👤 Xiaoyan Dong

Mounting evidence indicates that the short-chain fatty acid butyrate protects against obesity and associated comorbidities, partially through the induction of adipose tissue thermogenesis. However, the effects of butyrate on white adipose tissue (WAT) browning and its molecular mechanism are still elusive. The objective of this study was to investigate butyrate-induced thermogenesis in white adipose tissue and its underlying mechanism. We studied the effects of butyrate on diet-induced obesity in the humanized APOE*3-Leiden.CETP transgenic mouse model and explored factors related to white adipose browning. Specifically, mice were challenged with a high-fat diet supplemented with butyrate. Adiposity was measured to assess obesity development. Energy metabolism was detected using an indirect calorimetry system. RNA-seq analysis was conducted to analyze the transcription landscape of WAT and responsible targets. Furthermore, the revealed molecular mechanism was verified in vitro. Butyrate alleviated high-fat diet-induced obesity and promoted energy expenditure accompanied by brown adipose tissue activation and WAT browning. Mechanistically, RNA-seq analysis revealed that butyrate downregulated HDAC9 in WAT. Additionally, butyrate decreased HDAC9 while increasing thermogenesis in vitro. Inhibition of HDAC9 with TMP269 promoted thermogenic gene expression, mimicking the effects of butyrate. Butyrate protects against diet-induced obesity accompanied by decreasing the expression of HDAC9 in white adipose tissue and inducing browning. This study reveals a new mechanism whereby butyrate activates adaptive thermogenesis and provides new insights for the development of weight-loss drugs targeting adipose HDAC9. Show less

Gut microbiota not only biosynthesizes branched-chain amino acids (BCAA) but also catabolizes and utilizes them, while the effects of dietary BCAA supplementation on intestinal microbiota and metabolism remain largely elusive. Therefore, the present study aimed to investigate the impacts of dietary BCAA supplementation on productive performance, egg quality, gut microbiota and metabolism in laying hens. A total of 180 Fengda No.1 laying hens aged 41 weeks were randomly assigned to five groups, with each group consisting of six replicates of six hens, and the experiment lasted for 8 weeks. The control group (Ctrl AA) was fed a basal diet, while the other four groups were supplemented with 67% leucine (High Leu), isoleucine (High Ile), both leucine and isoleucine (High Leu + Ile), or a combination of the three BCAA (High BCAA), respectively, based on the Ctrl AA. The results demonstrated that compared with Ctrl AA, both High Ile and High BCAA significantly decreased egg mass and laying rate ( Show less

Autoimmunity towards podocyte antigens causes membranous nephropathy (MN). Numerous MN target antigens (MNTAgs) have been reported, including PLA2R1, THSD7A, NTNG1, TGFBR3, HTRA1, NDNF, SEMA3B, FAT1, EXT1, CNTN1, NELL1, PCDH7, EXT2, PCSK6, and NCAM1, but their podocyte expression has not been thoroughly studied. We screened CZ CELLxGene single-cell RNA (scRNA) sequence datasets for those of adult, fetal, and mouse kidneys and analyzed the above MNTAgs' expression. In adult kidneys, most MNTAgs are present in podocytes, except PCSK6 and NCAM1. PLA2R1 is expressed significantly more than other MNTAgs in podocytes and is a major podocyte marker, consistent with PLA2R1 as the dominant MNTAg. Additionally, PLA2R1 is a top-upregulated gene in the podocytes of chronic kidney disease, acute kidney injury, and diabetic nephropathy, indicating its general role in causing podocyte injury. PLA2R1, NTNG1, HTRA1, and NDNF display podocyte-enriched expression along with elevated chromatin accessibility in podocytes, suggesting transcription initiation contributing to their preference expression in podocytes. In the fetal kidney, most MNTAgs are expressed in podocytes. While PLA2R1 is weakly present in podocytes, SEMA3B is abundantly expressed in immature and mature podocytes, supporting SEMA3B as a childhood MNTAg. In mouse kidneys, Thsd7a is the only MNTAg with a prominent level and podocyte-specific expression. Show less

Fatty acid desaturase 1 (FADS1) is significantly and specifically upregulated following diabetic corneal injury. However, its role in diabetic keratopathy remains unclear. This study aimed to investigate the impact of FADS1 on wound healing and functional recovery of the diabetic corneal epithelium and explore its potential mechanisms. Using high-glucose-induced corneal epithelial cells and a streptozotocin-induced type 1 diabetic mouse model, FADS1 expression was suppressed via FADS1 small interfering RNA (siRNA). Cell migration was assessed using scratch and transwell assays. Wound healing and functional recovery of the corneal epithelium were evaluated using sodium fluorescein staining, anterior segment optical coherence tomography, hematoxylin and eosin staining, and immunofluorescence staining. FADS1 knockdown promoted wound healing and functional recovery of the diabetic corneal epithelium both in vivo and in vitro. Suppression of FADS1 enhanced high-glucose-induced corneal epithelial cell migration, which was dependent on elevated levels of the upstream metabolite γ-linolenic acid. This effect was mediated through the activation of the mitogen-activated protein kinase signaling pathway and the accumulation of autophagosomes. After diabetic corneal epithelial injury, FADS1 expression is specifically upregulated. Knockdown of FADS1 promotes wound healing and functional recovery, suggesting a novel therapeutic strategy for diabetic keratopathy. Show less

