Childhood cancer can disrupt family functioning, increase caregiver psychological distress, and impair caregiver quality of life. While family resilience is crucial for adaptation, most research has f Show more
Childhood cancer can disrupt family functioning, increase caregiver psychological distress, and impair caregiver quality of life. While family resilience is crucial for adaptation, most research has focused on individual-level factors, neglecting heterogeneity and multilevel influences on family resilience. Guided by the Social Ecological Model (SEM), this cross-sectional observational study used latent profile analysis (LPA) to identify distinct profiles of family resilience among caregivers of children with cancer and to explore factors associated with these profiles. Between July 2022 and March 2024, 292 caregivers were recruited. Family resilience was measured using the Family Resilience Assessment Scale. LPA was employed to identify resilience profiles, and binary logistic regression was used to explore influencing factors. Two latent profiles were identified: the Low Resources-Low Positivity profile (86%) and the High Internal Resilience profile (14%). The Low Resource-Low Positivity profile demonstrated generally lower scores, especially in utilizing social and economic resources and maintaining a positive outlook. The High Internal Resilience profile showed higher scores across all family resilience dimensions, particularly in communication/problem solving, positive outlook, and meaning-making, while the use of external social and economic resources remained relatively lower. Univariate analysis showed significant differences between profiles in residence, number of siblings, caregiver education, individual resilience, social support, caregivers' physical and psychological well-being and child communication (caregiver-reported). Binary logistic regression identified having more than one child (OR = 3.184, 95% CI: 1.437 ~ 7.057, P = 0.004) and higher individual resilience (OR = 1.095, 95% CI: 1.028 ~ 1.165, P = 0.005) as significant predictors of High Internal Resilience profile. This study identified two distinct family resilience profiles among caregivers of children with cancer. Limited use of social and economic resources was common, while caregiver resilience and having multiple children predicted higher family resilience. Interventions should enhance caregiver coping capacity, support one-child families through peer and family programs, and improve access to social support, flexible employment, and affordable care to strengthen family resilience. Not applicable. Show less
Inflammatory bowel disease (IBD) is a chronic, immune-mediated intestinal disorder driven by dysregulated immune responses in genetically susceptible individuals. Despite recent advances in treatment, Show more
Inflammatory bowel disease (IBD) is a chronic, immune-mediated intestinal disorder driven by dysregulated immune responses in genetically susceptible individuals. Despite recent advances in treatment, more than 30% of patients either fail to respond initially or lose response over time, underscoring the need for a deeper mechanistic understanding of immunogenetic pathways and the development of individualized therapeutic strategies. We first discuss how newly identified susceptibility genes (e.g., IL23R, NOD2, BDNF, SLC) and their polymorphisms influence immune cell function and epithelial barrier integrity. Single-cell technologies have further revealed novel cell subsets and interactions underlying disease heterogeneity. We then explore the clinical efficacy of classical and emerging targeted therapies, including cytokine-specific biologics, JAK inhibitors, and novel strategies aimed at restoring regulatory T-cell function or blocking integrin-mediated lymphocyte trafficking. Additionally, we highlight promising therapeutic approaches such as fecal microbiota transplantation, microbial metabolite-based interventions, and nanotherapeutics. We further discuss how genetic insights and immune biomarkers can facilitate treatment personalization and improve prognostic stratification. Ultimately, this review emphasizes the transition from broad immunosuppression to precision medicine and proposes integrated approaches-combining multiomics profiling, immune monitoring, and novel therapeutics-to achieve sustained remission and improve long-term outcomes in IBD patients. Show less
Cattle body size measurements constitute the conformation traits that facilitate their production, fertility, and longevity status. Prioritizing functional variants and causal genes of conformation tr Show more
Cattle body size measurements constitute the conformation traits that facilitate their production, fertility, and longevity status. Prioritizing functional variants and causal genes of conformation traits is essential for understanding their genetic basis. In this study, we conducted single-trait and multitrait GWAS for 20 body conformation traits using imputed sequence data in 7,674 Chinese Holstein individuals and identified 27 QTL regions. Leveraging these QTL regions, we performed multitrait Bayesian fine-mapping to identify 30 independent credible sets of putative causal variants. Incorporating GWAS and cis-acting expression QTL data, Mendelian randomization was used to infer 153 putative causal gene-trait relationships. The previously reported genes, such as CCND2, TMTC2, and NRG3, were confirmed in our study. Of note, several novel candidate causal genes were also identified, such as C1R, RIMS1, SERPINB8, NETO2, TTYH3, TTC3, ANAPC4, and PSMD13. Our results provide new insights into the regulatory mechanisms of body conformation traits in cattle. Show less
