Background Sepsis is a life-threatening organ dysfunction,and septic cardiomyopathy(SCM)may complicate the course of the disease.Infection with multidrug-resistant(MDR)pathogens has been linked with worse outcomes.Thi...Background Sepsis is a life-threatening organ dysfunction,and septic cardiomyopathy(SCM)may complicate the course of the disease.Infection with multidrug-resistant(MDR)pathogens has been linked with worse outcomes.This study aims to evaluate SCM in patients with infections caused by different antimicrobial-resistant phenotypes.Method This retrospective study included patients with sepsis/septic shock,hospitalized,and intubated in the intensive care unit of the University Hospital of Larissa between January 2022 and September 2023 with echocardiographic data during the first two days after infection onset.The patients were divided into two groups:non-MDR-SCM group and MDR-SCM group.The cardiac function was compared between the two groups.Result A total of 62 patients were included in the study.Forty-four patients comprised the MDR-SCM and 18 the non-MDR-SCM group.Twenty-six patients(41.9%)presented with left ventricular(LV)systolic dysfunction,and≤35%right ventricular fractional area change(RVFAC)was present in 56.4%.LV systolic function was more severely impaired in the non-MDR-SCM group(left ventricular ejection fraction,35.8%±4.9%vs.45.6%±2.4%,P=0.049;LV outflow tract velocity time integral,[10.1±1.4]cm vs.[15.3±0.74]cm,P=0.001;LV-Strain,–9.02%±0.9%vs.–14.02%±0.7%,P=0.001).The MDR-SCM group presented with more severe right ventricular(RV)dilatation(right ventricular end-diastolic area/left ventricular end-diastolic area,0.81±0.03 vs.0.7±0.05,P=0.042)and worse RV systolic function(RVFAC,32.3%±1.9%vs.39.6%±2.7%,P=0.035;tricuspid annular plane systolic excursion,[15.9±0.9]mm vs.[18.1±0.9]mm,P=0.165;systolic tissue Doppler velocity measured at the lateral tricuspid annulus,[9.9±0.5]cm/s vs.[13.1±0.8]cm/s,P=0.002;RV-strain,–11.1%±0.7%vs.–15.1%±0.9%,P=0.002).Conclusion SCM related to MDR infection presents with RV systolic dysfunction predominance,while non-MDR-SCM is mainly depicted with LV systolic dysfunction impairment.展开更多
BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC...BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC.The expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC.Under normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor growth.Therefore,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this research.AIM To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and prognosis.METHODS We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9.We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues.RESULTS The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy resistance.Further analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer.CONCLUSION This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.展开更多
Laterality is a crucial physiological process intricately linked to the cilium-centrosome complex during embryo development.Defects in the process can result in severe organ mispositioning.Coiled-coil domain containin...Laterality is a crucial physiological process intricately linked to the cilium-centrosome complex during embryo development.Defects in the process can result in severe organ mispositioning.Coiled-coil domain containing 141(CCDC141)has been previously known as a centrosome-related gene,but its role in left-right(LR)asymmetry has not been characterized.In this study,we utilize the zebrafish model and human exome analysis to elucidate the function of ccdc141 in laterality defects.The knockdown of ccdc141 in zebrafish disrupts early LR signaling pathways,cilia function,and Kupffer's vesicle formation.Unlike ccdc141-knockdown embryos exhibiting aberrant LR patterns,ccdc141-null mutants show no apparent abnormality,suggesting a genetic compensation response effect.In parallel,we observe a marked reduction inα-tubulin acetylation levels in the ccdc141 crispants.The treatment with histone deacetylase(HDAC)inhibitors,particularly the HDAC6 inhibitor,rescues the ccdc141 crispant phenotypes.Furthermore,exome analysis of 70 patients with laterality defects reveals an increased burden of CCDC141 mutations,with in-vivo studies verifying the pathogenicity of the patient mutation CCDC141-R123G.Our findings highlight the critical role of ccdc141 in ciliogenesis and demonstrate that CCDC141 mutations lead to abnormal LR patterns,identifying it as a candidate gene for laterality defects.展开更多
Levitation chassis, as an extremely important component of maglev vehicles, provides functions of transmitting levitation force and steering force, and directly affects the safety performance of the vehicle. Based on ...Levitation chassis, as an extremely important component of maglev vehicles, provides functions of transmitting levitation force and steering force, and directly affects the safety performance of the vehicle. Based on the vertical dynamics model of the levitation chassis, kinetic equations of the model are established, and a simulation program is designed to analyze the structural decoupling function of the chassis, especially under the influence of elastic constraints between the left and right modules, which are exclusively owned by maglev vehicles. A finite element model of the levitation chassis based on left-right decoupling is constructed. Analysis results of the model show that the mechanical properties of the chassis tailored for the vehicle meet the design requirements, and the stiffness and strength is adequate to bear the weight of the whole vehicle.展开更多