The thalamus is an important sensory relay station. It integrates all somatic sensory pathways (excluding olfaction) and transmits information through thalamic relay neurons before projecting to the cerebral cortex via thalamocortical axons (TCAs). Emerging evidence has shown that FGF3, a member of the morphogen family, is an axon guidance molecule that repels TCAs away from the hypothalamus and into the internal capsule so that they subsequently reach different regions of the cortex. However, current studies on FGF-mediated axon guidance predominantly focus on phenomenological observations, with limited exploration of the underlying molecular mechanisms. To address this gap, we investigated both direct and indirect downstream signaling pathways mediating FGF3-dependent chemorepulsion of TCAs at later developmental stages. Firstly, we used pharmacological inhibitors to identify the signaling cascade(s) responsible for FGF3-triggered direct chemorepulsion of TCAs, in vitro and in vivo. Our results demonstrate that the PC-PLC pathway is required for FGF3 to directly stimulate the asymmetrical repellent growth of developing TCAs. Then, we found the FGF3-mediated repulsion can be indirectly induced by Show less

Radiation-induced lung injury (RILI), manifesting in its initial phase as radiation pneumonitis (RP) and progressing over time to radiation-induced pulmonary fibrosis (RIPF), represents a significant adverse consequence associated with thoracic radiation therapy. Currently, there are limited therapeutic options for RILI. Anlotinib was confirmed the efficacy of pulmonary fibrosis. Therefore, anlotinib has the potential to treat RILI. To investigate the therapeutic role of anlotinib in RILI. RILI model in mice was successfully developed for evaluating the therapeutic efficacy of anlotinib. We used network pharmacology to find six target genes and analysed the correlation between these genes and RILI-related cytokines. Molecular docking further validates the binding ability of these target genes and anlotinib. We found the importance of TGF-β in anlotinib treatment of RILI by the results of network pharmacology and correlation analysis. We then used immunohistochemistry to demonstrate that anlotinib treats RILI by lowering TGF-β. Through enrichment analysis, we obtained potential therapeutic pathways and validated them with WB. In vivo investigations demonstrated that anlotinib is able to treat RILI: Inflammation, fibrosis, and apoptosis are reduced. This result is likely to be related to the reduction of TGF-β: The therapeutic mechanism potentially involves six genes, namely, FLT1, AKT1, KDR, TGFB2, PDGFRB1, and FGFR1; these targets bind well to anlotinib; we found that the expression of most of cytokines affecting the particular processes of RILI was closely associated with the six genes, in particular TGF-β1-3; immunohistochemistry further demonstrates that anlotinib treats RILI by lowering TGF-β1-3. In addition, KEGG enrichment analysis reveals possible pathways involving in therapeutic effects, including the PI3K-Akt, MAPK, Rap1, and Ras pathway. WB showed that anlotinib treatment significantly inhibited the PI3K/Akt signalling pathway. Therefore, anlotinib has the potential for treating RILI. Our results indicated the potential targets and molecular mechanism of anlotinib against RILI. Show less

Membrane protein degradation is a cutting-edge field in targeted protein degradation (TPD). Herein, we developed glypican-3 (GPC3)-mediated lysosome-targeting chimeras (GLTACs) as a novel strategy for the targeted degradation of tumor-specific membrane proteins. GLTACs utilize tumor-specific expression and endocytosis properties of GPC3 to degrade membrane proteins. By conjugating a GPC3-targeting peptide with the ligand of protein of interest (POI), GLTACs induce the formation of a ternary complex that is internalized into lysosomes, leading to the degradation of the POI. The effectiveness and specificity of GLTACs were validated by designing PD-L1, c-Met, and FGFR1 degraders. In particular, GLTAC Show less

Neurogenesis is the process of generating new neurons from neural stem cells (NSCs) and plays a crucial role in neurological diseases. The process involves a series of steps, including NSC proliferation, migration and differentiation, which are regulated by multiple pathways such as neurotrophic Trk and fibroblast growth factor receptors (FGFR) signalling. Despite the discovery of numerous compounds capable of modulating individual stages of neurogenesis, it remains challenging to identify an agent that can regulate multiple cellular processes of neurogenesis. Here, through screening of bioactive compounds in dietary functional foods, we identified a flavonoid chrysin that not only enhanced the human NSCs proliferation but also facilitated neuronal differentiation and neurite outgrowth. Further mechanistic study revealed the effect of chrysin was attenuated by inhibition of neurotrophic tropomyosin receptor kinase-B (TrkB) receptor. Consistently, chrysin activated TrkB and downstream ERK1/2 and AKT. Intriguingly, we found that the effect of chrysin was also reduced by FGFR1 blockade. Moreover, extended treatment of chrysin enhanced levels of brain-derived neurotrophic factor, as well as FGF1 and FGF8. Finally, chrysin was found to promote neurogenesis in human cerebral organoids by increasing the organoid expansion and folding, which was also mediated by TrkB and FGFR1 signalling. To conclude, our study indicates that activating both TrkB and FGFR1 signalling could be a promising avenue for therapeutic interventions in neurological diseases, and chrysin appears to be a potential candidate for the development of such treatments. Show less

