Sixteen pairs of two-component regulatory systems are identified in the genome of Staphylococcus epidermidis ATCC12228 strain, which is newly sequenced by our laboratory for Medical Molecular Virology and Chinese Nati...Sixteen pairs of two-component regulatory systems are identified in the genome of Staphylococcus epidermidis ATCC12228 strain, which is newly sequenced by our laboratory for Medical Molecular Virology and Chinese National Human Genome Center at Shanghai, by using bio- informatics analysis. Comparative analysis of the two- component regulatory systems in S. epidermidis and that of S. aureus and Bacillus subtilis shows that these systems may regulate some important biological functions, e.g. growth, biofilm formation, and expression of virulence factors in S. epidermidis. Two conserved domains, i.e. HATPase_c and REC domains, are found in all 16 pairs of two-component proteins. Homologous modelling analysis indicates that there are 4 similar HATPase_c domain structures of histidine kinases and 13 similar REC domain structures of response regulators, and there is one AMP-PNP binding pocket in the HATPase_c domain and three active aspartate residues in the REC domain. Preliminary experiment reveals that the bioinfor- matics analysis of the conserved domain structures in the two-component regulatory systems in S. epidermidis may provide useful information for discovery of potential drug target.展开更多
Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization o...Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.展开更多
Aerobic Treatment Units (ATU) and Greywater Treatment Systems (GTS) are onsite wastewater treatment systems (OWTS) designed to treat wastewater to secondary effluent quality standards. Consequently, the electrical, me...Aerobic Treatment Units (ATU) and Greywater Treatment Systems (GTS) are onsite wastewater treatment systems (OWTS) designed to treat wastewater to secondary effluent quality standards. Consequently, the electrical, mechanical and chemical components of these OWTS need to be regularly maintained to ensure their consistent and reliable operation to the required standards. In Western Australia (WA), the Department of Health set out the regulatory requirements for the maintenance of OWTS as well as when and how it is to occur. This paper reviews the maintenance requirements for ATU and GTS in WA and provides recommendations for the proposed changes in guidelines and regulations. State and national guidelines were reviewed and information from industry and regulators was obtained through surveys. The review found that although the guidelines are generally satisfactory there are a number of areas which could be improved and specific recommendations are discussed.展开更多
CD4＋CD25＋ regulatory T cells （Tregs） and the expression of their molecular markers （GITR, Foxp3） in peripheral blood of the patients with systemic lupus erythematosus （SLE） were investigated in order to reveal...CD4＋CD25＋ regulatory T cells （Tregs） and the expression of their molecular markers （GITR, Foxp3） in peripheral blood of the patients with systemic lupus erythematosus （SLE） were investigated in order to reveal the pathogenesis of SLE on the cellular and molecular levels. The level of Tregs in peripheral blood was detected by flow cytometry. The expression levels of GITR and Foxp3 mRNA in peripheral blood mononuclear cells （PBMCs） were assayed by reverse transcriptase-polymerase chain reaction （RT-PCR）. The level of IL-6 in the plasma was measured by ELISA. Comparisons were made among 3 groups： the active SLE group, the inactive SLE group, and normal control group. The level of Tregs in the active SLE group and the inactive SLE group was significantly lower than in the normal control group （P〈0.01）. The level of Tregs in the active group was lower than in the inactive group with the difference being not significant （P〉0.05）. The level of Tregs in SLE patients was significantly negatively correlated with the disease active index in SLE （SLEDAI） （r=-0.81, P〈0.01）. The expression levels of GITR mRNA in PBMCs of the active SLE group and the inactive SLE group were significantly higher than in the normal control group （P〈0.05）, and those of Foxp3 mRNA in SLE patients of both active and inactive SLE groups were significantly lower than in the normal control group （P〈0.05）. There was no significant difference in the expression of GITR and Foxp3 mRNA between the active SLE group and inactive SLE group （P〉0.05）. The plasma levels of IL-6 in both the inactive SLE group and active SLE group were significantly higher than in the normal control group （P〈0.01）. The plasma level of IL-6 in the active SLE group was sig- nificantly increased as compared with that in the inactive SLE group （P〈0.05）, and the plasma level of IL-6 in SLE was significantly positively correlated with SLEDAI scores （r=0.58, P〈0.01） and significantly negatively correlated with the ratio of CD4＋CD25＋ cells/CD4＋ cells （r=-0.389, P〈0.05）. It was concluded that the levels of Tregs and Foxp3 mRNA in peripheral blood of SLE patients were decreased and the levels of GITR mRNA and plasma IL-6 were increased. The Tregs and their molecular markers GITR, Foxp3 as well as the plasma IL-6 might play an important role in the pathogenesis of SLE.展开更多
Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain-containing 5(FNDC5)protein.Once released to circulation upon exercise or cold exposure,irisin stimulates browning of...Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain-containing 5(FNDC5)protein.Once released to circulation upon exercise or cold exposure,irisin stimulates browning of white adipose tissue(WAT)and uncoupling protein I(UCP1)expression,leading to an increase in total body energy expenditure by augmented UCPl-mediated thermogenesis.It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo.In this study,we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues.Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones,including growth plate,trabecular bone,cortical bone,articular cartilage,and bone-tendon interface.Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT,and led to bodyweight loss.Irisin intraperitoneal(IP)administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers,and concurrently induced UCP1 expression in subcutaneous WAT.Lentiviral FNDC5 IP administration increased cortical bone thickness.In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization,and inhibits receptor activator of nuclear factor-kB ligand(RANKL)-induced osteoclastogenesis.Taken together,our findings show that voluntary exercise increases irisin production in bone,and that an increase in circulating irisin levels enhances osteogenesis in mice.展开更多
The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 （1RF5） play a special role in systemic lupus erythematosus （SLE） but with inconclusive results. We conducted a meta-analysi...The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 （1RF5） play a special role in systemic lupus erythematosus （SLE） but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios （ORs） and the corresponding 95% confidence interval （95% CI）. A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results in- dicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rS10954213 G allele （A vs. G, P〈0.00001） in all subjects. The same pattern of the results was also ob- tained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele （49.1%） than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele （62.1%）. The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 （P=0.002）. The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 （P=-0.004）. This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype （rs2004640-rs2070197-rs10954213） in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.展开更多
The regulatory mechanisms in cellular signaling systems have been studied intensively from the viewpoint that the malfunction of the regulation is thought to be one of the substantial causes of cancer formation. On th...The regulatory mechanisms in cellular signaling systems have been studied intensively from the viewpoint that the malfunction of the regulation is thought to be one of the substantial causes of cancer formation. On the other hand, it is rather difficult to develop the theoretical framework for investigation of the regulatory mechanisms due to their complexity and nonlinearity. In this study, more general approach is proposed for elucidation of characteristics of the stability in cellular signaling systems by construction of mathematical models for a class of cellular signaling systems and stability analysis of the models over variation of the network architectures and the parameter values. The model system is formulated as regulatory network in which every node represents a phosphorylation-dephosphorylation cyclic reaction for respective constituent enzyme. The analysis is performed for all variations of the regulatory networks comprised of two nodes with multiple feedback regulation loops. It is revealed from the analysis that the regulatory networks become mono-stable, bi-stable, tri-stable, or oscillatory and that the negative mutual feedback or positive mutual feedback is favorable for multi-stability, which is augmented by a negatively regulated node with a positive auto-regulation. Furthermore, the multi-stability or the oscillation is more likely to emerge in the case of low value of the Michaelis constant than in the case of high value, implying that the condition of higher saturation levels induces stronger nonlinearity in the networks. The analysis for the parameter regions yielding the multi-stability and the oscillation clarified that the stronger regulation shifts the systems toward multi-stability.展开更多
Currently,the global carbon trading systems are fragmented and belong to different governments or are under the jurisdiction of different regions,resulting in a series of new problems,such as how to link dispersed tra...Currently,the global carbon trading systems are fragmented and belong to different governments or are under the jurisdiction of different regions,resulting in a series of new problems,such as how to link dispersed trading systems,how to compare the emission reduction of various markets and other issues.Since the development of the international carbon market is relatively immature with uncertain life expectancy and volatility during its short history,and there is a lack of quantitative data on the long-term record,the market could provide few risk management tools.Meanwhile,with the launches of China's regional carbon trading pilots in seven provinces since 2013 and combined with the national voluntary emission trading system,carbon trading will become an important mechanism for China in achieving its emission reduction target.In the first stage,the carbon finance market is at least faced with mechanism design risks,market supply risks and compliance risks.Therefore,to secure the development of the carbon market and for public interest,relevant government departments of China should identify the risks facing the market and should make the basic principles and goals,such as ensuring effective trading and pricing mechanisms to avoid fraud and price manipulation,and balancing transparency and confidentiality of information.Consequently,the governments should develop a comprehensive carbon finance regulatory system covering regulatory legislation,regulatory institutions and their authorities,regulatory scope as well as regulatory objects.展开更多
