针对视频多目标跟踪中由于目标间的遮挡、交错或目标漂移而导致跟踪失败的情况,提出一种基于卡尔曼滤波以及空间颜色直方图的遮挡预测跟踪算法。利用空间颜色直方图对目标进行建模,可以对不同目标进行区分进而在目标之间出现交错或目标...针对视频多目标跟踪中由于目标间的遮挡、交错或目标漂移而导致跟踪失败的情况,提出一种基于卡尔曼滤波以及空间颜色直方图的遮挡预测跟踪算法。利用空间颜色直方图对目标进行建模,可以对不同目标进行区分进而在目标之间出现交错或目标漂移时仍能跟踪到目标。通过卡尔曼滤波算法可以预测目标的状态,对预测位置之间存在交错的目标进行遮挡标记,以便在下一帧中仍然可以跟踪到被遮挡的目标。采用2D MOT 2015数据集进行实验,跟踪的平均精度达到了34.1%。实验结果表明,所提方法对多目标跟踪的效果有所提高。展开更多
AIM: To observe the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells(h UCMSCs) on the expression of vascular endothelial growth factor-A(VEGF-A) in blue light injured human retina...AIM: To observe the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells(h UCMSCs) on the expression of vascular endothelial growth factor-A(VEGF-A) in blue light injured human retinal pigment epithelial(RPE) cells and laser-induced choroidal neovascularization(CNV) in rats.METHODS: Exosomes were isolated from h UCMSCs and characterized by transmission electron microscope and Western blot. MSCs-derived exosomes were cultured with RPE cells exposed to blue light. The m RNA and protein expression of VEGF-A were determined by real time-polymerase chain reaction(PCR) and Western blot, respectively. Immunofluorescence assay was used for the detection of the expression level of VEGF-A. We injected different doses of MSCs-derived exosomes intravitreally to observe and compare their effects in a mouse model of laserinduced retinal injury. The histological structure of CNV in rats was inspected by hematoxylin-eosin(HE) staining and fundus fluorescein angiography. The expression of VEGF-A was detected by immunohistochemistry.RESULTS: Exosomes exhibited the typical characteristic morphology(cup-shaped) and size(diameter between 50 and 150 nm). The exosomes marker, CD63, and h UCMSCs marker, CD90, showed a robust presence. In vitro, MSCsderived exosomes downregulated the m RNA(Exo-L: t=6.485, 7.959, 9.286; Exo-M: t=7.517, 10.170, 13.413; Exo-H: t=10.317, 12.234, 14.592, P〈0.05) and protein(Exo-L: t=2.945, 4.477, 6.657; Exo-M: t=4.713, 6.421, 8.836; Exo-H:t=6.539, 12.194, 12.783; P〈0.05) expression of VEGF-A in RPE cells after blue light stimulation. In vivo, we found that the MSCs-derived exosomes reduced damage, distinctly downregulated VEGF-A(Exo-H: t=0.957, 1.382; P〈0.05), and gradually improved the histological structures of CNV for a better visual function(Exo-L: 0.346, Exo-M: 3.382, Exo-H: 8.571; P〈0.05). CONCLUSION: MSCs-derived exosomes ameliorate blue light stimulation in RPE cells and laser-induced retin展开更多
AIM To investigate the potential role of micro RNA-30 a(mi R-30 a) in esophageal squamous cell carcinoma(ESCC).METHODS Expression of mi R-30 a-3 p/5 p was analyzed using microarray data and fresh ESCC tissue samples. ...AIM To investigate the potential role of micro RNA-30 a(mi R-30 a) in esophageal squamous cell carcinoma(ESCC).METHODS Expression of mi R-30 a-3 p/5 p was analyzed using microarray data and fresh ESCC tissue samples. Both in vitro and in vivo assays were used to investigate the effects of mi R-30 a-3 p/5 p on ESCC cell proliferation. Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis was performed to explore underlying mechanisms involved in ESCC,and then,assays were carried out to verify the potential molecular mechanism of mi R-30 a in ESCC.RESULTS Low expression of mi R-30 a-3 p/5 p was closely associated with advanced ESCC progression and poor prognosis of patients with ESCC. Knock-down of mi R-30 a-3 p/5 p promoted ESCC cell proliferation. Increased mi R-30 a-3 p/5 p expression inhibited the Wnt signaling pathway by targeting Wnt2 and Fzd2.CONCLUSION Down-regulation of mi R-30 a-3 p/5 p promotes ESCC cell proliferation by activating the Wnt signaling pathway through inhibition of Wnt2 and Fzd2.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the main causes of human death.It is usually already in middle or advanced stage when diagnosed due to its hidden symptoms in early stage.Therefore,patients...