Cadmium (Cd) is a toxic heavy metal which induces vascular disorders. Previous studies suggest that Cd in the bloodstream affects vascular endothelial cells (ECs), potentially contributing to vascular-related diseases. However, the molecular mechanisms of effects of Cd on ECs remain poorly understood. Notch signaling pathway abnormalities have been implicated in ECs disruption. The present study aims to investigate the effect of low Cd concentrations on the Notch signaling pathway in ECs. Mice were treated with low concentration of Cd (2.28 mg/kg), and tissues were collected for examination of mRNA and protein levels of Notch pathway components and VE-cadherin, a major junctional protein in ECs. We found that Cd treatment increases expression of NICD1, Hes1, Hey1, Hey2 and decreases expression of VE-cadherin in brain and kidney tissues. In vitro, a low concentration of Cd (1 μM) also induces increase expression of NICD1, Hes1, Hey1, Hey2, and decrease expression of VE-cadherin in human umbilical vein endothelial cells (HUVECs). Low concentration of Cd increased the permeability of HUVECs. We also found that Notch signaling negatively regulates the expression of VE-cadherin. In addition, DAPT, a Notch pathway inhibitor, prevents Cd-induced reduction in VE-cadherin expression in HUVECs. In summary, these findings revealed that Cd exposure decreases VE-cadherin expression through activation of the Notch signaling pathway. Show less

This study aims to investigate how Bifidobacterium breve BBr60 improves obesity-related metabolic disorders by modulating the gut microbiota-SCFAs axis, thereby affecting inflammatory factors and metabolic hormones. A randomized, double-blind, placebo-controlled trial was conducted. A total of 75 individuals with obesity subjects (BMI ≥ 28) were enrolled and randomly assigned to either the BBr60 intervention group (10 billion CFU daily) and the placebo group. After the 12-week intervention, 65 participants (BBr60: n = 33; placebo: n = 32) completed the study and were included in the primary analysis. All participants received standardized nutritional counseling aimed at a moderate energy intake (~ 1800 kcal/day, including a daily intake of 25 g of dietary fiber.). Every week, we call participants at a fixed time to inquire about their weekly diet and weight changes, and provide dietary suggestions for the following week based on the inquiry results. Participants were instructed to maintain their usual physical activity levels throughout the study. The composition of the gut microbiota was analyzed by 16 S sequencing, fecal SCFAs were detected by GC-MS, and serum levels of IL-27, IL-1β, and metabolic hormones were measured using ELISA technology. Metabolic indicators such as body weight, body fat percentage, and HOMA-IR were also assessed. The BBr60 intervention significantly increased fecal butyrate levels (p < 0.001), accompanied by a decrease in IL-1β levels (p < 0.05) and an upregulation of IL-27 (p < 0.01). In terms of metabolic hormones, leptin (LEP), adiponectin (ADPN), connecting peptide (C-P), pancreatic polypeptide (PP), peptide YY (PYY), Glucose-dependent insulinotropic polypeptide (GIP), and Glucagon-Like Peptide-1 (GLP-1) were all significantly elevated (p < 0.05), while Homeostasis Model Assessment for Insulin Resistance(HOMA-IR) was significantly reduced in the BBr60 group (p < 0.05). In the control group, C-P, PP, and GIP were significantly increased (p < 0.05), whereas LEP, ADPN, PYY, GLP-1, and HOMA-IR showed no difference before and after the 12-week period. Correlation analysis indicated that butyrate levels were significantly positively correlated with GLP-1 and IL-27, and negatively correlated with IL-1β. Bifidobacterium breve BBr60, by remodeling the gut microbiota-SCFAs axis, inhibits the pro-inflammatory factor IL-1β, activates the anti-inflammatory signal IL-27, and synergistically regulates the metabolic hormone network (such as GLP-1, ADPN), significantly improving obesity-related metabolic disorders. This study provides a theoretical basis and intervention targets for the clinical application of probiotics targeting the "microbiota-SCFAs-inflammation/hormone axis," and future research can explore precise probiotic treatment regimens based on individual microbiota characteristics. Show less