Background:The study of regulatory B cells(Bregs)in systemic lupus erythematosus(SLE)has been in full swing in recent years,but the number and function of Bregs in SLE patients have also present quite contradictory re...Background:The study of regulatory B cells(Bregs)in systemic lupus erythematosus(SLE)has been in full swing in recent years,but the number and function of Bregs in SLE patients have also present quite contradictory results.Therefore,we conducted a meta-analysis to verify the changes in Bregs in active SLE.Methods:We identified studies reporting the proportions of Bregs in SLE patients by searching Pubmed,Embase,Web of Science,Cochrane and CNKI.Due to the degree of heterogeneity is very high,we used a random effects model to assess the mean differences in percentages of Bregs between active SLE and controls.Then,sensitivity analysis and subgroup analysis were performed to verify potential sources of heterogeneity.Results:Seven eligible articles involving 301 active SLE patients and 218 controls were included in the meta-analysis.The pooled percentages of Bregs were found no significant difference between active SLE patients and healthy controls[0.259,(−1.150,1.668),p=0.719],with great heterogeneity(I2=97.5%).The result of sensitivity analysis showed that exclusion of any single study or single article did not materially resolve the heterogeneity,but after excluding the article conducted by Cai X and his colleagues,the percentages of Bregs were significantly higher in active SLE than those in controls[1.394,(0.114,2.675),p=0.033].The results of subgroup analysis revealed that when the disease activity was judged by SLEDAI score≥5,the percentages of Bregs were significantly lower in the SLE groups than in the control groups[-1.99,(-3.241,-0.739),p=0.002],but when the threshold of SLEDAI score≥6 chosen for active SLE,the percentages of Bregs were significantly increased in the SLE groups[2.546,(1.333,3.759),p<0.001].Meanwhile,other subgroup analysis based on the different phenotypes of Bregs,diagnostic criteria,enrolled research countries,treatment status,and organ involvement did not differ in proportion of Bregs between SLE patients and controls.Conclusions:The study implies that Bregs may play a role in the pathogenesis of active SLE,and the thresholds of SLEDAI score to distinguish between active and inactive SLE patients are important factors affecting the percentages of Bregs.展开更多
This paper investigates the stochastic resonance （SR） induced by a multiplicative periodic signal in the gene transcriptional regulatory system with correlated noises. The expression of the signal-to-noise ratio （...This paper investigates the stochastic resonance （SR） induced by a multiplicative periodic signal in the gene transcriptional regulatory system with correlated noises. The expression of the signal-to-noise ratio （SNR） is derived. The results indicate that the existence of a maximum in SNR vs. the additive noise intensity α the multiplicative noise intensity D and the cross-correlated noise intensity λ is the identifying characteristic of the SR phenomenon and there is a critical phenomenon in the SNR as a function of λ, i.e., for the case of smaller values of noise intensity （α or D）, the SNR decreases as λ increases; however, for the case of larger values of noise intensity （α or D）, the SNR increases as λ increases.展开更多
We have investigated in the adiabatic limit the phenomenon of stochastic resonance in the gene transcriptional regulatory system subjected to an additive noise, a multiplicative noise, and a weakly periodic signal. Us...We have investigated in the adiabatic limit the phenomenon of stochastic resonance in the gene transcriptional regulatory system subjected to an additive noise, a multiplicative noise, and a weakly periodic signal. Using the general two-state approach for the asymmetry system, the analytic expression of signal-to-noise ratio is obtained. The effects of the additive noise intensity a, the multiplicative noise intensity D and the amplitude of input periodic signal A on the signal-to-noise ratio are analysed by numerical calculation. It is found that the existence of a maximum in the RSNR a and RSNR D plots is the identifying characteristic of the stochastic resonance phenomenon in the weakened noise intensity region. The stochastic resonance phenomena are restrained with increasing a and D, and enhanced with increasing A.展开更多
In Systems Biology, system identification, which infers regulatory network in genetic system and metabolic pathways using experimentally observed time-course data, is one of the hottest issues. The efficient numerical...In Systems Biology, system identification, which infers regulatory network in genetic system and metabolic pathways using experimentally observed time-course data, is one of the hottest issues. The efficient numerical optimization algorithm to estimate more than 100 real-coded parameters should be developed for this purpose. New real-coded genetic algorithm (RCGA), the combination of AREX (adaptive real-coded ensemble crossover) with JGG (just generation gap), have applied to the inference of genetic interactions involving more than 100 parameters related to the interactions with using experimentally observed time-course data. Compared with conventional RCGA, the combination of UNDX (unimodal normal distribution crossover) with MGG (minimal generation gap), new algorithm has shown the superiority with improving early convergence in the first stage of search and suppressing evolutionary stagnation in the last stage of search.展开更多
