Previous studies have demonstrated a bidirectional relationship between inflammation and depression.Activation of the nucleotide-binding oligomerization domain,leucine-rich repeat,and NLR family pyrin domain-containin...Previous studies have demonstrated a bidirectional relationship between inflammation and depression.Activation of the nucleotide-binding oligomerization domain,leucine-rich repeat,and NLR family pyrin domain-containing 3(NLRP3)inflammasomes is closely related to the pathogenesis of various neurological diseases.In patients with major depressive disorder,NLRP3 inflammasome levels are significantly elevated.Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies.In this review,we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome.Moreover,we outlined various therapeutic strategies that target the NLRP3 inflammasome,including NLRP3 inflammatory pathway inhibitors,natural compounds,and other therapeutic compounds that have been shown to be effective in treating depression.Additionally,we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression.Currently,there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment.The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression.Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.展开更多
The construction of expressway and high-speed rail is at the sacrifice of the soil ecological environment. It brings about much damaged land and bare slope. It is necessary to restore vegetation and rebuild landscape....The construction of expressway and high-speed rail is at the sacrifice of the soil ecological environment. It brings about much damaged land and bare slope. It is necessary to restore vegetation and rebuild landscape. In the design of target plant community and configuration plants,it is required to select as far as possible plants that can blossom and bear fruit or pods. Then seeds of these plants can be harvested,processed and sold,and applied for other projects,so as to develop into a complete forest and grass seed industry chain. This not only reasonably utilizes land resources,but also provides a new approach to the problem of insufficient fine forest seed sources in China. This paper discussed the use of land resources in road side slope and forest and grass seed selection and breeding technology,and elaborated the industrialized development paths for forest and grass seed industries in road side slope. Finally,it arrived at following recommendations.( i) The construction of forest and grass industry economic belt using land resources in road side slope can realize maximum land value. Building a road can help people there get rich,and the type of land and water cultivates its type of forest and grass.( ii) It can make up for the losses incurred from construction of expressway and high-speed rail or destroying forest land,and it can increase farmers' income.( iii) It can increase the supply of domestic seeds,reduce seed import,save foreign exchange,and partly solve the problem of insufficient supply of forest and grass seeds.( iv) It is able to form a complete forest and grass seed industry economic cycle chain,increase employment,and provide new approaches for enriching and benefiting farmers.展开更多
Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires’disease.During infections,L.pneumophila releases over 300...Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires’disease.During infections,L.pneumophila releases over 300 effector proteins into host cells through an Icm/Dot type IV secretion system to manipulate the host defense system for survival within the host.Notably,certain effector proteins mediate posttranslational modifications(PTMs),serving as useful approaches exploited by L.pneumophila to modify host proteins.Some effectors catalyze the addition of host protein PTMs,while others mediate the removal of PTMs from host proteins.In this review,we summarize L.pneumophila effector-mediated PTMs of host proteins,including phosphorylation,ubiquitination,glycosylation,AMPylation,phosphocholination,methylation,and ADP-ribosylation,as well as dephosphorylation,deubiquitination,deAMPylation,deADP-ribosylation,dephosphocholination,and delipidation.We describe their molecular mechanisms and biological functions in the regulation of bacterial growth and Legionella-containing vacuole biosynthesis and in the disruption of host immune and defense machinery.展开更多
Stimulator of interferon genes(STING)is an adaptor protein that is critical for effective innate antiviral and antitumor immunity.The activity of STING is heavily regulated by protein ubiquitination,which is fine-tune...Stimulator of interferon genes(STING)is an adaptor protein that is critical for effective innate antiviral and antitumor immunity.The activity of STING is heavily regulated by protein ubiquitination,which is fine-tuned by both E3 ubiquitin ligases and deubiquitinases.Here,we report that the deubiquitinase OTUD5 interacts with STING,cleaves its K48-linked polyubiquitin chains,and promotes its stability.Consistently,knockout of OTUD5 resulted in faster turnover of STING and subsequently impaired type I IFN signaling following cytosolic DNA stimulation.More importantly,Lyz2-Cre Otud5^(fl/Y) mice and CD11-Cre Otud5^(fl/Y) mice showed more susceptibility to herpes simplex virus type 1(HSV-1)infection and faster development of melanomas than their corresponding control littermates,indicating that OTUD5 is indispensable for STING-mediated antiviral and antitumor immunity.Our data suggest that OTUD5 is a novel checkpoint in the cGAS-STING cytosolic DNA sensing pathway.展开更多