Fatty acyl desaturases (Fads) are known to play critical roles in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) in fish species. To date, research on Fads in fish has predomina Show more
Fatty acyl desaturases (Fads) are known to play critical roles in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) in fish species. To date, research on Fads in fish has predominantly focused on Fads2, while studies on Fads1 have been rarely reported. Acipenseriformes, commonly known as Chondrostei, are an ancient fish lineage with unique evolutionary history. However, the biological roles and evolutionary status of Fads1 in Chondrostei remain unclear, which constrains our understanding of the evolutionary processes shaping LC-PUFA biosynthesis in this lineage. In this study, we identified and characterized a fads1 gene from Chinese sturgeon (Acipenser sinensis), a critically endangered Chondrostei, using molecular cloning and multiple bioinformatic analyses. The spatio-temporal expression patterns, functional characteristics, and transcriptional regulation in response to dietary fatty acids were investigated. The coding sequence of the fads1 gene was 1317 bp in length, encoding a protein of 438 amino acids. Bioinformatic analyses suggested high conservation of fads genes across Chondrostei despite their complex evolutionary history. Functional characterization in yeast showed that Chinese sturgeon Fads1 exhibited Δ5 desaturation activity, efficiently converting 20:3n-6 to arachidonic acid (ARA) and 20:4n-3 to eicosapentaenoic acid (EPA). Fatty acid composition analysis indicated that Chinese sturgeon could biosynthesize LC-PUFAs when they are deficient in their diets. Taken together, these results suggest that fads1 plays a crucial role in LC-PUFA biosynthesis in Chinese sturgeon, which provides solid theoretical basis for dietary LC-PUFA requirement of Chinese sturgeon. Furthermore, our findings provide novel insights into evolutionary diversification of fads genes in fish species. Show less
Castration-resistant prostate cancer (CRPC) marks the advanced phase of prostate malignancy, manifested through two principal subtypes: castration-resistant adenocarcinoma (CRPC-adeno) and neuroendocr Show more
Castration-resistant prostate cancer (CRPC) marks the advanced phase of prostate malignancy, manifested through two principal subtypes: castration-resistant adenocarcinoma (CRPC-adeno) and neuroendocrine prostate cancer (NEPC). This study aims to identify unique central regulatory genes, assess the immunological landscape, and explore potential therapeutic strategies specifically tailored to NEPC. We discovered 1444 differentially expressed genes (DEGs) distinguishing between the two cancer types and identified 12 critical hub genes. Notably, CHST1, MPPED2, and RIPPLY3 emerged as closely associated with the immune cell infiltration pattern, establishing them as top candidates. Prognostic analysis highlighted the potential critical roles of CHST1 and MPPED2 in prostate cancer development, findings corroborated through in vitro and in vivo assays. Moreover, we validated the functions and expression levels of CHST1, MPPED2, and RIPPLY3 in NEPC using cell lines, animal models and human tissues. In the final step, we found that imatinib might be the drug specific to NEPC, which was further confirmed by in vitro cell assay. Our results revealed the clinical characteristics, molecular features, immune cell infiltration pattern in CRPC-adeno and NEPC, and identified and confirmed CHST1, MPPED2, and RIPPLY3 as the critical genes in the development in prostate cancer and NEPC. We also predicted and validated imatinib as the potential specific drugs to NEPC. Show less
Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, over Show more
Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation Show less
β-Hydroxybutyrylation (Kbhb) modification regulates protein molecular fates in either physiology or pathology, including cancer. However, the function and regulatory mechanism of Kbhb remain completel Show more
β-Hydroxybutyrylation (Kbhb) modification regulates protein molecular fates in either physiology or pathology, including cancer. However, the function and regulatory mechanism of Kbhb remain completely unknown in cancer metastasis. Here, we report that β-hydroxybutyrate (BHB) is clinically associated with the progression of pancreatic cancer and functionally promotes pancreatic cancer cell metastasis. Mechanistically, BHB induces Kbhb modification of Snail at lysine 152 to enhance Snail stabilization, which is regulated by Kbhb modification enzyme CREB-binding protein (CBP), and subsequently prevents Snail degradation by blocking recognition of E3 ubiquitin ligases FBXL14. Furthermore, either targeting Snail Kbhb modification or CBP inhibitor decreases cancer metastasis and enhances the therapeutic efficacy of gemcitabine in pancreatic cancer cells. Collectively, our study reveals that Kbhb of Snail is critical to promote metastasis and provides a potential therapeutic strategy. Show less
The Tibetan sheep is a typical hypoxia-tolerant mammal, which lives on the plateau, at an altitude of between 2500 and 5000 m above sea level; the study of its hypoxic adaptation mechanism provides a Show more
