The common variant PNPLA3-I148M, globally, is the most significant genetic risk factor for fatty liver disease. However, it is unclear precisely how I148M drives disease risk. Using human hepatoma cel Show more
The common variant PNPLA3-I148M, globally, is the most significant genetic risk factor for fatty liver disease. However, it is unclear precisely how I148M drives disease risk. Using human hepatoma cells expressing endogenous I148M, we find that the variant impairs cellular secretion of apolipoprotein B (ApoB), the scaffolding protein of very-low-density lipoprotein (VLDL). This is not due to loss-of-function of wild-type PNPLA3. Expression of human I148M in primary hepatocytes and mice also hinders VLDL secretion. Lipidomic profiling reveals a shift from polyunsaturated phosphatidylcholine to polyunsaturated triglycerides in I148M cells, reducing membrane fluidity and, concomitantly, VLDL biogenesis. ApoB secretion is substantially rescued in I148M cells overexpressing ABHD5/CGI-58, an I148M-binding partner that normally activates ATGL/PNPLA2-mediated triglyceride lipolysis. Conversely, knocking down CGI-58 or PNPLA2 mimics I148M. We propose that I148M is a neomorph that exacerbates fatty liver risk by simultaneously impeding two major CGI-58-dependent pathways for liver triglyceride clearance: lipolysis and secretion. Show less
One of the recognized effects of systematic physical activity is the improvement of physical fitness, with a negative correlation found between physical fitness and cardiovascular and cardiometabolic Show more
One of the recognized effects of systematic physical activity is the improvement of physical fitness, with a negative correlation found between physical fitness and cardiovascular and cardiometabolic risk. The purpose of this study is to analyze the influence of single nucleotide polymorphisms (SNPs) of the adenylate cyclase 3 ( In the 12-week HIIT program, a total of 237 Chinese Han college students with non-regular exercise habits were recruited, and these volunteers participated in the training three times a week. Baseline and after the HIIT program, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured, respectively. DNA was extracted from the white blood cells of volunteers and genotyping was carried out. The PLINK v1.09 software was used to conduct quality control screening on the obtained SNPs, and a linear regression model was constructed to analyze the association between (1) Through the analysis of Illumina CGA chip scanning, a total of 22 SNPs of the (1) The implementation of a 12-week HIIT regimen can significantly enhance the blood lipid status of college students. (2) The locus rs2241759 of the Show less
Twenty types of GABAergic interneurons form intricate networks to fine-tune neural circuits in the brain. Parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons, which are the two la Show more
Twenty types of GABAergic interneurons form intricate networks to fine-tune neural circuits in the brain. Parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons, which are the two largest populations of neocortical interneurons, innervate the soma and/or proximal dendrites, and distal dendrites of pyramidal neurons, respectively. Using PV- and SST-specific knockout mouse models, we show that PV+ interneurons require FGFR2, which responds to FGF7, to drive PV+ inhibitory presynaptic maturation on perisomatic regions of Layer V pyramidal neurons. In contrast, SST+ interneurons rely on both FGFR1 and FGFR2, which respond to FGF10 or FGF22, to promote SST+ inhibitory presynaptic maturation on distal dendrites of pyramidal neurons in cortical Layer I. Mechanistically, FGF-FGFR signaling sustains VGAT protein levels in interneurons through PP2A and Akt pathways. Together, these findings demonstrate that distinct FGF ligand-receptor combinations regulate inhibitory presynaptic differentiation by PV+ and SST+ interneurons, contributing to the formation of compartment-specific synaptic patterns. 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
Neovascular age-related macular degeneration (nAMD) is an advanced stage of AMD and is associated with an increased risk of visual impairment. Disturbances in lipid metabolism have been proposed as a Show more