A Mechanism-Inferring method of networks exploited from machine learning theory caneffectively evaluate the predicting performance of a network model.The existing method for inferringnetwork mechanisms based on a cens...A Mechanism-Inferring method of networks exploited from machine learning theory caneffectively evaluate the predicting performance of a network model.The existing method for inferringnetwork mechanisms based on a census of subgraph numbers has some drawbacks,especially the needfor a runtime increasing strongly with network size and network density.In this paper,an improvedmethod has been proposed by introducing a census algorithm of subgraph concentrations.Networkmechanism can be quickly inferred by the new method even though the network has large scale andhigh density.Therefore,the application perspective of mechanism-inferring method has been extendedinto the wider fields of large-scale complex networks.By applying the new method to a case of proteininteraction network,the authors obtain the same inferring result as the existing method,which approvesthe effectiveness of the method.展开更多
Spleen tyrosine kinase(SYK)is a non-receptor tyrosine kinase,which plays an essential role in both innate and adaptive immunity.However,the key molecular mechanisms that regulate SYK activity are poorly understood.Her...Spleen tyrosine kinase(SYK)is a non-receptor tyrosine kinase,which plays an essential role in both innate and adaptive immunity.However,the key molecular mechanisms that regulate SYK activity are poorly understood.Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation.We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK.This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors(CLRs).展开更多
To understand the association between cardiometabolic risk factor(CMRF)clustering and physical activity(PA)levels,we included 86520 Chinese adults aged 18–64 years having at least one CMRF(hypertension,diabetes,dysli...To understand the association between cardiometabolic risk factor(CMRF)clustering and physical activity(PA)levels,we included 86520 Chinese adults aged 18–64 years having at least one CMRF(hypertension,diabetes,dyslipidemia,or obesity)from the China Chronic Disease and Nutrition Surveillance survey in 2015,a nationally and provincially representative investigation with a multistage clustering sampling design.Self-reported PA information was collected with the Global Physical Activity Questionnaire through face-to-face interviews.In view of the obesity epidemic in CMRF patients,PA energy expenditure(PAEE)per kilogram body weight was used,and was defined into four categories:(i)inactivity:0 kJ/kg/day;(ii)low activity:0–5 kJ/kg/day;(iii)moderate activity:6–11 kJ/kg/day;and(iv)vigorous activity:≥12 kJ/kg/day.The estimated weighted prevalence(95%confidence interval[CI])of having 1,2,3,and 4 CMRFs was 60.57%(59.48%–61.67%),28.10%(27.40%–28.79%),9.82%(9.22%–15.42%)and 1.50%(1.37%–1.63%),respectively.The rate(95%CI)of inactivity,low activity,moderate activity,and vigorous activity was 34.52%(32.69%–36.35%),22.22%(21.37%–23.37%),15.98%(15.38%–16.58%)and 27.28%(26.02%–28.53%),respectively.For those having 2,3 and 4 CMRFs(compared to those having 1 CMRF),the adjusted odds ratio(95%CI)for moderate activity and vigorous activity were 0.91(0.85–0.98)and 0.92(0.85–0.99),0.87(0.80–0.95)and 0.84(0.77–0.92),and 0.77(0.67–0.89)and 0.85(0.72–1.00),respectively.In conclusion,CMRF clustering was a pandemic among Chinese adults in 2015 and was inversely associated with PA level.PAEE(in kJ/kg/day)may be introduced into PA management practice,especially for populations with high body weight.展开更多
基金supported by Health Commission of Pudong New Area Health and Family Planning Scientific Research Project,No.PW2020E-4(to GL)Siming Youth Fund Project of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,No.SGKJ-202119(to RH)+5 种基金Medical Innovation Research Special Project of 2021“Science and Technology Innovation Action Plan”of Shanghai,No.21Y21920200(to GL)Shanghai Rising-Star Program and Shanghai Sailing Program,No.23YF1418200(to QH)Shanghai Municipal Health Commission Foundation grant,No.20234Y0294(to QH)Hundred Teacher Talent Program of Shanghai University of Medicine and Health Sciences,No.A1-2601-23-311007-21(to QH)the Scientific and Technological Innovation Program of Higher Education Institution in Shanxi,No.2021L350(to XC)the Fundamental Research Program of Shanxi Province,No.20210302124194(to XC).
