Vaginal bleeding is a common symptom in the emergency department of obstetrics and gynecology hospitals;however,post-hysterectomy vaginal bleeding is a rare phenomenon.Uterine artery pseudoaneurysm(UAP)is a rare condi...Vaginal bleeding is a common symptom in the emergency department of obstetrics and gynecology hospitals;however,post-hysterectomy vaginal bleeding is a rare phenomenon.Uterine artery pseudoaneurysm(UAP)is a rare condition that can lead to fatal bleeding and most commonly occurs as a long-term complication after invasive surgery or even in non-invasive procedures,such as cesarean section,myomectomy,dilatation and curettage,cervical conization and vaginal delivery.[1-3]Pseudoaneurysm is a pulsatile hematoma formed after arterial injury and rupture.展开更多
Since the founding of new China,the maize production pattern took on characteristic of " northern expansion and western movement" : there were great changes in ranking of main producing provinces; southern p...Since the founding of new China,the maize production pattern took on characteristic of " northern expansion and western movement" : there were great changes in ranking of main producing provinces; southern planting area gradually shrank,while central and northern planting area gradually expanded; apart from traditional main producing regions such as northeastern,north China,and southwestern regions,Shanxi- Shaanxi region and northwest region are gradually forming. To further analyze factors promoting changes in maize production pattern,based on 1987- 2013 panel data,we carried our empirical study and obtained five influencing factors: resource endowment,economic environment,market environment,technical conditions,and policies. Per capita farmland,multiple cropping index,water conservancy and irrigation,and benefit cost ratio,and traffic and transportation policies exert positive effect,non-agricultural employment level exerts negative effect,and the significance of natural disasters,market price,and science and technology are inadequate.展开更多
Exposure to the spike protein or receptor-binding domain(S-RBD)of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular endotheliopathy.In this study,angiotensin-converting enzyme 2 huma...Exposure to the spike protein or receptor-binding domain(S-RBD)of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular endotheliopathy.In this study,angiotensin-converting enzyme 2 humanized inbred(hACE2 Tg)mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular endothelium.Results show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration([Ca^(2+)]i)via acute activation of TRPV4,and prolonged upregulation of mechanosensitive channel Piezo1 and store-operated calcium channel(SOCC)key component Orai1 in cultured human pulmonary arterial endothelial cells(PAECs).In mechanism,S-RBD interacts with ACE2 to induce formation of clusters involving Orai1,Piezo1 and TRPC1,facilitate the channel activation of Piezo1 and SOCC,and lead to elevated apoptosis.These effects are blocked by Kobophenol A,which inhibits the binding between S-RBD and ACE2,or intracellular calcium chelator,BAPTA-AM.Blockade of Piezo1 and SOCC by GsMTx4 effectively protects the S-RBDinduced pulmonary microvascular endothelial damage in hACE2 Tg mice via normalizing the elevated[Ca^(2+)]i.Comparing to prototypic strain,Omicron variants(BA.5.2 and XBB)of S-RBD induces significantly less severe cell apoptosis.Transcriptomic analysis indicates that prototypic S-RBD confers more severe acute impacts than Delta or Lambda S-RBD.In summary,this study provides compelling evidence that S-RBD could induce persistent pulmonary vascular endothelial damage by binding to ACE2 and triggering[Ca^(2+)]i through upregulation of Piezo1 and Orai1.Targeted inhibition of ACE2-Piezo1/SOCC-[Ca^(2+)]i axis proves a powerful strategy to treat S-RBD-induced pulmonary vascular diseases.展开更多
Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus.Interleukin-18,an inflammasomeinduced cytokine,has emerged as a novel mediator of cardiopulmonary pathologies but its regulat...Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus.Interleukin-18,an inflammasomeinduced cytokine,has emerged as a novel mediator of cardiopulmonary pathologies but its regulation via SARS-CoV-2 signaling remains unknown.Based on a screening panel,IL-18 was identified amongst 19 cytokines to stratify mortality and hospitalization burden in patients hospitalized with COVID-19.Supporting clinical data,administration of SARS-CoV-2 Spike 1(S1)glycoprotein or receptor-binding domain(RBD)proteins into human angiotensin-converting enzyme 2(hACE2)transgenic mice induced cardiac fibrosis and dysfunction associated with higher NF-κB phosphorylation(pNF-κB)and cardiopulmonary-derived IL-18 and NLRP3 expression.IL-18 inhibition via IL-18BP resulted in decreased cardiac pNF-κB and improved cardiac fibrosis and dysfunction in S1-or RBD-exposed hACE2 mice.Through in vivo and in vitro work,both S1 and RBD proteins induced NLRP3 inflammasome and IL-18 expression by inhibiting mitophagy and increasing mitochondrial reactive oxygenation species.Enhancing mitophagy prevented Spike protein-mediated IL-18 expression.Moreover,IL-18 inhibition reduced Spike protein-mediated pNF-κB and EC permeability.Overall,the link between reduced mitophagy and inflammasome activation represents a novel mechanism during COVID-19 pathogenesis and suggests IL-18 and mitophagy as potential therapeutic targets.展开更多
Arsenic(As)is a cancerogenic metalloid ubiquitously distributed in the environment,which can be easily accumulated in food crops like rice.Jasmonic acid(JA)and its derivatives play critical roles in plant growth and s...Arsenic(As)is a cancerogenic metalloid ubiquitously distributed in the environment,which can be easily accumulated in food crops like rice.Jasmonic acid(JA)and its derivatives play critical roles in plant growth and stress response.However,the role of endogenous JA in As accumulation and detoxification is still poorly understood.In this study,we found that JA biosynthesis enzymes Allene Oxide Synthases,OsAOS1 and OsAOS2,regulate As accumulation and As tolerance in rice.Evolutionary bioinformatic analysis indicated that AOS1 and AOS2 have evolved from streptophyte algae(e.g.the basal lineage Klebsormidium flaccidum)-sister clade of land plants.Compared to other two AOSs,OsAOS1 and OsAOS2 were highly expressed in all examined rice tissues and their transcripts were highly induced by As in root and shoot.Loss-of-function of OsAOS1(osaos1-1)showed elevated As concentration in grains,which was likely attributed to the increased As translocation from root to shoot when the plants were subjected to arsenate[As(Ⅴ)]but not arsenite[As(Ⅲ)].However,the mutation of OsAOS2(osaos2-1)showed no such effect.Moreover,osaos1-1 and osaos2-1 increased the sensitivity of rice plants to both As(Ⅴ)and As(Ⅲ).Disrupted expression of genes involved in As accumulation and detoxification,such as OsPT4,OsNIP3;2,and OsOASTL-A1,was observed in both osaos1-1 and osaos2-1 mutant lines.In addition,a As(Ⅴ)-induced significant decrease in Reactive Oxygen Species(ROS)production was observed in the root of osaos1-1 but not in osaos2-1.Taken together,our results indicate OsAOS1 modulates both As allocation and detoxification,which could be partially attributed to the altered gene expression profiling and ROS homeostasis in rice while OsAOS2 is important for As tolerance.展开更多
基金Zhejiang Province Health Innovative Talent Project(A0466)Key Projects of the Science and Technology Coconstruction by National Administration of Traditional Chinese Medicine and Zhejiang Provincial Administration of Traditional Chinese Medicine(GZY-ZJ-KJ-23082)。
文摘Vaginal bleeding is a common symptom in the emergency department of obstetrics and gynecology hospitals;however,post-hysterectomy vaginal bleeding is a rare phenomenon.Uterine artery pseudoaneurysm(UAP)is a rare condition that can lead to fatal bleeding and most commonly occurs as a long-term complication after invasive surgery or even in non-invasive procedures,such as cesarean section,myomectomy,dilatation and curettage,cervical conization and vaginal delivery.[1-3]Pseudoaneurysm is a pulsatile hematoma formed after arterial injury and rupture.