Systemic lupus erythematosus(SLE)is a chronic autoimmune disease.Defects in the regulatory T cells(Treg cells)play a key role in breaking immune tolerance in SLE patients.This study investigates the causes of impaired...Systemic lupus erythematosus(SLE)is a chronic autoimmune disease.Defects in the regulatory T cells(Treg cells)play a key role in breaking immune tolerance in SLE patients.This study investigates the causes of impaired Treg cell function in SLE patients.Peripheral blood from 56 SLE patients and 33 healthy donors was used to assess Treg cell proportions among CD4^(+)T cells and plasma cytokine levels.Treg cells and naïve CD4^(+)T cells from healthy individuals were isolated,cultured under various conditions,and analyzed for phenotype and signal transduction mechanisms using flow cytometry,RT-qPCR,Western blotting,and calcium signaling assays.In SLE patients,the proportion of CD4^(+)CD25^(+)Foxp3^(+)and CD4^(+)Foxp3^(+)Treg cells decreased.Plasma CXCL11 levels were elevated in lupus patients.CXCL11 expression inversely correlated with Treg cell proportions and positively correlated with disease severity.CXCL11 impaired immune function and inhibited Treg cell differentiation.We present a novel pathological pathway in SLE,wherein CXCL11 impedes the immunosuppressive functions of Treg cells.展开更多
Xenocoumacins(Xcns),the major antimicrobial natural products produced by Xenorhabdus nematophila,have gained widespread attention for their potential application in crop protection.However,the regulatory mechanisms in...Xenocoumacins(Xcns),the major antimicrobial natural products produced by Xenorhabdus nematophila,have gained widespread attention for their potential application in crop protection.However,the regulatory mechanisms involved in the biosynthesis of Xcns remain poorly understood.In this study,we identified 21 potential twocomponent systems(TCSs)in X.nematophila CB6 by bioinformatic analysis.Among them,the response regulators(RRs),GlrR and ArcA,were proven to positively regulate the production of Xcns based on gene deletion and complementation experiments.In addition,our results showed that GlrR played an important role in cell growth,while ArcA was involved in both cell morphology and growth.Using a variety of molecular biological and biochemical techniques,we found that GlrR controlled the Xcns biosynthesis by indirectly regulating the expression levels of the biosynthetic gene cluster(BGC).ArcA directly binded to the promoter regions of xcn A and xcn B to regulate the transcription of the Xcns BGC,and the binding sites were also identified.This study provides valuable insights into the regulatory network of Xcns biosynthesis,which will contribute to the construction of a high-yielding strain.展开更多
Overview of root system architecture.The plant root system is a highly dynamic and multifunctional organ system composed of primary roots,lateral roots,adventitious roots,and root hairs.Based on topological morphology...Overview of root system architecture.The plant root system is a highly dynamic and multifunctional organ system composed of primary roots,lateral roots,adventitious roots,and root hairs.Based on topological morphology,root systems can be classified as taproot systems or fibrous root systems.Root system architecture(RSA)refers to the spatial distribution and extension patterns of roots within soil,encompassing characteristics such as root length,branching angle,density,and spatial arrangement.RSA not only determines the plant’s capacity to acquire water and nutrients but also influences other root functions,playing a decisive role in overall plant health.展开更多
We numerically investigate the effects of nonlinear time-delay on the stochastic system. With the delay time increasing, it is found that the peak of probability distribution in low steady states is decreased, and the...We numerically investigate the effects of nonlinear time-delay on the stochastic system. With the delay time increasing, it is found that the peak of probability distribution in low steady states is decreased, and the peak of probability distribution in high steady states is increased. The mean of state variable, the normalized variance, and the normalized autocorrelation function which quantifies the concentrated degree are slowly varied for small delay time. However, the mean of state variable is rapidly increased, and the normalized variance and the normalized autocorrelation function is rapidly decreased for large delay time.展开更多
Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated...Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.展开更多
文摘Sixteen pairs of two-component regulatory systems are identified in the genome of Staphylococcus epidermidis ATCC12228 strain, which is newly sequenced by our laboratory for Medical Molecular Virology and Chinese National Human Genome Center at Shanghai, by using bio- informatics analysis. Comparative analysis of the two- component regulatory systems in S. epidermidis and that of S. aureus and Bacillus subtilis shows that these systems may regulate some important biological functions, e.g. growth, biofilm formation, and expression of virulence factors in S. epidermidis. Two conserved domains, i.e. HATPase_c and REC domains, are found in all 16 pairs of two-component proteins. Homologous modelling analysis indicates that there are 4 similar HATPase_c domain structures of histidine kinases and 13 similar REC domain structures of response regulators, and there is one AMP-PNP binding pocket in the HATPase_c domain and three active aspartate residues in the REC domain. Preliminary experiment reveals that the bioinfor- matics analysis of the conserved domain structures in the two-component regulatory systems in S. epidermidis may provide useful information for discovery of potential drug target.
