In this in-depth exploration, I delve into the complex implications and costs of cybersecurity breaches. Venturing beyond just the immediate repercussions, the research unearths both the overt and concealed long-term ...In this in-depth exploration, I delve into the complex implications and costs of cybersecurity breaches. Venturing beyond just the immediate repercussions, the research unearths both the overt and concealed long-term consequences that businesses encounter. This study integrates findings from various research, including quantitative reports, drawing upon real-world incidents faced by both small and large enterprises. This investigation emphasizes the profound intangible costs, such as trade name devaluation and potential damage to brand reputation, which can persist long after the breach. By collating insights from industry experts and a myriad of research, the study provides a comprehensive perspective on the profound, multi-dimensional impacts of cybersecurity incidents. The overarching aim is to underscore the often-underestimated scope and depth of these breaches, emphasizing the entire timeline post-incident and the urgent need for fortified preventative and reactive measures in the digital domain.展开更多
After spinal cord injury, dysregulated miRNAs appear and can participate in inflammatory responses, as well as the inhibition of apoptosis and axon regeneration through multiple pathways. However, the functions of miR...After spinal cord injury, dysregulated miRNAs appear and can participate in inflammatory responses, as well as the inhibition of apoptosis and axon regeneration through multiple pathways. However, the functions of miRNAs in spinal cord ischemia-reperfusion injury progression remain unclear. miRCURY LNATM Arrays were used to analyze miRNA expression profiles of rats after 90 minutes of ischemia followed by reperfusion for 24 and 48 hours. Furthermore, subsequent construction of aberrantly expressed miRNA regulatory patterns involved cell survival, proliferation, and apoptosis. Remarkably, the mitogen-activated protein kinase(MAPK) signaling pathway was the most significantly enriched pathway among 24-and 48-hour groups. Bioinformatics analysis and quantitative reverse transcription polymerase chain reaction confirmed the persistent overexpression of miR-22-3 p in both groups. These results suggest that the aberrant miRNA regulatory network is possibly regulated MAPK signaling and continuously affects the physiological and biochemical status of cells, thus participating in the regulation of spinal cord ischemia-reperfusion injury. As such, miR-22-3 p may play sustained regulatory roles in spinal cord ischemia-reperfusion injury. All experimental procedures were approved by the Animal Ethics Committee of Jilin University, China [approval No. 2020(Research) 01].展开更多
Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
Background In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying ...Background In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying follicular ovulation in avians is a complex biological process that remains unclear.Results Critical biochemical events involved in ovulation in domestic chickens(Gallus gallus) were evaluated by transcriptomics, proteomics, and in vitro assays. Comparative transcriptome analyses of the largest preovulatory follicle(F1) and postovulatory follicle(POF1) in continuous laying(CL) and intermittent laying(IL) chickens indicated the greatest difference between CL_F1 and IL_F1, with 950 differentially expressed genes(DEGs), and the smallest difference between CL_POF1 and IL_POF1, with 14 DEGs. Additionally, data-independent acquisition proteomics revealed 252 differentially abundant proteins between CL_F1 and IL_F1. Perivitelline membrane synthesis, steroid biosynthesis, lysosomes, and oxidative phosphorylation were identified as pivotal pathways contributing to ovulation regulation. In particular, the regulation of zona pellucida sperm-binding protein 3, plasminogen activator, cathepsin A, and lactate dehydrogenase A(LDHA) was shown to be essential for ovulation. Furthermore, the inhibition of LDHA decreased cell viability and promoted apoptosis of ovarian follicles in vitro.Conclusions This study reveals several important biochemical events involved in the process of ovulation, as well as crucial role of LDHA. These findings improve our understanding of ovulation and its regulatory mechanisms in avian species.展开更多
In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding ...In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.展开更多
BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new ...BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis(UC).METHODS We obtained gene expression profiles of circRNAs,miRNAs,and mRNAs in UC from the Gene Expression Omnibus dataset.The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions.Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs.We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram,whose efficacy was tested with the C-index,receiver operating characteristic curve(ROC),and decision curve analysis(DCA).RESULTS A circRNA-miRNA-mRNA regulatory network was obtained,containing 12 circRNAs,three miRNAs,and 38 mRNAs.Two optimal prognostic-related differentially expressed circRNAs,hsa_circ_0085323 and hsa_circ_0036906,were included to construct a predictive nomogram.The model showed good discrimination,with a C-index of 1(>0.9,high accuracy).ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC.The circRNa-miRNA-mRNA network in UC could be more clinically significant.展开更多
