Ceramides play a central role in human health and disease, yet their role as systemic signaling molecules remain poorly understood. In this work, we identify FPR2 as a membrane receptor that specifically binds long-chain ceramides (C14-C20). In brown and beige adipocytes, C16:0 ceramide binding to FPR2 inhibits thermogenesis via G-cyclic AMP signaling pathways, an effect that is reversed in the absence of FPR2.
View Article and Find Full Text PDFBrain age gap (BAG), the deviation between estimated brain age and chronological age, is a promising marker of brain health. However, the genetic architecture and reliable targets for brain aging remains poorly understood. In this study, we estimate magnetic resonance imaging (MRI)-based brain age using deep learning models trained on the UK Biobank and validated with three external datasets.
View Article and Find Full Text PDFEmerging evidence indicates that lipid droplets (LDs) play important roles in lipid metabolism, energy homeostasis, and cell stress management. Notably, dysregulation of LDs is tightly linked to numerous diseases, including lipodystrophies, cancer, obesity, atherosclerosis, and others. The pivotal physiological roles of LDs have led to an exploration of research in recent years.
View Article and Find Full Text PDFLinking-site engineering, used to graft two or more monomers, is crucial for achieving high-performance Y-series giant molecule acceptors (Y-GMAs). However, the reported Y-GMAs all use a single-typed linking site, making it difficult to finely-tune their optoelectronic properties. Herein, we develop a non-fully conjugated Y-GMA (named 2Y-we), with hybrid linking sites at the wing and end-group of monomers, to combine the respective advantages of the wing and end-group site linked counterparts.
View Article and Find Full Text PDFBackground: The COVID-19 pandemic has posed unprecedented challenges to the nursing profession, exacerbating occupational stress, attrition rates, and staffing shortages. Although prior studies have examined factors influencing nursing turnover intention, no research has compared turnover intention among Chinese hospital nurses during the full liberalization of COVID-19 and the postpandemic era. The aim of this study was to investigate the prevalence and associated factors of turnover intention during these two critical periods.
View Article and Find Full Text PDFACS Appl Bio Mater
February 2025
Plant exosomes, small vesicles released by plant cells that contain various bioactive molecules, have garnered great attention for their potential applications in medicine, yet their delivery applications for skincare remain underexploited. Resveratrol (RES), renowned for its remarkable antiaging properties, faces challenges in transdermal absorption due to the stratum corneum barrier, hindering its efficacy. To address this, we developed a delivery system incorporating RES-loaded plant () exosome (EXO@RES).
View Article and Find Full Text PDFEquilibrioception (sensing of balance) is essential for mammals to perceive and navigate the three-dimensional world. A rapid mechanoelectrical transduction (MET) response in vestibular hair cells is crucial for detecting position and motion. Here, we identify the G protein-coupled receptor (GPCR) LPHN2/ADGRL2, expressed on the apical membrane of utricular hair cells, as essential for maintaining normal balance.
View Article and Find Full Text PDFSingle-cell ATAC-seq technology advances our understanding of single-cell heterogeneity in gene regulation by enabling exploration of epigenetic landscapes and regulatory elements. However, low sequencing depth per cell leads to data sparsity and high dimensionality, limiting the characterization of gene regulatory elements. Here, we develop scAGDE, a single-cell chromatin accessibility model-based deep graph representation learning method that simultaneously learns representation and clustering through explicit modeling of data generation.
View Article and Find Full Text PDFThe critical challenge in advancing liquid metal circuits (LMCs) lies in achieving interfacial compatibility with diverse substrates while dynamically balancing fabrication efficiency and quality to ensure robust conductive stability. Here we introduce an electrochemical redox synergistic liquid metal (E-rsLM) that enables the controllable generation of diverse intermetallic bond transition layers (Cu, Au, or Fe-based) between liquid metal and unrestricted substrate surfaces, applicable in pH-universal electrolytes. It involves enhanced locomotion of the liquid metal, driven by synergistic electrochemical energy transduction from cyclic changes in gallium redox states.
View Article and Find Full Text PDFPrevious research has established Type 2 Diabetes Mellitus as a significant risk factor for various disorders, adversely impacting human health. While evidence increasingly links type 2 diabetes to cognitive impairment and brain disorders, understanding the causal effects of its preclinical stage on brain health is yet to be fully known. This knowledge gap hinders advancements in screening and preventing neurological and psychiatric diseases.
View Article and Find Full Text PDFObesity increases the risk of depression. Evidence shows that peripheral inflammation, glycemic dysregulation, and hyperactivity within the hypothalamic-pituitary-adrenal axis are implicated in both obesity and depression. In this study we investigated the impact of visceral adipose tissue (VAT), a crucial characteristic of obesity, on stress susceptibility in obese mice.
View Article and Find Full Text PDFCherry eye, the common name for the prolapse of the third eyelid gland in dogs, is a widespread ophthalmic disease affecting dogs of various breeds. This condition severely affects the quality of life of affected dogs, and its underlying cause remains unresolved. In this study, 170K SNP microarray data were collected from 653 brachycephalic dogs and 788 brachycephalic and mesocephalic dogs.
