As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) ha Show more
As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation. After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and AΞ²1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca Rg1 therapy may improve neuronal injury and DACD via mediating PLC-CN-NFAT1 signal pathway to reduce AΞ² generation in T2DM mice. Show less
Several studies have confirmed that the pathophysiological progression of Alzheimer's disease (AD) is closely related to changes in the intestinal microbiota; thus, modifying the intestinal microbiota Show more
Several studies have confirmed that the pathophysiological progression of Alzheimer's disease (AD) is closely related to changes in the intestinal microbiota; thus, modifying the intestinal microbiota has emerged as a new way to treat AD. Effective interventions for gut microbiota include the application of probiotics and other measures such as fecal microbiota transplantation (FMT). However, the application of probiotics ignores that the intestine is a complete microecosystem with competition among microorganisms. FMT also has issues when applied to patient treatment. In a previous study, we found that eight species of bacteria that are isolated with high frequency in the normal intestinal microbiota (i.e., intestinal dominant microbiota) have biological activities consistent with the effects of FMT. In this article, we confirmed that the treatment of intestinal dominant microbiota significantly restored intestinal microbiota abundance and composition to normal levels in APP/PS1 mice; downregulated brain tissue pro-inflammatory cytokines (IL-1Ξ² and IL-6) and amyloid precursor protein (APP) and Ξ²-site APP cleavage enzyme 1 (BACE1) expression levels; and reduced the area of AΞ² plaque deposition in the brain hippocampus. Our study provides a new therapeutic concept for the treatment of AD, adjusting the intestinal microecological balance through dominant intestinal microbiota may be an alternative to FMT. Show less
Fatty acids are involved in a wide range of immunological responses in humans. Supplementation of polyunsaturated fatty acids has been reported to help alleviate symptoms and airway inflammation in as Show more
Fatty acids are involved in a wide range of immunological responses in humans. Supplementation of polyunsaturated fatty acids has been reported to help alleviate symptoms and airway inflammation in asthma patients, whereas the effects of fatty acids on the actual risk of asthma remain controversial. This study comprehensively investigated the causal effects of serum fatty acids on asthma risk using two-sample bidirectional Mendelian Randomization (MR) analysis. Genetic variants strongly associated with 123 circulating fatty acid metabolites were extracted as instrumental variables, and a large GWAS data of asthma was used to test effects of the metabolites on this outcome. The inverse-variance weighted method was used for primary MR analysis. The weighted median, MR-Egger regression, MR-PRESSO, and leave-one-out analyses were utilized to evaluate heterogeneity and pleiotropy. Potential confounders were adjusted by performing multivariable MR analyses. Reverse MR analysis was also conducted to estimate the causal effect of asthma on candidate fatty acid metabolites. Further, we performed colocalization analysis to examine the pleiotropy of variants within the fatty acid desaturase 1 (FADS1) locus between the significant metabolite traits and the risk of asthma. Cis-eQTL-MR and colocalization analysis were also performed to determine the association between RNA expression of FADS1 and asthma. Genetically instrumented higher average number of methylene groups was causally associated with a lower risk of asthma in primary MR analysis, while inversely, the higher ratio of bis-allylic groups to double bonds and the higher ratio of bis-allylic groups to total fatty acids, were associated with higher probabilities of asthma. Consistent results were obtained in multivariable MR when adjusted for potential confounders. However, these effects were completely eliminated after SNPs correlated with the FADS1 gene were excluded. The reverse MR also found no causal association. The colocalization analysis suggested that the three candidate metabolite traits and asthma likely share causal variants within the FADS1 locus. In addition, the cis-eQTL-MR and colocalization analyses demonstrated a causal association and shared causal variants between FADS1 expression and asthma. Our study supports a negative association between several PUFA traits and the risk of asthma. However, this association is largely attributed to the influence of FADS1 polymorphisms. The results of this MR study should be carefully interpreted given the pleiotropy of SNPs associated with FADS1. Show less
Nanoplastics and di(2-ethylhexyl) phthalate (DEHP) are ubiquitous emerging contaminants that are transferred among organisms through food chain in the ecosystem. This study evaluated the trophic trans Show more