In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2...In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.展开更多
AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies ha...AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies have provided us with nearly 6500 disease or trait-predisposing SNPs where 93% are located within non-coding regions such as gene regulatory or intergenic areas of the genome. In the regulatory region of a gene, a SNP can change the DNA sequence of a transcriptional factor(TF) motif and in turn may affect the process of gene regulation. SNP changes that affect gene expression and impact gene regulatory sequences such as promoters, enhancers, and silencers are known as rS NPs. Computational tools can be used to identify unique punitive TFBS created by rS NPs that are associated with disease or sickness. Computational analysis was used to identify punitive TFBS generated by the alleles of these rS NPs.RESULTS r SNPs within nine genes that have been significantly associated with disease or sickness were used to illustrate the tremendous diversity of punitive unique TFBS that can be generated by their alleles. The genes studied are the adrenergic, beta, receptor kinase 1, the v-akt murine thymoma viral oncogene homolog 3, the activating transcription factor 3, the type 2 demodkinase gene, the endothetal Per-Arnt-Sim domain protein 1, the lysosomal acid lipase A, the signal Transducer and Activator of Transcription 4, the thromboxane A2 receptor and the vascular endothelial growth factor A. From this sampling of SNPs among the nine genes, there are 73 potential unique TFBS generated by the common alleles comparedto 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of regulating these genes.CONCLUSION From the diversity of unique punitive binding sites for TFs, it was found that some TFs play a role in the disease or sickness being studied.展开更多
Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we...Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we introduced a comprehensive single-cell transcriptomic atlas of Arabidopsis seedlings.This atlas is the result of meticulous integration of 63 previously published scRNA-seq datasets,addressing batch effects and conserving biological variance.This integration spans a broad spectrum of tissues,including both below-and above-ground parts.Utilizing a rigorous approach for cell type annotation,we identified 47 distinct cell types or states,largely expanding our current view of plant cell compositions.We systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordinated manner to control cell-type specific gene expression.Taken together,our study not only offers extensive plant cell atlas exploration that serves as a valuable resource,but also provides molecular insights into gene-regulatory programs that varies from different cell types.展开更多
This study aimed to investigate the relationship between mental health literacy(MHL)and workplace well-being(WWB)of Chinese grassroots civil servants,with regulatory emotional self-efficacy(RESE)and resilience as media...This study aimed to investigate the relationship between mental health literacy(MHL)and workplace well-being(WWB)of Chinese grassroots civil servants,with regulatory emotional self-efficacy(RESE)and resilience as mediating variables.A questionnaire survey was conducted among Chinese grassroots civil servants,with a valid sample size of 2673 after excluding missing values and conducting relevant data processing.The PROCESS was used to examine the relationship between MHL,RESE,resilience,and WWB.The study found that MHL among grassroots civil servants was positively and significantly correlated with WWB(r=0.73,p<0.01).RESE partially mediated the relationship between MHL and WWB(β=0.25,95%CI[0.22,0.28]).Resilience partially mediated the relationship between MHL and WWB(β=0.22,95%CI[0.19,0.26]).MHL had a positive effect on WWB through the chain mediating effect of RESE and resilience(β=0.05,95%CI[0.03,0.07]).There is a close relationship between MHL and WWB,where Chinese grassroots civil servants with higher levels of MHL can develop stronger RESE and resilience,leading to higher WWB.The results of this study remind organizational institutions of Chinese grassroots civil servants that enhancing MHL,RESE,and resilience is an important pathway to promoting their WWB.展开更多