View Article and Find Full Text PDFFLASH radiotherapy holds promise for treating solid tumors given the potential lower toxicity in normal tissues but its therapeutic effects on tumor immunity remain largely unknown. Using a genetically engineered mouse model of medulloblastoma, we show that FLASH radiation stimulates proinflammatory polarization in tumor macrophages. Single-cell transcriptome analysis shows that FLASH proton beam radiation skews macrophages toward proinflammatory phenotypes and increases T cell infiltration.
View Article and Find Full Text PDFColonization of co-evolved, species-specific microbes in early life plays a crucial role in gastrointestinal development and immune function. This study hypothesized that modern pig production practices have resulted in the loss of co-evolved species and critical symbiotic host-microbe interactions. To test this, we reintroduced microbes from wild boars (WB) into conventional piglets to explore their colonization dynamics and effects on gut microbial communities, metabolite profiles, and immune responses.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Introduction: Traditional Miao and Dai Chinese medicines have used nicotine-rich leaf tobacco to treat traumatic injuries by promoting hemostasis. While nicotine is known to enhance platelet aggregation, its effects on other platelet functions and underlying mechanisms remain unclear.
Methods And Results: This study aimed to thoroughly investigate nicotine's effects on human platelets and its pharmacological mechanisms, using thromboelastography to assess nicotine's impact on platelet function during coagulation.
Androgens, such as 5α-dihydrotestosterone (5α-DHT), regulate numerous functions by binding to nuclear androgen receptors (ARs) and potential unknown membrane receptors. Here, we report that the androgen 5α-DHT activates membrane receptor GPR133 in muscle cells, thereby increasing intracellular cyclic AMP (cAMP) levels and enhancing muscle strength. Further cryoelectron microscopy (cryo-EM) structural analysis of GPR133-Gs in complex with 5α-DHT or its derivative methenolone (MET) reveals the structural basis for androgen recognition.
View Article and Find Full Text PDFBone defects are a prevalent issue resulting from various factors, such as trauma, degenerative diseases, congenital disabilities, and the surgical removal of tumors. Current methods for bone regeneration have limitations. In this context, the fusion of tissue engineering and microfluidics has emerged as a promising strategy in the field of bone regeneration.
View Article and Find Full Text PDFAims: To investigate the associations between influencing factors with length of stay (LOS) and hospitalisation expenses in oral cancer (OC) patients, and to explore the potential pathways through which these factors influence hospitalisation expenses using path analysis.
Design: Cross-sectional.
Setting: A comprehensive tertiary hospital in southeastern China.
Seed color is a key agronomic trait in crops such as peanut, where it is a vital indicator of both nutritional and commercial value. In recent years, peanuts with darker seed coats have gained market attention due to their high anthocyanin content. Here, we used bulk segregant analysis to identify the gene associated with the purplish-red coat trait and identified a novel gene encoding a basic/helix-loop-helix transcription factor, PURPLE RED SEED COAT1 (PSC1), which regulates the accumulation of anthocyanins in the seed coat.
View Article and Find Full Text PDFObjective: The primary objective of this study is to develop and validate a high-risk model for Arteriovenous Fistula Thrombosis (AVFT) in patients undergoing autogenous arteriovenous fistula surgery for hemodialysis.
Methods: Retrospectively, we collected general information, clinical characteristics, laboratory examinations, and dialysis-related factors from a cohort of 1465 patients who received continuous arteriovenous fistula surgery at the Hemodialysis Access Center of Sichuan Provincial People's Hospital between January 2019 and June 2022. The patients were randomly divided into a training set and a validation set in a 2:1 ratio.
Biomolecular condensates segregate nuclei into discrete regions, facilitating the execution of distinct biological functions. Here, it is identified that the WW domain containing adaptor with coiled-coil (WAC) is localized to nuclear speckles via its WW domain and plays a pivotal role in regulating alternative splicing through the formation of biomolecular condensates via its C-terminal coiled-coil (CC) domain. WAC acts as a scaffold protein and facilitates the integration of RNA-binding motif 12 (RBM12) into nuclear speckles, where RBM12 potentially interacts with the spliceosomal U5 small nuclear ribonucleoprotein (snRNP).
View Article and Find Full Text PDFBone fracture ruptures blood vessels and disrupts the bone marrow, the site of new red blood cell production (erythropoiesis). Current dogma holds that bone fracture causes severe hypoxia at the fracture site, due to vascular rupture, and that this hypoxia must be overcome for regeneration. Here, we show that the early fracture site is not hypoxic, but instead exhibits high oxygen tension (> 55 mmHg, or 8%), similar to the red blood cell reservoir, the spleen.
View Article and Find Full Text PDFAlthough emerging studies highlight the pivotal role of podocyte senescence in the pathogenesis of diabetic kidney disease (DKD) and aging-related kidney diseases, therapeutic strategies for preventing podocyte senescence are still lacking. Here, we identified a previously unrecognized role of GPR124, a novel adhesion G protein-coupled receptor, in maintaining podocyte structure and function by regulation of cellular senescence in DKD. Podocyte GPR124 was significantly reduced in db/db diabetic (a type 2 diabetic mouse model) and streptozocin-induced diabetic mice (a type 1 diabetic model), which was further confirmed in kidney biopsies from patients with DKD.
View Article and Find Full Text PDFOily sensitive skin is complex and requires accurate identification and personalized care. However, the current classification method relies on subjective assessment. This study aimed to classify skin type and subtype using objective biophysical parameters to investigate differences in skin characteristics across anatomical and morphological regions.
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