文摘Previous studies have demonstrated a bidirectional relationship between inflammation and depression.Activation of the nucleotide-binding oligomerization domain,leucine-rich repeat,and NLR family pyrin domain-containing 3(NLRP3)inflammasomes is closely related to the pathogenesis of various neurological diseases.In patients with major depressive disorder,NLRP3 inflammasome levels are significantly elevated.Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies.In this review,we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome.Moreover,we outlined various therapeutic strategies that target the NLRP3 inflammasome,including NLRP3 inflammatory pathway inhibitors,natural compounds,and other therapeutic compounds that have been shown to be effective in treating depression.Additionally,we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression.Currently,there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment.The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression.Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.
基金partly supported by the scientific research project of Baishanzu National Park(2021KFLY08)the National Natural Science Foundation of China(31970447)+1 种基金the Starting Fund for Doctoral Research of Lishui University(6004LMM01Z)the Special Fund for Scientific Research of Postdoctoral Work Station Assessment in Zhejiang Province,China(2021,2023)。
基金Supported by National Spark Plan Project(2010GA781004)Science and Technology Planning Project of Shenzhen(GCZX2015051514435234,CXZZ20150527171538718,and CXZZ20140422142833835)
文摘The construction of expressway and high-speed rail is at the sacrifice of the soil ecological environment. It brings about much damaged land and bare slope. It is necessary to restore vegetation and rebuild landscape. In the design of target plant community and configuration plants,it is required to select as far as possible plants that can blossom and bear fruit or pods. Then seeds of these plants can be harvested,processed and sold,and applied for other projects,so as to develop into a complete forest and grass seed industry chain. This not only reasonably utilizes land resources,but also provides a new approach to the problem of insufficient fine forest seed sources in China. This paper discussed the use of land resources in road side slope and forest and grass seed selection and breeding technology,and elaborated the industrialized development paths for forest and grass seed industries in road side slope. Finally,it arrived at following recommendations.( i) The construction of forest and grass industry economic belt using land resources in road side slope can realize maximum land value. Building a road can help people there get rich,and the type of land and water cultivates its type of forest and grass.( ii) It can make up for the losses incurred from construction of expressway and high-speed rail or destroying forest land,and it can increase farmers' income.( iii) It can increase the supply of domestic seeds,reduce seed import,save foreign exchange,and partly solve the problem of insufficient supply of forest and grass seeds.( iv) It is able to form a complete forest and grass seed industry economic cycle chain,increase employment,and provide new approaches for enriching and benefiting farmers.
基金funded by the National Natural Science Foundation of China(32170185,22011530161,31801166,and 91854101)the Natural Science Foundation of Chongqing,China(cstc2021jcyj-msxmX0030 and CSTB2022NSCQ-MSX0463)+2 种基金the Venture Innovation Support Program for Chongqing Overseas Returnees(cx2022066)the Fundamental Research Funds for the Central Universities(2022CDJYGRH-002)the National Training Program of Innovation and Entrepreneurship for Undergraduates(202210611088).
文摘Legionella pneumophila is a Gram-negative bacterium ubiquitously present in freshwater environments and causes a serious type of pneumonia called Legionnaires’disease.During infections,L.pneumophila releases over 300 effector proteins into host cells through an Icm/Dot type IV secretion system to manipulate the host defense system for survival within the host.Notably,certain effector proteins mediate posttranslational modifications(PTMs),serving as useful approaches exploited by L.pneumophila to modify host proteins.Some effectors catalyze the addition of host protein PTMs,while others mediate the removal of PTMs from host proteins.In this review,we summarize L.pneumophila effector-mediated PTMs of host proteins,including phosphorylation,ubiquitination,glycosylation,AMPylation,phosphocholination,methylation,and ADP-ribosylation,as well as dephosphorylation,deubiquitination,deAMPylation,deADP-ribosylation,dephosphocholination,and delipidation.We describe their molecular mechanisms and biological functions in the regulation of bacterial growth and Legionella-containing vacuole biosynthesis and in the disruption of host immune and defense machinery.
基金This work was supported by grants from the National Natural Science Foundation of China(31730026,81930039,and 81525012).