This study examines the key factors that have impact on the successful adoption of Human Resource Information System (HRIS) within the Aqaba Special Economic Zone Authority (ASEZA)/Jordan. In order to accomplish the p...This study examines the key factors that have impact on the successful adoption of Human Resource Information System (HRIS) within the Aqaba Special Economic Zone Authority (ASEZA)/Jordan. In order to accomplish the purpose of the study four critical factors are inquired. So, four critical factors are inquired: First, TAM Model (Perceived Ease of Use (PEOU) and Perceived Usefulness (PU)). Second, Information Technology Infrastructure (ITI). Third, Top Management Support (TMS). Finally, Individual Experience with Computer (IEC). The research model was applied to collect data from the questionnaires answered by 45 users of HRIS as a source of primary data, based on a convenience sample the response rate was about 91%. In addition, the results were analyzed by utilizing the Statistical Package for Social Software (SPSS). Furthermore, the findings were analyzed;multiple Regression analysis indicated that all research variables have significant relationship on successful adoption of HRIS. The findings indicated IT infrastructures have a positive and significant effect on the successful adoption of HRIS. But there is no significant of PU, PEOU, TMS, and IEC on the successful adoption of HRIS. Finally, the results indicated that no significant statistical differences of demographic characteristics on HRIS adoption. Depending on the research’s findings;the researchers proposed a set of recommendations for better adoption of HRIS in SEZA.展开更多
Soybean (Glycine max L.) plays an essential role in human nutrition as a protein source, and in plant nutrition as a N source. The rate of N fixation varies depending on the cultivars and compatibility between the ino...Soybean (Glycine max L.) plays an essential role in human nutrition as a protein source, and in plant nutrition as a N source. The rate of N fixation varies depending on the cultivars and compatibility between the inoculated Rhizobium strain and the host cultivar. Characterizing the nodulation regulatory (Rj) genes is necessary to determine the compatibility of cultivars and Rhizobium strains. Rj genes were previously identified based on inoculation tests and PCR analyses. The six cultivars Yezin-3, Yezin-7, Yezin-11, Shan Seine (Local), Madaya (Local), and Hinthada (Local) were identified as harboring the Rj4 gene. Two cultivars, Yezin-6 and Yezin-8, were classified as non-Rj-gene harboring. Two other cultivars, Yezin-9 and Yezin-10, were identified as Rj3- and Rj2Rj3-gene harboring, respectively. Ours is the first report on Rj3- and Rj2Rj3-gene harboring cultivars in Myanmar. We evaluated Myanmar soybean cultivars for symbiotic effectiveness, relying on the standard strain Bradyrhizobium japonicum USDA110. In our first experiment, the soybean cultivar Yezin-11 (Rj4) showed the highest N fixing potential. Based on their potential for fixing N and nodulation, the top six soybean cultivars were Yezin-11 (Rj4), Yezin-9 (Rj3), Yezin-6 (non-Rj), Yezin-8 (non-Rj), Yezin-3 (Rj4) and Yezin-10 (Rj2Rj3). These cultivars were selected for a second experiment, which revealed that the N fixation, nodulation, and plant growth of Yezin-11 (Rj4) *Corresponding author. A. Z. Htwe et al. 2800 were superior to the other cultivars. We conclude that Yezin-11 (Rj4) is the most efficient cultivar for nodulation and N fixation when inoculated with B. japonicum USDA110.展开更多
AIM To determine the immune-modulatory and thehepatoprotective effects of oral administration of twosoy extracts in immune mediated liver injury and nonalcoholicsteatohepatitis (NASH).METHODS: Two soy extracts, M1 ...AIM To determine the immune-modulatory and thehepatoprotective effects of oral administration of twosoy extracts in immune mediated liver injury and nonalcoholicsteatohepatitis (NASH).METHODS: Two soy extracts, M1 and OS, were orallyadministered to mice with concanavalin A (ConA)immune-mediated hepatitis, to high-fat diet (HFD) miceand to methionine and choline reduced diet combinedwith HFD mice. Animals were followed for disease andimmune biomarkers.RESULTS: Oral administration of OS and M1 had anadditive effect in alleviating ConA hepatitis manifestedby a decrease in alanine aminotransferase and aspartateaminotransferase serum levels. Oral administration ofthe OS and M1 soy derived fractions, ameliorated liverinjury in the high fat diet model of NASH, manifested bya decrease in hepatic triglyceride levels, improvementin liver histology, decreased serum cholesterol andtriglycerides and improved insulin resistance. In themethionine and choline reduced diet combined withthe high fat diet model, we noted a decrease inhepatic triglycerides and improvement in blood glucoselevels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha andalteration of regulatory T cell distribution.CONCLUSION: Oral administration of the combinationof OS and M1 soy derived extracts exerted an adjuvanteffect in the gut-immune system, altering the distributionof regulatory T cells, and alleviating immune mediatedliver injury, hyperlipidemia and insulin resistance.展开更多
Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early mar...Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.展开更多
Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer...Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.展开更多
Dynamic nitrification and denitrification processes are affected by changes in soil redox conditions,and they play a vital role in regulating soil N_(2)O emissions in rice-based cultivation.It is imperative to underst...Dynamic nitrification and denitrification processes are affected by changes in soil redox conditions,and they play a vital role in regulating soil N_(2)O emissions in rice-based cultivation.It is imperative to understand the influences of different upland crop planting systems on soil N_(2)O emissions.In this study,we focused on two representative rotation systems in Central China:rapeseed–rice(RR)and wheat–rice(WR).We examined the biotic and abiotic processes underlying the impacts of these upland plantings on soil N_(2)O emissions.The results revealed that during the rapeseed-cultivated seasons in the RR rotation system,the average N_(2)O emissions were 1.24±0.20 and 0.81±0.11 kg N ha^(–1)for the first and second seasons,respectively.These values were comparable to the N_(2)O emissions observed during the first and second wheat-cultivated seasons in the WR rotation system(0.98±0.25 and 0.70±0.04 kg N ha^(–1),respectively).This suggests that upland cultivation has minimal impacts on soil N_(2)O emissions in the two rotation systems.Strong positive correlations were found between N_(2)O fluxes and soil ammonium(NH_(4)^(+)),nitrate(NO_(3)^(–)),microbial biomass nitrogen(MBN),and the ratio of soil dissolved organic carbon(DOC)to NO_(3)^(–)in both RR and WR rotation systems.Moreover,the presence of the AOA-amoA and nirK genes were positively associated with soil N_(2)O fluxes in the RR and WR systems,respectively.This implies that these genes may have different potential roles in facilitating microbial N_(2)O production in various upland plantation models.By using a structural equation model,we found that soil moisture,mineral N,MBN,and the AOA-amoA gene accounted for over 50%of the effects on N_(2)O emissions in the RR rotation system.In the WR rotation system,soil moisture,mineral N,MBN,and the AOA-amoA and nirK genes had a combined impact of over 70%on N_(2)O emissions.These findings demonstrate the interactive effects of functional genes and soil factors,including soil physical characteristics,available carbon and nitrogen,and their ratio,on soil N_(2)O emissions during upland cultivation seasons under rice-upland rotations.展开更多
Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the targe...Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.展开更多
文摘In this in-depth exploration, I delve into the complex implications and costs of cybersecurity breaches. Venturing beyond just the immediate repercussions, the research unearths both the overt and concealed long-term consequences that businesses encounter. This study integrates findings from various research, including quantitative reports, drawing upon real-world incidents faced by both small and large enterprises. This investigation emphasizes the profound intangible costs, such as trade name devaluation and potential damage to brand reputation, which can persist long after the breach. By collating insights from industry experts and a myriad of research, the study provides a comprehensive perspective on the profound, multi-dimensional impacts of cybersecurity incidents. The overarching aim is to underscore the often-underestimated scope and depth of these breaches, emphasizing the entire timeline post-incident and the urgent need for fortified preventative and reactive measures in the digital domain.
基金supported by the National Natural Science Foundation of China,No.81350013(to XYY)。
文摘After spinal cord injury, dysregulated miRNAs appear and can participate in inflammatory responses, as well as the inhibition of apoptosis and axon regeneration through multiple pathways. However, the functions of miRNAs in spinal cord ischemia-reperfusion injury progression remain unclear. miRCURY LNATM Arrays were used to analyze miRNA expression profiles of rats after 90 minutes of ischemia followed by reperfusion for 24 and 48 hours. Furthermore, subsequent construction of aberrantly expressed miRNA regulatory patterns involved cell survival, proliferation, and apoptosis. Remarkably, the mitogen-activated protein kinase(MAPK) signaling pathway was the most significantly enriched pathway among 24-and 48-hour groups. Bioinformatics analysis and quantitative reverse transcription polymerase chain reaction confirmed the persistent overexpression of miR-22-3 p in both groups. These results suggest that the aberrant miRNA regulatory network is possibly regulated MAPK signaling and continuously affects the physiological and biochemical status of cells, thus participating in the regulation of spinal cord ischemia-reperfusion injury. As such, miR-22-3 p may play sustained regulatory roles in spinal cord ischemia-reperfusion injury. All experimental procedures were approved by the Animal Ethics Committee of Jilin University, China [approval No. 2020(Research) 01].