The integration of serum biomarkers and gene polymorphisms may enhance early prognostic assessment in sepsis. Early and accurate prediction of outcomes is crucial for optimizing treatment strategies and improving survival. However, the clinical utility of combining genetic markers with conventional inflammatory indicators remains insufficiently validated. In this retrospective cohort ( 6 predictors were retained - PCT, CRP, lactate (LAC), lactate clearance rate (LCR), TLR4 rs4986790, and PPARγ rs1801282. The nomogram achieved AUC 0.885 (95% CI 0.812-0.943) with sensitivity 88.6% and specificity 73.9%; calibration was good (H - L χ This integrative biomarker-genotype model demonstrated strong internal performance and potential clinical utility for individualized risk stratification in sepsis. The results support combining genetic susceptibility and inflammatory biomarkers for enhanced prognostic precision, although external and multi-ethnic validation remains warranted before widespread adoption. Show less

Although studies have suggested a potential link between the nervous system and prostate cancer, the underlying regulatory mechanisms remain unclear. Therefore, it is crucial to identify the genes involved in regulating prostate cancer within the nervous system. We utilized eQTL data from eight neural cell types as exposure factors and GWAS data for prostate cancer as outcome events. Mendelian randomization (MR) analyses were performed to identify causative genes associated with prostate, bladder, and renal cancers in Astrocytes, Endothelial cells, Excitatory neurons, Inhibitory neurons, Microglia, Oligodendrocytes, OPCs/COPs, and Pericytes. Bladder and renal cancers were used as controls. Sensitivity analyses (heterogeneity, pleiotropy, and leave-one-out tests) were conducted to ensure reliability. In astrocytes, seven positive genes were identified as being causally related to prostate cancer: KANSL1, AC005670.2, ARL17B, LRRC37A2, LRRC37A, MAPT, and LINC02210. In. Endothelial cells, Inhibitory neuron and Microglia, three genes (LRRC37A2, ARL17B, and KANSL1) were identified as risk genes that are associated with prostate cancer. Four protective genes were identified in excitatory neurons, including LRRC37A2, ARL17B, KANSL1 and LINC02210. In oligodendrocytes, eight genes were identified, with LRRC37A2, ARL17B, and KANSL1 acting as protective factors, while OR2L13, OR2L3, OR2L5, OR2L2, and OR2M4 were identified as risk factors. Additionally, sensitivity analyses showed no heterogeneity or horizontal pleiotropy in the MR results, confirming their reliability and stability. In addition, no positive genes were found in bladder cancer and renal cancer. Our study highlights the role of the nervous system, particularly astrocytes, in regulating prostate cancer. We identified three genes, with LRRC37A2, ARL17B, and KANSL1 emerging as key protective factors. These findings provide potential targets for prostate cancer diagnosis and treatment. The online version contains supplementary material available at 10.1007/s12672-025-03711-9. Show less

Congenital heart disease (CHD) is the most common type of birth defects in humans. Genetic factors have been identified as an important contributor to the etiology of CHD. However, the underlying genetic causes in most individuals remain unclear. Here, 101 individuals with CHD and their unaffected parents were included in this study. Chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic tool was applied for all affected individuals, followed by trio-based whole exome sequencing (WES) of 76 probands and proband-only WES of 3 probands. We detected aneuploidies in 2 individuals (trisomy 21 and monosomy X), 21 pathogenic and likely pathogenic copy number variants (CNVs) in 19 individuals, and pathogenic and likely pathogenic SNVs/InDels in 8 individuals. The combined genetic diagnostic yield was 28.7%, including 20.8% with chromosomal abnormalities and 7.9% with sequence-level variants. Eighteen CNVs in 17 individuals were associated with 13 recurrent chromosomal microdeletion/microduplication syndromes, the most common being 22q11.2 deletion syndrome. Pathogenic/likely pathogenic sequence-level variants were identified in 8 genes, including GATA6, FLNA, KANSL1, TRAF7, KAT6A, PKD1L1, RIT1, and SMAD6. Trio sequencing facilitated the identification of pathogenic variation (55.6% were de novo missense variants). In individuals with extracardiac features, the overall detection rate was significantly higher (61.5%) than in individuals with isolated CHD (17.3%) (P = 4.6 × 10 Show less

Age-related (AR) hearing loss (HL) is the most prevalent sensorineural disorder in older adults. Here we demonstrate that rare-variants in well-established Mendelian HL genes play an important role in ARHL etiology. In all we identified 32 Mendelian HL genes which are associated with ARHL. We performed single and rare-variant aggregate association analyses using exome data obtained from white-Europeans with self-reported hearing phenotypes from the UK Biobank. Our analysis revealed previously unreported associations between ARHL and rare-variants in Mendelian non-syndromic and syndromic HL genes, including MYO15A, and WFS1. Additionally, rare-variant aggregate association analyses identified associations with Mendelian HL genes i.e., ACTG1, GRHL2, KCNQ4, MYO7A, PLS1, TMPRSS3, and TNRC6B. Four novel ARHL genes were also detected: FBXO2 and PALM3, implicated in HL in mice, TWF1, associated with HL in Dalmatian dogs, and TXNDC17. In-silico analyses provided further evidence of inner ear expression of these genes in both murine and human models, supporting their relevance to ARHL. Analysis of variants with minor allele frequency >0.005 revealed additional ARHL associations with known e.g., ILDR1 and novel i.e., ABHD12, COA8, KANSL1, SERAC1, and UBE3B Mendelian non-syndromic and syndromic HL genes as well as ARHL associations with genes that have not been previously reported to be involved in HL e.g., VCL. Rare-variants in Mendelian HL genes typically exhibited higher effect sizes for ARHL compared to those in other associated genes. In conclusion, this study highlights the critical role Mendelian non-syndromic and syndromic HL genes play in the etiology of ARHL. Show less

