The climate change in Shandong Peninsula, China was analyzed in this paper by the non-parametric Mann-Kendall test, Accumulated Difference Curve and Order Cluster Analysis methods, based upon the datas of annual mean,...The climate change in Shandong Peninsula, China was analyzed in this paper by the non-parametric Mann-Kendall test, Accumulated Difference Curve and Order Cluster Analysis methods, based upon the datas of annual mean, maximum and minimum temperature and annual precipitation, precipitation from June to September over the past 50 years. Results obtained showed a number of observations: 1) The annual mean temperature of Shandong Peninsula showed a significant increasing trend, with a distinct abrupt change point detected around 1990, during the past 5 decades. The warming of the Peninsula over the last 50 years was due mainly to the significant increase of annual minimum temperature. The annual maximum temperature demonstrated a mixed trend of decreasing and increasing, but was statistically insignificant, and no abrupt change was detected;2) The annual precipitation exhibited a decreasing trend during the past 5 decades, with an abrupt change detected around 1980 at most stations;but there was an earlier transition point at 1966, at a few stations. The reduction in precipitation, from June to September, was responsible mainly for the decrease of annual precipitation. Besides, the proportion of the June-September precipitation in the year declined slightly over the last 50 years;3) In comparison, the temperature evolution in Shandong Peninsula was basically consistent with most parts of China, but warmed at a faster rate over the same period;the decreasing trend of precipitation was more significant compared with the other climate zones of China. Within the Peninsula, the abrupt change of temperature and precipitation in the Southeast was earlier than that in the Northwest;the reduction of precipitation was larger in the Southeast while the increase of temperature was more significant in the Northwest. This research was of great importance to understand the climate change and its environmental effects in the coastal zone.展开更多
Comprehensive experimental and numerical studies have been undertaken to investigate wave energy dissipation performance and main influencing factors of a lower arc-plate breakwater. The numerical model, which conside...Comprehensive experimental and numerical studies have been undertaken to investigate wave energy dissipation performance and main influencing factors of a lower arc-plate breakwater. The numerical model, which considers nonlinear interactions between waves and the arc-plate breakwater, has been constructed by using the velocity wave- generating method, the volume of fluid (VOF) method and the finite volume method. The results show that the relative width, relative height and relative submergence of the breakwater are three main influencing factors and have significant influence on wave energy dissipation of the lower arc-plate open breakwater. The transmission coefficient is found to decrease with the increasing relative width, and the minimum transmission coefficient is 0.15 when the relative width is 0.45. The reflection coefficient is found to vary slightly with the relative width, and the maximum reflection coefficient is 0.53 when the relative width is 0.45. The transmission and reflection coefficients are shown to increase with the relative wave height for approximately 85% of the experimental tests when the relative width is 0.19 0.45. The transmission coefficients at relative submergences of 0.04, 0.02 and 0 are clearly shown to be greater than those at relative submergences of 0.02 and 0.04, while the reflection coefficient exhibits the opposite relationship. After the wave interacts with the lower arc-plate breakwater, the wave energy is mainly converted into transmission, reflection and dissipation energies. The wave attenuation performance is clearly weakened for waves with greater heights and longer periods.展开更多
Objective To explore critical care clinicians’knowledge,attitudes and perceptions toward early mobilization of critically ill patients in ICUs.Design A cross-sectional national survey was conducted.From January to Au...Objective To explore critical care clinicians’knowledge,attitudes and perceptions toward early mobilization of critically ill patients in ICUs.Design A cross-sectional national survey was conducted.From January to August 2020,ICU nurses in 11 hospitals were surveyed by using a questionnaire on the knowledge,attitudes and perceptions of ICU early mobilization.Results Totally 512 nurses completed the questionnaire.The respondents’mean score for knowledge of early mobilization was 6.89±2.91.The level of knowledge was good in 2.5%(13/512),fair in 52.3%(268/512).The attitudes toward early mobilization were positive in 31.4%(161/512).In terms of perceived implementation of ICU early mobilization,42.9%(220/512)of nurses did not believe that this should be a top priority in intensive care.The attitudes of nurses from different ICUs were significantly different(F=3.58,P<0.05).The knowledge(7.34±2.78 vs.6.49±2.97,t=3.37,P<0.001)and attitudes(3.82±0.58 vs.3.52±0.56,t=5.63,P<0.001)of nurses who had early mobilization related training were higher than those of nurses who had no training.Conclusions The importance of early ICU early mobilization is increasingly recognized by critical care providers.However,there is still a gap in the knowledge,attitudes and perceptions of ICU early mobilization among nurses.In future studies,it is necessary to further systematically identify the reasons leading to the gaps in these aspects and implement targeted interventions around these gaps.Meanwhile,more nurses should be encouraged to participate in decision-making to ensure the efficient and quality implementation of ICU early mobilization practices.展开更多
