The aim of this study is to screen key target genes of osteoarthritis associated with aging and to preliminarily explore the associated immune infiltration cells and potential drugs. Differentially ex Show more
The aim of this study is to screen key target genes of osteoarthritis associated with aging and to preliminarily explore the associated immune infiltration cells and potential drugs. Differentially expressed senescence-related genes (DESRGs) selected from Cellular senescence-related genes (SRGs) and differentially expressed genes (DEGs) were analyzed using Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and protein-protein interaction networks. Hub genes in DESRGs were selected based on degree, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. CIBERSORTx and ssGSEA algorithms were then used to assess immune cell infiltration and to analyse the correlation between key DESRGs and immune infiltration. Finally, a miRNA-gene network of diagnostic genes was constructed and targeted drug prediction was performed. Combined with the DEGs and SRGs, we screened 19 DESRGs for further study. Five diagnostic genes were ultimately identified: CDKN1A, VEGFA, MCL1, SNAI1 and MYC. ROC analysis showed that the area under the curve (AUC). Correlation analysis showed that the five hub genes were closely associated with neutrophil, plasmacytoid dendritic cell, activated CD4 T-cell and type 2 T-helper cell infiltration in the development of Osteoarthritis (OA). Finally, we found that drugs such as lithium chloride, acetaminophen, curcumin, celecoxib and resveratrol could be targeted for the treatment of senescence-related OA. The results of this study indicate that CDKN1A, VEGFA, MCL1, SNAI1, and MYC are key biomarkers that can be used to predict and prevent early aging-related OA. Lithium chloride, acetaminophen, curcumin, celecoxib, and resveratrol can be used for personalized treatment of aging-related OA. Show less
Retinal neovascularization poses heightened risks of vision loss and blindness. Despite its clinical significance, the molecular mechanisms underlying the pathogenesis of retinal neovascularization re Show more
Retinal neovascularization poses heightened risks of vision loss and blindness. Despite its clinical significance, the molecular mechanisms underlying the pathogenesis of retinal neovascularization remain elusive. This study utilized single-cell multiomics profiling in an oxygen-induced retinopathy (OIR) model to comprehensively investigate the intricate molecular landscape of retinal neovascularization. Mice were exposed to hyperoxia to induce the OIR model, and retinas were isolated for nucleus isolation. The cellular landscape of the single-nucleus suspensions was extensively characterized through single-cell multiomics sequencing. Single-cell data were integrated with genome-wide association study (GWAS) data to identify correlations between ocular cell types and diabetic retinopathy. Cell communication analysis among cells was conducted to unravel crucial ligand-receptor signals. Trajectory analysis and dynamic characterization of Müller cells were performed, followed by integration with human retinal data for pathway analysis. The multiomics dataset revealed six major ocular cell classes, with Müller cells/astrocytes showing significant associations with proliferative diabetic retinopathy (PDR). Cell communication analysis highlighted pathways that are associated with vascular proliferation and neurodevelopment, such as Vegfa-Vegfr2, Igf1-Igf1r, Nrxn3-Nlgn1, and Efna5-Epha4. Trajectory analysis identified a subset of Müller cells expressing genes linked to photoreceptor degeneration. Multiomics data integration further unveiled positively regulated genes in OIR Müller cells/astrocytes associated with axon development and neurotransmitter transmission. This study significantly advances our understanding of the intricate cellular and molecular mechanisms underlying retinal neovascularization, emphasizing the pivotal role of Müller cells. The identified pathways provide valuable insights into potential therapeutic targets for PDR, offering promising directions for further research and clinical interventions. Show less
Brown adipose tissue (BAT) combusts lipids and glucose to generate heat. Via this process of nonshivering thermogenesis, BAT plays a pivotal role in thermoregulation in cold environments, but its cont Show more
Brown adipose tissue (BAT) combusts lipids and glucose to generate heat. Via this process of nonshivering thermogenesis, BAT plays a pivotal role in thermoregulation in cold environments, but its contribution to immune-induced fever is less clear. Male APOE∗3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism, and wild-type mice were given an intraperitoneal injection of Salmonella enterica serovar Typhimurium (S.tm). Energy expenditure and substrate utilization, plasma lipid levels, fatty acid (FA) uptake by adipose tissues, and lipid content and thermogenic markers in adipose tissues were examined. S.tm infection led to a set of characteristic symptoms, including elevated body temperature and decreased body weight. Whole-body energy expenditure was significantly decreased 72 h