Neovascular age-related macular degeneration (nAMD) is an advanced stage of AMD and is associated with an increased risk of visual impairment. Disturbances in lipid metabolism have been proposed as a major contributing factor to the pathogenesis of AMD. This study aims to investigate whether lipid profiles in the serum and components of dyslipidemia can be used as indicators for predicting progression to nAMD. A retrospective analysis was conducted involving 125 participants with nAMD. 125 non-AMD controls, matched by age, sex, and BMI, were incorporated into the study. The comparative analysis between the groups involved six lipid biomarkers in the serum: HDL-C, LDL-C TG, TC, ApoA1, and ApoB. Moreover, the existence of dyslipidemia and its constituents was assessed through t-tests, as well as univariate and multivariable logistic regression models. Individuals with nAMD exhibited significantly higher serum HDL-C (P = 0.02) compared to the controls without AMD. Furthermore, the concentrations of ApoB were significantly less in the nAMD cohort (P < 0.01) when compared to the control group. During the investigation of the correlation between levels of serum HDL-C (P < 0.01) and serum ApoB (P < 0.01) with nAMD through logistic regression analysis, notable findings indicated a significant association between both variables and nAMD. However, by multivariate logistic regression analysis, neither serum HDL-C nor serum ApoB was an independent risk factor for nAMD. While individuals with nAMD demonstrated elevated serum HDL-C and reduced serum ApoB levels, these lipid markers may not be suitable as biomarkers for monitoring or preventing nAMD. Show less
Diabetes mellitus and dyslipidemia are major risk factors for atherosclerosis. Hypoechoic plaques, which indicate vulnerable or unstable plaques, may rupture and lead to ischemic stroke, cognitive imp Show more
Diabetes mellitus and dyslipidemia are major risk factors for atherosclerosis. Hypoechoic plaques, which indicate vulnerable or unstable plaques, may rupture and lead to ischemic stroke, cognitive impairment, increased adverse cardiac events, and even death. This study aimed to investigate the correlation between plasma lipid levels and the characteristics of atherosclerotic plaques in adult patients with type 2 diabetes mellitus. A retrospective analysis was conducted on adult patients with type 2 mellitus who were hospitalized in the Department of Endocrinology at Affiliated Hospital of Hebei University between January 2017 and December 2021.Patients were categorized into two groups based on arterial ultrasound results. Statistical analyses were performed to compare plasma lipid levels and plaque characteristics across the groups. 1) Statistically significant differences were observed among the two groups in terms of gender, hypertension, age, duration of diabetes mellitus, plaque location, triglycerides (TG),total cholesterol (TC), Apolipoprotein A1 (Apo A1),very-low-density lipoprotein (VLDL), VLDL/apolipoprotein B(ApoB), high-density lipoprotein cholesterol (HDL)/ApoA1 ( In clinical practice, the characteristics of atherosclerotic plaques and lipid profiles should be jointly evaluated to guide targeted treatment and effectively reduce the risk of atherosclerotic cardiovascular disease. Show less
Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related mortality worldwide due to its high aggressive potential and drug resistance. Previous studies have revealed an impor Show more
Oral squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related mortality worldwide due to its high aggressive potential and drug resistance. Previous studies have revealed an important function of HECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 5 (HERC5) in cancer. Six GEO gene microarrays identified HERC5 as a significant upregulated gene in OSCC tissues or cells (log2 Fold change > 1 and adj.p < 0.05). This study aimed to explore the role and underlying mechanisms of HERC5 in OSCC development. High HERC5 expression in OSCC tissues was confirmed by our hospital validation cohort and positively correlated with primary tumor stages. Subsequent functional studies demonstrated that knockdown of HERC5 inhibited the migratory and invasive capabilities with decrease of Vimentin and increase of E-cadherin in OSCC cells. In cisplatin treatment, cell survival rates were significantly reduced in HERC5-silencing OSCC cells, accompanied by the increase in cytotoxicity, DNA damage and apoptosis. OSCC cell-derived tumor xenograft displayed that HERC5 depletion inhibited pulmonary metastasis as well as restored the cisplatin-induced