The Tibetan sheep is a typical hypoxia-tolerant mammal, which lives on the plateau, at an altitude of between 2500 and 5000 m above sea level; the study of its hypoxic adaptation mechanism provides a reference for exploring the hypoxic adaptation mechanism of other animals. To grope for the genetic mechanism of adaptation to the hypoxic environment at the transcriptional level in Tibetan sheep testicular tissue, and to identify candidate genes and key pathways related to sheep adaptation, histological observation of testicular tissues from two sheep breeds was carried out using haematoxylin-eosin (HE) conventional staining. A total of 103 differentially expressed genes (DEGs) were authenticated in high altitude Tibetan sheep (ZYH) and low altitude Tibetan sheep (ZYM) by RNA sequencing technology (RNA-Seq), which included 50 up-regulated genes and 53 down-regulated genes. Functional analyses revealed several terms and pathways that were closely related to testis adaptation to the plateau. Several genes (including GGT5, AGTR2, EDN1, LPAR3, CYP2C19, IGFBP3, APOC3 and PKC1) were remarkably enriched in several pathways and terms, which may impact the Plateau adaptability of sheep by adjusting its reproductive activity and sexual maturation, and protecting Sertoli cells, various spermatocytes, and spermatogenesis processes. The results make a reasonable case for a better understanding of the molecular mechanisms of adaptation to altitude in sheep. Show less
This study investigates the relationship between serum homocysteine, blood lipids, and perinatal outcomes in patients with diet-controlled gestational diabetes mellitus (GDM) and those with normal glu Show more
This study investigates the relationship between serum homocysteine, blood lipids, and perinatal outcomes in patients with diet-controlled gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT). A prospective cohort of 150 diet-controlled GDM patients and 150 pregnant women with NGT, all delivering at our hospital, were selected based on predefined criteria. Data on demographics, physical parameters, and perinatal outcomes were compiled. Blood samples for fasting plasma glucose (FPG), homocysteine (Hcy), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and apolipoprotein A1 (apoA1) were collected before delivery. GDM patients exhibited higher levels of FPG, Hcy, and the apoB/apoA1 ratio, but lower HDL-C and apoA1 levels compared to the NGT group. Adverse outcomes such as macrosomia, premature rupture of membranes, and postpartum hemorrhage were more prevalent in the GDM group. In GDM patients, neonatal birth weight positively correlated with FPG and TG levels. Stratified Hcy analysis in GDM showed no significant differences in perinatal outcomes. However, the third quartile of the apoB/apoA1 ratio had a lower incidence of macrosomia compared to the first quartile, and the second quartile showed a higher incidence of birth asphyxia. GDM patients demonstrated increased levels of Hcy, FPG, and the apoB/apoA1 ratio, correlating with more adverse perinatal outcomes than healthy pregnant individuals. The relationships between Hcy, lipids, and these outcomes remain inconclusive, highlighting the need for further research. Show less
Hypoglycemia is a commonly neglected complication in elderly diabetic patients, which can lead to cardiovascular events. Endothelial cell dysfunction is the primary inducer of cardiovascular events, a Show more
Hypoglycemia is a commonly neglected complication in elderly diabetic patients, which can lead to cardiovascular events. Endothelial cell dysfunction is the primary inducer of cardiovascular events, and it is associated with hypoglycemia-triggered cytokine release and inflammatory programmed cell death. A comprehensive understanding of lineage-specific variations in pathological vascular changes is essential to mitigate cardiovascular events and ensure therapeutic efficacy. Herein, unbiased clustering analyses and single-nucleus RNA sequencing are performed on cells of the thoracic aorta in db/db and insulin-induced hypoglycemic db/db mice. Comparative analyses show changes in lineage-specific genes, subpopulation composition, intercellular communication, and molecular biology in hypoglycemic diabetic mice. The analyses also revealed the changes of different cells, particularly endothelial cell PANoptosis, macrophage inflammatory polarization, and vascular smooth muscle cell (VSMC) fibrosis. Pseudo-time sequencing, differential expression, and regulation network analyses revealed the association of potential hub genes Klf2, ETS2, Elavl1, C3, and Nr4a1 with the mentioned pathological processes. It is demonstrated that hypoglycemia induces VSMC fibrosis in vivo, whereas Angptl4 knockdown can attenuate VSMC fibrosis in vitro. These findings demonstrate the hypoglycemic macroangiopathy mechanism and provide important references for future disease intervention and treatment. Show less
Residual feed intake (RFI) has recently gained attention as a key indicator of feed efficiency in poultry. In this study, 800 slow-growing ducks with similar initial body weights were reared in an exp Show more