Nanoplastics and di(2-ethylhexyl) phthalate (DEHP) are ubiquitous emerging contaminants that are transferred among organisms through food chain in the ecosystem. This study evaluated the trophic transfer of polystyrene nanoplastics (PSNPs) and DEHP in a food chain including Chlorella pyrenoidosa, Daphnia magna and Micropterus salmoides (algae-crustacean-fish) and lipid metabolism at a higher trophic level in fish. Our results showed that the PSNPs and DEHP accumulated in C. pyrenoidosa or D. magna were transferred to the M. salmoides, of which the DEHP were not biomagnified, while the PSNPs were trophically amplified by the food chain. It is suggested that more PSNPs might be accumulated by higher level consumers in a longer food chain. Additionally, the trophic transfer of PSNPs and DEHP resulted in antioxidant response and histopathological damage in M. salmoides. Moreover, the lipid biochemical parameters and lipid metabolism related genes (fasn, hsl, cpt1a, atgl, apob, fabp1, lpl, cetp) of M. salmoides were significantly affected, which indicated disturbance of lipid metabolism. This study offers great insight into the transfer of contaminants by trophic transfer and their negative effects on organisms at higher trophic levels, which cause human exposure to MNPs and organic contaminants in the ecosystem. Show less
To detect differentially expressed genes in patients with neonatal necrotizing enterocolitis (NEC) by bioinformatics methods and to provide new ideas and research directions for the prevention, early Show more
To detect differentially expressed genes in patients with neonatal necrotizing enterocolitis (NEC) by bioinformatics methods and to provide new ideas and research directions for the prevention, early diagnosis and treatment of NEC. Gene chip data were downloaded from the Gene Expression Omnibus database. The genes that were differentially expressed in NEC compared with normal intestinal tissues were screened with GEO2R. The functions, pathway enrichment and protein interactions of these genes were analyzed with DAVID and STRING. Then, the core network genes and significant protein interaction modules were detected using Cytoscape software. Overall, a total of 236 differentially expressed genes were detected, including 225 upregulated genes and 11 downregulated genes, and GO and KEGG enrichment analyses were performed. The results indicated that the upregulated differentially expressed genes were related to the dimerization activity of proteins, while the downregulated differentially expressed genes were related to the activity of cholesterol transporters. KEGG enrichment analysis revealed that the differentially expressed genes were significantly concentrated in metabolism, fat digestion and absorption pathways. Through STRING analysis, 9 key genes in the protein network interaction map were identified: EPCAM, CDH1, CFTR, IL-6, APOB, APOC3, APOA4, SLC2A and NR1H4. Metabolic pathways and biological processes may play important roles in the development of NEC. The screening of possible core targets by bioinformatics is helpful in clarifying the pathogenesis of NEC at the gene level and in providing references for further research. Show less
The pathogenic mechanism of dilated cardiomyopathy (DCM) remains to be defined. This study aimed to identify hub genes and immune cells that could serve as potential therapeutic targets for DCM. We do Show more
The pathogenic mechanism of dilated cardiomyopathy (DCM) remains to be defined. This study aimed to identify hub genes and immune cells that could serve as potential therapeutic targets for DCM. We downloaded four datasets from the Gene Expression Omnibus (GEO) database: GSE141910, GSE3585, GSE42955 and GSE79962. Weighted gene coexpression network analysis (WGCNA) and differential expression analysis were performed to identify gene panels related to DCM. Meanwhile, the CIBERSORT algorithm was used to estimate the immune cells in DCM tissues. Multiple machine learning approaches were used to screen the hub genes and immune cells. Finally, the diagnostic value of the hub genes was assessed by receiver operating characteristic (ROC) analysis. An experimental mouse model of dilated cardiomyopathy was used to validate the bioinformatics results. FRZB and EXT1 were identified as hub biomarkers, and the ROC curves suggested an excellent diagnostic ability of the above genes for DCM. In addition, naive B cells were upregulated in DCM tissues, while eosinophils, M2 macrophages, and memory CD4 T cells were downregulated in DCM tissues. The increase in two hub genes and naive B cells wasΒ validatedΒ inΒ animalΒ experiments. These results indicated that FRZB and EXT1 could be used as promising biomarkers, and eosinophils, M2 macrophages, resting memory CD4 T cells and naive B cells may also affect the occurrence of DCM. Show less
Neuritic plaques are one of the major pathological hallmarks of Alzheimer's disease. They are formed by the aggregation of extracellular amyloid-Ξ² protein (AΞ²), which is derived from the sequential cl Show more