The inner shelf mud wedge(ISMW)located in the East China Sea(ECS)is the fine-grained sedimentary area with high sedimentation rate and has provided an ideal study area for understanding the East Asian Summer Monsoon(E...The inner shelf mud wedge(ISMW)located in the East China Sea(ECS)is the fine-grained sedimentary area with high sedimentation rate and has provided an ideal study area for understanding the East Asian Summer Monsoon(EASM)evolution during the Holocene.In this paper,we presented the high-resolution geochemical data of the sediments from the core MD06-3040 in the ISMW of the ECS determined by X-ray fluorescence core scanning(XRF-CS)analysis,a high-resolution,continuous,and multielement method.Geochemical and factor analysis results reveal that the variations of elemental compositions(Al,Si,K,Ti,Fe),the elemental ratios of Al/Zr,Ca/Ti and Rb/Sr,and the factor scores(F1 are correlated with the changes of the EASM during the period of 6000–1300 cal yr BP.The higher values of geochemical compositions indicating the terrigenous inputs implied the intensification of anthropogenic activities after 1300 cal yr BP.Meanwhile,the significant decrease of most geochemical compositions and the F1 factor scores during 4500–3500 cal yr BP and 1700–1500 cal yr BP,within the dating errors,coincided with the weak EASM events(presumably drought and cold events).The spectral analysis results of K concentrations,Al/Zr ratios and F1 factor scores show the millennial and centennial climatic fluctuations,which are consistent with other marine sedimentary records in the adjacent areas.All the findings show that the geochemical compositions of sediments from core MD06-3040 are influenced by the EASM evolution,the variable El Niño/Southern Oscillation(ENSO)and the local oceanic thermohaline circulation(e.g.,Kuroshio Current).These results are greatly helpful in uncovering the forcing mechanism of the monsoonal climate in the east China over the Holocene and also contribute to the understanding of EASM variability.展开更多
Objective:This study aimed to explore the lived experiences of the disease journey and patients'care needs with idiopathic pulmonary fibrosis(IPF).Methods:Face-to-face semi-structured interviews were conducted wit...Objective:This study aimed to explore the lived experiences of the disease journey and patients'care needs with idiopathic pulmonary fibrosis(IPF).Methods:Face-to-face semi-structured interviews were conducted with a purposive sampling of IPF patients admitted to the department of respiratory medicine in a tertiary hospital in Beijing.Interview data were analyzed using the thematic analysis method.In the end,16 patients were interviewed.Results:Four themes emerged from the qualitative data included the long and confusing journey to reach a diagnosis,living with the disease,understanding the disease and treatment and desire for continuity of care.A series of subthemes were also identified,including uncertainty of diagnosis,delaying the process,living with physical symptoms,living with emotional distress,loss of independence,uncertainty with the prognosis,questioning the cause of the disease,concerning the side effects of treatments,lacking continuity of care,and wanting a better quality ofhealthcare in community hospitals.Conclusions:Based on the findings,there is an urgent need to improve the care delivery to this vulnerable population in China.To meet their health needs,it is of paramount importance to develop effective education programs for health professionals and IPF patients and improve care models of healthcare systems,especially in remote areas,to enhance care continuity in the communities.展开更多
This study explores the impact of China’s Belt and Road Initiative on improving vocational education quality and employment rates in Kenya through a collaborative educational program known as the Kenya-China Technica...This study explores the impact of China’s Belt and Road Initiative on improving vocational education quality and employment rates in Kenya through a collaborative educational program known as the Kenya-China Technical and Vocational Education and Training(TVET)project.The opinions and narratives of teachers and students with vibrant knowledge of the project were analyzed through the theoretical lenses of globalization and vocationalism.The results show that the Kenya-China TVET Project has improved Kenyan TVET classrooms with modern equipment to meet industrial standards and allowed essential skills to be developed through various collaborative opportunities with Chinese corporations.Despite minor challenges and obstacles,early evidence suggests benefits brought by the project including increased self-employment,a growth in Kenya’s manufacturing,and more mutual understanding between the two countries.展开更多