postinfection, but fat oxidation was increased and accompanied by a substantial reduction in plasma triglyceride (TG) levels as demonstrated in APOE∗3-Leiden.CETP mice. S.tm infection strongly increased uptake of FAs from TG-rich lipoproteins by BAT, which showed a positive correlation with body temperature in infected mice. Upon histological examination of BAT from wild-type or APOE∗3-Leiden.CETP mice, elevated levels of tyrosine hydroxylase were observed, indicative of stimulated sympathetic activity. In addition, the gene expression profile was consistent with more adrenergic stimulation, while lipid content was reduced. Furthermore, browning of white adipose tissue was observed, evidenced by a modest increase in TG-derived FA uptake, the presence of multilocular cells, and induction of uncoupling protein 1 expression. We proposed that BAT, or thermogenic adipose tissue in general, is involved in the maintenance of elevated body temperature upon invasive bacterial infection. Show less
Class B1 G protein-coupled receptors (GPCRs) are important regulators of many physiological functions such as glucose homeostasis, which is mainly mediated by three peptide hormones, i.e., glucagon-li Show more
Class B1 G protein-coupled receptors (GPCRs) are important regulators of many physiological functions such as glucose homeostasis, which is mainly mediated by three peptide hormones, i.e., glucagon-like peptide-1 (GLP-1), glucagon (GCG), and glucose-dependent insulinotropic polypeptide (GIP). They trigger a cascade of signaling events leading to the formation of an active agonist-receptor-G protein complex. However, intracellular signal transducers can also activate the receptor independent of extracellular stimuli, suggesting an intrinsic role of G proteins in this process. Here, we report cryo-electron microscopy structures of the human GLP-1 receptor (GLP-1R), GCG receptor (GCGR), and GIP receptor (GIPR) in complex with G Show less
The integration of chemotherapy and immunotherapy as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC) has been adopted in clinical practice, yet the response to immune check Show more
The integration of chemotherapy and immunotherapy as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC) has been adopted in clinical practice, yet the response to immune checkpoint inhibitors (ICIs) is variable, benefiting only a fraction of patients. The current absence of reliable biomarkers for predicting treatment response and prognosis represents a significant gap in knowledge, hindering the optimization of patient stratification and treatment planning. This retrospective cohort study aims to assess the potential predictive and prognostic significance of clinicopathological baseline features in ES-SCLC patients. Our study retrospectively analyzed the data of consecutive patients with ES-SCLC treated with first-line etoposide plus platinum chemotherapy ± immunotherapy at The Affiliated Lihuili Hospital of Ningbo University from April 2017 to April 2023. Data on clinical information, serum laboratory indicators, pathological immunohistochemical markers, and progression-free survival (PFS) times were collected. Univariate and multivariate Cox regression analyses were employed to determine whether these indicators could serve as independent prognostic factors for PFS. Further, potential predictive markers for treatment efficacy were identified using a Cox regression model that incorporated an interaction term between treatment modality and the indicator. A total of 121 patients with ES-SCLC were enrolled in the study, of whom 62 received chemotherapy alone, and 59 received chemotherapy in combination with immunotherapy. Compared to chemotherapy alone, the addition of immunotherapy to first-line chemotherapy significantly extended the PFS time [P<0.001; hazard ratio (HR) =0.42; 95% confidence interval (CI): 0.28, 0.64] of the ES-SCLC patients. The multivariate analysis revealed that an immunochemotherapy regimen (P<0.001, HR =0.40; 95% CI: 0.24, 0.68), a low-density lipoprotein (LDL) level of >1.8 mmol/L (P=0.02; HR =0.41; 95% CI: 0.20, 0.85) were independent prognostic factors of favorable PFS in the first-line treatment of all ES-SCLC, while a lactate dehydrogenase (LDH) level of >273 U/L (P=0.04; HR =1.78; 95% CI: 1.03, 3.07), a neuron-specific enolase (NSE) concentration of >102.6 ng/mL (P=0.009; HR =6.49; 95% CI: 1.60, 26.32), an apolipoprotein A1 (ApoA1) concentration of >0.9 g/L (P<0.001; HR =4.15; 95% CI: 1.98, 8.71), and an apolipoprotein B (ApoB) concentration of >0.8 g/L (P=0.002; HR =2.24; 95% CI: 1.34, 3.75) were independent prognostic factors of poorer PFS. Further, the interaction effect analysis demonstrated that an LDL level of >1.8 mmol/L and the absence of bone metastasis were potential predictors of an improved response to ICI therapy compared to chemotherapy alone. This study showed the survival benefit of receiving a chemoimmunotherapy regimen as the first-line treatment in a real-world scenario. It also suggests the prognostic significance of pre-treatment LDL, LDH, NSE, ApoA1, and ApoB with optimal cut-off values in the first-line treatment of all ES-SCLC, and the potential utility of baseline LDL level or the presence of bone metastasis in guiding first-line treatment strategies. Show less