Neuritic plaques are one of the major pathological hallmarks of Alzheimer's disease. They are formed by the aggregation of extracellular amyloid-Ξ² protein (AΞ²), which is derived from the sequential cleavage of amyloid-Ξ² precursor protein (APP) by Ξ²- and Ξ³-secretase. BACE1 is the main Ξ²-secretase in the pathogenic process of Alzheimer's disease, which is believed to be a rate-limiting step of AΞ² production. Presenilin 1 (PS1) is the active center of the Ξ³-secretase that participates in the APP hydrolysis process. Mutations in the PS1 gene ( Show less
Carbon emission trading is not only a market-based instrument but also one of the government's macro-policies, which is extremely crucial to fulfilling both carbon peak attainment and carbon neutralit Show more
Carbon emission trading is not only a market-based instrument but also one of the government's macro-policies, which is extremely crucial to fulfilling both carbon peak attainment and carbon neutrality goals. For this purpose, this paper adopts a 30-region dataset for the period from 2008 to 2020 in China and employs the difference-in-difference (DID) method to quantify the effect of the carbon emission trading pilot policy (CETP) on carbon emissions on the basis of introducing industrial structure upgrading and green technology innovation as moderating variables. The results show that (1) CETP has a statistically significant dampening effect on carbon emissions, while its carbon emission reduction effect follows a significant strengthening trend as the policy year of CETP implementation is delayed. (2) CETP has a significant carbon emission reduction effect. However, its effect demonstrates a gradual decrease from the eastern to the central and finally to the western regions. (3) CETP can inhibit carbon emissions depending on industrial structure upgrading to a certain extent, and this dependence is significant in the national and eastern regions but not in the central and western regions. (4) CETP's carbon emission reduction effect is dependent on green technology innovation, which is only revealed in the western region and performs as a dampening effect in the national, eastern, and central regions, but not significantly. Show less
Systemic amyloidosis is classified according to the deposited amyloid fibril protein (AFP), which determines its best therapeutic scheme. The most common type of AFP found are immunoglobulin light cha Show more
Systemic amyloidosis is classified according to the deposited amyloid fibril protein (AFP), which determines its best therapeutic scheme. The most common type of AFP found are immunoglobulin light chains. The laser microdissection combined with mass spectrometry (LMD-MS) technique is a promising approach for precise typing of amyloidosis, however, the major difficulty in interpreting the MS data is how to accurately identify the precipitated AFP from background. The objective of the present study is to establish a complete data interpretation procedure for LMD-MS based amyloidosis typing. Formalin-fixed paraffin-embedded specimens from patients with renal amyloidosis and non-amyloid nephropathies (including diabetic nephropathy, fibrillary glomerulonephritis, IgA nephropathy, lupus nephritis, membranous nephropathy, and normal tissue adjacent to tumors) were analyzed by LMD-MS. Forty-two specimens were used to train the data interpretation procedure, which was validated by another 50 validation specimens. Area under receiver operating curve (AUROC) analysis of amyloid accompanying proteins (AAPs, including apolipoprotein A-IV, apolipoprotein E and serum amyloid P-component) for discriminating amyloidosis from non-amyloid nephropathies was performed. A stepwise data interpretation procedure that includes or excludes the types of amyloidosis group by group was established. The involvement of AFPs other than immunoglobulin was determined by P-score, as well as immunoglobulin light chain by variable of Ξ»-ΞΊ, and immunoglobulin heavy chain by H-score. This achieved a total of 88% accuracy in 50 validation specimens. The AAPs showed significantly different expression levels between amyloidosis specimens and non-amyloid nephropathies. Each of the single AAP had a AUROC value more than 0.9 for diagnosis of amyloidosis from non-amyloid control, and the averaged level of the three AAPs showed the highest AUROC (0.966), which might be an alternative indicator for amyloidosis diagnosis. The proteomic data interpretation procedure for LMD-MS based amyloidosis typing was established successfully that has a high practicability in clinical application. Show less
Chicken internal organs are indispensable parts of the body, but their genetic architectures have not been commonly understood. Herein, we estimated the genetic parameters for heart weight (HW), liver Show more
Chicken internal organs are indispensable parts of the body, but their genetic architectures have not been commonly understood. Herein, we estimated the genetic parameters for heart weight (HW), liver weight (LW), spleen weight (SpW), testis weight (TW), glandular stomach weight (GSW), muscular stomach weight (MSW) and identified single nucleotide polymorphisms (SNPs) and potential candidate genes associated with internal organ weights in an F Show less
Alzheimer disease (AD) is a degenerative brain disease, which may lead to severe memory loss and other cognitive disorders. However, few effective drugs are available in the clinic at present. Curcumi Show more