The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules.Six“core”proteins,including Friz zled,Flami...The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules.Six“core”proteins,including Friz zled,Flamingo(Celsr),Van Gogh(Vangl),Dishevelled,Prickle,and Diego(Ankrd6),are major components of the Wnt/planar cell polarity pathway.The Fat/Dchs protocadherins and the Scrib polarity complex also function to instruct cellular polarization.In vertebrates,all these pathways are essential for tissue and organ morphogenesis,such as neural tube closure,left-right symmetry breaking,heart and gut morphogenesis,lung and kidney branching,stereociliary bundle orientation,and proximal-distal limb elongation.Mutations in planar polarity genes are closely linked to various congenital diseases.Striking advances have been made in deciphering their contribution to the establishment of spatially oriented pattern in developing or gans and the maintenance of tissue homeostasis.The challenge remains to clarify the complex interplay of different polarity pathways in organogenesis and the link of cell polarity to cell fate specification.Inter disciplinary approaches are also important to understand the roles of mechanical forces in coupling cellular polarization and differentiation.This review outlines current advances on planar polarity regulators in asymmetric organ formation,with the aim to identify questions that deserve further investigation.展开更多
With the high older-related accident ratio and increasing population aging problem, understanding older drivers＇ driving behaviors has become more and more important for building and improving transportation system. ...With the high older-related accident ratio and increasing population aging problem, understanding older drivers＇ driving behaviors has become more and more important for building and improving transportation system. This paper examines older driver＇s driving behavior which includes road selection, left/right turn and driving speed. A two-month experiment of 108 participants was carried out in Aichi Prefecture, Japan. Since apparently contradictory statements were often drawn in survey-based or simulators-based studies, this study collected not only drivers＇ basic information but also GPS data. Analysis of road selection demonstrates that older drivers are reluctant to drive on expressway not only in short trips but also in long trips. The present study did not find significant difference be- tween older drivers and others while turning at the intersections. To investigate the impact factors on driving speed, a random-effects regression model is constructed with explan- atory variables including age, gender, road types and the interaction terms between age and road types. Compared with other variables, it fails to find that age （60 years old or over） has significant impact on driving speed. Moreover, the results reflect that older drivers drive even faster than others at particular road types： national road and ordinary municipal road. The results in this study are expected to help improve transportation planning and develop driving assistance systems for older drivers.展开更多
The ruled surfaces of normals and binormals of a space curve is locally classified under the left-right action according to the types of the curve. In order to do this some useful results are obtained on the relations...The ruled surfaces of normals and binormals of a space curve is locally classified under the left-right action according to the types of the curve. In order to do this some useful results are obtained on the relationship of the powers of terms in the Taylor series of an invertible function and its inverse.展开更多
For the unfolding of equivariant bifurcation problems with two types of state variables in the presence of parameter symmetry,the versal unfolding theorem with respect to left-right equivalence is obtained by using th...For the unfolding of equivariant bifurcation problems with two types of state variables in the presence of parameter symmetry,the versal unfolding theorem with respect to left-right equivalence is obtained by using the related methods and techniques in the singularity theory of smooth map-germs.The corresponding results in[4,9]can be considered as its special cases.A relationship between the versal unfolding w.r.t.left-right equivalence and the versal deformation w.r.t.contact equivalence is established.展开更多
基金the Institutional Review Board of the University Hospital of Larissa(approval number:55944/2022).