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the main causes of human death.It is usually already in middle or advanced stage when diagnosed due to its hidden symptoms in early stage.Therefore,patients have already lost the best surgical timing when diagnosed.Radiotherapy and chemotherapy are standard treatment methods for ESCC clinically,but the efficacy and prognosis of patients from them are still unsatisfactory.Therefore,it is of great clinical significance to seek for biomarkers that can predict the radiotherapy and chemotherapy response and prognosis of ESCC patients.AIM To explore the clinical value of plasma miR-21 and miR-93 in ESCC.METHODS A total of 128 ESCC patients admitted to the First Affiliated Hospital of Zhenzhou University were enrolled as a study group and treated with concurrent radiotherapy and chemotherapy,and other 45 healthy people during the same period were enrolled as a control group.The expression of plasma miR-21 and miR-93 was determined using quantitative real-time polymerase chain reaction,and the correlation of expression of plasma miR-21 and miR-93 with clinical pathological parameters about the patients was analyzed.The receiver operating characteristic(ROC)curve was adopted to assess the diagnostic value of plasma miR-21 and miR-93 for clinical pathological features of ESCC patients,the Logistic regression analysis adopted to analyze the risk factors for radiotherapy and chemotherapy efficacy in ESCC patients,and the Cox regression analysis to identify the prognostic factors for ESCC patients.RESULTS The study group showed significantly higher relative expression of plasma miR-21 and miR-93 than the control group(P<0.01).The area under the ROC curve(AUC)of plasma miR-21 for diagnosing T stage,N stage,M stage,and pathological differentiation of ESCC was 0.819,0.758,0.824,and 0.725,respectively,and that of plasma miR-93 for diagnosing T stage,N stage,and M stage of ESCC was 0.827,0.815,and 0.814,respectively.The AUC of combined plasma miR-21 and miR-93 for predic展开更多
BACKGROUND Cervical cancer is one of the most common gynecological malignant tumors.Radiation enteritis(RE)leads to radiotherapy intolerance or termination of radiotherapy,which negatively impacts the therapeutic effe...BACKGROUND Cervical cancer is one of the most common gynecological malignant tumors.Radiation enteritis(RE)leads to radiotherapy intolerance or termination of radiotherapy,which negatively impacts the therapeutic effect and seriously affects the quality of life of patients.If the incidence of RE in patients can be predicted in advance,and targeted clinical preventive treatment can be carried out,the side effects of radiotherapy in cervical cancer patients can be significantly reduced.Furthermore,accurate prediction of RE is essential for the selection of individualized radiation dose and the optimization of the radiotherapy plan.AIM To analyze the relationships between severe acute RE(SARE)of cervical cancer radiotherapy and clinical factors and dose-volume parameters retrospectively.METHODS We included 50 cervical cancer patients who received volumetric modulated arc therapy(VMAT)from September 2017 to June 2018 in the Department of Radiotherapy at The First Affiliated Hospital Soochow University.Clinical and dose-volume histogram factors of patients were collected.Logistic regression analysis was used to evaluate the predictive value of each factor for SARE.A nomogram to predict SARE was developed(SARE scoring system≥3 points)based on the multiple regression coefficients;validity was verified by an internal verification method.RESULTS Gastrointestinal and hematological toxicity of cervical cancer VMAT gradually increased with radiotherapy and reached the peak at the end of radiotherapy.The main adverse reactions were diarrhea,abdominal pain,colitis,anal swelling,and blood in the stool.There was no significant difference in the incidence of gastrointestinal toxicity between the radical and postoperative adjuvant radiotherapy groups(P>0.05).There were significant differences in the small intestine V_(20),V_(30),V_(40),and rectal V40 between adjuvant radiotherapy and radical radiotherapy after surgery(P<0.05).Univariate and multivariate analyses revealed anal bulge rating(OR:14.779,95%CI:1.281-170.547,P=0.031)an展开更多
