The triple bond in N_(2)has an extremely high bond energy and is thus difficult to break.N_(2)is commonly converted into NH3 artificially via the Haber-Bosch process,and NH_(3)can be utilized to produce other nitrogen...The triple bond in N_(2)has an extremely high bond energy and is thus difficult to break.N_(2)is commonly converted into NH3 artificially via the Haber-Bosch process,and NH_(3)can be utilized to produce other nitrogen-containing chemicals.Here,we developed an electron catalyzed method to directly fix N_(2)into azos,by pushing and pulling the electron into and from the aromatic halide with the cyclic voltammetry method.The round-trip journey of electron can successfully weaken the triple bond in N_(2)through the electron pushing-induced aryl radical via a“brick trowel”transition state,and then produce the diazonium ions by pulling the electron out from the diazo radical intermediate.Different azos can be synthesized with this developed electron catalyzed approach.This approach provides a novel concept and practical route for the fixation of N_(2)at atmospheric pressure into chemical products valuable for industrial and commercial applications.展开更多
In this paper, we investigate the dynamic properties of an SIR epidemic model with saturated growth rate. Under the conditions of an arbitrary initial value, we prove that the system exists unique positive solution, a...In this paper, we investigate the dynamic properties of an SIR epidemic model with saturated growth rate. Under the conditions of an arbitrary initial value, we prove that the system exists unique positive solution, and give the sufficient conditions caused by random environmental factors leading to the extinction of infectious diseases. Moreover, we verify the conditions for the persistence of infectious diseases in the mean sense. Finally, we provide the biology interpretation and some strategies to control the infectious diseases.展开更多
Gut-derived metabolites are essential for liver fibrogenesis.The aim of this study was to determine the alteration of indole-3-propionic acid(IPA),a crucial tryptophan metabolite,in liver fibrosis and delineate the ro...Gut-derived metabolites are essential for liver fibrogenesis.The aim of this study was to determine the alteration of indole-3-propionic acid(IPA),a crucial tryptophan metabolite,in liver fibrosis and delineate the roles of enterogenic IPA in fibrogenesis.In the present study,metabolomics assays focused on tryptophan metabolism were applied to explore the decreased levels of IPA in the feces and serum of cirrhotic patients,as well as in the feces and portal vein serum of fibrotic mice.Oral IPA administration exerted strong antifibrotic effects with favorable biosafety in three fibrotic models via multicellular modulation.Multiplex immunohistochemical staining and DAOSLIMIT imaging demonstrated that gut-derived IPA was directly captured by hepatic macrophages.Macrophage-specific AhR knockout blocked the antifibrotic effect of IPA,while the therapeutic efficacy was maintained in mice with HSC-or hepatocyte-specific AhR depletion.Furthermore,IPA governed macrophage recruitment,S100A8/A9+phenotype transformation and profibrotic and proinflammatory functions,resulting in amelioration of hepatic fibrogenesis.Mechanistically,IPA targeted the AhR/NF-κB/S100A8/A9 axis and AhR/SPHK2/S1P signaling to inhibit the profibrotic biological characteristics of macrophages and subsequently interrupted the profibrogenic crosstalk between macrophages and hepatic stellate cells(HSCs)in coculture systems and 3D liver spheroid models.These findings increase the understanding of the effects of enterogenic tryptophan metabolites on liver fibrogenesis via the gut-liver axis and support the translational potential of IPA.By targeting profibrogenic macrophages,IPA could serve as a promising candidate for the clinical management of liver fibrosis.展开更多
Objective To identify factors that likely contribute to potentially inappropriate prescriptions(PIPs)among older adults in primary care settings,as well as barriers to medicines optimisation and recommended potential ...Objective To identify factors that likely contribute to potentially inappropriate prescriptions(PIPs)among older adults in primary care settings,as well as barriers to medicines optimisation and recommended potential solutions.Design Systematic review.Eligibility criteria Quantitative studies that analysed the factors associated with PIPs among older adults(≥65 years)in primary care settings,and qualitative studies that explored perceived barriers and potential solutions to medicines