Residual feed intake (RFI) has recently gained attention as a key indicator of feed efficiency in poultry. In this study, 800 slow-growing ducks with similar initial body weights were reared in an experimental facility until they were culled at 42 d of age. Thirty high RFI (HRFI) and 30 low RFI (LRFI) birds were selected to evaluate their growth performance, carcass characteristics, and muscle development. Transcriptome and weighted gene co-expression correlation network analyses of pectoral muscles were conducted on six LRFI and six HRFI ducks. The results revealed that selecting for LRFI significantly reduced feed consumption (P < 0.05) and improved feed efficiency without affecting the growth performance, slaughter rate, or meat quality of ducks (P > 0.05). Moreover, compared with HRFI ducks, LRFI ducks had a lower pectoral muscle fat content (P < 0.05), larger muscle fiber diameter and area (P < 0.05), and lower muscle fiber density (P < 0.05). There were significant differences in gene expression between LRFI and HRFI ducks, with 102 upregulated and 258 downregulated genes, which were enriched in the PPAR signaling pathway, adipocytokine signaling pathway, actin cytoskeleton regulation, ECM-receptor interaction, and focal adhesion. The expression of genes associated with fat and energy metabolism, including ACSL6, PCK1, APOC3, HMGCS2, PRKAG3, and G6PC1, was downregulated in LRFI ducks, and weighted gene co-expression correlation network analysis identified PRKAG3 as a hub gene. Our findings indicate that reduced mitochondrial energy metabolism may contribute to the RFI of slow-growing ducks, with PRKAG3 playing a pivotal role in this biological process. These findings provide novel insights into the molecular changes underlying RFI variation in slow-growing ducks. Show less
Mengru Pan, Yifan Qian, Linlin Jiang+2 more · 2025 · Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology · Taylor & Francis · added 2026-04-24
To assess the potential therapeutic effects of glucose-dependent insulinotropic peptide (GIP) on hyperandrogenism. Polycystic ovary syndrome (PCOS) mouse models induced by dehydroepiandrosterone (DHEA Show more
To assess the potential therapeutic effects of glucose-dependent insulinotropic peptide (GIP) on hyperandrogenism. Polycystic ovary syndrome (PCOS) mouse models induced by dehydroepiandrosterone (DHEA) were established to evaluate the impact of GIP on androgen synthesis Administration of GIP significantly reduced testosterone secretion in a DHEA-induced PCOS mouse model. Consistent with these findings, GIP treatment decreased testosterone release and downregulated the expression of GIP receptor (GIPR), steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (CYP11A1), and cytochrome P450 family 17 subfamily A member 1 (CYP17A1) in NCI-H295R cells. Notably, RNA-seq revealed that Our study demonstrated that the administration of GIP reduces androgen synthesis in PCOS mouse models and at the cellular level, suggesting its potential as a novel therapeutic target for managing PCOS. Show less
High-abundance serum proteins, mostly modified by N-glycans, are usually depleted from human sera to achieve in-depth analyses of serum proteome and sub-proteomes. In this study, we show that these hi Show more
High-abundance serum proteins, mostly modified by N-glycans, are usually depleted from human sera to achieve in-depth analyses of serum proteome and sub-proteomes. In this study, we show that these high-abundance glycoproteins (HAGPs) can be used as valuable standard glycopeptide resources, as long as the structural features of their glycans have been well defined at the glycosite-specific level. By directly analyzing intact glycopeptides enriched from serum, we identified 1322 unique glycopeptides at 48 N-glycosites from the top 12 HAGPs (19 subclasses). These HAGPs could be further classified into four major groups based on the structural features of their attached N-glycans. Immunoglobins including IGHG1/2/3/4, IGHA1/2 and IGHM were mostly modified by core fucosylated and bisected N-glycans with rarely sialic acids. Alpha-1-acid glycoproteins (ORM1/2) and haptoglobins (HP) were mainly modified by tri-and tetra-antennary (40 %) N-glycans with antenna-fucoses and sialic acids. Complement components C3 and C4A/B were highly modified by oligo-mannose glycans. The other HAGPs including SERPINA1, A2M, TF, FGB/G and APOB mainly contain bi-antennary complex glycans with the common core structure and (sialyl-) LacNAc branch structures. These HAGPs are easily detected by LC-MS analysis and therefore could be used as standard glycopeptides for glycoproteomic methodology studies as well as possible clinical utilities. Show less
This study focuses on the impacts of polystyrene/polylactic acid microplastics (PS/PLA-MPs) on ovarian reserve and oocyte maturation in female mice, along with the underlying mechanisms. 1 μm PS-MPs a Show more
This study focuses on the impacts of polystyrene/polylactic acid microplastics (PS/PLA-MPs) on ovarian reserve and oocyte maturation in female mice, along with the underlying mechanisms. 1 μm PS-MPs and PLA-MPs were prepared, with PLA-MPs having a rougher surface and broader size distribution. In vitro, PLA-MPs showed higher cytotoxicity to granulosa cells compared to PS-MPs. In vivo, MPs exposure disrupted the estrous cycle, and damaged ovarian reserve. Granulosa cell apoptosis and cytokine activation led to transzonal projection retraction, oocyte oxidative stress, meiotic abnormalities, and reduced oocyte retrieval and polar body extrusion rate, thus reducing litter size. PS-MPs induced more severe intestinal and ovarian impairment. Analysis of feces 16S rRNA, serum metabolomics, and ovarian RNA sequencing revealed that lipoprotein lipase (LPL) was suppressed by both MPs, linking gut microbiota, lipid metabolism, and ovarian injury. Fecal microbiota transplantation as a rescue strategy in MPs exposed mice upregulated LPL, alleviating ovarian reserve decline. In PLA-MPs exposed mice, ovarian reserve related indicators partially recovered after a two-week exposure cessation. These results clarify the similarities and differences in how PS-MPs and PLA-MPs impair ovarian function via gut-ovary axis and lipid metabolism dysregulation. Show less