The ever-increasing prevalence of noncommunicable diseases(NCDs)represents a major public health burden worldwide.The most common form of NCD is metabolic diseases,which affect people of all ages and usually manifest ...The ever-increasing prevalence of noncommunicable diseases(NCDs)represents a major public health burden worldwide.The most common form of NCD is metabolic diseases,which affect people of all ages and usually manifest their pathobiology through life-threatening cardiovascular complications.A comprehensive understanding of the pathobiology of metabolic diseases will generate novel targets for improved therapies across the common metabolic spectrum.Protein posttranslational modification(PTM)is an important term that refers to biochemical modification of specific amino acid residues in target proteins,which immensely increases the functional diversity of the proteome.The range of PTMs includes phosphorylation,acetylation,methylation,ubiquitination,SUMOylation,neddylation,glycosylation,palmitoylation,myristoylation,prenylation,cholesterylation,glutathionylation,S-nitrosylation,sulfhydration,citrullination,ADPribosylation,and several novel PTMs.Here,we offer a comprehensive review of PTMs and their roles in common metabolic diseases and pathological consequences,including diabetes,obesity,fatty liver diseases,hyperlipidemia,and atherosclerosis.Building upon this framework,we afford a through description of proteins and pathways involved in metabolic diseases by focusing on PTM-based protein modifications,showcase the pharmaceutical intervention of PTMs in preclinical studies and clinical trials,and offer future perspectives.Fundamental research defining the mechanisms whereby PTMs of proteins regulate metabolic diseases will open new avenues for therapeutic intervention.展开更多
This study examines the geomorphic evolution of Dingzi Bay, East China in response to human activity and variations in fluvial input since the 1950s. The analysis is based on data from multiple mathematical methods, a...This study examines the geomorphic evolution of Dingzi Bay, East China in response to human activity and variations in fluvial input since the 1950s. The analysis is based on data from multiple mathematical methods, along with information obtained from Remote Sensing, Geographic Information System and Global Position System technology. The results show that the annual runoff and sediment load discharged into Dingzi Bay display significant decreasing trends overall, and marked downward steps were observed in 1966 and 1980. Around 60%-80% of the decline is attributed to decreasing precipitation in the Wulong River Basin. The landform types in Dingzi Bay have changed significantly since the 1950s, especially over the period between 1981 and 1995. Large areas of tidal fiats, swamp, salt fields, and paddy fields have been reclaimed, and aquaculture ponds have been constructed. Consequently, the patterns of erosion and deposition in the bay have changed substantially. Despite a reduction in sediment input of 65.68% after 1966, low rates of sediment deposition continued in the bay. However, deposition rates changed significantly after 1981 owing to large-scale development in the bay, with a net depositional area approximately 10 times larger than that during 1961-1981. This geomorphic evolution stabilized following the termination of large-scale human activity in the bay after 1995. Overall, Dingzi Bay has shown a tendency towards silting-up during 1952-2010, with the bay head migrating seaward, the number of channels in the tidal creek system decreasing, and the tidal inlet becoming narrower and shorter. In conclusion, large- scale development and human activity in Dingzi Bay have controlled the geomorphic evolution of the bay since the 1950s.展开更多
Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a we...Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries.Preclinical studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease models.Of clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia stroke.Here,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy.We highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and others.Finally,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.展开更多