This investigation aimed to evaluate the efficacy and safety of rosuvastatin in treating moderate to severe metabolic associated fatty liver disease (MAFLD). This prospective, open-label, randomized s Show more
This investigation aimed to evaluate the efficacy and safety of rosuvastatin in treating moderate to severe metabolic associated fatty liver disease (MAFLD). This prospective, open-label, randomized study included non-diabetic participants with metabolic syndrome and intrahepatocellular lipid (IHCL) levels >10 %, as determined by proton magnetic resonance spectroscopy ( Thirty-two participants completed the study. Rosuvastatin resulted in a significant absolute (△IHCL: 7.61 ± 4.51 vs. 1.54 ± 5.33, p = 0.002) and relative reduction in IHCL (△IHCL%: -42.28 ± 24.90 % vs. -8.91 ± 31.93 %, p = 0.003) compared to the control. Reduction in IHCL correlated significantly with decreases in low-density lipoprotein cholesterol (LDL-C) (r = 0.574, p < 0.01), apolipoprotein B (ApoB) (r = 0.660, p < 0.001), and free fatty acids (FFA) (r = 0.563, p = 0.005). No significant safety differences were observed between groups. Rosuvastatin significantly reduced hepatic steatosis in individuals with moderate to severe MAFLD and metabolic syndrome over 52 weeks, while maintaining a favorable safety profile. Show less
Tunable luminescence-assisted information storage and encryption holds increasing significance in today's society. A promising approach to incorporating the benefits of both organic long persistent lu Show more
Tunable luminescence-assisted information storage and encryption holds increasing significance in today's society. A promising approach to incorporating the benefits of both organic long persistent luminescent (LPL) materials and rare-earth (RE) luminescence lies in utilizing organic host materials to sensitize RE luminescence, as well as employing Förster resonance energy transfer from hydrogen-bonded organic framework (HOF) phosphorescence to RE compound luminescence. This work introduces a one-pot, in situ pyrolytic condensation method, achieved through high-temperature melting calcination, to synthesize lanthanide ion-doped HOF materials. This method circumvents the drawback of molecular triplet energy annihilation, enabling the creation of organic LPL materials with RE characteristics. The HOF material serves as the host, exhibiting blue phosphorescence and cyan LPL. By fine-tuning the doping amount, the composite material U-Tb-100 achieves green LPL with a luminescent quantum yield of 56.4 %, and an LPL duration of approximately 2-3 s, demonstrating tunable persistence. Single-crystal X-ray diffraction, spectral analysis, and theoretical calculation unveil that U-Tb-100 exhibits exceptional quantum yield and long-lived luminescence primarily due to the efficient sensitization of U monomer to RE ions and the PRET process between U and RE complexes. This ingenious strategy not only expands the repertoire of HOF materials but also facilitates the design of multifunctional LPL materials. Show less
Cardiovascular disease (CVD) is the leading cause of death worldwide, and statin therapy is the cornerstone of atherosclerotic cardiovascular disease. However, clinical practice is unsatisfactory, and Show more
Cardiovascular disease (CVD) is the leading cause of death worldwide, and statin therapy is the cornerstone of atherosclerotic cardiovascular disease. However, clinical practice is unsatisfactory, and there is significant interest in the risk of residual cardiovascular events. Traditional study methods make it difficult to exclude the crosstalk of confounding factors, and we investigated the impact of the ApoB/ApoA1 ratio on CVD using two-sample Mendelian randomization (MR) and multivariate Mendelian randomization (MVMR) methods. Two-sample MR and MVMR analyses were performed using pooled statistics from genome-wide association studies (GWAS) of ApoB/ApoA1 ratio (BAR), lipoprotein (a) (Lp(a)), and triglyceride (TG) in Europeans to assess the causal relationship between BAR, Lp(a), and TG with coronary artery disease (CAD). The genetic prediction of BAR was significantly correlated with CAD (Inverse variance weighted (IVW) beta = 0.255; OR = 1.291; 95 % CI = 1.061-1.571; P = 0.011) in a two-sample MR analysis. MVMR studies showed that BAR (beta = 0.373; OR = 1.452; 95 % CI = 1.305-1.615; P = 7.217e-12), Lp (a) (beta = 0.238; OR = 1.269; 95 % CI = 1.216-1.323; P = 2.990e-28), and TG (beta = 0.155; OR = 1.168; 95 % CI = 1.074-1.270; P = 2.829e-04) were significantly associated with CAD. After further colinearity analyses of LASSO regressions, the results of multivariate analyses were similar for IVW, MR-Egger, MR-Lasso, and median methods. BAR is causally related to coronary artery disease. BAR is an independent predictor of CAD risk, independent of routine lipid measurements and other risk factors. TG and Lp(a) may be causally related to CAD, subject to verification in clinical practice. Show less
Yuan-Zheng Zhu, Jian-Kun Liu, Xue-Er Li+7 more · 2024 · The journals of gerontology. Series A, Biological sciences and medical sciences · Oxford University Press · added 2026-04-24
Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associat Show more
Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associated secretory phenotype (SASP). How SASP contributes to atherosclerosis and CAD, however, remains unclear. Here, we integrated RNA-array datasets of senescent human coronary arterial endothelial cells (HCAECs) and aortic smooth muscle cells (HASMCs) as well as genome-wide association data for CAD. We identified 26 genes from HCAECs and 6 genes from HASMCs related to SASP and CAD in both in-house and published datasets. Of which, Cystatin C (CST3), a CAD susceptibility gene, was found to be expressed in both HCAECs and HASMCs, thus, it was prioritized for further investigation. We demonstrated it was significantly elevated in senescent vascular cells, aged arteries, and early atherosclerosis. In vitro experiments showed that CST3 enhances the monocyte-endothelial cell adhesion. Additionally, ligand-receptor pairing analyses revealed two important pathways, COL4A1-ITGA1 and LPL-LRP1 pathways, linked to the critical processes in the development of atherosclerosis, including cell adhesion, inflammation response, extracellular matrix organization, and lipid metabolism. We further demonstrated a reduced monocyte-endothelial cell adhesion following the knockdown of COL4A1 or ITGA1 and a significantly increased expression of COL4A1, ITGA1, and LPL in arterial intima of aged mice and ApoE-/- mice. Our findings demonstrate that vascular cell-derived SASP proteins increase the CAD susceptibility and identify CST3 functionally contributing to atherosclerosis. Show less
Age at first egg (AFE) has consistently garnered interest as a crucial reproductive indicator within poultry production. Previous studies have elucidated the involvement of the hypothalamic-pituitary- Show more
Age at first egg (AFE) has consistently garnered interest as a crucial reproductive indicator within poultry production. Previous studies have elucidated the involvement of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-thyroid (HPT) axes in regulating poultry sexual maturity. Concurrently, there was evidence suggesting a potential co-regulatory relationship between these 2 axes. However, as of now, no comprehensive exploration of the key pathways and genes responsible for the crosstalk between the HPO and HPT axes in the regulation of AFE has been reported. In this study, we conducted a comparative analysis of morphological differences and performed transcriptomic analysis on the hypothalamus, pituitary, thyroid, and ovarian stroma between normal laying group (NG) and abnormal laying group (AG). Morphological results showed that the thyroid index difference (D-) value (thyroid index D-value=right thyroid index-left thyroid index) was significantly (P < 0.05) lower in the NG than in the AG, while the ovarian index was significantly (P < 0.01) higher in the NG than in the AG. Furthermore, between NG and AG, we identified 99, 415, 167, and 1182 differentially expressed genes (DEGs) in the hypothalamus, pituitary, thyroid, and ovarian stroma, respectively. Gene ontology (GO) analysis highlighted that DEGs from 4 tissues were predominantly enriched in the "biological processes" category. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that 16, 14, 3, and 26 KEGG pathways were significantly enriched (P < 0.05) in the hypothalamus, pituitary, thyroid, and ovarian stroma. The MAPK signaling pathway emerged as the sole enriched pathway across all 4 tissues. Employing an integrated analysis of the protein-protein interaction (PPI) network and correlation analysis, we found GREB1 emerged as a pivotal component within the HPO axis to regulate estrogen-related signaling in the HPT axis, meanwhile, the HPT axis influenced ovarian development by regulating thyroid hormone-related signaling mainly through OPN5. Then, 10 potential candidate genes were identified, namely IGF1, JUN, ERBB4, KDR, PGF, FGFR1, GREB1, OPN5, DIO3, and THRB. These findings establish a foundation for elucidating the physiological and genetic mechanisms by which the HPO and HPT axes co-regulate goose AFE. Show less
Vision-Language Models (VLMs), such as CLIP, excel in zero-shot image-level visual understanding but struggle with object-based tasks requiring precise localization and recognition. Visual prompts, li Show more
Vision-Language Models (VLMs), such as CLIP, excel in zero-shot image-level visual understanding but struggle with object-based tasks requiring precise localization and recognition. Visual prompts, like colorful boxes or circles, are suggested to enhance local perception. However, these methods often include irrelevant and noisy pixels, leading to suboptimal performance. The design of better visual prompts and their collaboration with text prompting remains underexplored. This paper introduces Fine-Grained Visual Text Prompting (FGVTP), a new zero-shot framework for object-based tasks using precise semantic masks and reinforced image-text alignment. FGVTP comprises Fine-Grained Visual Prompting (FGVP) and Consistency-Enhanced Text Prompting (CETP). Specifically, we carefully study visual prompting designs by exploring more visual markings that vary in shape and form. FGVP uses semantic masks from a segmenter like the Segment Anything Model (SAM) and employs background blurring (Blur Reverse Mask) to highlight targets while maintaining spatial coherence. Further, CETP enhances image-text alignment by prompting captions based on FGVP-processed images. As a result, FGVTP achieves superior zero-shot referring expression comprehension on RefCOCO/+/g benchmarks, outperforming previous SOTA methods by 5.8% on average. Part detection experiments conducted on the PACO dataset further validate the preponderance of FGVTP over existing works. Code is available at https://github.com/ylingfeng/FGVP. Show less