tumor burden. In line with this, overexpression of HERC5 yielded the opposite alterations both in vivo and in vitro. Mechanistically, UDP-glucose 6-dehydrogenase (UGDH) was identified as a HERC5-binding protein. Cysteine residue at position 994 in the HECT domain of HERC5 catalyzed the conjugation of ubiquitin-like protein Interferon-induced 15 kDa protein (ISG15) to UGDH (ISGylation of UGDH) and facilitated its phosphorylation, therefore enhancing SNAI1 mRNA stability. SNAI1 depletion inhibited HERC5 overexpression-triggered invasion and cisplatin resistance of OSCC cells. Our study indicates that HERC5 may be a promising therapeutic target for OSCC. Show less
This study explored latent mental health profiles among adolescents in southwestern China and the association with emotional regulation using the dual-factor model framework. 1,682 junior middle schoo Show more
This study explored latent mental health profiles among adolescents in southwestern China and the association with emotional regulation using the dual-factor model framework. 1,682 junior middle school students completed the LPA revealed three profiles: Troubled (31.51%, high negative symptoms/low well-being), complete mental health (61.30%, low negative symptoms/high well-being), and more troubled (7.19%, severe negative symptoms/extremely low well-being). Cognitive reappraisal positively predicted complete mental health (vs. Troubled; Three distinct profiles emerged, differing from the traditional dual-factor model. Cognitive reappraisal protects mental health, while expressive suppression correlates with poorer outcomes, highlighting the need for targeted interventions promoting cognitive reappraisal. Show less
The quality of eggshells holds substantial economic significance and serves as a critical selection criterion in poultry breeding. Eggshell translucency significantly impairs their aesthetic quality, Show more
The quality of eggshells holds substantial economic significance and serves as a critical selection criterion in poultry breeding. Eggshell translucency significantly impairs their aesthetic quality, which is structurally attributed to the thinning of the eggshell membrane or reduced tensile strength. In this study, 836 dwarf white hens were selected, with 45 hens each assigned to the opaque group and the translucent group. Grading for eggshell translucency was conducted at 75, 80, and 85 weeks of age. Based on the results from these three gradings, 35 hens that consistently produced translucent eggs and 35 hens that consistently produced opaque eggs were reclassified into the translucent group and the opaque group, respectively. The thickness of the eggshell membrane, latitudinal and longitudinal tensile force and length, and other indicators related to eggshell membrane quality were measured. Correlation analysis was performed using RNA-seq genomics and DIA proteomics based on the relationships among these indicators. Transcriptome analysis revealed 179 significantly differentially expressed genes, indicating that the causes of translucent eggshells are associated with metabolism, signal transduction, the immune system, molecular binding, transport, and catabolism. Seven potential candidate genes, including Show less
To investigate the association between polymorphisms of the A case-control study was conducted, enrolling 100 HTG patients and 100 age-matched controls with normal triglyceride levels from the physica Show more
To investigate the association between polymorphisms of the A case-control study was conducted, enrolling 100 HTG patients and 100 age-matched controls with normal triglyceride levels from the physical examination cohort at Guangzhou 11th People's Hospital (January-December 2023) The observation group showed significant differences in genotype frequencies of Show less
Chronic diseases have become a major public health challenge facing the world. Identifying key factors and developing effective management strategies to promote proactive health behaviors in patients Show more