Vascular cell functionality is critical to blood vessel homeostasis. Constitutive NF-κB activation in vascular cells results in chronic vascular inflammation, leading to various cardiovascular diseases. However, how ...Vascular cell functionality is critical to blood vessel homeostasis. Constitutive NF-κB activation in vascular cells results in chronic vascular inflammation, leading to various cardiovascular diseases. However, how NF-κB regulates human blood vessel homeostasis remains largely elusive. Here, using CRISPR/Cas9-mediated gene editing, we generated RelA knockout human embryonic stem cells (hESCs) and differentiated them into various vascular cell derivatives to study how NF- KS modulates human vascular cells under basal and inflammatory conditions. Multi-dimensional phenotypic assessments and transcriptomic analyses revealed that RelA deficiency affected vascular cells via modulatinginflammation, survival, vasculogenesis, cell differentia- tion and extracellular matrix organization in a cell type- specific manner under basal condition, and that RelA protected vascular cells against apoptosis and modu- lated vascular inflammatory response upon tumor necrosis factor a (TNFa) stimulation. Lastly, further evaluation of gene expression patterns in IKBo knockout vascular cells demonstrated that IKBa acted largely independent of RelA signaling. Taken together, our data reveal a protective role of NF-κB/ReiA in modulating human blood vessel homeostasis and map the human vascular transcriptomic landscapes for the discovery of novel therapeutic targets.展开更多
Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders,the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown.Here,we report that the expression of ...Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders,the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown.Here,we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem celis(hMSCs).Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration,increases mitochondrial reactive oxygen species(Ros)production,and accelerates cellular senescence.Mechanistically,the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes,especially several key subunits of complex III including UQCRC2.Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs.These findings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis,particularly for the mitochondrial respiration complex Il,thus providing a new potential target to counteract human stem cell senescence.展开更多
AIM:To investigate the effect of the overexpression of C-X-C chemokine receptor type 4(CXCR4) on homing of mesenchymal stem cells(MSCs) in vitro and therapeutic effects of diabetic retinopathy(DR) in vivo.METH...AIM:To investigate the effect of the overexpression of C-X-C chemokine receptor type 4(CXCR4) on homing of mesenchymal stem cells(MSCs) in vitro and therapeutic effects of diabetic retinopathy(DR) in vivo.METHODS:MSCs were infected by lentivirus constructed with CXCR4.The expression of CXCR4 was examined by immunofluorescence,Western blot,and quantitative polymerase chain reaction.CXCR4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis,migration,and apoptotic activities.CXCR4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of DR.The histological structure of DR in rats was inspected by hematoxylin and eosin staining.The expression of rhodopsin,neuron-specific enolase(NSE),and inflammatory cytokines interleukin(IL)-6 and tumor necrosis factor(TNF)-α was examined by Western blot and immunohistochemical analyses.RESULTS:The transduction of MSCs by lentivirus was effective,and the transduced MSCs had high expression levels of CXCR4 gene and protein.Improved migration activities were observed in CXCR4-overexpressing MSCs.Further,reduced retinal damage,upregulation of rhodopsin and NSE protein,and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in vivo.CONCLUSION:The homing of MSCs can be enhanced by upregulating CXCR4 levels,possibly improving histological structures of DR.CXCR4-overexpressing MSCs can be a novel strategy for treating DR.展开更多