Microplastics and nanoplastics (MPs and NPs) are abundant, persistent, and widespread environmental pollutants that are of increasing concern as they pose a serious threat to ecosystems and aquatic sp Show more
Microplastics and nanoplastics (MPs and NPs) are abundant, persistent, and widespread environmental pollutants that are of increasing concern as they pose a serious threat to ecosystems and aquatic species. Identifying the ecological effects of NPs pollution requires understanding the effects of changing nanoplastics concentrations in aquatic organisms. Monopterus albus were orally fed three different concentrations of 100 nm polystyrene nanoplastics (PS-NPs): 0.05 %, 0.5 %, and 1 % of the feed for 28 days. Nanoplastics significantly activated the PPAR signaling pathway, Acyl-CoA oxidase 1 (ACOX1), carnitine palmitoyltransferase 1a (CPT1A), angiopoietin-like 4 (ANGPTL4), and phosphoenolpyruvate carboxykinase (PCK) at the mRNA level, resulting in disturbed lipid metabolism. Glutathione peroxidase (GSH-px) activity, catalase (CAT) activity, and malondialdehyde (MDA) were significantly elevated in the high nanoplastics-feeding exposure group, leading to oxidative stress in the liver. Overexpression of the cytokines genes Interleukin 1 (IL1B) and Interleukin-8 (IL8), Tumor necrosis factor alpha (TNF-α), activation of MAPK signaling pathway, and increased gene expression of c-Jun amino-terminal kinases (JNK) and p38 indicate that exposure to NPs may lead to hepatopancreas apoptosis through oxidative stress and inflammation. In summary, dietary PS-NPs exposure alters hepatic glycolipid metabolism, triggering inflammatory responses and apoptosis in M. albus. The results of this study provide valuable ecotoxicological data for a better understanding of the biological fate and effects of nanoplastics in M. albus. Show less
Telomere-related genes (TRGs) play a critical role in various types of tumors. However, there is a lack of comprehensive exploration of their relevance in lung cancer. This research aimed to verify th Show more
Telomere-related genes (TRGs) play a critical role in various types of tumors. However, there is a lack of comprehensive exploration of their relevance in lung cancer. This research aimed to verify the relationship between TRGs gene expression and the prognosis of patients with lung adenocarcinoma (LUAD), as well as the prediction of drug treatment efficiency. A total of 2093 TRGs were acquired from TelNet. The clinical information including age, tumor stage, follow up and outcome (death/survival) and TRGs expression profile of LUAD were obtained from the patients in The Cancer Genome Atlas (TCGA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. The two databases were used to construct and verify a prognostic model based on the expression of hubTRGs. The tumor mutation burden, immune infiltration and subtypes, as well as IC50 prediction of multiple targeted drugs were also evaluated in TRGs-divided risk groups. A total of 335 TRGs were significantly differentially expressed in LUAD as compared with normal control. Among them, 9 TRGs (ABCC2, ABCC8, ALDH2, FOXP3, GNMT, JSRP1, MACF1, PLCD3, SULT4A1) were finally identified as hubGenes and used to construct a TRG risk score. The TRG risk score showed favorable performance in constructing a prognostic nomogram in predicting survival of LUAD, and the ROC curves at 1, 3 and 5 years were plotted and the AUROC values were 0.743, 0.754 and 0.735, respectively. Higher TRGs risk score correlated with worse immune subtypes and higher tumor mutation burden in LUAD tissues. In addition, the patients in TRG high risk group harbored a lower TIDE score which indicated potentially better response to immunotherapy. This study proposed a broad molecular signature of telomere-related genes that can be used in further functional and therapeutic investigations, and also represents an integrated modality for characterizing critical molecules when exploring novel targets for lung cancer immunotherapy. Show less
The objective of this study was to investigate the phylogenetic and expression analysis of the angiopoietin-like (ANGPTL) gene family and their role in lipid metabolism in pigs. In this study, the ami Show more