Chronic diseases have become a major public health challenge facing the world. Identifying key factors and developing effective management strategies to promote proactive health behaviors in patients is crucial for improving health outcomes. This study aims to construct a comprehensive model of proactive health behaviors in chronic disease patients, elucidate multilevel determinants, and guide targeted policy interventions in China. A cross-sectional survey was conducted among 805 patients with chronic diseases in China. Latent profile analysis (LPA) was conducted to identify distinct profiles of proactive health behaviors among patients. Binary logistic regression analysis was used to verify and analyze the determinants affecting the proactive health behaviors of patients. Among the 805 participants, 471 were classified as highly proactive, and 334 were classified as less proactive. The average score for proactive health behaviors was 70.37 ± 10.93. Several factors positively predicted proactive health behaviors: patients aged > 74 years (AOR = 8.85, 95% CI 2.06-39.45), married patients (AOR = 1.78, 95% CI 1.02-3.11), urban residents (AOR= 1.33, 95% CI 1.04-1.70), those with stronger health intentions (AOR = 1.42, 95% CI 1.28-1.60), higher self-efficacy (AOR = 1.12, 95% CI 1.04-1.20), positive health beliefs (AOR = 1.21, 95% CI 1.09-1.34)), and greater community support (AOR = 1.18, 95% CI 1.07-1.32). Regarding policy support, perceiving an adequate upper payment limit for drugs was associated with twice the odds of proactive health behaviors (AOR = 2.61, 95% CI 1.44-4.78). Additionally, age and the medication reimbursement policy for drug expenses exerted negative effects on proactive health behaviors (β = -0.507, P < 0.01). Governments should transform medical insurance from a passive payer into an active health investor. By incorporating behavioral economics principles, such a reform reallocates policy design, resources, and decision-making power toward disadvantaged populations. This shift breaks the "well-intentioned policy trap", achieving lower medical costs alongside improved population health. Show less
Glioma is a highly aggressive malignancy with no effective treatment. This study investigates the role of protein tyrosine phosphatase receptor type N (PTPRN) in glioma progression. The U87 human glio Show more
Glioma is a highly aggressive malignancy with no effective treatment. This study investigates the role of protein tyrosine phosphatase receptor type N (PTPRN) in glioma progression. The U87 human glioma cell line was used to monitor proliferation, invasion, and migration during PTPRN knockdown. The viability, migration, and invasion were analyzed using the Cell Counting Kit-8 assay, transwell migration, and invasion assays. Additionally, the expression of proteins associated with the cell cycle was examined using western blotting. The knockdown of PTPRN resulted in a reduction in glioma cell proliferation, migration, and invasion, as well as the expression of cell cycle markers like Show less
The differential impact of serum lipids and their targets for lipid modification on cardiometabolic disease risk is debated. This study used Mendelian randomization to investigate the causal relations Show more
The differential impact of serum lipids and their targets for lipid modification on cardiometabolic disease risk is debated. This study used Mendelian randomization to investigate the causal relationships and underlying mechanisms. Genetic variants related to lipid profiles and targets for lipid modification were sourced from the Global Lipids Genetics Consortium. Summary data for 10 cardiometabolic diseases were compiled from both discovery and replication data sets. Expression quantitative trait loci data from relevant tissues were employed to evaluate significant lipid-modifying drug targets. Comprehensive analyses including colocalization, mediation, and bioinformatics were conducted to validate the results and investigate potential mediators and mechanisms. Significant causal associations were identified between lipids, lipid-modifying drug targets, and various cardiometabolic diseases. Notably, genetic enhancement of LPL (lipoprotein lipase) was linked to reduced risks of myocardial infarction (odds ratio [OR] The study substantiates the causal role of lipids in specific cardiometabolic diseases, highlighting LPL as a potent drug target. The effects of LPL are suggested to be influenced by changes in glucose and blood pressure, providing insights into its mechanism of action. Show less
Ischemic injury induces a partial mesenchymal shift in endothelial cells (ECs), contributing to impaired vascular regeneration. However, the molecular regulators of this transitional state remain poor Show more