Coronavirus disease 2019(COVID-19)is regarded as an endothelial disease(endothelialitis)with its patho-mechanism being incompletely understood.Emerging evidence has demonstrated that endothelial dysfunction precipitat...Coronavirus disease 2019(COVID-19)is regarded as an endothelial disease(endothelialitis)with its patho-mechanism being incompletely understood.Emerging evidence has demonstrated that endothelial dysfunction precipitates COVID-19 and its accompanying multi-organ injuries.Thus,pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications.The objective of the present study is to evaluate whether kruppel-like factor 2(KLF2),a master regulator of vascular homeostasis,represents a therapeutic target for C0VID-19-induced endothelial dysfunction.Here,we demonstrate that the expression of KLF2 was reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules,ICAM1 and VCAM1.IL-1β and TNF-α;two cytokines elevated in cytokine release syndrome in COVID-19 patients,decreased KLF2 gene expression.Pharmacologic(atorvastatin and tannic acid)and genetic(adenoviral overexpression)approaches to augment KLF2 levels attenuated COVID-19-serum-induced increase in endothelial inflammation and monocyte adhesion.Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function(vasodilation,antiinflammation,antioxidant status,anti-thrombosis/-coagulation,anti-fibrosis,and reduced angiogenesis).Finally,knockdown of KLF2 partially reversed the ameliorative effect of atorvastatin on COVID-19-serum-induced endothelial inflammation and monocyte adhesion.Collectively,the present study implicates loss of KLF2 as an important molecular event in the development of COVID-19-induced vascular disease and suggests that efforts to augment KLF2 levels may be therapeutically beneficial.展开更多
文摘The climate change in Shandong Peninsula, China was analyzed in this paper by the non-parametric Mann-Kendall test, Accumulated Difference Curve and Order Cluster Analysis methods, based upon the datas of annual mean, maximum and minimum temperature and annual precipitation, precipitation from June to September over the past 50 years. Results obtained showed a number of observations: 1) The annual mean temperature of Shandong Peninsula showed a significant increasing trend, with a distinct abrupt change point detected around 1990, during the past 5 decades. The warming of the Peninsula over the last 50 years was due mainly to the significant increase of annual minimum temperature. The annual maximum temperature demonstrated a mixed trend of decreasing and increasing, but was statistically insignificant, and no abrupt change was detected;2) The annual precipitation exhibited a decreasing trend during the past 5 decades, with an abrupt change detected around 1980 at most stations;but there was an earlier transition point at 1966, at a few stations. The reduction in precipitation, from June to September, was responsible mainly for the decrease of annual precipitation. Besides, the proportion of the June-September precipitation in the year declined slightly over the last 50 years;3) In comparison, the temperature evolution in Shandong Peninsula was basically consistent with most parts of China, but warmed at a faster rate over the same period;the decreasing trend of precipitation was more significant compared with the other climate zones of China. Within the Peninsula, the abrupt change of temperature and precipitation in the Southeast was earlier than that in the Northwest;the reduction of precipitation was larger in the Southeast while the increase of temperature was more significant in the Northwest. This research was of great importance to understand the climate change and its environmental effects in the coastal zone.
基金supported by the NSFC-Shandong Joint Fund(Grant Nos.U1706220 and U1806227)the National Natural Science Foundation of China(Grant Nos.51709140 and 51879019)the Key Laboratory of Coastal Disasters and Defence of Ministry of Education(Grant No.201703)
文摘Comprehensive experimental and numerical studies have been undertaken to investigate wave energy dissipation performance and main influencing factors of a lower arc-plate breakwater. The numerical model, which considers nonlinear interactions between waves and the arc-plate breakwater, has been constructed by using the velocity wave- generating method, the volume of fluid (VOF) method and the finite volume method. The results show that the relative width, relative height and relative submergence of the breakwater are three main influencing factors and have significant influence on wave energy dissipation of the lower arc-plate open breakwater. The transmission coefficient is found to decrease with the increasing relative width, and the minimum transmission coefficient is 0.15 when the relative width is 0.45. The reflection coefficient is found to vary slightly with the relative width, and the maximum reflection coefficient is 0.53 when the relative width is 0.45. The transmission and reflection coefficients are shown to increase with the relative wave height for approximately 85% of the experimental tests when the relative width is 0.19 0.45. The transmission coefficients at relative submergences of 0.04, 0.02 and 0 are clearly shown to be greater than those at relative submergences of 0.02 and 0.04, while the reflection coefficient exhibits the opposite relationship. After the wave interacts with the lower arc-plate breakwater, the wave energy is mainly converted into transmission, reflection and dissipation energies. The wave attenuation performance is clearly weakened for waves with greater heights and longer periods.