基金supported by the National Key Research and Development Program of China(2022YFD1800904)the National Natural Science Foundation of China(31972650 and 32102673)+1 种基金the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX22_0780)the China Postdoctoral Science Foundation(2020M682297)。
文摘Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.
文摘Aerobic Treatment Units (ATU) and Greywater Treatment Systems (GTS) are onsite wastewater treatment systems (OWTS) designed to treat wastewater to secondary effluent quality standards. Consequently, the electrical, mechanical and chemical components of these OWTS need to be regularly maintained to ensure their consistent and reliable operation to the required standards. In Western Australia (WA), the Department of Health set out the regulatory requirements for the maintenance of OWTS as well as when and how it is to occur. This paper reviews the maintenance requirements for ATU and GTS in WA and provides recommendations for the proposed changes in guidelines and regulations. State and national guidelines were reviewed and information from industry and regulators was obtained through surveys. The review found that although the guidelines are generally satisfactory there are a number of areas which could be improved and specific recommendations are discussed.
基金a grant from the Natural Sciences Foundation of Hubei, China (No. 2007ABA110).
文摘CD4＋CD25＋ regulatory T cells （Tregs） and the expression of their molecular markers （GITR, Foxp3） in peripheral blood of the patients with systemic lupus erythematosus （SLE） were investigated in order to reveal the pathogenesis of SLE on the cellular and molecular levels. The level of Tregs in peripheral blood was detected by flow cytometry. The expression levels of GITR and Foxp3 mRNA in peripheral blood mononuclear cells （PBMCs） were assayed by reverse transcriptase-polymerase chain reaction （RT-PCR）. The level of IL-6 in the plasma was measured by ELISA. Comparisons were made among 3 groups： the active SLE group, the inactive SLE group, and normal control group. The level of Tregs in the active SLE group and the inactive SLE group was significantly lower than in the normal control group （P〈0.01）. The level of Tregs in the active group was lower than in the inactive group with the difference being not significant （P〉0.05）. The level of Tregs in SLE patients was significantly negatively correlated with the disease active index in SLE （SLEDAI） （r=-0.81, P〈0.01）. The expression levels of GITR mRNA in PBMCs of the active SLE group and the inactive SLE group were significantly higher than in the normal control group （P〈0.05）, and those of Foxp3 mRNA in SLE patients of both active and inactive SLE groups were significantly lower than in the normal control group （P〈0.05）. There was no significant difference in the expression of GITR and Foxp3 mRNA between the active SLE group and inactive SLE group （P〉0.05）. The plasma levels of IL-6 in both the inactive SLE group and active SLE group were significantly higher than in the normal control group （P〈0.01）. The plasma level of IL-6 in the active SLE group was sig- nificantly increased as compared with that in the inactive SLE group （P〈0.05）, and the plasma level of IL-6 in SLE was significantly positively correlated with SLEDAI scores （r=0.58, P〈0.01） and significantly negatively correlated with the ratio of CD4＋CD25＋ cells/CD4＋ cells （r=-0.389, P〈0.05）. It was concluded that the levels of Tregs and Foxp3 mRNA in peripheral blood of SLE patients were decreased and the levels of GITR mRNA and plasma IL-6 were increased. The Tregs and their molecular markers GITR, Foxp3 as well as the plasma IL-6 might play an important role in the pathogenesis of SLE.
基金supported by a R01DE21464 through the National Institutes of Healthan Innovation in Oral Care Award through International Association for Dental Research and Glaxo Smith Kline Consumer Healthcare+2 种基金an Award through International Team of Implantology to JCby GZUCM Science Fund for Creative Research Groups(2016KYTD10)GZUCM Torch Program(A1-AFD015142Z08)to JZ
文摘Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain-containing 5(FNDC5)protein.Once released to circulation upon exercise or cold exposure,irisin stimulates browning of white adipose tissue(WAT)and uncoupling protein I(UCP1)expression,leading to an increase in total body energy expenditure by augmented UCPl-mediated thermogenesis.It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo.In this study,we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues.Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones,including growth plate,trabecular bone,cortical bone,articular cartilage,and bone-tendon interface.Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT,and led to bodyweight loss.Irisin intraperitoneal(IP)administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers,and concurrently induced UCP1 expression in subcutaneous WAT.Lentiviral FNDC5 IP administration increased cortical bone thickness.In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization,and inhibits receptor activator of nuclear factor-kB ligand(RANKL)-induced osteoclastogenesis.Taken together,our findings show that voluntary exercise increases irisin production in bone,and that an increase in circulating irisin levels enhances osteogenesis in mice.