Ischemic injury induces a partial mesenchymal shift in endothelial cells (ECs), contributing to impaired vascular regeneration. However, the molecular regulators of this transitional state remain poorly defined. To address this, we performed circular RNA profiling of endothelial cells under ischemic-like conditions and identified a marked upregulation of a circular RNA, named circATXN1. Functional studies revealed that circATXN1 knockdown modulates endothelial phenotype and vascular response after ischemia. Functional studies have shown that knockdown of circATXN1 can regulate the endothelial cell phenotype and vascular response after ischemia. Mechanistically, circATXN1 knockdown enhances the demethylase protein ALKBH5 to reduce the RNA methylation level of the key transcription factor SLUG, thereby stabilizing SLUG. In animal models, suppression of circATXN1 enhances angiogenesis and improves recovery following ischemic injury. Here, we show that circATXN1 regulates partial endothelial-to-mesenchymal transition (EndMT) and angiogenesis by controlling SLUG mRNA methylation dynamics, highlighting its potential as a therapeutic target in ischemic disease. Show less
Cholesterol-loaded macrophage foam cells are a key feature of atherosclerotic plaques. Oxysterol-binding protein-related protein 2 (ORP2) facilitates the transport of cholesterol from lysosomes to the Show more
Cholesterol-loaded macrophage foam cells are a key feature of atherosclerotic plaques. Oxysterol-binding protein-related protein 2 (ORP2) facilitates the transport of cholesterol from lysosomes to the plasma membrane in cultured cell lines. However, the role of ORP2 in macrophages and its involvement in atherosclerosis remain unclear. In this study, we found ORP2 expression was reduced in atherosclerotic vessels and in macrophages exposed to oxidized LDL (ox-LDL). Myeloid-specific human ORP2 overexpression (hORP2 Show less
Tumor fibrosis is recognized as a malignant hallmark in various solid tumors; however, the clinical importance and associated molecular characteristics of tumor fibrosis in liver metastases (LM) from Show more
Tumor fibrosis is recognized as a malignant hallmark in various solid tumors; however, the clinical importance and associated molecular characteristics of tumor fibrosis in liver metastases (LM) from colorectal cancer (CRLM) remain poorly understood. Here we show that patients with CRLM whose liver metastases (LM) exhibited tumor fibrosis (Fibrosis+ LM) had significantly worse progression-free survival (P = 0.025) and overall survival (P = 0.008). Single-cell RNA sequencing revealed that the tumor microenvironment of the Fibrosis+ LM was characterized by T cells with an exhausted phenotype, macrophages displaying a profibrotic and suppressive phenotype and fibrosis-promoting fibroblasts. Further investigation highlighted the pivotal role of VCAN_eCAF in remodeling the tumor fibrosis in the tumor microenvironment of Fibrosis+ LM, emphasizing potential targetable interactions such as FGF23 or FGF3-FGFR1. Validation through multiplex immunohistochemistry/immunofluorescence and spatial transcriptomics supported these findings. Here we present a comprehensive single-cell atlas of tumor fibrosis in LM, revealing the intricate multicellular environment and molecular features associated with it. These insights deepen our understanding of tumor fibrosis mechanisms and inform improved clinical diagnosis and treatment strategies. Show less
Infantile hemangioma (IH) is a common benign vascular tumor in infants, often requiring intervention due to potential functional impairment and cosmetic concerns. Propranolol, a nonselective β-adrener Show more
Infantile hemangioma (IH) is a common benign vascular tumor in infants, often requiring intervention due to potential functional impairment and cosmetic concerns. Propranolol, a nonselective β-adrenergic receptor blocker, is the first-line therapy for IH, yet its mechanisms remain incompletely elucidated. This prospective study investigated the systemic angiogenic protein profile changes in response to propranolol in 14 treatment-naïve IH infants compared to 14 healthy controls using antibody array analysis. We identified twenty-six angiogenic proteins significantly downregulated in pretreatment IH patients compared to healthy controls. After 3 months of propranolol treatment, six proteins including HB-EGF, TGFα, ANGPTL4, Follistatin, Tie-1 and PLGF were significantly upregulated. Bioinformatic enrichment analysis revealed that these proteins are involved in key biological processes and signaling pathways, including epithelial cell proliferation, angiogenesis regulation, VEGF signaling, ERBB-EGFR axis, Ras-MAPK, and PI3K-Akt pathways. These results suggest that propranolol treatment is associated with a rebalancing of dysregulated angiogenic proteins in IH, through modulating both pro- and anti-angiogenic factors to rebalance vascular homeostasis. Our study provides novel insights into the systems-level pharmacological actions of propranolol and proposes potential biomarkers for treatment response evaluation. Show less