optimisation for this population.Information sources PubMed,EMBASE,Scopus,CINAHL,PsycINFO,Web of Science,CNKI and Wanfang.Results Of the 13167 studies identified,50 were included(14 qualitative,34 cross-sectional and 2 cohort).Nearly all quantitative studies examined patient-related non-clinical factors(eg,age)and clinical factors(eg,number of medications)and nine studies examined prescriber-related factors(eg,physician age).A greater number of medications were identified as positively associated with PIPs in 25 quantitative studies,and a higher number of comorbidities,physical comorbidities and psychiatric comorbidities were identified as patient-related clinical risk factors for PIPs.However,other factors showed inconsistent associations with the PIPs.Barriers to medicines optimisation emerged within four analytical themes:prescriber related(eg,inadequate knowledge,concerns of adverse consequences,clinical inertia,lack of communication),patient related(eg,limited understanding,patient non-adherence,drug dependency),environment related(eg,lack of integrated care,insufficient investment,time constraints)and technology related(eg,complexity of implementation and inapplicable guidance).Recommended potential solutions were based on each theme of the barriers identified accordingly(eg,prescriber-related factors:incorporating training courses into continuing medical education).Conclusions Older adults with more drugs prescribed and comorbidities may have a greater risk of receiving PIPs in the primary care setting,but it remains unclear whether other factors are related.Barriers to medicines optimisation among primary care older adults comprise multiple factors,and evidence-based and targeted interventions are needed to address these difficulties.PROSPERO registration number CRD42020216258.展开更多
Hypertension is a global problem that affects more than 1 billion people worldwide with the increased prevalence year by year[1,2].It contributes to major impacts on health including morbidity and all-cause mortality,...Hypertension is a global problem that affects more than 1 billion people worldwide with the increased prevalence year by year[1,2].It contributes to major impacts on health including morbidity and all-cause mortality,as well as consumption of substantial health care expenses.Understanding the complex pathophysiology and risk factors involved in the development of elevated blood pressure can help treat the disease to better prevent life-threatening conditions and alleviate the socio-economic burden.The hereditary nature of hypertension relies on that up to 30%of blood pressure variation is due to genetics and an individual’s genetic predisposition to hypertensive disease ranges from 15%to 35%[3].展开更多
文摘The triple bond in N_(2)has an extremely high bond energy and is thus difficult to break.N_(2)is commonly converted into NH3 artificially via the Haber-Bosch process,and NH_(3)can be utilized to produce other nitrogen-containing chemicals.Here,we developed an electron catalyzed method to directly fix N_(2)into azos,by pushing and pulling the electron into and from the aromatic halide with the cyclic voltammetry method.The round-trip journey of electron can successfully weaken the triple bond in N_(2)through the electron pushing-induced aryl radical via a“brick trowel”transition state,and then produce the diazonium ions by pulling the electron out from the diazo radical intermediate.Different azos can be synthesized with this developed electron catalyzed approach.This approach provides a novel concept and practical route for the fixation of N_(2)at atmospheric pressure into chemical products valuable for industrial and commercial applications.
文摘In this paper, we investigate the dynamic properties of an SIR epidemic model with saturated growth rate. Under the conditions of an arbitrary initial value, we prove that the system exists unique positive solution, and give the sufficient conditions caused by random environmental factors leading to the extinction of infectious diseases. Moreover, we verify the conditions for the persistence of infectious diseases in the mean sense. Finally, we provide the biology interpretation and some strategies to control the infectious diseases.
基金supported by the National Key R&D Program of China(2023YFC2507500)the National Natural Science Foundation of China(82470661,82070616,82270636,82100608,82300607)+1 种基金the New Quality Clinical Specialties of High-end Medical Disciplinary Construction in Pudong New Area(2025-PWXZ-04)the Talent Plan of the Shanghai Municipal Health Commission for Academic Leaders(2022XD028).