文摘Background Sepsis is a life-threatening organ dysfunction,and septic cardiomyopathy(SCM)may complicate the course of the disease.Infection with multidrug-resistant(MDR)pathogens has been linked with worse outcomes.This study aims to evaluate SCM in patients with infections caused by different antimicrobial-resistant phenotypes.Method This retrospective study included patients with sepsis/septic shock,hospitalized,and intubated in the intensive care unit of the University Hospital of Larissa between January 2022 and September 2023 with echocardiographic data during the first two days after infection onset.The patients were divided into two groups:non-MDR-SCM group and MDR-SCM group.The cardiac function was compared between the two groups.Result A total of 62 patients were included in the study.Forty-four patients comprised the MDR-SCM and 18 the non-MDR-SCM group.Twenty-six patients(41.9%)presented with left ventricular(LV)systolic dysfunction,and≤35%right ventricular fractional area change(RVFAC)was present in 56.4%.LV systolic function was more severely impaired in the non-MDR-SCM group(left ventricular ejection fraction,35.8%±4.9%vs.45.6%±2.4%,P=0.049;LV outflow tract velocity time integral,[10.1±1.4]cm vs.[15.3±0.74]cm,P=0.001;LV-Strain,–9.02%±0.9%vs.–14.02%±0.7%,P=0.001).The MDR-SCM group presented with more severe right ventricular(RV)dilatation(right ventricular end-diastolic area/left ventricular end-diastolic area,0.81±0.03 vs.0.7±0.05,P=0.042)and worse RV systolic function(RVFAC,32.3%±1.9%vs.39.6%±2.7%,P=0.035;tricuspid annular plane systolic excursion,[15.9±0.9]mm vs.[18.1±0.9]mm,P=0.165;systolic tissue Doppler velocity measured at the lateral tricuspid annulus,[9.9±0.5]cm/s vs.[13.1±0.8]cm/s,P=0.002;RV-strain,–11.1%±0.7%vs.–15.1%±0.9%,P=0.002).Conclusion SCM related to MDR infection presents with RV systolic dysfunction predominance,while non-MDR-SCM is mainly depicted with LV systolic dysfunction impairment.
基金the Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.2020KJ133Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-009A.
文摘BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC.The expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC.Under normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor growth.Therefore,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this research.AIM To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and prognosis.METHODS We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9.We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues.RESULTS The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy resistance.Further analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer.CONCLUSION This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.
基金supported by the National Natural Science Foundation of China(81970264).
文摘Laterality is a crucial physiological process intricately linked to the cilium-centrosome complex during embryo development.Defects in the process can result in severe organ mispositioning.Coiled-coil domain containing 141(CCDC141)has been previously known as a centrosome-related gene,but its role in left-right(LR)asymmetry has not been characterized.In this study,we utilize the zebrafish model and human exome analysis to elucidate the function of ccdc141 in laterality defects.The knockdown of ccdc141 in zebrafish disrupts early LR signaling pathways,cilia function,and Kupffer's vesicle formation.Unlike ccdc141-knockdown embryos exhibiting aberrant LR patterns,ccdc141-null mutants show no apparent abnormality,suggesting a genetic compensation response effect.In parallel,we observe a marked reduction inα-tubulin acetylation levels in the ccdc141 crispants.The treatment with histone deacetylase(HDAC)inhibitors,particularly the HDAC6 inhibitor,rescues the ccdc141 crispant phenotypes.Furthermore,exome analysis of 70 patients with laterality defects reveals an increased burden of CCDC141 mutations,with in-vivo studies verifying the pathogenicity of the patient mutation CCDC141-R123G.Our findings highlight the critical role of ccdc141 in ciliogenesis and demonstrate that CCDC141 mutations lead to abnormal LR patterns,identifying it as a candidate gene for laterality defects.