The prognosis for colorectal cancer (CRC) patients with liver metastasis remains poor, and the molecular mechanisms driving CRC liver metastasis are not fully understood. Tumor-derived hypoxia-induced Show more
The prognosis for colorectal cancer (CRC) patients with liver metastasis remains poor, and the molecular mechanisms driving CRC liver metastasis are not fully understood. Tumor-derived hypoxia-induced extracellular vesicles have emerged as key players in inducing angiogenesis by transferring noncoding RNAs. However, the specific role of CRC-derived hypoxic extracellular vesicles (H-EVs) in regulating premetastatic microenvironment (PMN) formation by inducing angiogenesis remains unclear. Our study demonstrates that H-EVs induce angiogenesis and liver metastasis. Through microRNA microarray analysis, we identified a reduction in miR-6084 levels within H-EVs. We found that miR-6084 inhibited angiogenesis by being transferred to endothelial cells via EVs. In endothelial cells, miR-6084 directly targeted angiopoietin like 4 (ANGPTL4) mRNA, thereby suppressing angiogenesis through the ANGPTL4-mediated JAK2/STAT3 pathway. Furthermore, we uncovered that specificity protein 1 (SP1) acted as a transcription factor regulating miR-6084 transcription, while hypoxia-inducible factor 1A (HIF1A) decreased miR-6084 expression by promoting SP1 protein dephosphorylation and facilitating ubiquitin-proteasome degradation in SW620 cells. In clinical samples, we observed low expression of miR-6084 in plasma-derived EVs from CRC patients with liver metastasis. In summary, our findings suggest that CRC-derived H-EVs promote angiogenesis and liver metastasis through the HIF1A/SP1/miR-6084/ANGPTL4 axis. Additionally, miR-6084 holds promise as a diagnostic and prognostic biomarker for CRC liver metastasis. Show less
The established body of knowledge attests to the pivotal influence of ANGPTL4 on lipid metabolism and vascular biology. Nevertheless, its potential implication in neurodegenerative disease remains to Show more
The established body of knowledge attests to the pivotal influence of ANGPTL4 on lipid metabolism and vascular biology. Nevertheless, its potential implication in neurodegenerative disease remains to be fully characterized. The present investigation delves into the involvement of ANGPTL4 in the pathological progression of PD, both in vitro and in vivo. PD models were induced by intraperitoneal administration of MPTP and LPS in WT and ANGPTL4 The observations unveiled that ANGPTL4 deficiency exacerbated behavioral aberrations, intensified dopaminergic neuron loss, and stimulated microglial activation along with p21-dependent senescence. There was an elevation in the expression of proinflammatory cytokines in the PD model. Furthermore, the administration of rANGPTL4 protein reversed the observed phenotypes in ANGPTL4 Our findings posit a salutary role for ANGPTL4 in counteracting PD, rendering it a prospective therapeutic target for the development of innovative drugs aimed at treating neuroinflammation-associated neurological diseases, including PD. Show less
Spatial representation is a core element of spatial cognition in orienteering, but the visual-spatial neural modulation mechanisms underlying spatial representations with differently oriented maps hav Show more