Bridge-like lipid transfer proteins (BLTPs) play central roles in redistributing lipids from their primary site of synthesis in the endoplasmic reticulum to other organelles. They comprise bridge-doma Show more
Bridge-like lipid transfer proteins (BLTPs) play central roles in redistributing lipids from their primary site of synthesis in the endoplasmic reticulum to other organelles. They comprise bridge-domains spanning between organelles at contact sites that allow lipids to transit the cytosol between adjacent membranes. The assembly of BLTPs into complexes with adaptor proteins enables their lipid transfer ability. To address the mechanisms underlying assembly and regulation of BLTP complexes, we used cryo-EM to resolve the structure of one such BLTP, the Parkinson's protein VPS13C, at near-atomic resolution. The structure identifies a lipid-transfer-nonpermissive conformation, where the built-in C-terminal VAB adaptor module blocks the end of the lipid transfer bridge, interfering with lipid delivery. We also identify calmodulin, central to calcium signaling, as a VPS13 partner, suggesting calcium regulation of VPS13 function. Altogether, this structure of intact VPS13C serves as starting point to understand its regulation and, more broadly, that of other BLTPs. Show less
To determine whether insulin controls hepatic de novo lipogenesis (DNL) through an HCF-1-dependent modulation of ChREBP that is distinct from the canonical SREBP1c pathway. AML-12 mouse hepatocytes we Show more
To determine whether insulin controls hepatic de novo lipogenesis (DNL) through an HCF-1-dependent modulation of ChREBP that is distinct from the canonical SREBP1c pathway. AML-12 mouse hepatocytes were subjected to 10 μg/mL insulin and 25 mM glucose for 6 h. IRβ or HCF-1 was knocked down with lentiviral shRNA (≈80 % efficiency). Lipid droplets were quantified by Nile-Red staining; mRNA and protein levels were measured by RT-qPCR, Western blot, immunofluorescence and RNA-seq. Co-immunoprecipitation was used to test complex formation. Insulin reduced lipid accumulation and suppressed ChREBP protein and its nuclear localization in AML-12 hepatocytes without altering SREBP1c. Knock-down of IRβ or HCF-1 abolished insulin-mediated ChREBP suppression, increased lipid droplets and up-regulated lipogenic genes. HCF-1 co-immunoprecipitated with IRβ, indicating formation of an insulin-responsive IRβ/HCF-1 complex that restrains ChREBP-driven lipogenesis. We identify an IRβ/HCF-1/ChREBP regulatory node in hepatocytes that can repress lipogenic genes independently of SREBP1c. The axis constitutes a testable target for understanding selective insulin action on hepatic lipid metabolism and for future in-vivo studies of fatty-liver disease. Show less
Egg weight is a primary economic trait in poultry breeding. Putian Black duck, an excellent local laying duck breed in Fujian Province, includes two different strains, black feather strain and white f Show more
Egg weight is a primary economic trait in poultry breeding. Putian Black duck, an excellent local laying duck breed in Fujian Province, includes two different strains, black feather strain and white feather strain. The white feather strain of Putian Black duck is also known as Putian White duck. Except for the different feather colors, these two strains differ in egg weight. In this study, whole-genome resequencing was conducted on Putian Black duck and Putian White duck to explore the differences in the genetic mechanism of egg weight. Show less
Homologous recombination repair (HRR) is crucial for maintaining genomic stability by repairing DNA damage. Despite its importance, HRR's role in cancer progression is not fully elucidated. Here, this Show more
Homologous recombination repair (HRR) is crucial for maintaining genomic stability by repairing DNA damage. Despite its importance, HRR's role in cancer progression is not fully elucidated. Here, this work shows that nuclear-localized branched-chain α-ketoacid dehydrogenase kinase (BCKDK) acts as a modulator of HRR, promoting cell resistance against DNA damage-inducing therapy in breast cancer. Mechanistically, this work demonstrates that BCKDK is localized in the nucleus and phosphorylates RNF8 at Ser157, preventing the ubiquitin-mediated degradation of RAD51, thereby facilitating HRR-mediated DNA repair under replication stress. Notably, aberrant expression of the BCKDK/p-RNF8/RAD51 axis correlates with breast cancer progression and poor patient survival. Furthermore, this work identifies a small molecule inhibitor of BCKDK, GSK180736A, that disrupts its HRR function and exhibits strong tumor suppression when combined with DNA damage-inducing drugs. Collectively, this study reveals a new role of BCKDK in regulating HRR, independent of its metabolic function, presenting it as a potential therapeutic target and predictive biomarker in breast cancer. Show less