The objective of this study was to investigate the phylogenetic and expression analysis of the angiopoietin-like (ANGPTL) gene family and their role in lipid metabolism in pigs. In this study, the amino acid sequence analysis, phylogenetic analysis, and chromosome adjacent gene analysis were performed to identify the ANGPTL gene family in pigs. According to the body weight data from 60 Jinhua pigs, different tissues of 6 pigs with average body weight were used to determine the expression profile of ANGPTL1-8. The ileum, subcutaneous fat, and liver of 8 pigs with distinct fatness were selected to analyze the gene expression of ANGPTL3, ANGPTL4, and ANGPTL8. The sequence length of ANGPTLs in pigs was between 1,186 and 1,991 bp, and the pig ANGPTL family members shared common features with human homologous genes, including the high similarity of the amino acid sequence and chromosome flanking genes. Amino acid sequence analysis showed that ANGPTL1-7 had a highly conserved domain except for ANGPTL8. Phylogenetic analysis showed that each ANGPTL homologous gene shared a common origin. Quantitative reverse-transcription polymerase chain reaction analysis showed that ANGPTL family members had different expression patterns in different tissues. ANGPTL3 and ANGPTL8 were mainly expressed in the liver, while ANGPTL4 was expressed in many other tissues, such as the intestine and subcutaneous fat. The expression levels of ANGPTL3 in the liver and ANGPTL4 in the liver, intestine and subcutaneous fat of Jinhua pigs with low propensity for adipogenesis were significantly higher than those of high propensity for adipogenesis. These results increase our knowledge about the biological role of the ANGPTL family in this important economic species, it will also help to better understand the role of ANGPTL3, ANGPTL4, and ANGPTL8 in lipid metabolism of pigs, and provide innovative ideas for developing strategies to improve meat quality of pigs. Show less
Ferroptosis is an important mode of regulated cell death (RCD). Its inhibition is closely related to therapeutic resistance and poor prognosis in hepatocellular carcinoma (HCC). Previous reports have Show more
Ferroptosis is an important mode of regulated cell death (RCD). Its inhibition is closely related to therapeutic resistance and poor prognosis in hepatocellular carcinoma (HCC). Previous reports have demonstrated ferroptosis as a biological process highly dependent on selective autophagy, such as ferritinophagy, lipophagy, and clockophagy. Our study also revealed a role for ER-phagy-mediated ferroptosis in HCC cells treated with multi-targeted tyrosine kinase inhibitors (TKIs). In the current study, we found that the homologous circular RNA (circRNA) of the family with sequence similarity 134, member B ( Show less
Mi Li, Xian Wang, Lijie Yang+3 more · 2023 · Technology and health care : official journal of the European Society for Engineering and Medicine · added 2026-04-24
Microglia express phosphatidylinositol 3-kinase (PI3K) has been implicated in the induction and maintenance of long-term potentiation (LTP) and in hippocampal synaptic plasticity. However, there are f Show more
Microglia express phosphatidylinositol 3-kinase (PI3K) has been implicated in the induction and maintenance of long-term potentiation (LTP) and in hippocampal synaptic plasticity. However, there are few studies on the interference of PI3K signal pathway in microglia. The study goal is to gain a better understanding of the mechanism by which EA affects synapses provides insights into how electroacupuncture (EA) modulates synaptic plasticity in learning and memory. Rat models of posttraumatic stress disorder (PTSD) were used to explore the effects of EA on microglial PI3K pathway, brain-derived neurotrophic factor (BDNF) and LTP, and the target and mechanism underlying the effects of EA on PI3K from the perspective of protein ubiquitination. EA induced microglial BDNF expression by activating the PI3K-AKT pathway, thereby facilitating LTP and synaptic plasticity. EA inhibited lincRNA 02023 to rescue the binding of WWP2 to PTEN, thereby promoting PTEN ubiquitination and degradation. The mechanism of EA improving the learning and memory ability of PTSD rats may be that it can promote the competitive combination of WWP2 and PTEN by inhibiting Linc RNA02023, and then lead to microglial PI3K and its pathway activation, BDNF up-regulation, and finally induce LTP and repair damaged synaptic plasticity. Show less
Excessive NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation has an important function in the pathogenesis of Sjögren's syndrome (SS). Increased and dysfunct Show more
Excessive NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation has an important function in the pathogenesis of Sjögren's syndrome (SS). Increased and dysfunctional myeloid-derived suppressor cells (MDSCs) promoted SS. However, NLRP3 inflammasome activation of MDSCs in SS and its regulated components are unclear. Splenic MDSCs were purified by immunomagnetic beads and cultured. Western blot was used to assess NLRP3 inflammasomes. Interleukin-1β (IL-1β) and IL-18 were measured using enzyme-linked immunosorbent assay. Here we showed that the NLRP3 inflammasome was activated in non-obese diabetic (NOD) mice with SS-like manifestations. We found that NLRP3 inflammasome activation was augmented in MDSCs of SS mice and NLRP3 inflammasome activation was suppressed in IL-27-deficient NOD mice. Consistent with findings of SS mice in vivo, we observed that NLRP3 inflammasome activation by adenosine triphosphate and lipopolysaccharide was remarkably intensified in MDSCs with IL-27 treatment in vitro. Collectively, our data highlighted that IL-27 regulates NLRP3 inflammasome activation of MDSCs in experimental SS. Show less