基金supported by the Program for New Century Excellent Talents from the Ministry of Education of China (No.NCET-09-0390)
文摘The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 （1RF5） play a special role in systemic lupus erythematosus （SLE） but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios （ORs） and the corresponding 95% confidence interval （95% CI）. A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results in- dicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rS10954213 G allele （A vs. G, P〈0.00001） in all subjects. The same pattern of the results was also ob- tained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele （49.1%） than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele （62.1%）. The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 （P=0.002）. The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 （P=-0.004）. This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype （rs2004640-rs2070197-rs10954213） in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.
文摘The regulatory mechanisms in cellular signaling systems have been studied intensively from the viewpoint that the malfunction of the regulation is thought to be one of the substantial causes of cancer formation. On the other hand, it is rather difficult to develop the theoretical framework for investigation of the regulatory mechanisms due to their complexity and nonlinearity. In this study, more general approach is proposed for elucidation of characteristics of the stability in cellular signaling systems by construction of mathematical models for a class of cellular signaling systems and stability analysis of the models over variation of the network architectures and the parameter values. The model system is formulated as regulatory network in which every node represents a phosphorylation-dephosphorylation cyclic reaction for respective constituent enzyme. The analysis is performed for all variations of the regulatory networks comprised of two nodes with multiple feedback regulation loops. It is revealed from the analysis that the regulatory networks become mono-stable, bi-stable, tri-stable, or oscillatory and that the negative mutual feedback or positive mutual feedback is favorable for multi-stability, which is augmented by a negatively regulated node with a positive auto-regulation. Furthermore, the multi-stability or the oscillation is more likely to emerge in the case of low value of the Michaelis constant than in the case of high value, implying that the condition of higher saturation levels induces stronger nonlinearity in the networks. The analysis for the parameter regions yielding the multi-stability and the oscillation clarified that the stronger regulation shifts the systems toward multi-stability.
基金supported by National Social Science Fund project"The study of carbon finance mechanisms supporting the development of low-carbon economy"[grant number10CJY076]Beijing Philosophy and Social Science Project"The market pricing mechanism and price management strategy of carbon emission in Beijing"[grant number 13JGC068]+2 种基金National Science&Technology Pillar Program"The research of key support policies and techniques in green low-carbon development in China"[grant number 2012BAC20B08]grant project from China Clean Development Mechanism Fund in the Ministry of Finance:"The study of financing,strategies,mechanism and policy system addressing climate change in China"[grant number 2012064]the project of research innovation teams in Central University of Finance and Economics and China Financial Development Collaborative Innovation Center
文摘Currently,the global carbon trading systems are fragmented and belong to different governments or are under the jurisdiction of different regions,resulting in a series of new problems,such as how to link dispersed trading systems,how to compare the emission reduction of various markets and other issues.Since the development of the international carbon market is relatively immature with uncertain life expectancy and volatility during its short history,and there is a lack of quantitative data on the long-term record,the market could provide few risk management tools.Meanwhile,with the launches of China's regional carbon trading pilots in seven provinces since 2013 and combined with the national voluntary emission trading system,carbon trading will become an important mechanism for China in achieving its emission reduction target.In the first stage,the carbon finance market is at least faced with mechanism design risks,market supply risks and compliance risks.Therefore,to secure the development of the carbon market and for public interest,relevant government departments of China should identify the risks facing the market and should make the basic principles and goals,such as ensuring effective trading and pricing mechanisms to avoid fraud and price manipulation,and balancing transparency and confidentiality of information.Consequently,the governments should develop a comprehensive carbon finance regulatory system covering regulatory legislation,regulatory institutions and their authorities,regulatory scope as well as regulatory objects.
基金This work was supported by funding from the National Natural Science Foundation of China Grants[81760286].