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
基金supported by the National Key Research and Development Program of China (2022YFD1600902)Key Research and Development Program of Shandong (2022LZGC013)China Agriculture Research System (CARS-40)。
文摘Background In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying follicular ovulation in avians is a complex biological process that remains unclear.Results Critical biochemical events involved in ovulation in domestic chickens(Gallus gallus) were evaluated by transcriptomics, proteomics, and in vitro assays. Comparative transcriptome analyses of the largest preovulatory follicle(F1) and postovulatory follicle(POF1) in continuous laying(CL) and intermittent laying(IL) chickens indicated the greatest difference between CL_F1 and IL_F1, with 950 differentially expressed genes(DEGs), and the smallest difference between CL_POF1 and IL_POF1, with 14 DEGs. Additionally, data-independent acquisition proteomics revealed 252 differentially abundant proteins between CL_F1 and IL_F1. Perivitelline membrane synthesis, steroid biosynthesis, lysosomes, and oxidative phosphorylation were identified as pivotal pathways contributing to ovulation regulation. In particular, the regulation of zona pellucida sperm-binding protein 3, plasminogen activator, cathepsin A, and lactate dehydrogenase A(LDHA) was shown to be essential for ovulation. Furthermore, the inhibition of LDHA decreased cell viability and promoted apoptosis of ovarian follicles in vitro.Conclusions This study reveals several important biochemical events involved in the process of ovulation, as well as crucial role of LDHA. These findings improve our understanding of ovulation and its regulatory mechanisms in avian species.
基金supported by the Grant for Development of New Faculty Staff,Ratchadaphiseksomphot Endowment Fund,Chula-longkorn University,Thailand(Grant No.:DNS64_047_33_003_1 to Patanachai K.Limpikirati)Grant for Development of New Scholar,Office of the Permanent Secretary,Ministry of Higher Ed-ucation,Science,Research and Innovation,Thailand(Grant No.:RGNS64_012 to Patanachai K.Limpikirati).
文摘In this review,we focus on providing basics and examples for each component of the protein therapeutic specifications to interested pharmacists and biopharmaceutical scientists with a goal to strengthen understanding in regulatory science and compliance.Pharmaceutical specifications comprise a list of important quality attributes for testing,references to use for test procedures,and appropriate acceptance criteria for the tests,and they are set up to ensure that when a drug product is administered to a patient,its intended therapeutic benefits and safety can be rendered appropriately.Conformance of drug substance or drug product to the specifications is achieved by testing an article according to the listed tests and analytical methods and obtaining test results that meet the acceptance criteria.Quality attributes are chosen to be tested based on their quality risk,and consideration should be given to the merit of the analytical methods which are associated with the acceptance criteria of the specifications.Acceptance criteria are set forth primarily based on efficacy and safety profiles,with an increasing attention noted for patient-centric specifications.Discussed in this work are related guidelines that support the biopharmaceutical specification setting,how to set the acceptance criteria,and examples of the quality attributes and the analytical methods from 60 articles and 23 pharmacopeial monographs.Outlooks are also explored on process analytical technologies and other orthogonal tools which are on-trend in biopharmaceutical characterization and quality control.
基金Supported by the National Natural Science Foundation of China,No.81774093,No.81904009,No.81974546 and No.82174182Key R&D Project of Hubei Province,No.2020BCB001.