Calcified chondroid mesenchymal neoplasm (CCMN) is a recently identified category of soft tissue neoplasms defined by cartilage or cartilaginous matrix formation and We conducted a clinicopathological Show more
Calcified chondroid mesenchymal neoplasm (CCMN) is a recently identified category of soft tissue neoplasms defined by cartilage or cartilaginous matrix formation and We conducted a clinicopathological analysis of five newly identified CCMN cases and reviewed 87 cases documented in PubMed. Next-generation sequencing was used to detect molecular alterations, while clinical, radiological and histopathological features were extensively reviewed. CCMN typically affects adults, presenting as a slow-growing, painless mass in soft tissue. Histologically, CCMN exhibits a chondroid matrix with variable calcification. Molecular analyses in our cases identified CCMN should be considered in the differential diagnosis of soft tissue tumours with chondroid and calcified components. Detecting Show less
Tafolecimab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), represents a significant therapeutic advancement in the management of hypercholesterolem Show more
Tafolecimab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), represents a significant therapeutic advancement in the management of hypercholesterolemia and has been approved for use in the Chinese population. Elevated low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic cardiovascular disease, and traditional treatments often fall short due to challenges such as statin intolerance. Clinical trials have demonstrated that tafolecimab can effectively reduce LDL-C levels, achieving reductions of over 60% in many patients. It also improves other lipid parameters, including lipoprotein(a) [Lp(a)], non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (ApoB). It has a favorable safety profile, primarily characterized by mild to moderate adverse events. The long-acting formulation of tafolecimab enables less frequent dosing, thereby promoting compliance. As cardiovascular diseases continue to escalate globally, tafolecimab holds promise not only for patients in China but also for broader international applications, representing a critical advancement in the evolving landscape of lipid-lowering therapies. Show less
This study aimed to explore active ingredients in Scrophularia ningpoensis Hemsl (SNH) with potential effects on ameloblastoma (AM) using network pharmacological approach, bioinformatic gene analysis Show more
This study aimed to explore active ingredients in Scrophularia ningpoensis Hemsl (SNH) with potential effects on ameloblastoma (AM) using network pharmacological approach, bioinformatic gene analysis and in vitro cell experiments. The active ingredients and their corresponding targets of SNH were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP), as well as SwissTargetPrediction. Disease targets of AM were selected from GeneCards and DisGeNET databases. Differentially expressed genes (DEGs) of AM were identified, and Gene Ontology enrichment analysis were performed using the Gene Expression Omnibus (GEO) dataset GSE38494 through bioinformatic analysis. The STRING database platform was utilized to generate a protein-protein interaction network diagram, followed by hub gene analysis using Cytoscape software. AutoDock Vina software was used to perform molecular docking verification of the effects of the active ingredients on potential core targets. Additionally, in vitro experiments including quantitative reverse transcription polymerase chain reaction (RT-qPCR), EdU assay and CCK-8 cell proliferation assay were conducted using AM cell line AM-1 after SNH extract treatment. The study revealed that SNH contains eight active ingredients and a total of 388 drug targets, including 10 potential core targets in AM. Hub genes identified in the analysis were CCNA2, HRAS, PTGS2, PIK3CB, FGFR1, CASP3, MMP1, SLC2A1, MMP14, and MME. Molecular docking analysis demonstrated strong binding activity between key active ingredients (β-sitosterol, scropolioside A_qt, scropolioside D, scropolioside D_qt, and sugiol) and target genes (CASP3, FGFR1, HRAS, PTGS2, and SLC2A1). Gene Ontology enrichment analysis indicated that SNH exerts its effects on AM through pathways related to cellular response to abiotic stimulus, cellular response to hypoxia, and exopeptidase activity. Immunohistochemical analysis using tissue microarray showed higher expression of MMP14 and PTGS2 in AM compared to dentigerous cyst. Using AM-1 cell line, RT-qPCR results confirmed that SNH suppressed the expression of MMP14 and PTGS2 at mRNA level. Additionally, the EdUassay and CCK-8 assay indicated the inhibitory effect of SNH on the proliferation of AM-1 cells. These findings showed that SNH could suppress expression of MMP14 and PTGS2 and restrain the proliferation of AM. Our study highlights the potential of SNH as a promising therapeutic candidate for AM, which may provide more options for clinical treatment. Show less
Lactylation, a recently identified post-translational modification, plays a critical role in tumor progression and immune regulation. However, its cellular heterogeneity and functional impact in lung Show more