基金This project is supported by the Fundamental Research Funds for the Central Universities(Project number:3332019171).
文摘Objective To explore critical care clinicians’knowledge,attitudes and perceptions toward early mobilization of critically ill patients in ICUs.Design A cross-sectional national survey was conducted.From January to August 2020,ICU nurses in 11 hospitals were surveyed by using a questionnaire on the knowledge,attitudes and perceptions of ICU early mobilization.Results Totally 512 nurses completed the questionnaire.The respondents’mean score for knowledge of early mobilization was 6.89±2.91.The level of knowledge was good in 2.5%(13/512),fair in 52.3%(268/512).The attitudes toward early mobilization were positive in 31.4%(161/512).In terms of perceived implementation of ICU early mobilization,42.9%(220/512)of nurses did not believe that this should be a top priority in intensive care.The attitudes of nurses from different ICUs were significantly different(F=3.58,P<0.05).The knowledge(7.34±2.78 vs.6.49±2.97,t=3.37,P<0.001)and attitudes(3.82±0.58 vs.3.52±0.56,t=5.63,P<0.001)of nurses who had early mobilization related training were higher than those of nurses who had no training.Conclusions The importance of early ICU early mobilization is increasingly recognized by critical care providers.However,there is still a gap in the knowledge,attitudes and perceptions of ICU early mobilization among nurses.In future studies,it is necessary to further systematically identify the reasons leading to the gaps in these aspects and implement targeted interventions around these gaps.Meanwhile,more nurses should be encouraged to participate in decision-making to ensure the efficient and quality implementation of ICU early mobilization practices.
基金the National Natural Science Foundation of China(Nos.41991323,41702185,41977378,U1706220)the National Key Basic Research Program of China(No.2015CB953804)+5 种基金the Na-tural Science Foundation of Shandong Province(No.ZR 2018PD005)the Jiangsu Provincial Basic Research Pro-gram Natural Science Foundation General Project of China(No.BK20171340)the Open Foundation of CAS Key La-boratory of Coastal Environmental Processes and Ecolo-gical Remediation,YICCAS(No.2020KFJJ10)the Open Foundation of State Key Laboratory of Loess and Quater-nary Geology,Institute of Earth Environment,CAS(No.SK LLQG2024)the Laboratory for Marine Geology,Qingdao National Laboratory for Marine Science and Technology(No.MGQNLM-KF201704)the Foundation of School and Land Integration Development in Yantai(No.2021 XDRHXMQT18).
文摘The inner shelf mud wedge(ISMW)located in the East China Sea(ECS)is the fine-grained sedimentary area with high sedimentation rate and has provided an ideal study area for understanding the East Asian Summer Monsoon(EASM)evolution during the Holocene.In this paper,we presented the high-resolution geochemical data of the sediments from the core MD06-3040 in the ISMW of the ECS determined by X-ray fluorescence core scanning(XRF-CS)analysis,a high-resolution,continuous,and multielement method.Geochemical and factor analysis results reveal that the variations of elemental compositions(Al,Si,K,Ti,Fe),the elemental ratios of Al/Zr,Ca/Ti and Rb/Sr,and the factor scores(F1 are correlated with the changes of the EASM during the period of 6000–1300 cal yr BP.The higher values of geochemical compositions indicating the terrigenous inputs implied the intensification of anthropogenic activities after 1300 cal yr BP.Meanwhile,the significant decrease of most geochemical compositions and the F1 factor scores during 4500–3500 cal yr BP and 1700–1500 cal yr BP,within the dating errors,coincided with the weak EASM events(presumably drought and cold events).The spectral analysis results of K concentrations,Al/Zr ratios and F1 factor scores show the millennial and centennial climatic fluctuations,which are consistent with other marine sedimentary records in the adjacent areas.All the findings show that the geochemical compositions of sediments from core MD06-3040 are influenced by the EASM evolution,the variable El Niño/Southern Oscillation(ENSO)and the local oceanic thermohaline circulation(e.g.,Kuroshio Current).These results are greatly helpful in uncovering the forcing mechanism of the monsoonal climate in the east China over the Holocene and also contribute to the understanding of EASM variability.