文摘BACKGROUND Circular RNAs(circRNAs)are involved in the pathogenesis of many diseases through competing endogenous RNA(ceRNA)regulatory mechanisms.AIM To investigate a circRNA-related ceRNA regulatory network and a new predictive model by circRNA to understand the diagnostic mechanism of circRNAs in ulcerative colitis(UC).METHODS We obtained gene expression profiles of circRNAs,miRNAs,and mRNAs in UC from the Gene Expression Omnibus dataset.The circRNA-miRNA-mRNA network was constructed based on circRNA-miRNA and miRNA-mRNA interactions.Functional enrichment analysis was performed to identify the biological mechanisms involved in circRNAs.We identified the most relevant differential circRNAs for diagnosing UC and constructed a new predictive nomogram,whose efficacy was tested with the C-index,receiver operating characteristic curve(ROC),and decision curve analysis(DCA).RESULTS A circRNA-miRNA-mRNA regulatory network was obtained,containing 12 circRNAs,three miRNAs,and 38 mRNAs.Two optimal prognostic-related differentially expressed circRNAs,hsa_circ_0085323 and hsa_circ_0036906,were included to construct a predictive nomogram.The model showed good discrimination,with a C-index of 1(>0.9,high accuracy).ROC and DCA suggested that the nomogram had a beneficial diagnostic ability.CONCLUSION This novel predictive nomogram incorporating hsa_circ_0085323 and hsa_circ_0036906 can be conveniently used to predict the risk of UC.The circRNa-miRNA-mRNA network in UC could be more clinically significant.
基金Supported by the Kuwait Foundation for the Advancement of Sciences(KFAS)and Dasman Diabetes Institute,No.RACB-2021-007.
文摘In this editorial,we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes(Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria).Type 2 diabetes mellitus(T2DM)is a chronic disorder characterized by dysregulated glucose homeostasis.The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications,including cardiovascular disease,re-tinopathy,neuropathy,and nephropathy.T2DM arises from a complex interplay between genetic,epigenetic,and environmental factors.Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM.Specifically,variations within the glucokinase regulatory protein(GCKR)gene have been linked to heightened susceptibility to T2DM and its associated complications.The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development.Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype.These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.
文摘AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies have provided us with nearly 6500 disease or trait-predisposing SNPs where 93% are located within non-coding regions such as gene regulatory or intergenic areas of the genome. In the regulatory region of a gene, a SNP can change the DNA sequence of a transcriptional factor(TF) motif and in turn may affect the process of gene regulation. SNP changes that affect gene expression and impact gene regulatory sequences such as promoters, enhancers, and silencers are known as rS NPs. Computational tools can be used to identify unique punitive TFBS created by rS NPs that are associated with disease or sickness. Computational analysis was used to identify punitive TFBS generated by the alleles of these rS NPs.RESULTS r SNPs within nine genes that have been significantly associated with disease or sickness were used to illustrate the tremendous diversity of punitive unique TFBS that can be generated by their alleles. The genes studied are the adrenergic, beta, receptor kinase 1, the v-akt murine thymoma viral oncogene homolog 3, the activating transcription factor 3, the type 2 demodkinase gene, the endothetal Per-Arnt-Sim domain protein 1, the lysosomal acid lipase A, the signal Transducer and Activator of Transcription 4, the thromboxane A2 receptor and the vascular endothelial growth factor A. From this sampling of SNPs among the nine genes, there are 73 potential unique TFBS generated by the common alleles comparedto 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of regulating these genes.CONCLUSION From the diversity of unique punitive binding sites for TFs, it was found that some TFs play a role in the disease or sickness being studied.
基金supported by the National Natural Science Foundation of China (No.32070656)the Nanjing University Deng Feng Scholars Program+1 种基金the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions,China Postdoctoral Science Foundation funded project (No.2022M711563)Jiangsu Funding Program for Excellent Postdoctoral Talent (No.2022ZB50)
文摘Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors(TFs)in intricate regulatory networks in a cell-type specific manner.Here we introduced a comprehensive single-cell transcriptomic atlas of Arabidopsis seedlings.This atlas is the result of meticulous integration of 63 previously published scRNA-seq datasets,addressing batch effects and conserving biological variance.This integration spans a broad spectrum of tissues,including both below-and above-ground parts.Utilizing a rigorous approach for cell type annotation,we identified 47 distinct cell types or states,largely expanding our current view of plant cell compositions.We systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordinated manner to control cell-type specific gene expression.Taken together,our study not only offers extensive plant cell atlas exploration that serves as a valuable resource,but also provides molecular insights into gene-regulatory programs that varies from different cell types.
基金supported by the National Social Science Foundation of China(Grant No.21XDJ002).