Alzheimer disease (AD) is a degenerative brain disease, which may lead to severe memory loss and other cognitive disorders. However, few effective drugs are available in the clinic at present. Curcumin, a major ingredient of traditional Chinese medicine, Curcuma Longa, has various pharmacological activities. Therefore, exploring clinical drugs based on the inhibition of AD pathological features is imperative. First, we utilized the HERB database and Swisstarget Prediction database to get the related targets of curcumin and intersected with the AD targets. The intersection targets were used to construct the protein-protein interaction network and performed gene ontology and kyoto encyclopedia of genes and genomes analyses. Further, we obtained targets of curcumin against AD-related tau and aΞ² pathology via the AlzData database. These targets were applied to perform GEO and receiver operating characteristic analyses. Finally, the reliability of the core targets was evaluated using molecular docking technology. We identified 49 targets of curcumin against AD, and kyoto encyclopedia of genes and genomes pathway enrichment analysis demonstrated that the Alzheimer disease pathway (has05010) was significantly enriched. Even more, we obtained 16 targets of curcumin-related AΞ² and tau pathology. Among these targets, 8 targets involved the Alzheimer disease pathway and the biological process analyses showed that positive regulation of cytokine production (GO:0001819) was significantly enriched. Bioinformatic analyses indicated that HMOX1, CSF1R, NFKB1, GSK3B, BACE1, AR, or PTGS1 expression was significantly different compared to the control group in the AD patients. Finally, molecular docking studies suggested these genes have a good binding force with curcumin. In this study, we identified curcumin exerted the effect of treating AD by regulating multitargets and multichannels through the method of network pharmacology. Show less
Alzheimer disease (AD), a progressive neurodegenerative disorder, is mainly caused by the interaction of genetic and environmental factors. The impact of environmental factors on the genetic mutation Show more
Alzheimer disease (AD), a progressive neurodegenerative disorder, is mainly caused by the interaction of genetic and environmental factors. The impact of environmental factors on the genetic mutation in the amyloid precursor protein (APP) is not well characterized. We hypothesized that endoplasmic reticulum (ER) stress would promote disease for the patient carrying the APP D678H mutation. Therefore, we analyzed the impact of a familial AD mutation on amyloid precursor protein (APP D678H) under ER stress. Induced pluripotent stem cells (iPSCs) from APP D678H mutant carrier was differentiated into neurons, which were then analyzed for AD-like changes. Immunocytochemistry and whole-cell patch-clamp recording revealed that the derived neurons on day 28 after differentiation showed neuronal markers and electrophysiological properties similar to those of mature neurons. However, the APP D678H mutant neurons did not have significant alterations in the levels of amyloid-Ξ² (AΞ²) and phosphorylated tau (pTau) compared to its isogenic wild-type neurons. Only under ER stress, the neurons with the APP D678H mutation had more AΞ² and pTau via immune detection assays. The higher level of AΞ² in the APP D678H mutant neurons was probably due to the increased level of Ξ²-site APP cleaving enzyme (BACE1) and decreased level of AΞ²-degrading enzymes under ER stress. Increased AΞ² and pTau under ER stress reduced the N-methyl-D-aspartate receptor (NMDAR) in Western blot analysis and altered electrophysiological properties in the mutant neurons. Our study provides evidence that the interaction between genetic mutation and ER stress would induce AD-like changes. Cover Image for this issue: https://doi.org/10.1111/jnc.15420. Show less
IKBKE, a non-canonical inflammatory kinase, is frequently amplified or activated, and plays predominantly oncogenic roles in human cancers, especially in breast cancer. However, the potential function Show more
IKBKE, a non-canonical inflammatory kinase, is frequently amplified or activated, and plays predominantly oncogenic roles in human cancers, especially in breast cancer. However, the potential function and underlying mechanism of IKBKE contributing to breast cancer metastasis remain largely elusive. Here, we report that depletion of Ikbke markedly decreases polyoma virus middle T antigen (PyVMT)-induced mouse mammary tumorigenesis and subsequent lung metastasis. Biologically, ectopic expression of IKBKE accelerates, whereas depletion of IKBKE attenuates breast cancer invasiveness and migration in vitro and tumor metastasis in vivo. Mechanistically, IKBKE tightly controls the stability of transcriptional factor Snail in different layers, in particular by directly phosphorylating Snail, which markedly blocks the E3 ligase Ξ²-TRCP1-mediated Snail degradation, resulting in breast cancer epithelial-mesenchymal transition (EMT) and metastasis. These findings together reveal a novel oncogenic function of IKBKE in promoting breast cancer metastasis by governing Snail abundance, and highlight the potential of targeting IKBKE for metastatic breast cancer therapies. Show less