文摘Gut-derived metabolites are essential for liver fibrogenesis.The aim of this study was to determine the alteration of indole-3-propionic acid(IPA),a crucial tryptophan metabolite,in liver fibrosis and delineate the roles of enterogenic IPA in fibrogenesis.In the present study,metabolomics assays focused on tryptophan metabolism were applied to explore the decreased levels of IPA in the feces and serum of cirrhotic patients,as well as in the feces and portal vein serum of fibrotic mice.Oral IPA administration exerted strong antifibrotic effects with favorable biosafety in three fibrotic models via multicellular modulation.Multiplex immunohistochemical staining and DAOSLIMIT imaging demonstrated that gut-derived IPA was directly captured by hepatic macrophages.Macrophage-specific AhR knockout blocked the antifibrotic effect of IPA,while the therapeutic efficacy was maintained in mice with HSC-or hepatocyte-specific AhR depletion.Furthermore,IPA governed macrophage recruitment,S100A8/A9+phenotype transformation and profibrotic and proinflammatory functions,resulting in amelioration of hepatic fibrogenesis.Mechanistically,IPA targeted the AhR/NF-κB/S100A8/A9 axis and AhR/SPHK2/S1P signaling to inhibit the profibrotic biological characteristics of macrophages and subsequently interrupted the profibrogenic crosstalk between macrophages and hepatic stellate cells(HSCs)in coculture systems and 3D liver spheroid models.These findings increase the understanding of the effects of enterogenic tryptophan metabolites on liver fibrogenesis via the gut-liver axis and support the translational potential of IPA.By targeting profibrogenic macrophages,IPA could serve as a promising candidate for the clinical management of liver fibrosis.
基金ZX is funded through Scientific Research Fund of Zhejiang Provincial Education Department(Grant ID,Y201941691)YQ is funded through National Natural Science Foundation of China(Grant ID,72004050).
文摘Objective To identify factors that likely contribute to potentially inappropriate prescriptions(PIPs)among older adults in primary care settings,as well as barriers to medicines optimisation and recommended potential solutions.Design Systematic review.Eligibility criteria Quantitative studies that analysed the factors associated with PIPs among older adults(≥65 years)in primary care settings,and qualitative studies that explored perceived barriers and potential solutions to medicines optimisation for this population.Information sources PubMed,EMBASE,Scopus,CINAHL,PsycINFO,Web of Science,CNKI and Wanfang.Results Of the 13167 studies identified,50 were included(14 qualitative,34 cross-sectional and 2 cohort).Nearly all quantitative studies examined patient-related non-clinical factors(eg,age)and clinical factors(eg,number of medications)and nine studies examined prescriber-related factors(eg,physician age).A greater number of medications were identified as positively associated with PIPs in 25 quantitative studies,and a higher number of comorbidities,physical comorbidities and psychiatric comorbidities were identified as patient-related clinical risk factors for PIPs.However,other factors showed inconsistent associations with the PIPs.Barriers to medicines optimisation emerged within four analytical themes:prescriber related(eg,inadequate knowledge,concerns of adverse consequences,clinical inertia,lack of communication),patient related(eg,limited understanding,patient non-adherence,drug dependency),environment related(eg,lack of integrated care,insufficient investment,time constraints)and technology related(eg,complexity of implementation and inapplicable guidance).Recommended potential solutions were based on each theme of the barriers identified accordingly(eg,prescriber-related factors:incorporating training courses into continuing medical education).Conclusions Older adults with more drugs prescribed and comorbidities may have a greater risk of receiving PIPs in the primary care setting,but it remains unclear whether other factors are related.Barriers to medicines optimisation among primary care older adults comprise multiple factors,and evidence-based and targeted interventions are needed to address these difficulties.PROSPERO registration number CRD42020216258.
基金supported by the National Key Research and Development Program of China(2016YFC1300100)the National Natural Science Foundation of China(81974042)+1 种基金the CAMS Innovation Fund for Medical Sciences(2022-I2M-C&T-A-010,2022I2M-C&T-A-011,and 2022-I2M-C&T-B-041)the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019XK320057 and 2019XK320058)。
基金This work was supported by the National Key Research and Development Program of China(2016YFC1300100)the CAMS Innovation Fund for Medical Sciences(2022-I2M-C&T-A-010 and 2022-I2M-C&T-A-011).
文摘Hypertension is a global problem that affects more than 1 billion people worldwide with the increased prevalence year by year[1,2].It contributes to major impacts on health including morbidity and all-cause mortality,as well as consumption of substantial health care expenses.Understanding the complex pathophysiology and risk factors involved in the development of elevated blood pressure can help treat the disease to better prevent life-threatening conditions and alleviate the socio-economic burden.The hereditary nature of hypertension relies on that up to 30%of blood pressure variation is due to genetics and an individual’s genetic predisposition to hypertensive disease ranges from 15%to 35%[3].