文摘This study aimed to investigate the relationship between mental health literacy(MHL)and workplace well-being(WWB)of Chinese grassroots civil servants,with regulatory emotional self-efficacy(RESE)and resilience as mediating variables.A questionnaire survey was conducted among Chinese grassroots civil servants,with a valid sample size of 2673 after excluding missing values and conducting relevant data processing.The PROCESS was used to examine the relationship between MHL,RESE,resilience,and WWB.The study found that MHL among grassroots civil servants was positively and significantly correlated with WWB(r=0.73,p<0.01).RESE partially mediated the relationship between MHL and WWB(β=0.25,95%CI[0.22,0.28]).Resilience partially mediated the relationship between MHL and WWB(β=0.22,95%CI[0.19,0.26]).MHL had a positive effect on WWB through the chain mediating effect of RESE and resilience(β=0.05,95%CI[0.03,0.07]).There is a close relationship between MHL and WWB,where Chinese grassroots civil servants with higher levels of MHL can develop stronger RESE and resilience,leading to higher WWB.The results of this study remind organizational institutions of Chinese grassroots civil servants that enhancing MHL,RESE,and resilience is an important pathway to promoting their WWB.
文摘This study examines the key factors that have impact on the successful adoption of Human Resource Information System (HRIS) within the Aqaba Special Economic Zone Authority (ASEZA)/Jordan. In order to accomplish the purpose of the study four critical factors are inquired. So, four critical factors are inquired: First, TAM Model (Perceived Ease of Use (PEOU) and Perceived Usefulness (PU)). Second, Information Technology Infrastructure (ITI). Third, Top Management Support (TMS). Finally, Individual Experience with Computer (IEC). The research model was applied to collect data from the questionnaires answered by 45 users of HRIS as a source of primary data, based on a convenience sample the response rate was about 91%. In addition, the results were analyzed by utilizing the Statistical Package for Social Software (SPSS). Furthermore, the findings were analyzed;multiple Regression analysis indicated that all research variables have significant relationship on successful adoption of HRIS. The findings indicated IT infrastructures have a positive and significant effect on the successful adoption of HRIS. But there is no significant of PU, PEOU, TMS, and IEC on the successful adoption of HRIS. Finally, the results indicated that no significant statistical differences of demographic characteristics on HRIS adoption. Depending on the research’s findings;the researchers proposed a set of recommendations for better adoption of HRIS in SEZA.
文摘Soybean (Glycine max L.) plays an essential role in human nutrition as a protein source, and in plant nutrition as a N source. The rate of N fixation varies depending on the cultivars and compatibility between the inoculated Rhizobium strain and the host cultivar. Characterizing the nodulation regulatory (Rj) genes is necessary to determine the compatibility of cultivars and Rhizobium strains. Rj genes were previously identified based on inoculation tests and PCR analyses. The six cultivars Yezin-3, Yezin-7, Yezin-11, Shan Seine (Local), Madaya (Local), and Hinthada (Local) were identified as harboring the Rj4 gene. Two cultivars, Yezin-6 and Yezin-8, were classified as non-Rj-gene harboring. Two other cultivars, Yezin-9 and Yezin-10, were identified as Rj3- and Rj2Rj3-gene harboring, respectively. Ours is the first report on Rj3- and Rj2Rj3-gene harboring cultivars in Myanmar. We evaluated Myanmar soybean cultivars for symbiotic effectiveness, relying on the standard strain Bradyrhizobium japonicum USDA110. In our first experiment, the soybean cultivar Yezin-11 (Rj4) showed the highest N fixing potential. Based on their potential for fixing N and nodulation, the top six soybean cultivars were Yezin-11 (Rj4), Yezin-9 (Rj3), Yezin-6 (non-Rj), Yezin-8 (non-Rj), Yezin-3 (Rj4) and Yezin-10 (Rj2Rj3). These cultivars were selected for a second experiment, which revealed that the N fixation, nodulation, and plant growth of Yezin-11 (Rj4) *Corresponding author. A. Z. Htwe et al. 2800 were superior to the other cultivars. We conclude that Yezin-11 (Rj4) is the most efficient cultivar for nodulation and N fixation when inoculated with B. japonicum USDA110.