基金The study was supported by grants from Beijing Excellent Talents Training Programme(2018000021469G220)Beijing Hospitals Authority Youth Programme(QML20200309),Beijing,China.
文摘Objective:This study aimed to explore the lived experiences of the disease journey and patients'care needs with idiopathic pulmonary fibrosis(IPF).Methods:Face-to-face semi-structured interviews were conducted with a purposive sampling of IPF patients admitted to the department of respiratory medicine in a tertiary hospital in Beijing.Interview data were analyzed using the thematic analysis method.In the end,16 patients were interviewed.Results:Four themes emerged from the qualitative data included the long and confusing journey to reach a diagnosis,living with the disease,understanding the disease and treatment and desire for continuity of care.A series of subthemes were also identified,including uncertainty of diagnosis,delaying the process,living with physical symptoms,living with emotional distress,loss of independence,uncertainty with the prognosis,questioning the cause of the disease,concerning the side effects of treatments,lacking continuity of care,and wanting a better quality ofhealthcare in community hospitals.Conclusions:Based on the findings,there is an urgent need to improve the care delivery to this vulnerable population in China.To meet their health needs,it is of paramount importance to develop effective education programs for health professionals and IPF patients and improve care models of healthcare systems,especially in remote areas,to enhance care continuity in the communities.
文摘This study explores the impact of China’s Belt and Road Initiative on improving vocational education quality and employment rates in Kenya through a collaborative educational program known as the Kenya-China Technical and Vocational Education and Training(TVET)project.The opinions and narratives of teachers and students with vibrant knowledge of the project were analyzed through the theoretical lenses of globalization and vocationalism.The results show that the Kenya-China TVET Project has improved Kenyan TVET classrooms with modern equipment to meet industrial standards and allowed essential skills to be developed through various collaborative opportunities with Chinese corporations.Despite minor challenges and obstacles,early evidence suggests benefits brought by the project including increased self-employment,a growth in Kenya’s manufacturing,and more mutual understanding between the two countries.
基金supported by grants from the National Key R&D Program of China(Grant No.2021YFC2500500)the National Natural Science Foundation of China(Grant Nos.82070464,81941022,81530025)+4 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB38010100)supported by Program for Innovative Research Team of The First Affliated Hospital of USTC(CXGG02)Anhui Provincial Key Research and Development Program(Grant No.202104j07020051)Anhui Provincial Natural Science Foundation(Grant No.2208085J08)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(Grant No.2017BT01S131)。
文摘The ever-increasing prevalence of noncommunicable diseases(NCDs)represents a major public health burden worldwide.The most common form of NCD is metabolic diseases,which affect people of all ages and usually manifest their pathobiology through life-threatening cardiovascular complications.A comprehensive understanding of the pathobiology of metabolic diseases will generate novel targets for improved therapies across the common metabolic spectrum.Protein posttranslational modification(PTM)is an important term that refers to biochemical modification of specific amino acid residues in target proteins,which immensely increases the functional diversity of the proteome.The range of PTMs includes phosphorylation,acetylation,methylation,ubiquitination,SUMOylation,neddylation,glycosylation,palmitoylation,myristoylation,prenylation,cholesterylation,glutathionylation,S-nitrosylation,sulfhydration,citrullination,ADPribosylation,and several novel PTMs.Here,we offer a comprehensive review of PTMs and their roles in common metabolic diseases and pathological consequences,including diabetes,obesity,fatty liver diseases,hyperlipidemia,and atherosclerosis.Building upon this framework,we afford a through description of proteins and pathways involved in metabolic diseases by focusing on PTM-based protein modifications,showcase the pharmaceutical intervention of PTMs in preclinical studies and clinical trials,and offer future perspectives.Fundamental research defining the mechanisms whereby PTMs of proteins regulate metabolic diseases will open new avenues for therapeutic intervention.