Consumer demand for tasty and quality meat has been quickly increasing. This study investigated how dietary supplemented rutin affects meat quality, muscle fatty acid profile, and antioxidant capacity Show more
Consumer demand for tasty and quality meat has been quickly increasing. This study investigated how dietary supplemented rutin affects meat quality, muscle fatty acid profile, and antioxidant capacity in the Chinese indigenous Qingyuan partridge chicken. A cohort of 180 healthy 119-day-old chickens was subjected to a randomized assignment into three groups, identified as the control, R200, and R400 groups, with respective supplementation of 0, 200, and 400 mg/kg of rutin. The results revealed insignificance in growth performance, namely, average daily gain, average daily feed intake, and feed-to-gain ratio, across the various treatment groups ( Show less
Qi Jiang, Ruolan Miao, Yuhuan Wang+8 more · 2023 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Polycystic ovary syndrome (PCOS) is one of the most common, heterogenous endocrine disorders and is the leading cause of ovulatory obstacle associated with abnormal folliculogenesis. Dysfunction of ov Show more
Polycystic ovary syndrome (PCOS) is one of the most common, heterogenous endocrine disorders and is the leading cause of ovulatory obstacle associated with abnormal folliculogenesis. Dysfunction of ovarian granulosa cells (GCs) is recognized as a major factor that underlies abnormal follicle maturation. Angiopoietin-like 4 (ANGPTL4) expression in GCs differs between patients with and without PCOS. However, the role and mechanism of ANGPTL4 in impaired follicular development are still poorly understood. Here, the case-control study was designed to investigate the predictive value of ANGPTL4 in PCOS while cell experiments in vitro were set for mechanism research. Results found that ANGPTL4 levels in serum and in follicular fluid, and its expression in GCs, were upregulated in patients with PCOS. In KGN and SVOG cells, upregulation of ANGPTL4 inhibited the proliferation of GCs by blocking G1/S cell cycle progression, as well as the molecular activation of the EGFR/JAK1/STAT3 cascade. Moreover, the STAT3-dependent CDKN1A(p21) promoter increased CDKN1A transcription, resulting in remarkable suppression effect on GCs. Together, our results demonstrated that overexpression of ANGPTL4 inhibited the proliferation of GCs through EGFR/JAK1/STAT3-mediated induction of p21, thus providing a novel epigenetic mechanism for the pathogenesis of PCOS. Show less
Genome-wide association studies have reported 23 gene loci related to abdominal aortic aneurysm (AAA)-a potentially lethal condition characterized by a weakened dilated vessel wall. This study aimed t Show more
Genome-wide association studies have reported 23 gene loci related to abdominal aortic aneurysm (AAA)-a potentially lethal condition characterized by a weakened dilated vessel wall. This study aimed to identify proteomic signatures and pathways related to these risk loci to better characterize AAA genetic susceptibility. Plasma concentrations of 4870 proteins were determined using a DNA aptamer-based array. Linear regression analysis estimated the associations between the 23 risk alleles and plasma protein levels with adjustments for potential confounders in a race-stratified analysis of 1671 Black and 7241 White participants. Significant proteins were then evaluated for their prediction of clinical AAA (454 AAA events in 11 064 individuals), and those significantly associated with AAA were further interrogated using Mendelian randomization analysis. Risk variants proximal to Low levels of neogenin and kit ligand may be novel risk factors for AAA development in potentially causal pathways. These findings provide insights and potential targets to reduce AAA susceptibility. Show less
Arabidopsis nucleoporin involved in the regulation of ethylene signaling via controlling of nucleocytoplasmic transport of mRNAs. The two-way transport of mRNAs between the nucleus and cytoplasm are c Show more
Arabidopsis nucleoporin involved in the regulation of ethylene signaling via controlling of nucleocytoplasmic transport of mRNAs. The two-way transport of mRNAs between the nucleus and cytoplasm are controlled by the nuclear pore complex (NPC). In higher plants, the NPC contains at least 30 nucleoporins. The Arabidopsis nucleoporins are involved in various biological processes such as pathogen interaction, nodulation, cold response, flowering, and hormone signaling. However, little is known about the regulatory functions of the nucleoporin NUP160 and NUP96 in ethylene signaling pathway. In the present study, we provided data showing that the Arabidopsis nucleoporin NUP160 and NUP96 participate in ethylene signaling-related mRNAs nucleocytoplasmic transport. The Arabidopsis nucleoporin mutants (nup160, nup96-1, nup96-2) exhibited enhanced ethylene sensitivity. Nuclear qRT-PCR analysis and poly(A)-mRNA in situ hybridization showed that the nucleoporin mutants affected the nucleocytoplasmic transport of all the examined mRNAs, including the ethylene signaling-related mRNAs such as ETR2, ERS1, ERS2, EIN4, CTR1, EIN2, and EIN3. Transcriptome analysis of the nucleoporin mutants provided clues suggesting that the nucleoporin NUP160 and NUP96 may participate in ethylene signaling via various molecular mechanisms. These observations significantly advance our understanding of the regulatory mechanisms of nucleoporin proteins in ethylene signaling and ethylene response. Show less