Lactylation, a recently identified post-translational modification, plays a critical role in tumor progression and immune regulation. However, its cellular heterogeneity and functional impact in lung adenocarcinoma (LUAD) remain poorly understood. This study was designed as exploratory biological research to characterize lactylation-associated patterns at the single-cell level and to propose a potential lactylation-related prognostic model. Single-cell transcriptomic data from LUAD and normal lung tissues were analyzed to quantify lactylation activity using AUCell based on 332 lactylation-related genes. Cell-cell communication was inferred using CellChat to identify ligand-receptor interactions among subpopulations. Candidate genes were selected by integrating ligand-receptor pair genes, marker genes from highly lactylated subtypes, and previously reported lactylation-related genes. A total of 101 machine learning model combinations were evaluated to construct the prognostic model. Selected genes were further validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the potential relationship between Lactylation activity was higher in tumor epithelial and stromal cells, with particularly elevated levels in specific epithelial subpopulations. A 12-gene signature was identified, comprising nine risk genes (e.g., This study presents a lactylation-based prognostic model for LUAD and uncovers potential immune-related mechanisms by which highly lactylated epithelial cells may contribute to immune evasion and tumor progression. Show less
Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (P Show more
Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (PZI) and trioxytriphenylamine (TOT) ligands, was synthesized. PZI-Au-TOT displays decent thermally activated delayed fluorescence (TADF) with a quantum yield of 93 % in doped film. The crystals of PZI-Au-TOT show simultaneous TADF, polymorphism, and linearly polarized luminescence (LPL). The polymorph-dependent emission properties with widely varied peaks from 560 to 655 nm are attributed to different packing modes in terms of isolated monomers, discrete π-π stacked dimers or dimer PLUS. Two well-defined microcrystals of PZI-Au-TOT exhibit linearly polarized thermally activated delayed fluorescence with a degree of polarization up to 0.64. This work demonstrates that the molecular rotational flexibility of D-M-A type complexes endows an integration of multiple functions into one complex through manipulation of supramolecular aggregation. This type of complexes is expected to serve as a versatile platform for the fabrication of crystal materials for advanced photonic applications. Show less
This study examines pediatric cardiomyopathies by analyzing genetic and clinical data from 55 patients (2021-2024) at Beijing Anzhen Hospital. Four subtypes were studied: dilated (DCM, 24), hypertroph Show more
This study examines pediatric cardiomyopathies by analyzing genetic and clinical data from 55 patients (2021-2024) at Beijing Anzhen Hospital. Four subtypes were studied: dilated (DCM, 24), hypertrophic (HCM, 22), arrhythmogenic right ventricular (ARVC, 7), and restrictive (RCM, 2). Clinical data, imaging, labs, and family histories were collected, with whole-exome sequencing (WES) identifying disease-causing variants classified via ACMG guidelines. Statistical analysis revealed a median age of 11 years, a proportion of 58% male participants, and ethnic diversity (21 northern Han, 29 southern Han, 5 minorities). In the cohort, 13 cases had an LVEF below 35%. Pathogenic/likely pathogenic (P/LP) variants were found in 21.8% of the patients, and variants of uncertain significance (VUS) were present in 38.2%, with Show less
Muscle wasting, characterized by loss of muscle mass and strength, severely impacts patient quality of life and is associated with numerous chronic diseases and aging. The molecular mechanisms are com Show more
Muscle wasting, characterized by loss of muscle mass and strength, severely impacts patient quality of life and is associated with numerous chronic diseases and aging. The molecular mechanisms are complex, involving protein synthesis/degradation imbalance. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) and ubiquitin-specific peptidase 7 (USP7) have diverse cellular roles, but their coordinated function in skeletal muscle homeostasis remains poorly understood. DYRK1A overexpression in vivo induced muscle atrophy phenotypes, including reduced muscle mass, grip strength, fiber cross-sectional area (CSA), altered fiber type composition, and neuromuscular junction integrity, accompanied by elevated atrophy markers: muscle atrophy F-box protein (Atrogin-1), muscle ring finger 1 (MuRF-1), myostatin and suppressed myogenic markers: myoblast determination protein 1 (MyoD), myogenin (MyoG), myocyte enhancer factor 2C (Mef2c), myogenic factor 5 (Myf5). Conversely, pharmacological inhibition of DYRK1A with Harmine ameliorated these atrophy phenotypes in transgenic DYRK1A overexpressing (TgD) mice. In vivo, USP7 deficiency resulted in similar muscle wasting phenotypes. In vitro, DYRK1A overexpression or USP7 overexpression inhibited C2C12 myoblast proliferation and differentiation, effects rescued by Wnt3a treatment or USP7 knockdown, respectively. Mechanistically, DYRK1A activity suppressed active β-catenin levels. USP7 was found to interact with and deubiquitinate axis inhibition protein 1 (Axin1), leading to its stabilization. Knockdown of USP7 increased Axin1 ubiquitination and degradation, thereby promoting β-catenin signaling and myogenesis, counteracting the effects of DYRK1A. Our findings reveal a novel signaling axis where DYRK1A and USP7 cooperatively suppress Wnt/β-catenin signaling to promote muscle wasting. DYRK1A likely acts upstream, potentially phosphorylating pathway components, whereas USP7 stabilizes the β-catenin destruction complex scaffold protein Axin1 through deubiquitination. This coordinated action inhibits myogenesis and activates atrophy pathways. Targeting DYRK1A or USP7 could represent promising therapeutic strategies for muscle wasting disorders. Show less
Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disease. Genetic linkage analyses have identified that mutations in the exostosin glycosyltransferase (EXT)1 and EXT2 genes are li Show more
Hereditary multiple exostoses (HME) is an autosomal dominant skeletal disease. Genetic linkage analyses have identified that mutations in the exostosin glycosyltransferase (EXT)1 and EXT2 genes are linked to HME pathogenesis, with EXT1 mutation being the most frequent. The aim of this study was to generate a mice model with Ext1 gene editing to simulate human EXT1 mutation and investigate the genetic pathogenicity of Ext1 through phenotypic analyses. We designed a pair of dual sgRNAs targeting exon 1 of the mice Ext1 gene for precise deletion of a 46 bp DNA fragment, resulting in frameshift mutation of the Ext1 gene. The designed dual sgRNAs and Cas9 proteins were injected into mice zygotes cytoplasm. A total of 14 mice were obtained via embryo transfer, among which two genotypic chimera mice had a deletion of the 46 bp DNA fragment in exon 1 of the Ext1 gene. By hybridization and breeding, we successfully generated heterozygous mice with edited Ext1 gene (Ext Show less
This study aims to investigate the effect of fermented onion on Liangshan black sheep's growth performance, health, meat quality, and rumen metabolite profiles. A total of 80 four-month-old female Lia Show more
This study aims to investigate the effect of fermented onion on Liangshan black sheep's growth performance, health, meat quality, and rumen metabolite profiles. A total of 80 four-month-old female Liangshan black sheep were randomly divided into four groups of five replicate pens (four sheep per pen). Sheep were fed a basal diet supplemented with 0 (control), 10, 20% or 30% fermented onion. Compared to that of the control group, dietary supplementation with 20% fermented onion improved final body weight, ADG and ADFI; enhanced GPT and GOT activities and increased IgA, IgG, IgM, C3, and C4 levels; increased the levels of IL-4, IL-10, TGF- Show less
Yu Gan, Kangning Wang, Xiang Chen+4 more · 2025 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Renal fibrosis is a common pathological process in various chronic kidney diseases. The accumulation of senescent renal tubular epithelial cells (TECs) in renal tissues plays an important role in the Show more
Renal fibrosis is a common pathological process in various chronic kidney diseases. The accumulation of senescent renal tubular epithelial cells (TECs) in renal tissues plays an important role in the development of renal fibrosis. Eliminating senescent TECs has been proven to effectively reduce renal fibrosis. Procyanidin C1 (PCC1) plays a senolytic role by specifically eliminating senescent cells and extending its overall lifespan. However, whether PCC1 can alleviate unilateral ureteral obstruction (UUO)-induced renal fibrosis and the associated therapeutic mechanisms remains unclear. Here, we observed a marked increase in senescent TECs within obstructed human renal tissue and demonstrated the positive correlation between the accumulation of senescent TECs and renal fibrosis in UUO-induced renal fibrosis in mice. We found that PCC1 reduced the number of senescent TECs, restored the regenerative phenotype in kidneys with reduced fibrosis, and improved tubular repair after UUO-induced injury. In vitro, PCC1 effectively cleared senescent HK2 cells by inducing apoptosis via ANGPTL4/NOX4 signaling. Incubation with culture medium from senescent HK2 cells promoted fibroblast activation, whereas PCC1 impeded profibrotic effects by downregulating senescence-associated secretory phenotype (SASP) factors from senescent HK2 cells. Therefore, PCC1 alleviated interstitial renal fibrosis not only by clearing senescent TECs and improving tubular repair but also by indirectly attenuating myofibroblast activation by reducing the level of SASP. In summary, PCC1 may be a novel therapeutic senolytic agent for treating renal fibrosis. Show less
Breast cancer (BC) is one of the most prevalent malignant diseases affecting women. Cytochrome c (Cyt c) plays a critical role in various pathological processes, however, its precise mechanism in BC r Show more
Breast cancer (BC) is one of the most prevalent malignant diseases affecting women. Cytochrome c (Cyt c) plays a critical role in various pathological processes, however, its precise mechanism in BC remains unclear. This study aimed to identify prognostic genes linked to Cyt c in BC and explore their underlying mechanisms. Transcriptome data related to BC were initially obtained from TCGA and GEO database. Prognostic genes were identified through differential expression analysis, univariate Cox regression, and LASSO analysis. A risk model was subsequently developed and validated. Additionally, enrichment analysis, immune microenvironment analysis, and the construction of a TFs-mRNA network were conducted. Finally, the expression levels of prognostic genes were examined in both tumor and normal tissue samples, with confirmation through RT-qPCR. Eight prognostic genes ( Show less