文摘This study examines the geomorphic evolution of Dingzi Bay, East China in response to human activity and variations in fluvial input since the 1950s. The analysis is based on data from multiple mathematical methods, along with information obtained from Remote Sensing, Geographic Information System and Global Position System technology. The results show that the annual runoff and sediment load discharged into Dingzi Bay display significant decreasing trends overall, and marked downward steps were observed in 1966 and 1980. Around 60%-80% of the decline is attributed to decreasing precipitation in the Wulong River Basin. The landform types in Dingzi Bay have changed significantly since the 1950s, especially over the period between 1981 and 1995. Large areas of tidal fiats, swamp, salt fields, and paddy fields have been reclaimed, and aquaculture ponds have been constructed. Consequently, the patterns of erosion and deposition in the bay have changed substantially. Despite a reduction in sediment input of 65.68% after 1966, low rates of sediment deposition continued in the bay. However, deposition rates changed significantly after 1981 owing to large-scale development in the bay, with a net depositional area approximately 10 times larger than that during 1961-1981. This geomorphic evolution stabilized following the termination of large-scale human activity in the bay after 1995. Overall, Dingzi Bay has shown a tendency towards silting-up during 1952-2010, with the bay head migrating seaward, the number of channels in the tidal creek system decreasing, and the tidal inlet becoming narrower and shorter. In conclusion, large- scale development and human activity in Dingzi Bay have controlled the geomorphic evolution of the bay since the 1950s.
基金This work is supported by National Natural Science Foundation of China(82270500,81870324,82203304,82070464,U1401225,U21A20419)National Mega-Project for Innovative Drugs(2019ZX09735002)+1 种基金Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y036,2017BT01Y093,China)National Engineering and Technology Research Center for New drug Druggability Evaluation(Seed Program of Guangdong Province,2017B090903004,China).
文摘Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases(CVDs),the world’s primary cause of death.Ginkgo biloba,a well-known traditional Chinese medicine with notable cardiovascular actions,has been used as a cardio-and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries.Preclinical studies have shown that ginkgolide B,a bioactive component in Ginkgo biloba,can ameliorate atherosclerosis in cultured vascular cells and disease models.Of clinical relevance,several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases,such as ischemia stroke.Here,we present a comprehensive review of the pharmacological activities,pharmacokinetic characteristics,and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy.We highlight new molecular targets of ginkgolide B,including nicotinamide adenine dinucleotide phosphate oxidases(NADPH oxidase),lectin-like oxidized LDL receptor-1(LOX-1),sirtuin 1(SIRT1),platelet-activating factor(PAF),proprotein convertase subtilisin/kexin type 9(PCSK9)and others.Finally,we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.
基金This study is funded by the Fundamental Research Funds for the Central Universities(Grant Nos.YD9110004001 and,YD9110002002,and YD9110002008)Hefei Municipal Development and Reform Commission Emergency Funding for COVID-19 disease(Grant No.BJ9100000005)+4 种基金This study was also supported by grants from National Natural Science Foundation of China(Grant Nos.81941022,82070464)Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB38010100)This work was also supported by Program for Innovative Research Team of The First Affiliated Hospital of USTC(CXGG02)Anhui Provincial Key Research and Development Program(Grant No.202104j07020051)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(Grant No.2017BT01S131).
文摘Coronavirus disease 2019(COVID-19)is regarded as an endothelial disease(endothelialitis)with its patho-mechanism being incompletely understood.Emerging evidence has demonstrated that endothelial dysfunction precipitates COVID-19 and its accompanying multi-organ injuries.Thus,pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications.The objective of the present study is to evaluate whether kruppel-like factor 2(KLF2),a master regulator of vascular homeostasis,represents a therapeutic target for C0VID-19-induced endothelial dysfunction.Here,we demonstrate that the expression of KLF2 was reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules,ICAM1 and VCAM1.IL-1β and TNF-α;two cytokines elevated in cytokine release syndrome in COVID-19 patients,decreased KLF2 gene expression.Pharmacologic(atorvastatin and tannic acid)and genetic(adenoviral overexpression)approaches to augment KLF2 levels attenuated COVID-19-serum-induced increase in endothelial inflammation and monocyte adhesion.Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function(vasodilation,antiinflammation,antioxidant status,anti-thrombosis/-coagulation,anti-fibrosis,and reduced angiogenesis).Finally,knockdown of KLF2 partially reversed the ameliorative effect of atorvastatin on COVID-19-serum-induced endothelial inflammation and monocyte adhesion.Collectively,the present study implicates loss of KLF2 as an important molecular event in the development of COVID-19-induced vascular disease and suggests that efforts to augment KLF2 levels may be therapeutically beneficial.