Icariin (ICA) is the main active component of Epimedium, a traditional Chinese medicine (TCM), known to enhance cognitive function in Alzheimer's disease (AD). This study aims to investigate and summa Show more
Icariin (ICA) is the main active component of Epimedium, a traditional Chinese medicine (TCM), known to enhance cognitive function in Alzheimer's disease (AD). This study aims to investigate and summarize the mechanisms through which ICA treats AD. The PubMed and CNKI databases were utilized to review the advancements in ICA's role in AD prevention and treatment by analyzing literature published between January 2005 and April 2023. To further illustrate ICA's impact on AD development, tables, and images are included to summarize the relationships between various mechanisms. The study reveals that ICA ameliorates cognitive deficits in AD model mice by modulating Aβ via multiple pathways, including BACE-1, NO/cGMP, Wnt/Ca This study indicates that ICA possesses multiple beneficial effects in AD treatment. Through the integration of pharmacological and molecular biological research, ICA may emerge as a promising candidate to expedite the advancement of TCM in the clinical management of AD. Show less
Locally advanced and metastatic pancreatic cancer (PC) frequently grows in adipose tissue and has a poor prognosis. Although adipose tissue is largely composed of adipocytes, the mechanisms by which a Show more
Locally advanced and metastatic pancreatic cancer (PC) frequently grows in adipose tissue and has a poor prognosis. Although adipose tissue is largely composed of adipocytes, the mechanisms by which adipocytes impact PC are poorly understood. Using an Show less
Chicken is considered an ideal model species to study the synthesis of polyunsaturated fatty acids (PUFAs) due to its appropriate proportions of fatty acids and abundant content of PUFAs, suitable for Show more
Chicken is considered an ideal model species to study the synthesis of polyunsaturated fatty acids (PUFAs) due to its appropriate proportions of fatty acids and abundant content of PUFAs, suitable for human consumption. However, the molecular mechanisms regulating poultry PUFA synthesis remain unclear. Here, we systematically explored the transcriptional regulation activity of the gene family related to PUFA synthesis in chicken by carrying out the Dual-Luciferase Reporter Assay. We identified the core promoter regions of members of the chicken PUFA synthesis-related gene family, including ELOVL1, ELOVL2, ELOVL3, ELOVL4, ELOVL5, ELOVL6, ELOVL7, FADS1, FADS2, FADS6, SCD, and SCD5. Additionally, changes in relative fluorescence values of different truncated segments in the upstream regulatory region of these genes indicate the existence of regulatory regions. Furthermore, we predicted the transcription factors that bind to the identified core promoter regions of multiple genes, including Sp1, NF-1, C/EBPalpha, etc. These findings provide a basis for the molecular mechanisms regulating poultry PUFA synthesis and offer new scientific insight into the potential improvement of poultry meat quality in the future. Show less
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and irreversible cartilage and bone damage. Despite its predominant osteoarticular and peria Show more
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and irreversible cartilage and bone damage. Despite its predominant osteoarticular and periarticular manifestations, RA is also a systematic disease associated with organ-specific extra-articular manifestation. Increasing evidence indicates that RA patients are susceptible to diabetes mellitus (DM), and RA aggravates metabolic disordered in DM, indicating the close association between RA and DM. Many factors involved in RA stimulate insulin resistance and DM development. These factors include proinflammatory cytokines (such as TNF-α, IL-6, IL-1β), RA autoantibodies (such as rheumatoid factor, cyclic citrullinated peptide antibodies), excess RA related adipokines (such as leptin, resistin, ANGPTL4), C-creative protein, and other protein (such as TXNDC5, NLRP3, RBP4). Furthermore, commonly used RA drugs, such as conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological disease-modifying antirheumatic drugs (bDMARDs), and glucocorticoids, provide potential benefits in improving insulin resistance and inhibiting DM development. This review discusses the mechanistic and therapeutic links between RA and DM, aiming to provide valuable information for the prevention and treatment of DM in RA patients. Show less