文摘Stimulator of interferon genes(STING)is an adaptor protein that is critical for effective innate antiviral and antitumor immunity.The activity of STING is heavily regulated by protein ubiquitination,which is fine-tuned by both E3 ubiquitin ligases and deubiquitinases.Here,we report that the deubiquitinase OTUD5 interacts with STING,cleaves its K48-linked polyubiquitin chains,and promotes its stability.Consistently,knockout of OTUD5 resulted in faster turnover of STING and subsequently impaired type I IFN signaling following cytosolic DNA stimulation.More importantly,Lyz2-Cre Otud5^(fl/Y) mice and CD11-Cre Otud5^(fl/Y) mice showed more susceptibility to herpes simplex virus type 1(HSV-1)infection and faster development of melanomas than their corresponding control littermates,indicating that OTUD5 is indispensable for STING-mediated antiviral and antitumor immunity.Our data suggest that OTUD5 is a novel checkpoint in the cGAS-STING cytosolic DNA sensing pathway.
基金supported by the National Natural Science Foundation of China under Grant No. 70401019
文摘A Mechanism-Inferring method of networks exploited from machine learning theory caneffectively evaluate the predicting performance of a network model.The existing method for inferringnetwork mechanisms based on a census of subgraph numbers has some drawbacks,especially the needfor a runtime increasing strongly with network size and network density.In this paper,an improvedmethod has been proposed by introducing a census algorithm of subgraph concentrations.Networkmechanism can be quickly inferred by the new method even though the network has large scale andhigh density.Therefore,the application perspective of mechanism-inferring method has been extendedinto the wider fields of large-scale complex networks.By applying the new method to a case of proteininteraction network,the authors obtain the same inferring result as the existing method,which approvesthe effectiveness of the method.
基金This work was supported by grants from the National Natural Science Foundation of China(81930039,31730026,81525012)the Key Research and Development Projects of Shandong Province(2019GSF108133).
文摘Spleen tyrosine kinase(SYK)is a non-receptor tyrosine kinase,which plays an essential role in both innate and adaptive immunity.However,the key molecular mechanisms that regulate SYK activity are poorly understood.Here we identified the E3 ligase TRIM31 as a crucial regulator of SYK activation.We found that TRIM31 interacted with SYK and catalyzed K27-linked polyubiquitination at Lys375 and Lys517 of SYK.This K27-linked polyubiquitination of SYK promoted its plasma membrane translocation and binding with the C-type lectin receptors(CLRs).
基金The funding resources for surveillance were provided by the Chinese Central Government(Key Project of Public Health Program)the National Key Research and Development Program of China(grant numbers 2018YFC1311700,2018YFC1311701,2018YFC1311702,2018YFC1311703).
文摘To understand the association between cardiometabolic risk factor(CMRF)clustering and physical activity(PA)levels,we included 86520 Chinese adults aged 18–64 years having at least one CMRF(hypertension,diabetes,dyslipidemia,or obesity)from the China Chronic Disease and Nutrition Surveillance survey in 2015,a nationally and provincially representative investigation with a multistage clustering sampling design.Self-reported PA information was collected with the Global Physical Activity Questionnaire through face-to-face interviews.In view of the obesity epidemic in CMRF patients,PA energy expenditure(PAEE)per kilogram body weight was used,and was defined into four categories:(i)inactivity:0 kJ/kg/day;(ii)low activity:0–5 kJ/kg/day;(iii)moderate activity:6–11 kJ/kg/day;and(iv)vigorous activity:≥12 kJ/kg/day.The estimated weighted prevalence(95%confidence interval[CI])of having 1,2,3,and 4 CMRFs was 60.57%(59.48%–61.67%),28.10%(27.40%–28.79%),9.82%(9.22%–15.42%)and 1.50%(1.37%–1.63%),respectively.The rate(95%CI)of inactivity,low activity,moderate activity,and vigorous activity was 34.52%(32.69%–36.35%),22.22%(21.37%–23.37%),15.98%(15.38%–16.58%)and 27.28%(26.02%–28.53%),respectively.For those having 2,3 and 4 CMRFs(compared to those having 1 CMRF),the adjusted odds ratio(95%CI)for moderate activity and vigorous activity were 0.91(0.85–0.98)and 0.92(0.85–0.99),0.87(0.80–0.95)and 0.84(0.77–0.92),and 0.77(0.67–0.89)and 0.85(0.72–1.00),respectively.In conclusion,CMRF clustering was a pandemic among Chinese adults in 2015 and was inversely associated with PA level.PAEE(in kJ/kg/day)may be introduced into PA management practice,especially for populations with high body weight.
