and the silencer‐promoter interaction, thereby increasing ST7L ...
Xiaoyang Wang   +14 more
wiley   +1 more source

GPCRs in CAR‐T Cell Immunotherapy: Expanding the Target Landscape and Enhancing Therapeutic Efficacy

open access: yesAdvanced Science, EarlyView.
Chimeric antigen receptor T cell therapy faces dual challenges of target scarcity and an immunosuppressive microenvironment in solid tumors. This review highlights how G protein‐coupled receptors can serve as both novel targets to expand the therapeutic scope and functional modules to enhance CAR‐T cell efficacy.
Zhuoqun Liu   +11 more
wiley   +1 more source

Distinct Immunomodulatory Strategies Guide Mesenchymal Stromal/Stem Cell‐Mediated Bone Regeneration

open access: yesAdvanced Science, EarlyView.
Bone regeneration by mesenchymal stem cells is strongly influenced by immune signals. This study shows that priming stem cells with regulatory immune cells or an inflammation‐resolving lipid molecule enhances bone formation through distinct immune pathways.
Salwa Suliman   +5 more
wiley   +1 more source

Identification of A p300–SP1–BRD4 Transcriptional Axis as a Key Driver of AR Hyperactivation in Polycystic Ovarian Syndrome

open access: yesAdvanced Science, EarlyView.
This study reveals a pivotal epigenetic regulatory role for the histone acetyltransferase p300, demonstrating that its acetylation of histone 3 at lysine 18 and 27 (H3K18ac and H3K27ac), alongside the formation of the p300/BRD4/SP1 complex, drives AR activation and ovarian fibrosis in PCOS.
Zhengquan Zhu   +11 more
wiley   +1 more source

Sensory Nerve‐Derived CGRP Controls Osteoclastogenesis by Limiting Macrophage Bioenergetics in Bone Repair

open access: yesAdvanced Science, EarlyView.
Sensory nerves help bones heal. This study shows that the neuropeptide CGRP, released from sensory nerves, slows down macrophage energy production, preventing excessive bone breakdown. By revealing this nerve–immune–metabolism connection, the work provides new insight into how the body balances bone repair and opens doors to targeted treatments ...
Jiaying Liu   +10 more
wiley   +1 more source

Combination Immunotherapy as a Promising Strategy to Overcome Immunotherapy Resistance: From Emergence to Next‐Generation Approaches

open access: yesAdvanced Science, EarlyView.
This review examines emerging combination immunotherapy strategies tailored to distinct tumor microenvironments and highlights next‐generation biomarkers that guide response prediction and treatment personalization. It integrates lessons from unsuccessful trials, addresses toxicity challenges, and outlines approaches for early biomarker discovery and ...
Asmita Pandey   +6 more
wiley   +1 more source

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