This study aimed to examine reticulon 4 (RTN4), neurite outgrowth inhibitor protein expression that changes in high-altitude traumatic brain injury (HA-TBI) and affects on blood-brain barrier's (BBB) function. C57BL/6J 6-8-week-old male mice were used for TBI model induction and randomized into the normal altitude group and the 5000-m high-altitude (HA) group, each group was divided into control (C) and 8h/12h/24h/48h-TBI according to different times post-TBI. Brain water content (BWC) and modified Neurological Severity Score were measured, RTN4 and autophagy-related indexes (Beclin1, LC3B, and SQSTM1/p62) were detected by western blot, immunofluorescence technique, and PCR in peri-injury cortical tissues. The expression of NgR1, Lingo-1, TROY, P75, PirB, S1PR2, and RhoA receptors' downstream of RTN4 was detected by PCR. HA-TBI caused increased neurological deficits including motor, sensory, balance and reflex deficits, increased BWC, earlier peak RTN4 expression and a longer duration of high expression in peri-injury cortical tissues, and enhanced levels of Beclin1, LC3B, and SQSTM1/p62 to varying degrees. Concurrently, the transcription of S1PR2 and PirB, the main signaling molecules downstream of RTN4, was significantly increased. In HA-TBI's early stages, the increased RTN4 may regulate enhanced autophagic initiation and impaired autolysosome degradation in vascular endothelial cells via S1PR2 receptor activation, thereby reducing BBB function. This suggests that autophagy could be a new target using RTN4 intervention as a clinical HA-TBI mechanism. Show less

Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors, however, its function in osteosarcoma is unclear. This study aimed to explore the role of glycerolipid metabolism in osteosarcoma. We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and single-cell RNA sequencing. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma. Tumor-associated macrophages (TAMs) and their interactions with immune cells were examined through single-cell analysis and co-culture experiments. Virtual screening was employed to identify the potential lysophosphatidic acid receptor 6 (LPAR6) inhibitors. Glycerolipid metabolism-related genes 1-acylglycerol-3-phosphate O-acyltransferase 3 ( Show less

The influence of lactic acid bacteria (LAB) strains of various species isolated from Chinese traditional sourdough on the properties of rice sourdough and the textural and flavor qualities of steamed rice bread (SRB) was investigated. Show less

Demyelination diseases are characterized by injury to large (A-type) myelinated nerve fibers, and by secondary damage to small (C-type) sensory fibers, which leads to chronic pain symptoms, such as allodynia. The mechanisms underlying the interactions between the two fiber types are not clear. This study aims to investigate the role of lysophosphatidic acid (LPA) signaling in satellite glial cells (SGCs) within the dorsal root ganglia (DRG) in demyelination-induced chronic pain. A demyelination model was established by injecting cobra venom into the tibial nerve of 8-10-week-old Sprague-Dawley rats to selectively damage A-fiber myelin. Myelin morphology was observed via transmission electron microscopy (TEM) at 1, 3, 7, and 14 days post-injection. Pain behaviors (mechanical hypersensitivity, thermal hyperalgesia, and spontaneous pain) were assessed to evaluate progression. In vivo electrophysiology was performed to analyze sensory conduction and excitability changes in A- and C-type neurons. Immunofluorescence staining assessed SGC activation, LPA1 receptor (LPA1R) expression, and connexin 43 (Cx43) dynamics in the L4 DRG over time. Pharmacological interventions targeting LPA1R and SGC activation were applied to evaluate their effects on pain behaviors, cytokine release, and neuronal excitability using RT-PCR, ELISA, and spinal electrophysiology. Cobra venom induced a selective A-fiber demyelination and persistent pain in rats. It also upregulated the expression of LPA1R on SGCs that surround large DRG neurons, which normally mediate non-noxious input, and increased gap junction-mediated coupling via Cx43, leading to the activation of SGCs surrounding small nociceptive neurons. The activated SGCs released inflammatory mediators that increased nociceptive neuron excitability, driving chronic pain. In support of these results, pharmacological inhibition of LPA1R-mediated SGCs activation reversed this process. Our study demonstrates that LPA-LPA1R signaling in SGCs drives A-fiber demyelination-induced neuropathic pain by promoting Cx43-mediated SGC-neuron crosstalk and cytokine release. Targeting this pathway may represent a promising strategy to alleviate demyelination-associated chronic pain. Show less