基金Supported by Grants from The Roaman-Epstein Liver Research Foundation(partly,to Ilan Y)
文摘AIM To determine the immune-modulatory and thehepatoprotective effects of oral administration of twosoy extracts in immune mediated liver injury and nonalcoholicsteatohepatitis (NASH).METHODS: Two soy extracts, M1 and OS, were orallyadministered to mice with concanavalin A (ConA)immune-mediated hepatitis, to high-fat diet (HFD) miceand to methionine and choline reduced diet combinedwith HFD mice. Animals were followed for disease andimmune biomarkers.RESULTS: Oral administration of OS and M1 had anadditive effect in alleviating ConA hepatitis manifestedby a decrease in alanine aminotransferase and aspartateaminotransferase serum levels. Oral administration ofthe OS and M1 soy derived fractions, ameliorated liverinjury in the high fat diet model of NASH, manifested bya decrease in hepatic triglyceride levels, improvementin liver histology, decreased serum cholesterol andtriglycerides and improved insulin resistance. In themethionine and choline reduced diet combined withthe high fat diet model, we noted a decrease inhepatic triglycerides and improvement in blood glucoselevels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha andalteration of regulatory T cell distribution.CONCLUSION: Oral administration of the combinationof OS and M1 soy derived extracts exerted an adjuvanteffect in the gut-immune system, altering the distributionof regulatory T cells, and alleviating immune mediatedliver injury, hyperlipidemia and insulin resistance.
基金funded by the Central Hessen Research Campus,Flexi Fund,Project No.20121_1_1.
文摘Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82172723)the Natural Science Foundation of Sichuan(Grant Nos.2023NSFSC1828 and 2022NSFSC1289)+2 种基金the“Xinglin Scholar”Scientific Research Promotion Plan of Chengdu University of Transitional Chinese Medicine(Grant No.BSH2021003)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.ZYYCXTD-D-202209)the Research Funding of Department of Science and Technology of Qinghai Province(Grant No.2023-ZJ-729)。
文摘Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.
基金the National Key Research and Development Program of China(2017YFD0800102)the Hubei Provincial Key Research and Development Program,China(2021BCA156)。
文摘Dynamic nitrification and denitrification processes are affected by changes in soil redox conditions,and they play a vital role in regulating soil N_(2)O emissions in rice-based cultivation.It is imperative to understand the influences of different upland crop planting systems on soil N_(2)O emissions.In this study,we focused on two representative rotation systems in Central China:rapeseed–rice(RR)and wheat–rice(WR).We examined the biotic and abiotic processes underlying the impacts of these upland plantings on soil N_(2)O emissions.The results revealed that during the rapeseed-cultivated seasons in the RR rotation system,the average N_(2)O emissions were 1.24±0.20 and 0.81±0.11 kg N ha^(–1)for the first and second seasons,respectively.These values were comparable to the N_(2)O emissions observed during the first and second wheat-cultivated seasons in the WR rotation system(0.98±0.25 and 0.70±0.04 kg N ha^(–1),respectively).This suggests that upland cultivation has minimal impacts on soil N_(2)O emissions in the two rotation systems.Strong positive correlations were found between N_(2)O fluxes and soil ammonium(NH_(4)^(+)),nitrate(NO_(3)^(–)),microbial biomass nitrogen(MBN),and the ratio of soil dissolved organic carbon(DOC)to NO_(3)^(–)in both RR and WR rotation systems.Moreover,the presence of the AOA-amoA and nirK genes were positively associated with soil N_(2)O fluxes in the RR and WR systems,respectively.This implies that these genes may have different potential roles in facilitating microbial N_(2)O production in various upland plantation models.By using a structural equation model,we found that soil moisture,mineral N,MBN,and the AOA-amoA gene accounted for over 50%of the effects on N_(2)O emissions in the RR rotation system.In the WR rotation system,soil moisture,mineral N,MBN,and the AOA-amoA and nirK genes had a combined impact of over 70%on N_(2)O emissions.These findings demonstrate the interactive effects of functional genes and soil factors,including soil physical characteristics,available carbon and nitrogen,and their ratio,on soil N_(2)O emissions during upland cultivation seasons under rice-upland rotations.
基金supported by grants from the National Natural Science Foundation of China (82070676)Jiangsu Provincial Medi-cal Innovation Center (CXZX202203)Jiangsu Provincial Medi-cal Key Laboratory (ZDXYS202201)。
文摘Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.