基金supported by the National Natural Science Foundation of China (No. 51175442)the Fundamental Research Funds for the Central Universities (SWJTU12CX040)
文摘Levitation chassis, as an extremely important component of maglev vehicles, provides functions of transmitting levitation force and steering force, and directly affects the safety performance of the vehicle. Based on the vertical dynamics model of the levitation chassis, kinetic equations of the model are established, and a simulation program is designed to analyze the structural decoupling function of the chassis, especially under the influence of elastic constraints between the left and right modules, which are exclusively owned by maglev vehicles. A finite element model of the levitation chassis based on left-right decoupling is constructed. Analysis results of the model show that the mechanical properties of the chassis tailored for the vehicle meet the design requirements, and the stiffness and strength is adequate to bear the weight of the whole vehicle.
基金supported by grants from the National Natural Science Foundation of China(grant number 32070813)the French Muscular Dystrophy Association (AFM-Telethon grant number 23545)+1 种基金the Centre National de la Recherche Scientifiquethe Sorbonne University
文摘The phenomenon of planar cell polarity is critically required for a myriad of morphogenetic processes in metazoan and is accurately controlled by several conserved modules.Six“core”proteins,including Friz zled,Flamingo(Celsr),Van Gogh(Vangl),Dishevelled,Prickle,and Diego(Ankrd6),are major components of the Wnt/planar cell polarity pathway.The Fat/Dchs protocadherins and the Scrib polarity complex also function to instruct cellular polarization.In vertebrates,all these pathways are essential for tissue and organ morphogenesis,such as neural tube closure,left-right symmetry breaking,heart and gut morphogenesis,lung and kidney branching,stereociliary bundle orientation,and proximal-distal limb elongation.Mutations in planar polarity genes are closely linked to various congenital diseases.Striking advances have been made in deciphering their contribution to the establishment of spatially oriented pattern in developing or gans and the maintenance of tissue homeostasis.The challenge remains to clarify the complex interplay of different polarity pathways in organogenesis and the link of cell polarity to cell fate specification.Inter disciplinary approaches are also important to understand the roles of mechanical forces in coupling cellular polarization and differentiation.This review outlines current advances on planar polarity regulators in asymmetric organ formation,with the aim to identify questions that deserve further investigation.
文摘With the high older-related accident ratio and increasing population aging problem, understanding older drivers＇ driving behaviors has become more and more important for building and improving transportation system. This paper examines older driver＇s driving behavior which includes road selection, left/right turn and driving speed. A two-month experiment of 108 participants was carried out in Aichi Prefecture, Japan. Since apparently contradictory statements were often drawn in survey-based or simulators-based studies, this study collected not only drivers＇ basic information but also GPS data. Analysis of road selection demonstrates that older drivers are reluctant to drive on expressway not only in short trips but also in long trips. The present study did not find significant difference be- tween older drivers and others while turning at the intersections. To investigate the impact factors on driving speed, a random-effects regression model is constructed with explan- atory variables including age, gender, road types and the interaction terms between age and road types. Compared with other variables, it fails to find that age （60 years old or over） has significant impact on driving speed. Moreover, the results reflect that older drivers drive even faster than others at particular road types： national road and ordinary municipal road. The results in this study are expected to help improve transportation planning and develop driving assistance systems for older drivers.
基金This work was supported by the National Natural Science Foundation of China (Grant Nos. 10261002 and 10671009)
文摘The ruled surfaces of normals and binormals of a space curve is locally classified under the left-right action according to the types of the curve. In order to do this some useful results are obtained on the relationship of the powers of terms in the Taylor series of an invertible function and its inverse.
文摘For the unfolding of equivariant bifurcation problems with two types of state variables in the presence of parameter symmetry,the versal unfolding theorem with respect to left-right equivalence is obtained by using the related methods and techniques in the singularity theory of smooth map-germs.The corresponding results in[4,9]can be considered as its special cases.A relationship between the versal unfolding w.r.t.left-right equivalence and the versal deformation w.r.t.contact equivalence is established.