文摘Background:The study of regulatory B cells(Bregs)in systemic lupus erythematosus(SLE)has been in full swing in recent years,but the number and function of Bregs in SLE patients have also present quite contradictory results.Therefore,we conducted a meta-analysis to verify the changes in Bregs in active SLE.Methods:We identified studies reporting the proportions of Bregs in SLE patients by searching Pubmed,Embase,Web of Science,Cochrane and CNKI.Due to the degree of heterogeneity is very high,we used a random effects model to assess the mean differences in percentages of Bregs between active SLE and controls.Then,sensitivity analysis and subgroup analysis were performed to verify potential sources of heterogeneity.Results:Seven eligible articles involving 301 active SLE patients and 218 controls were included in the meta-analysis.The pooled percentages of Bregs were found no significant difference between active SLE patients and healthy controls[0.259,(−1.150,1.668),p=0.719],with great heterogeneity(I2=97.5%).The result of sensitivity analysis showed that exclusion of any single study or single article did not materially resolve the heterogeneity,but after excluding the article conducted by Cai X and his colleagues,the percentages of Bregs were significantly higher in active SLE than those in controls[1.394,(0.114,2.675),p=0.033].The results of subgroup analysis revealed that when the disease activity was judged by SLEDAI score≥5,the percentages of Bregs were significantly lower in the SLE groups than in the control groups[-1.99,(-3.241,-0.739),p=0.002],but when the threshold of SLEDAI score≥6 chosen for active SLE,the percentages of Bregs were significantly increased in the SLE groups[2.546,(1.333,3.759),p<0.001].Meanwhile,other subgroup analysis based on the different phenotypes of Bregs,diagnostic criteria,enrolled research countries,treatment status,and organ involvement did not differ in proportion of Bregs between SLE patients and controls.Conclusions:The study implies that Bregs may play a role in the pathogenesis of active SLE,and the thresholds of SLEDAI score to distinguish between active and inactive SLE patients are important factors affecting the percentages of Bregs.
基金Project supported by the National Natural Science Foundation of China (Grant No.10865006)the Science Foundation of Yunnan University (Grant No.2009A01Z)
文摘This paper investigates the stochastic resonance （SR） induced by a multiplicative periodic signal in the gene transcriptional regulatory system with correlated noises. The expression of the signal-to-noise ratio （SNR） is derived. The results indicate that the existence of a maximum in SNR vs. the additive noise intensity α the multiplicative noise intensity D and the cross-correlated noise intensity λ is the identifying characteristic of the SR phenomenon and there is a critical phenomenon in the SNR as a function of λ, i.e., for the case of smaller values of noise intensity （α or D）, the SNR decreases as λ increases; however, for the case of larger values of noise intensity （α or D）, the SNR increases as λ increases.
基金Project supported by the National Natural Science Foundation of China (Grant No. 10865006)the Science Foundation of the Education Bureau of Shaanxi Province of China (Grant No. 09JK331)the Science Foundation of Baoji University of Science and Arts of China (Grant No. Zk0834)
文摘We have investigated in the adiabatic limit the phenomenon of stochastic resonance in the gene transcriptional regulatory system subjected to an additive noise, a multiplicative noise, and a weakly periodic signal. Using the general two-state approach for the asymmetry system, the analytic expression of signal-to-noise ratio is obtained. The effects of the additive noise intensity a, the multiplicative noise intensity D and the amplitude of input periodic signal A on the signal-to-noise ratio are analysed by numerical calculation. It is found that the existence of a maximum in the RSNR a and RSNR D plots is the identifying characteristic of the stochastic resonance phenomenon in the weakened noise intensity region. The stochastic resonance phenomena are restrained with increasing a and D, and enhanced with increasing A.
文摘In Systems Biology, system identification, which infers regulatory network in genetic system and metabolic pathways using experimentally observed time-course data, is one of the hottest issues. The efficient numerical optimization algorithm to estimate more than 100 real-coded parameters should be developed for this purpose. New real-coded genetic algorithm (RCGA), the combination of AREX (adaptive real-coded ensemble crossover) with JGG (just generation gap), have applied to the inference of genetic interactions involving more than 100 parameters related to the interactions with using experimentally observed time-course data. Compared with conventional RCGA, the combination of UNDX (unimodal normal distribution crossover) with MGG (minimal generation gap), new algorithm has shown the superiority with improving early convergence in the first stage of search and suppressing evolutionary stagnation in the last stage of search.
基金supported by the National Natural Science Foundation of China(No.82071838)the Key Medical Discipline Construction Unit of Jiangsu Province(No.JSDW202205)+1 种基金the Research Hospital of Jiangsu Province(No.YJXYY202204)Natural Science Foundation of Nantong City(No.JC2023053).