This study aimed to investigate the effect of lipoprotein(a) (Lp(a)) on major adverse cardiovascular events (MACEs) among individuals with chronic coronary syndrome (CCS) according to ABO blood groups. Two independent cohorts of patients with CCS were included consecutively. Blood groups and Lp(a) levels were measured. Patients with the AB group were excluded due to the small sample size. In the exploratory cohort ( Show less

Undergraduate nursing students face significant academic and practical challenges, with their responses reflecting their academic resilience. However, most studies have overlooked the differences in their levels of academic resilience and the factors contributing to these differences. To identify the latent profiles of undergraduate nursing students' academic resilience and to analyze their influencing factors. A cross-sectional study was carried out among 1795 undergraduate nursing students from November 2022 to October 2023 by employing the general information questionnaire, the academic resilience questionnaire for college students, and the brief 2-way social support scale. Latent profile analysis (LPA) was used to analyze the latent profiles of academic resilience, and multiple logistic regression was utilized to explore the factors associated with the identified profiles. Four potential profiles were identified: low academic resilience group, moderate academic resilience group, high academic resilience but low focus and dissociation group, and high academic resilience group. Residence, attitude towards the nursing profession, self-directed study duration, academic performance rank, received and provided instrumental support were found to be associated with the different profiles. These findings highlight the heterogeneity in academic resilience and support tailored educational interventions based on students' specific academic resilience profiles. Show less

This study used objectively measured data and compositional data analysis to examine the relationship between 24-hour movement behaviors and perceived stress in Chinese university students. Cross-sectional data were collected from 208 Chinese university students (mean age = 20.23 years, 52.9% female). Accelerometers were used to measure 24-hour movement behaviors, including moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep. The Perceived Stress Scale (PSS-14) assessed perceived stress. Compositional data methods were applied to analyze the relationship between the proportion of time spent in 24-hour activities and perceived stress. Compositional regression analysis indicated that time spent in MVPA ( The proportion of time spent in MVPA and LPA was negatively associated with perceived stress among university students. Replacing sedentary behavior with MVPA or LPA was associated with lower perceived stress. However, these findings should be interpreted with caution due to the study's cross-sectional design and reliance on self-reported sleep data. Show less

Inflammation and hyperlipidaemia contribute with similar magnitude to the risk of future atherothrombotic events. However, the relative importance of high-sensitivity CRP (hsCRP) and lipoprotein(a) (Lp[a]) as determinants of risk of major adverse cardiovascular events (MACE) are not well defined among patients aged 75 years or older with established atherosclerotic cardiovascular disease (ASCVD). The present study prospectively enrolled 2,333 patients aged 75 years or older diagnosed with ASCVD with measurement of hsCRP and Lp(a) at Fuwai Hospital. The primary endpoint was MACE, defined as a composite of all-cause death, myocardial infarction (MI), stroke or ischaemia-driven coronary revascularisation. The median follow-up time was 3.0 years (interquartile range [IQR]: 2.5-3.2 years). hsCRP was significantly associated with an increased risk of MACE (adjusted hazard ratio [aHR]: 1.05, 95% confidence interval [CI]: 1.03-1.08 per 1 mg/l increment, P < 0.001; highest versus lowest quartile: aHR: 1.70 [1.22-2.38]), whereas there was no significant association between Lp(a) and MACE risk (aHR: 1.02 [0.98-1.06] per 10 mg/dl increment, P = 0.341; highest versus lowest quartile: aHR: 1.06 [0.77-1.47]). Risks of MACE were significantly higher in participants with hsCRP ≥2 mg/l than in those with hsCRP <2 mg/l, irrespective of Lp(a) strata (aHR: 1.41 [1.12-1.79]; P = 0.004). Concomitant elevation of hsCRP (≥2 mg/l) and Lp(a) (≥30 mg/dl) was associated with the greatest risk of MACE (aHR, 1.54 [1.13-2.12]; P = 0.007). Inflammation assessed by hsCRP predicted risk of future cardiovascular events more strongly than Lp(a) in patients aged 75 years or older with established ASCVD. These results provided real-world evidence on older patients potentially benefit by targeted anti-inflammatory strategies for secondary ASCVD prevention. Show less

Autism spectrum disorder (ASD) is characterized by core and associated symptoms that adversely affect the quality of life (QOL) of both children with ASD and their parents. Although physical activity (PA) has been shown to promote QOL and well-being, limited research has examined these associations within parent-child dyads in families affected by ASD. This cross-sectional study recruited 85 parent-child dyads from two autism rehabilitation centers in Central China. Children had a mean age of 5.25 years, and 75.3% of parents were aged between 31 and 40 years. Partial Pearson correlation analyses were conducted to examine associations between children's and parents' PA levels and multiple domains of QOL, controlling for child age, sex, and symptom severity. Significant reciprocal associations were observed between the PA levels of children with ASD and their parents. Specifically, children's light-intensity physical activity (LPA) was positively associated with parents' LPA ( These findings underscore the potential of LPA as a feasible and accessible form of joint activity that may support QOL within families of children with ASD. Framed through reciprocal determinism, the results highlight the interconnected roles of children's PA (behavior), parents' psychological well-being (personal factor), and the family context (environment). Further longitudinal and intervention studies are warranted to confirm these relationships and inform family-centered PA interventions. Show less