Adult muscle stem cells, also known as satellite cells (SCs), play pivotal roles in muscle regeneration, and long non-coding RNA (lncRNA) functions in SCs remain largely unknown. Here, we identify a l Show more
Adult muscle stem cells, also known as satellite cells (SCs), play pivotal roles in muscle regeneration, and long non-coding RNA (lncRNA) functions in SCs remain largely unknown. Here, we identify a lncRNA, Lockd, which is induced in activated SCs upon acute muscle injury. We demonstrate that Lockd promotes SC proliferation; deletion of Lockd leads to cell-cycle arrest, and inΒ vivo repression of Lockd in mouse muscles hinders regeneration process. Mechanistically, we show that Lockd directly interacts with RNA helicase DHX36 and the 5'end of Lockd possesses the strongest binding with DHX36. Furthermore, we demonstrate that Lockd stabilizes the interaction between DHX36 and EIF3B proteins; synergistically, this complex unwinds the RNA G-quadruplex (rG4) structure formed at Anp32e mRNA 5' UTR and promotes the translation of ANP32E protein, which is required for myoblast proliferation. Altogether, our findings identify a regulatory Lockd/DHX36/Anp32e axis that promotes myoblast proliferation and acute-injury-induced muscle regeneration. Show less
Mei Wang, Shaoqi Xu, Ya Li+8 more Β· 2022 Β· Comparative biochemistry and physiology. Part A, Molecular & integrative physiology Β· Elsevier Β· added 2026-04-24
Amylin is a 37-amino acid polypeptide that has been found to be involved in feeding regulation in some mammals, birds, and goldfish. We cloned amylin of Siberian sturgeon and detected its distribution Show more
Amylin is a 37-amino acid polypeptide that has been found to be involved in feeding regulation in some mammals, birds, and goldfish. We cloned amylin of Siberian sturgeon and detected its distribution pattern in 15 tissues. The expression levels in the periprandial period (pre-and post-feeding), the changes in the food intake, and the expression levels of related appetite factors after the intraperitoneal injection of amylin were detected. The expression of amylin was found to be the highest in the hypothalamus. Compared with 1Β h pre-feeding, the expression levels of amylin in the hypothalamus and duodenum were increased significantly 1Β h post-feeding. Compared with the control group (saline), intraperitoneal injection of 50Β ng/g, 100Β ng/g, and 200Β ng/g of amylin significantly inhibited food intake at 1Β h post injection, but not at 3Β h and 6Β h. The injection of 50Β ng/g, 100Β ng/g, and 200Β ng/g amylin significantly inhibited the cumulative feed. After 1Β h of 50Β ng/g amylin injection, the levels of MC4R and somatostatin in the hypothalamus increased significantly, while the levels of amylin and NPY decreased significantly. The levels of CCK in the valvular intestine were increased significantly. Insulin in the duodenum was also increased significantly, but there was no significant change in ghrelin in the duodenum. These results show that amylin inhibits feeding in Siberian sturgeon by down-regulating the appetite-stimulating factor NPY and up-regulating the appetite-suppressing factors somatostatin, MC4R, CCK, and insulin. This study provides a theoretical basis for studying the feeding function and action mechanisms of amylin in Siberian sturgeon. Show less
Bicuspid aortic valve (BAV) is the most common congenital heart defect in human beings, with an estimated prevalence in the general population of between 0.5 and 2%. Moreover, BAV is the most common c Show more
Bicuspid aortic valve (BAV) is the most common congenital heart defect in human beings, with an estimated prevalence in the general population of between 0.5 and 2%. Moreover, BAV is the most common cause of aortic stenosis in the pediatric population. Patients with BAV may have no symptoms for life, and some of them may progress to aortic stenosis. Genetic factors increase the susceptibility and development of BAV. However, the pathogenesis and BAV are still unclear, and more genetic variants are still needed for elucidating the molecular mechanism and stratification of patients. The present study carried out screening of variants implicated in disease in BAV patients. The whole-exome sequencing (WES) was performed in 20 BAV patients and identified 40 different heterozygous missense mutations in 36 genes (MIB2, FAAH, S100A1, RGS16, MAP3K19, NEB, TTN, TNS1, CAND2, CCK, KALRN, ATP10D, SLIT3, ROS1, FABP7, NUP205, IL11RA, NPR2, COL5A1, CUBN, JMJD1C, ANXA7, TRIM8, LGR4, TPCN2, APOA5, GPR84, LRP1, NCOR2, AKAP11, ESRRB, NGB, AKAP13, WWOX, KCNJ12, ARHGEF1). The mutations in these genes were identified as recurrent variants implicated in disease by in silico prediction tool analysis. Nine genes (MIB2, S100A1, TTN, CCK, NUP205, LGR4, NCOR2, ESRRB, and WWOX) among the 36 genes were identified as variants implicated in disease via unanimous agreement of in silico prediction tool analysis and sequenced in an independent cohort of 137 BAV patients to validate the results of WES. BAV patients carrying these variants demonstrated reduced left ventricular ejection fractions (LVEF) (63.8βΒ±β7.5% vs. 58.4βΒ±β5.2%, Pβ<β0.001) and larger calcification volume [(1129.3βΒ±β154) mm Show less