Spatial representation is a core element of spatial cognition in orienteering, but the visual-spatial neural modulation mechanisms underlying spatial representations with differently oriented maps have not yet been systematically elucidated. This study recruited 67 orienteering athletes as participants and employed a single-factor (map orientation: normal vs. rotated) between-subjects experimental design. Eye-tracking and functional near-infrared spectroscopy (fNIRS) techniques were used simultaneously to collect behavioral, eye movement, and brain activity data, investigating the effects of map orientation on visual attention and brain activity characteristics during terrain symbol representation processing in orienteering athletes. The results revealed that compared to the normal orientation, the rotated orientation led to significantly decreased task accuracy, significantly prolonged reaction times, and significantly increased saccade amplitude and pupil diameter. Brain activation analysis showed that the rotated orientation elicited significantly higher activation levels in the right dorsolateral prefrontal cortex (R-DLPFC), bilateral parietal lobe cortex (L-PL, R-PL), right temporal lobe (R-TL), and visual cortex (VC) compared to the normal orientation, along with enhanced functional connectivity. Correlation analysis revealed that under normal map orientation, accuracy was positively correlated with both saccade amplitude and pupil diameter; accuracy was positively correlated with activation in the R-DLPFC; saccade amplitude was positively correlated with activation in the R-DLPFC and R-PL; and pupil diameter was positively correlated with activation in the R-DLPFC. Under rotated map orientation, accuracy was positively correlated with saccade amplitude and pupil diameter, and pupil diameter was positively correlated with activation in both the L-PL and R-PL. The results indicate that map orientation significantly influences the visual search patterns and neural activity characteristics of orienteering athletes, impacting task performance through the coupling mode of visual-neural activity. Show less
Light-responsive porous liquids (LPLs) attract significant attention for their controllable gas uptake under light irradiation, while their preparation has remained a great challenge. Here we report t Show more
Light-responsive porous liquids (LPLs) attract significant attention for their controllable gas uptake under light irradiation, while their preparation has remained a great challenge. Here we report the fabrication of type II LPLs with enhanced light-responsive efficiency by tailoring the host's functionality for the first time. The functionality of light-responsive metal-organic cage (MOC-RL, constructed from dicopper and responsive ligands) is modified by introducing the second long-chain alkyl ligand, producing MOC-RL-AL as a new host. A spatially hindered solvent based on polyethylene glycol, IL-NTf Show less
Second-generation antipsychotics (SGAs) are widely used to treat schizophrenia (SCZ), but they often induce metabolic side effects like dyslipidemia and obesity. We conducted genome-wide association s Show more
Second-generation antipsychotics (SGAs) are widely used to treat schizophrenia (SCZ), but they often induce metabolic side effects like dyslipidemia and obesity. We conducted genome-wide association studies (GWASs) to identify genetic variants associated with SGA-induced lipid and BMI changes in Chinese SCZ patients. A longitudinal cohort of Chinese SCZ receiving SGAs was followed for up to 18.7 years (mean = 5.7 years, SD = 3.3 years). We analysed the patients' genotypes (N = 669), lipid profiles, and BMI using 19 316 prescription records and 3 917 to 7 596 metabolic measurements per outcome. Linear mixed models were employed to evaluate seven SGAs' random effects on metabolic changes for each patient, followed by GWAS and gene set analyses with Bonferroni and FDR correction. Five SNPs achieved p-value < 5 × 10 Show less
Pheochromocytomas and paragangliomas (PPGLs) exhibit the highest degree of heritability among all human tumors, yet the genetics of urinary bladder paragangliomas (UBPGLs) remains poorly understood. T Show more
Pheochromocytomas and paragangliomas (PPGLs) exhibit the highest degree of heritability among all human tumors, yet the genetics of urinary bladder paragangliomas (UBPGLs) remains poorly understood. The present study aims to examine the characteristics of a cohort of Chinese patients with UBPGLs, focusing particularly on genetics. The study included 70 Chinese patients with UBPGLs from 15 centers in China, 240 patients with non-head and neck PGLs (non-HNPGLs) outside the urine bladder, and 16 Caucasian patients with UBPGLs. Tumor DNA samples were sequenced by next generation sequencing. All identified pathogenic variants (PVs) were confirmed by Sanger sequencing. Among the 70 Chinese patients, PVs were identified in 38 cases: 23 in cluster 1 A (13 SDHB, 