Evidence has linked self-reported sedentary behaviors with dementia and cognitive impairment; however, the underlying mechanisms remain poorly understood. We investigated the associations of accelerometer-measured sedentary behavior patterns with gray matter atrophy patterns in rural-dwelling older adults, while taking into account the manner in which sedentary time is accrued (in short or long bouts). This community-based study involved 911 dementia-free older adults (age ≥ 60 years, 59% women) who participated in both ActiGraph and brain MRI substudies within MIND-China (2018-2020). Sedentary behavior parameters (total sedentary time, mean sedentary bout duration, and sedentary breaks) were recorded with accelerometers. Regional gray matter volumes (GMV) were measured using voxel-based morphometry (VBM) methods. Data were analyzed using the general linear regression models, restricted cubic spline curves, and VBM analysis. There was an inverted U-shaped association between daily sedentary time and GMV in temporal, cingulate, and medial temporal cortex, while longer mean sedentary bout duration was linearly related to decreased GMV in total, frontal, temporal, insula, cingulate, and medial temporal cortex. Greater daily time spent in light or moderate-to-vigorous physical activity (LPA and MVPA) was correlated with larger insula GMV. The VBM analysis suggested that prolonged daily total sedentary time and mean sedentary bout duration were significantly associated with smaller GMV in extensive brain regions, especially in thalamus and insula. In conclusion, gray matter atrophy associated with sedentary behavior in older adults is characterized by reduced GMV in global, frontal, temporal, medial temporal, and cingulate cortex, especially in the insula and thalamus regions. Show less

Lipoprotein lipase (LPL) is the rate-limiting enzyme responsible for hydrolyzing triglycerides in circulating lipoproteins. Reduced LPL activity contributes to hypertriglyceridemia, a major cardiovascular risk factor. LPL activity is thought to depend on the conformation of the lid domain, the lipid pore, N- and C-terminal domains (NTD, CTD), and stabilization of these domains by endogenous activators such as apolipoprotein C-II (ApoC-II). Despite major clinical significance, the structure-function relationship of LPL's functional domains and cofactors remain incompletely understood. To address this, we performed the longest known (1-μs) molecular dynamics simulations of LPL independently and in complex with an ApoC-II mimetic peptide (ApoC-II-P). For the first time, we show that LPL's flexible lid can adopt multiple orientations, transitioning between open and closed states that regulate lipid pore access and catalytic activity. We also observed 'flipping' of ~180° by the CTD, a unique characteristic that dictates LPL activity when not in a closed lid state. Furthermore, ApoC-II-P stabilizes LPL by bridging its NTD and CTD, while maintaining an optimal lid orientation. Biochemical and cellular assays corroborate these findings, demonstrating that ApoC-II-P enhances LPL hydrolysis and supports noncanonical LPL functions. Together, these insights reveal previously unrecognized mechanisms governing LPL regulation and activity dynamics. Show less

Heat stress induces metabolic adaptations in fish, including the regulation of triglyceride (TG) synthesis/degradation to preserve cellular lipid balance and energy homeostasis. Diacylglycerol acyltransferase (DGAT) catalyzes the final step in TG synthesis. However, the molecular mechanisms by which DGAT regulates TG metabolism in heat-stressed fish remain unexplored. Our previous study suggested that miR-10c regulates Show less

Diabetic kidney disease (DKD) is a common and serious complication of diabetes, affecting approximately 40% of patients with the condition. The pathogenesis of DKD is complex, involving multiple processes such as metabolism, inflammation, and fibrosis. Given its increasing incidence and associated mortality, there is an urgent need to identify novel pathogenic genes and therapeutic targets. This study systematically identified hub DKD-associated genes and their potential molecular mechanisms through bioinformatic analysis. Gene expression datasets from DKD patients and healthy controls were obtained from the GEO database. Hub genes were screened using differential expression analysis, weighted gene co-expression network analysis (WGCNA), LASSO regression, random forest (RF) algorithms, and consensus clustering for DKD patient classification. Additionally, immune cell infiltration analysis was performed on differentially expressed genes to explore the relationship between hub genes and the immune microenvironment. Potential drugs targeting LPL were predicted based on gene-drug interaction analysis. Immunohistochemistry was used to verify the expression of LPL and TNF-α in kidney tissues from patients with varying degrees of DKD severity, as well as their relationship with kidney function impairment. This study revealed that LPL, a lipoprotein metabolism gene, plays a crucial role in DKD, participating in cholesterol and glycerolipid metabolism as well as PPAR signaling. LPL expression was negatively correlated with pro-inflammatory M1 macrophages and various subsets of T cells, including naïve CD4 T cells and gamma delta T cells, while positively correlated with follicular helper T cells, suggesting its immune-regulation effects in DKD progression. Potential LPL-targeting drugs, such as Ibrolipim, anabolic steroid, and acarbose, might mitigate DKD. LPL expression was decreased with DKD severity and was correlated with TNF-α and kidney dysfunction markers, indicating its key role in DKD progression. LPL is a pivotal regulator of lipid metabolism and immune inflammation in DKD. Potential drugs targeting LPL offer new candidates for precision treatment of DKD. These findings lay a theoretical foundation for understanding the molecular mechanisms of DKD and developing LPL-based therapeutic strategies. Show less