Polyunsaturated fatty acid (PUFA) in breast milk provides physiological benefits for offspring and is closely related to endogenous biosynthesis in lactating women. Few studies have addressed the asso Show more
Polyunsaturated fatty acid (PUFA) in breast milk provides physiological benefits for offspring and is closely related to endogenous biosynthesis in lactating women. Few studies have addressed the association between fatty acid desaturase ( Show less
The search for potential gene loci that affect the pharmacodynamics and pharmacokinetics of ticagrelor is a matter of broad clinical interest. The objective of this study was to investigate the effect Show more
The search for potential gene loci that affect the pharmacodynamics and pharmacokinetics of ticagrelor is a matter of broad clinical interest. The objective of this study was to investigate the effect of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of ticagrelor in healthy Chinese subjects. This is a multi-center study in China, including three hospitals from Beijing, Nanchang, and Changsha. Healthy Chinese subjects aged 18-45 years with unknown genotypes were included. All subjects received a single oral dose of 90βmg of ticagrelor. Platelet aggregation and the area under the concentration-time curve for ticagrelor and its major active metabolite in plasma samples were assessed. Genome-wide association studies and candidate gene association analysis related to ticagrelor were performed. One hundred and seventy-five native Chinese subjects were enrolled and completed the study. According to the p value, the threshold of ticagrelor population was 6.57 Γ 10 Genetic variation affects the pharmacokinetics and pharmacodynamics of ticagrelor in healthy individuals. The detection of NUP153, SVEP1 gene variation will be helpful for pharmacodynamic prediction and evaluation, and the regulation of these genes may be the target of new drug development. Further studies are required to confirm the results and explore whether these single-nucleotide polymorphisms are associated only with platelet activity or also with cardiovascular events and all-cause mortality. NCT03161002. Show less
Heat stress is one of the most prevalent issues in poultry production that reduces performance, robustness, and economic gains. Previous studies have demonstrated that native chickens are more toleran Show more
Heat stress is one of the most prevalent issues in poultry production that reduces performance, robustness, and economic gains. Previous studies have demonstrated that native chickens are more tolerant of heat than commercial breeds. However, the underlying mechanisms of the heat tolerance observed in native chicken breeds remain unelucidated. Therefore, we performed a phenotypical, physiological, liver transcriptome comparative analysis and WGCNA in response to heat stress in one native (Beijing You, BY) and one commercial (Guang Ming, GM) chicken breed. The objective of this study was to evaluate the heat tolerance and identify the potential driver and hub genes related to heat stress in these two genetically distinct chicken breeds. In brief, 80 BY and 60 GM, 21 days old chickens were submitted to a heat stress experiment for 5 days (33 Β°C, 8 h/day). Each breed was divided into experimental groups of control (Ctl) and heat stress (HS). The results showed that BY chickens were less affected by heat stress and displayed reduced DEGs than GM chickens, 365 DEGs and 382 DEGs, respectively. The transcriptome analysis showed that BY chickens exhibited enriched pathways related to metabolism activity, meanwhile GM chickens' pathways were related to inflammatory reactions. Show less
The early diagnosis of tuberculous pleural effusion (TPE) is challenging due to the difficulty of isolating A total of 48 children with TPE and 64 children with severe The level of p-IL-27 in TPE show Show more
The early diagnosis of tuberculous pleural effusion (TPE) is challenging due to the difficulty of isolating A total of 48 children with TPE and 64 children with severe The level of p-IL-27 in TPE showed statistically no significant difference when compared with SMPPE ( Pleural fluid IL-27 alone was not accurate in distinguishing pediatric TPE from SMPPE, which was different from the diagnostic value of IL-27 in adult studies due to the different disease spectra between children and adults. Our results implied that the p-IL-27/s-IL-27 ratio had a potential value in distinguishing TPE from SMPPE. However, the specificity of IL-27 was relatively lower and it is necessary to find a more specific marker in tuberculous pleurisy of children. Show less
To investigate if a traditional Chinese medicine formulation, called "Yiqihuoxue" (YQHX), could improve diabetic atherosclerosis (DA) and explore potential mechanisms based on DNA methylation. Apolipo Show more