文摘Since the founding of new China,the maize production pattern took on characteristic of " northern expansion and western movement" : there were great changes in ranking of main producing provinces; southern planting area gradually shrank,while central and northern planting area gradually expanded; apart from traditional main producing regions such as northeastern,north China,and southwestern regions,Shanxi- Shaanxi region and northwest region are gradually forming. To further analyze factors promoting changes in maize production pattern,based on 1987- 2013 panel data,we carried our empirical study and obtained five influencing factors: resource endowment,economic environment,market environment,technical conditions,and policies. Per capita farmland,multiple cropping index,water conservancy and irrigation,and benefit cost ratio,and traffic and transportation policies exert positive effect,non-agricultural employment level exerts negative effect,and the significance of natural disasters,market price,and science and technology are inadequate.
基金The study was supported and funded by National Key Research and Development Program(2022YFE0131500,2018YFC1311900)National Natural Science Foundation of China(81970057,82120108001,82170065,82241012)+4 种基金Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01S155)Guangzhou Basic Research Program Municipal School(Hospital)Joint Funded Foundation and Application Basic Research Project(ZNSA-2020003)Guangdong Basic and Applied Basic Research Foundation(2021A1515010767)Open Research Funds from The Sixth Affiliated Hospital of Guangzhou Medical University(Qingyuan People’s Hospital)(202201-101,202201-309)Independent Project of State Key Laboratory of Respiratory Disease(SKLRD-Z-202219).
文摘Exposure to the spike protein or receptor-binding domain(S-RBD)of SARS-CoV-2 significantly influences endothelial cells and induces pulmonary vascular endotheliopathy.In this study,angiotensin-converting enzyme 2 humanized inbred(hACE2 Tg)mice and cultured pulmonary vascular endothelial cells were used to investigate how spike protein/S-RBD impacts pulmonary vascular endothelium.Results show that S-RBD leads to acute-to-prolonged induction of the intracellular free calcium concentration([Ca^(2+)]i)via acute activation of TRPV4,and prolonged upregulation of mechanosensitive channel Piezo1 and store-operated calcium channel(SOCC)key component Orai1 in cultured human pulmonary arterial endothelial cells(PAECs).In mechanism,S-RBD interacts with ACE2 to induce formation of clusters involving Orai1,Piezo1 and TRPC1,facilitate the channel activation of Piezo1 and SOCC,and lead to elevated apoptosis.These effects are blocked by Kobophenol A,which inhibits the binding between S-RBD and ACE2,or intracellular calcium chelator,BAPTA-AM.Blockade of Piezo1 and SOCC by GsMTx4 effectively protects the S-RBDinduced pulmonary microvascular endothelial damage in hACE2 Tg mice via normalizing the elevated[Ca^(2+)]i.Comparing to prototypic strain,Omicron variants(BA.5.2 and XBB)of S-RBD induces significantly less severe cell apoptosis.Transcriptomic analysis indicates that prototypic S-RBD confers more severe acute impacts than Delta or Lambda S-RBD.In summary,this study provides compelling evidence that S-RBD could induce persistent pulmonary vascular endothelial damage by binding to ACE2 and triggering[Ca^(2+)]i through upregulation of Piezo1 and Orai1.Targeted inhibition of ACE2-Piezo1/SOCC-[Ca^(2+)]i axis proves a powerful strategy to treat S-RBD-induced pulmonary vascular diseases.
基金National Key Research and Development Program of China(2019YFE0119400)Natural Science Foundation of China(81770059,81970052 and 82000055)+4 种基金NIH NHLBI Grant(R01HL136603 to A.A.D.)National Science Foundation CCF PIPP Grant(2200138 to J.S.C.)ZHONGNANSHAN MEDICAL FOUNDATION OF GUANGDONG PROVINCE(ZNSA-2020013)Shenzhen Science and Technology Program(JCYJ20210324122410028)Open Project of State Key Laboratory of Respiratory Disease(SKLRD-OP-202301/202114).