Lung adenocarcinoma (LUAD) has become the most common pathological pattern of lung cancer in recent decades. Prediction of biological behavior of LUAD is crucial for disease management and treatment options. The objective of this study was to identify significant genes related with prognosis of LUAD, and to investigate the role and biological mechanism of caveolin-1 (CAV1) in LUAD. Bioinformatical analysis was used to identify significant genes related to the prognosis of LUAD based on GEO datasets. Then the mechanisms underlying these critical genes were explored. Enrichment analysis was implemented based on CAV1 related differentially expressed genes subsequently. The expressions of CAV1 and EGFR in LUAD tissues and adjacent tissues were detected by Western blotting, immunohistochemistry and microarray technology. Kaplan-Meier survival analysis and cox regression analysis were performed to verify the correlation between CAV1 expression level and the prognosis of LUAD. The expression of CAV1 in PC-9, H1299 and H1975 cells was inhibited by siRNA transfection. CAV1 overexpression plasmid was constructed and transfected into A549 cells. Cell proliferation was detected by cell Titer-Glo, CCK-8 and colony formation assay. Scratch test was used to compare cell migration ability. Transwell assay was used to compare cell invasion ability. Cell apoptosis and cell cycle were detected by flow cytometry. The effect of CAV1 on EGFR degradation was verified by cycloheximide inhibition assay. Western blotting was used to detect the phosphorylation of AKT and STAT3, the expression of epithelial-mesenchymal transition (EMT) -related molecular markers and apoptosis-related Bax/Caspase-3/Bcl-2 pathway. The GFP plasmid loaded with shRNA was transfected into PC-9 cell line by lentivirus infection. Three groups of stable PC-9 cell lines, including shNC, shCAV1-1 and shCAV1-2 were obtained. The phenotypic experiments of proliferation, invasion, migration and apoptosis were completed. Western blotting was used to detect the phosphorylation of AKT and STAT3, as well as apoptosis-related Bax/Caspase-3/Bcl-2 pathway markers. In vivo experiments, including subcutaneous tumor formation experiment and immunohistochemical detection of CAV1, EGFR and Ki-67 were performed. Comprehensive analysis of GSE130779, GSE32863 and GSE85841 datasets identified 3 up-regulated DEGs and 86 down-regulated DEGs, which were significantly enriched in malaria pathway and proteoglycans in cancer pathway. CAV1 and CAV2 may inhibit tumor growth by degrading EGFR. Thirteen core genes including ADH1B, ALDH1A1, CAV1, CAV2, CLDN18, CXCL2 (GRO2), EDNRB, GNG11, LPL, PDK4, SCGB1A1, SDPR and SFTPC were down-regulated in LUAD tissues, which were associated with better prognosis of lung cancer significantly. Enrichment analysis of CAV1-related DEGs identified the endocytosis pathway, suggesting that CAV1 was involved in the development of LUAD by degrading EGFR through endocytosis. CAV1 was highly expressed in paracancerous tissues, and there was a negative correlation between the tissue locations of CAV1 and EGFR. Kaplan-Meier survival analysis of the cohort study showed that higher Cav-1 levels were associated with longer overall survival, and the difference was significant. Both in vitro and in vivo, CAV1 knockdown increased EGFR level, while CAV1 overexpression decreased EGFR level. This effect was mediated by Cav-1 promoting EGFR degradation. Cav-1 further inhibited the phosphorylation of downstream AKT/STAT3 pathway of EGFR. Caveolin-1 positively regulated the Bax/Caspase-3/Bcl-2 pathway, thereby participating in mediating apoptosis. Cav-1 can suppress the proliferation, migration and invasion of LUAD, while promote cell apoptosis. Our findings demonstrate that CAV1 exerts its anti-tumor effects, at least in part, by inhibiting EGFR degradation and modulating the AKT/STAT3 pathway, as well as enhancing the Bax/Caspase-3/Bcl-2 signaling pathway in LUAD cells. These results suggest that targeting CAV1 may represent a promising therapeutic strategy for the treatment of LUAD patients. Show less