1 SDHD, 1 SDHA, 4 IDH1, 2 SLC25A11, and 2 FH), 4 in cluster 1B (3 EPAS1 and 1 EGLN1), and 11 in cluster 2 genes (7 HRAS, 1 FGFR1, 2 NF1, and 1 H3F3A). Compared with other non-HNPGLs, UBPGLs had more PVs in cluster 1 A genes (32.9% vs. 14.2%, p < 0.001), but fewer in cluster 1B (5.7% vs. 19.2%, p = 0.002) and cluster 2 genes (15.7% vs. 42.5%, p < 0.001). PVs in SDHB (18.6%) was the most common in Chinese patients with UBPGLs, followed by HRAS (10.0%). No PVs was found in 45.7% of all UBPGLs. PVs in HRAS, SLC25A11, EPAS1, and FH were also identified in Caucasians with UBPGLs. Chinese patients with UBPGLs have a diverse genetic profile. PVs in cluster 1 A genes underlie nearly 1/3 of patients, highlighting the importance of genetic testing. Diverse germline and somatic PVs are also present in Caucasian patients with UBPGLs. Show less
This study aimed to explore the genotype and phenotype correlation of patients with multiple osteochondroma (MO), and validate phenotypic differences in ATDC5 cell model with Mutation analysis was emp Show more
This study aimed to explore the genotype and phenotype correlation of patients with multiple osteochondroma (MO), and validate phenotypic differences in ATDC5 cell model with Mutation analysis was employed in 27 families with MO using polymerase chain reaction (PCR)-Sanger sequencing and targeted next-generation sequencing (t-NGS). ATDC5 cell model with A total of 27 pathogenic mutations were identified in Clinical research identified nine novel mutations in Show less
Cardiac hypertrophy as one of the major predisposing factors for chronic heart failure lacks effective interventions. It has been shown that protein ubiquitination plays an important role in cardiac h Show more
Cardiac hypertrophy as one of the major predisposing factors for chronic heart failure lacks effective interventions. It has been shown that protein ubiquitination plays an important role in cardiac hypertrophy. SMURF2 (SMAD-specific E3 ubiquitin ligase 2) is an important member of NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) family of HECT E3 ubiquitin ligases. In this study we investigated the regulatory role of SMURF2 in cardiac hypertrophy. Experiment models were established in mice by transverse aortic constriction (TAC) in vivo, as well as in neonatal rat cardiomyocytes (NRCMs) by treatment with angiotensin II (Ang II, 1 μM) in vitro. We showed that the expression levels of SMURF2 were significantly elevated in cardiac tissues from patients with cardiac hypertrophy and the two experiment models. In NRCMs, SMURF2 knockdown or treatment with a specific SMURF2 inhibitor heclin (8 μM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, evidenced by reduced mRNA levels of Anp, Bnp and β-Mhc as well as cell surface. Prophylactic or therapeutic administration of heclin (10 mg·kg Show less
Women diagnosed with PCOS exhibit a high prevalence of obstructive sleep apnea (OSA). This study aims to assess risk factors of OSA among patients with PCOS. This retrospective study included 126 pati Show more
Women diagnosed with PCOS exhibit a high prevalence of obstructive sleep apnea (OSA). This study aims to assess risk factors of OSA among patients with PCOS. This retrospective study included 126 patients with PCOS who were categorized into an OSA group (n = 30) and a non-OSA group (n = 96) according to the apnea-hypopnea index (AHI). A control group comprised 72 patients without PCOS who presented during the same period for infertility due to fallopian tube, pelvic, or male factors. Patients with PCOS A multivariate logistic regression model was used to analyze independent risk factors for OSA in the PCOS group. Patients with PCOS had significantly higher AHI values and elevated values for various physical indicators, including body mass index (BMI) and neck, waist, and hip circumferences; prolactin (PRL); fasting plasma glucose (FPG); insulin (FINS); triglycerides (TG); homeostasis model assessment of insulin resistance (HOMA-IR); 2-hour postprandial glucose (2-hPG) and insulin (2-hINS); AHI; and oxygen desaturation index (ODI). Conversely, levels of high-density lipoprotein cholesterol (HDL-C) and lowest oxygen saturation (LSaO OSA in PCOS patients is linked to metabolic indicators. High neck circumference and BMI levels were independent risk factors, highlighting the need for OSA in routine PCOS screening, particularly in the context of metabolic dysregulation. Show less