文摘Cardiopulmonary complications are major drivers of mortality caused by the SARS-CoV-2 virus.Interleukin-18,an inflammasomeinduced cytokine,has emerged as a novel mediator of cardiopulmonary pathologies but its regulation via SARS-CoV-2 signaling remains unknown.Based on a screening panel,IL-18 was identified amongst 19 cytokines to stratify mortality and hospitalization burden in patients hospitalized with COVID-19.Supporting clinical data,administration of SARS-CoV-2 Spike 1(S1)glycoprotein or receptor-binding domain(RBD)proteins into human angiotensin-converting enzyme 2(hACE2)transgenic mice induced cardiac fibrosis and dysfunction associated with higher NF-κB phosphorylation(pNF-κB)and cardiopulmonary-derived IL-18 and NLRP3 expression.IL-18 inhibition via IL-18BP resulted in decreased cardiac pNF-κB and improved cardiac fibrosis and dysfunction in S1-or RBD-exposed hACE2 mice.Through in vivo and in vitro work,both S1 and RBD proteins induced NLRP3 inflammasome and IL-18 expression by inhibiting mitophagy and increasing mitochondrial reactive oxygenation species.Enhancing mitophagy prevented Spike protein-mediated IL-18 expression.Moreover,IL-18 inhibition reduced Spike protein-mediated pNF-κB and EC permeability.Overall,the link between reduced mitophagy and inflammasome activation represents a novel mechanism during COVID-19 pathogenesis and suggests IL-18 and mitophagy as potential therapeutic targets.
基金financially supported by the National Natural Science Foundation of China(32170276,32001456,32370285)Major International(Regional)Joint Research Project from NSFC-ASRT(32061143044)+2 种基金the Hubei Hongshan Laboratory(2021hskf004)funded by Australian Research Council(FT210100366),Grains Research&Development Corporation(WSU2303-001RTX)Horticulture Innovation Australia(LP18000).
文摘Arsenic(As)is a cancerogenic metalloid ubiquitously distributed in the environment,which can be easily accumulated in food crops like rice.Jasmonic acid(JA)and its derivatives play critical roles in plant growth and stress response.However,the role of endogenous JA in As accumulation and detoxification is still poorly understood.In this study,we found that JA biosynthesis enzymes Allene Oxide Synthases,OsAOS1 and OsAOS2,regulate As accumulation and As tolerance in rice.Evolutionary bioinformatic analysis indicated that AOS1 and AOS2 have evolved from streptophyte algae(e.g.the basal lineage Klebsormidium flaccidum)-sister clade of land plants.Compared to other two AOSs,OsAOS1 and OsAOS2 were highly expressed in all examined rice tissues and their transcripts were highly induced by As in root and shoot.Loss-of-function of OsAOS1(osaos1-1)showed elevated As concentration in grains,which was likely attributed to the increased As translocation from root to shoot when the plants were subjected to arsenate[As(Ⅴ)]but not arsenite[As(Ⅲ)].However,the mutation of OsAOS2(osaos2-1)showed no such effect.Moreover,osaos1-1 and osaos2-1 increased the sensitivity of rice plants to both As(Ⅴ)and As(Ⅲ).Disrupted expression of genes involved in As accumulation and detoxification,such as OsPT4,OsNIP3;2,and OsOASTL-A1,was observed in both osaos1-1 and osaos2-1 mutant lines.In addition,a As(Ⅴ)-induced significant decrease in Reactive Oxygen Species(ROS)production was observed in the root of osaos1-1 but not in osaos2-1.Taken together,our results indicate OsAOS1 modulates both As allocation and detoxification,which could be partially attributed to the altered gene expression profiling and ROS homeostasis in rice while OsAOS2 is important for As tolerance.