To investigate if a traditional Chinese medicine formulation, called "Yiqihuoxue" (YQHX), could improve diabetic atherosclerosis (DA) and explore potential mechanisms based on DNA methylation. Apolipoprotein E-knockout mice were administered streptozotocin (50 mg/d, i.p.) for 5 days and fed a high-fat diet for 16 weeks. Mice were divided randomly into DA model, rosiglitazone, as well as low-, medium-, and high-dose YQHX groups. Ten healthy C57BL/6J mice were the control group. Serum levels of fasting insulin, blood glucose, homeostasis model-insulin resistance index (HOMA-IR), serum lipids, and inflammatory factors were analyzed after the final treatment. Aorta tissues were collected for staining (hematoxylin and eosin, and Oil red O). Genomic DNA was extracted for methyl-capture sequencing (MC-seq). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases were used to analyze differentially methylated genes. Pyrosequencing was used to verify MC-seq data. Low-dose and high-dose YQHX could reduce the HOMA-IR ( YQHX decoction had positive treatment effects against DA, because it could regulate aberrant hypomethylation of DNA. Show less
Triple-negative breast cancer (TNBC) is a highly aggressive type of cancer with few available treatment methods. The aim of the current study was to provide a prognostic autophagy-related gene (ARG) m Show more
Triple-negative breast cancer (TNBC) is a highly aggressive type of cancer with few available treatment methods. The aim of the current study was to provide a prognostic autophagy-related gene (ARG) model to predict the outcomes for TNBC patients using bioinformatic analysis. mRNA expression data and its clinical information for TNBC samples obtained from The Cancer Genome Atlas (TCGA) and Metabric databases were extracted for bioinformatic analysis. Differentially expressed autophagy genes were identified using the Wilcoxon rank sum test in R software. ARGs were downloaded from the Human Autophagy Database. The Kaplan-Meier plotter was employed to determine the prognostic significance of the ARGs. The sample splitting method and Cox regression analysis were employed to establish the risk model and to demonstrate the association between the ARGs and the survival duration. The corresponding ARG-transcription factor interaction network was visualized using the Cytoscape software. A signature-based risk score model was established for eight genes ( An eight-gene autophagic signature model was developed in this study to predict the survival risk for TNBC. The genes identified in the study may favor the design of target agents for autophagy control in advanced TNBC. Show less
Cholangiocarcinoma (CCA) remains one of the most lethal malignancies with an increasing incidence globally. Through whole-exome sequencing of 67 CCA tissues, we identified new mutated genes in CCA, in Show more
Cholangiocarcinoma (CCA) remains one of the most lethal malignancies with an increasing incidence globally. Through whole-exome sequencing of 67 CCA tissues, we identified new mutated genes in CCA, including MACF1, METTL14, ROBO1, and so on. The study was designed to explore the effects and mechanism of ROBO1 wild type (ROBO1 Whole-exome sequencing was performed to identify novel mutations in CCAs. Through whole-exome sequencing, we identified a novel CCA-related mutation, ROBO1 These results suggest that ROBO1 may act as a tumor suppressor and potential prognostic marker for CCA. ROBO1 Show less
Clear cell renal cell carcinoma (ccRCC) accounts for 85% of all malignant renal tumors. Currently, the pathogenesis of ccRCC is not fully understood. Chromobox (CBX) family proteins are the major subu Show more
Clear cell renal cell carcinoma (ccRCC) accounts for 85% of all malignant renal tumors. Currently, the pathogenesis of ccRCC is not fully understood. Chromobox (CBX) family proteins are the major subunits of PcG complexes and are implicated in regulating mammalian development. The CBX family consists of eight members, namely, CBX1-8. Numerous studies have highlighted that each CBX protein exhibits distinct functions and prognostic roles in specific cancer types. In this study, in silico analysis indicated that CBX7 was downregulated in ccRCC and correlated with favorable prognosis in a ccRCC cohort. Subsequent studies showed that CBX7 inhibited cancer cell proliferation and invasion. Then, we showed that CBX7 downregulated ETS1 to inactivate the tumor necrosis factor (TNF) signaling pathway, which inhibited tumor proliferation and enhanced the sensitivity of ccRCC cells to tyrosine kinase inhibitors (TKIs). Moreover, we found that CBX7 was a bona fide substrate of RNF26. RNF26 promoted the degradation of CBX7 and enhanced ccRCC tumor growth. Therefore, our results revealed a novel RNF26/CBX7 axis that modulates the TNF signaling pathway in ccRCC. Show less
Melanocortin 4 receptor (MC4R) in the paraventricular nucleus of the hypothalamus (PVH) shows bidirectional characterization in modulating food intake and energy homeostasis. We demonstrate that MC4R Show more