文摘Systemic lupus erythematosus(SLE)is a chronic autoimmune disease.Defects in the regulatory T cells(Treg cells)play a key role in breaking immune tolerance in SLE patients.This study investigates the causes of impaired Treg cell function in SLE patients.Peripheral blood from 56 SLE patients and 33 healthy donors was used to assess Treg cell proportions among CD4^(+)T cells and plasma cytokine levels.Treg cells and naïve CD4^(+)T cells from healthy individuals were isolated,cultured under various conditions,and analyzed for phenotype and signal transduction mechanisms using flow cytometry,RT-qPCR,Western blotting,and calcium signaling assays.In SLE patients,the proportion of CD4^(+)CD25^(+)Foxp3^(+)and CD4^(+)Foxp3^(+)Treg cells decreased.Plasma CXCL11 levels were elevated in lupus patients.CXCL11 expression inversely correlated with Treg cell proportions and positively correlated with disease severity.CXCL11 impaired immune function and inhibited Treg cell differentiation.We present a novel pathological pathway in SLE,wherein CXCL11 impedes the immunosuppressive functions of Treg cells.
基金support from the National Natural Science Foundation of China(31972327)the Key Research and Development Program Project of Xinjiang,China(2022B02044)+2 种基金the National Key R&D Program of China(2023YFD1700700)the Agricultural Science and Technology Innovation Program of CAASthe Chinese Academy of Agriculture Sciences for the fund of Elite Youth Program。
文摘Xenocoumacins(Xcns),the major antimicrobial natural products produced by Xenorhabdus nematophila,have gained widespread attention for their potential application in crop protection.However,the regulatory mechanisms involved in the biosynthesis of Xcns remain poorly understood.In this study,we identified 21 potential twocomponent systems(TCSs)in X.nematophila CB6 by bioinformatic analysis.Among them,the response regulators(RRs),GlrR and ArcA,were proven to positively regulate the production of Xcns based on gene deletion and complementation experiments.In addition,our results showed that GlrR played an important role in cell growth,while ArcA was involved in both cell morphology and growth.Using a variety of molecular biological and biochemical techniques,we found that GlrR controlled the Xcns biosynthesis by indirectly regulating the expression levels of the biosynthetic gene cluster(BGC).ArcA directly binded to the promoter regions of xcn A and xcn B to regulate the transcription of the Xcns BGC,and the binding sites were also identified.This study provides valuable insights into the regulatory network of Xcns biosynthesis,which will contribute to the construction of a high-yielding strain.
文摘Overview of root system architecture.The plant root system is a highly dynamic and multifunctional organ system composed of primary roots,lateral roots,adventitious roots,and root hairs.Based on topological morphology,root systems can be classified as taproot systems or fibrous root systems.Root system architecture(RSA)refers to the spatial distribution and extension patterns of roots within soil,encompassing characteristics such as root length,branching angle,density,and spatial arrangement.RSA not only determines the plant’s capacity to acquire water and nutrients but also influences other root functions,playing a decisive role in overall plant health.
基金Supported by the National Natural Science Foundation of China under Grant Nos 10575041 and 90303007, and the SRFDP of the Ministry of Education of China under Project No 20040511005.
文摘We numerically investigate the effects of nonlinear time-delay on the stochastic system. With the delay time increasing, it is found that the peak of probability distribution in low steady states is decreased, and the peak of probability distribution in high steady states is increased. The mean of state variable, the normalized variance, and the normalized autocorrelation function which quantifies the concentrated degree are slowly varied for small delay time. However, the mean of state variable is rapidly increased, and the normalized variance and the normalized autocorrelation function is rapidly decreased for large delay time.
基金the National Natural Science Foundation of China,Nos.81571213(to BW),81800583(to YYX),81601539(to DM)and 81601084(to YC)+3 种基金the National Key Research and Development Program of China,No.2017YFA0104304(to BW)the Nanjing Medical Science and Technique Development Foundation of China,Nos.QRX17006(to BW),QRX17057(to DM)the Key Project Medical Science and Technology Development Foundation,Nanjing Department of Health and the Nanjing Medical Science of China,No.201803024(to TYG)Innovation Platform,No.ZDX16005(to BW)。
文摘Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury.This study aimed to decipher the dynamics of systemic immune responses,initiated by spinal cord injury.The spinal cord in mice was completely transected at T8.Changes in the in vivo inflammatory response,between the acute and subacute stages,were observed.A rapid decrease in C-reactive protein levels,circulating leukocytes and lymphocytes,spleen-derived CD4~+interferon-γ+T-helper cells,and inflammatory cytokines,and a marked increase in neutrophils,monocytes,and CD4~+CD25~+FOXP3~+regulatory T-cells were observed during the acute phase.These systemic immune alterations were gradually restored to basal levels during the sub-acute phase.During the acute phase of spinal cord injury,systemic immune cells and factors showed significant inhibition;however,this inhibition was transient,and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase.All experiments were performed in accordance with the institutional animal care guidelines,approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital,China(approval No.2019 AE01040)on June 25,2019.