Melanocortin 4 receptor (MC4R) in the paraventricular nucleus of the hypothalamus (PVH) shows bidirectional characterization in modulating food intake and energy homeostasis. We demonstrate that MC4R knockdown (KD) in the PVH can attenuate AMPA receptor (AMPAR)-mediated postsynaptic responses by altering the phosphorylation of AMPAR GluA1 subunit through the protein kinase A (PKA)-dependent signaling cascade and simultaneously lead to rapid body weight gain. Furthermore, PKA KD in the PVH engendered similar electrophysiological and behavioral phenotypes as in MC4R KD mice. Importantly, we observed that the reduction of AMPAR GluA1 expression not only led to attenuated synaptic responses but also caused body weight gain, suggesting that the aberration of synaptic responses may be one of the crucial pathogeny of obesity. Our study provides the synaptic and molecular explanations of how body weight is regulated by MC4R in the PVH. Show less
Human Tau (hTau) accumulation and synapse loss are two pathological hallmarks of tauopathies. However, whether and how hTau exerts toxic effects on synapses remain elusive. Mutated hTau (P301S) was ov Show more
Human Tau (hTau) accumulation and synapse loss are two pathological hallmarks of tauopathies. However, whether and how hTau exerts toxic effects on synapses remain elusive. Mutated hTau (P301S) was overexpressed in the N2a cell line, primary hippocampal neurons and hippocampal CA3. Western blotting and quantitative polymerase chain reaction were applied to examine the protein and mRNA levels of synaptic proteins. The protein interaction was tested by co-immunoprecipitation and proximity ligation assays. Memory and emotion status were evaluated by a series of behavioural tests. The transcriptional activity of nuclear factor-erythroid 2-related factor 2 (NRF2) was detected by dual luciferase reporter assay. Electrophoresis mobility shift assay and chromosome immunoprecipitation were conducted to examine the combination of NRF2 to specific anti-oxidative response element (ARE) sequences. Neuronal morphology was analysed after Golgi staining. Overexpressing P301S decreased the protein levels of post-synaptic density protein 93 (PSD93), PSD95 and synapsin 1 (SYN1). Simultaneously, NRF2 was decreased, whereas Kelch-like ECH-associated protein 1 (KEAP1) was elevated. Further, we found that NRF2 could bind to the specific AREs of DLG2, DLG4 and SYN1 genes, which encode PSD93, PSD95 and SYN1, respectively, to promote their expression. Overexpressing NRF2 ameliorated P301S-reduced synaptic proteins and synapse. By means of acetylation at K312, P301S increased the protein level of KEAP1 via inhibiting KEAP1 degradation from ubiquitin-proteasome pathway, thereby decreasing NRF2 and reducing synapse. Blocking the P301S-KEAP1 interaction at K312 rescued the P301S-suppressed expression of synaptic proteins and memory deficits with anxiety efficiently. P301S-hTau could acetylate KEAP1 to trigger synaptic toxicity via inhibiting the NRF2/ARE pathway. These findings provide a novel and potential target for the therapeutic intervention of tauopathies. Show less
Papillary thyroid cancer (PTC), accounting for more than 80 percent of all cases of thyroid cancer, is a form of a cancerous tumor that has a very favorable prognosis. However, patients diagnosed with Show more
Papillary thyroid cancer (PTC), accounting for more than 80 percent of all cases of thyroid cancer, is a form of a cancerous tumor that has a very favorable prognosis. However, patients diagnosed with PTC who are already in an advanced state have a dismal outlook. This study aimed to establish the diagnostic relevance of PRR15 expression in PTC patients as well as its levels in PTC samples and its connection with immune infiltrates. The TCGA and GEO datasets were combed through to obtain information on PTC patients. The "Limma" program was used to screen for differentially expressed mRNAs (DEMs), and the results were displayed using volcano plots and heat maps. The Wilcoxon test was used to examine the level of PRR15 expression in PTC patients in comparison with that of normal tissues. To study the connection between the immune infiltration level and PRR15 expression in PTC, the single-sample sequence set enrichment analysis (ssGSEA) from the R package was utilized. The expression of PRR15 was analyzed with RT-PCR in PTC cells and normal cells. In order to evaluate the diagnostic significance of PRR15 expression, ROC assays were carried out. Experiments using CCK-8 were carried out to investigate the impact that PRR15 knockdown could have on the proliferation of PTC cells. In this study, 17 overlapped DEMs between PTC specimens and normal specimens were identified, including MPPED2, IPCEF1, SLC4A4, PKHD1L1, DIO1, CRABP1, TPO, TFF3, SPX, TCEAL2, ZCCHC12, SYTL5, PRR15, CHI3L1, SERPINA1, GABRB2, and CITED1. Our attention focused on PRR15 which was highly expressed in PTC specimens as compared with nontumor specimens. PRR15 had an AUC value of 0.926 (95% CI 0.902-0.950) for PTC based on TCGA datasets. Pan-cancer assays suggested PRR15 as an oncogenic gene in many types of tumors. Moreover, we found that PRR15 expression was positively correlated with eosinophils, NK cells, NK CD56bright cells, IDC, macrophages, DC, mast cells, and Th1 cells. Further investigations with CCK-8 demonstrated that inhibiting PRR15 resulted in a decrease in the proliferation of PTC cells. Overall, PRR15 was confirmed to be a biomarker for PTC patients and a predictor of response to immunotherapy. Show less