Perleididae is a group of stem neopterygian fishes known only from the Triassic.Here,we report the discovery of a new perleidid,Teffichthys wui sp.nov.,based on six well-preserved specimens from the late Smithian(Olen...Perleididae is a group of stem neopterygian fishes known only from the Triassic.Here,we report the discovery of a new perleidid,Teffichthys wui sp.nov.,based on six well-preserved specimens from the late Smithian(Olenekian,Early Triassic)marine deposits of Jurong,Jiangsu and Chaohu,Anhui,China.This new discovery documents the third and youngest species of Teffichthys,which is slightly younger than the Dienerian(Induan)T.elegans from Guizhou and the early Smithian T.madagascariensis from Madagascar.The new species shows diagnostic features of Teffichthys(presence of a spiracular,38-41 lateral line scales,and no more than three epaxial rays in the caudal fin)but differs from T.madagascariensis and T.elegans in some autapomorphies(e.g.,a horizontal opercle/subopercle contact and smooth scales with a nearly straight posterior margin).The diagnostic features for the genus Teffichthys and the family Perleididae are emended based on detailed comparisons of the new taxon with other perleidids.The phylogenetic relationships of perleidids with other stem neopterygians are discussed using a cladistic approach,and the results provide new insights into the phylogeny and classification of main stem neopterygian clades.展开更多
Dear Editor,Myocardial infarction(MI)is the irreversible cardiomyocyte death resulting from prolonged oxygen deprivation due to obstructed blood supply(ischemia),leading to contractile dysfunction and cardiac remodeli...Dear Editor,Myocardial infarction(MI)is the irreversible cardiomyocyte death resulting from prolonged oxygen deprivation due to obstructed blood supply(ischemia),leading to contractile dysfunction and cardiac remodeling.In recent decades,stem cell transplantation has been extensively investigated for the repair of injured heart in animal studies and clinical trials(Kanelidis et al.,2017;Gyongyosi et al.,2018).展开更多
文摘针对视频多目标跟踪中由于目标间的遮挡、交错或目标漂移而导致跟踪失败的情况,提出一种基于卡尔曼滤波以及空间颜色直方图的遮挡预测跟踪算法。利用空间颜色直方图对目标进行建模,可以对不同目标进行区分进而在目标之间出现交错或目标漂移时仍能跟踪到目标。通过卡尔曼滤波算法可以预测目标的状态,对预测位置之间存在交错的目标进行遮挡标记,以便在下一帧中仍然可以跟踪到被遮挡的目标。采用2D MOT 2015数据集进行实验,跟踪的平均精度达到了34.1%。实验结果表明,所提方法对多目标跟踪的效果有所提高。
基金Supported by the National Natural Science Foundation of China(No.81700846)Tianjin Science and Technology Project of China(No.14JCYBJC27400)Science and technology Project of Tianjin Municipal Health Bureau(No.2015KZ073)
文摘AIM: To observe the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells(h UCMSCs) on the expression of vascular endothelial growth factor-A(VEGF-A) in blue light injured human retinal pigment epithelial(RPE) cells and laser-induced choroidal neovascularization(CNV) in rats.METHODS: Exosomes were isolated from h UCMSCs and characterized by transmission electron microscope and Western blot. MSCs-derived exosomes were cultured with RPE cells exposed to blue light. The m RNA and protein expression of VEGF-A were determined by real time-polymerase chain reaction(PCR) and Western blot, respectively. Immunofluorescence assay was used for the detection of the expression level of VEGF-A. We injected different doses of MSCs-derived exosomes intravitreally to observe and compare their effects in a mouse model of laserinduced retinal injury. The histological structure of CNV in rats was inspected by hematoxylin-eosin(HE) staining and fundus fluorescein angiography. The expression of VEGF-A was detected by immunohistochemistry.RESULTS: Exosomes exhibited the typical characteristic morphology(cup-shaped) and size(diameter between 50 and 150 nm). The exosomes marker, CD63, and h UCMSCs marker, CD90, showed a robust presence. In vitro, MSCsderived exosomes downregulated the m RNA(Exo-L: t=6.485, 7.959, 9.286; Exo-M: t=7.517, 10.170, 13.413; Exo-H: t=10.317, 12.234, 14.592, P〈0.05) and protein(Exo-L: t=2.945, 4.477, 6.657; Exo-M: t=4.713, 6.421, 8.836; Exo-H:t=6.539, 12.194, 12.783; P〈0.05) expression of VEGF-A in RPE cells after blue light stimulation. In vivo, we found that the MSCs-derived exosomes reduced damage, distinctly downregulated VEGF-A(Exo-H: t=0.957, 1.382; P〈0.05), and gradually improved the histological structures of CNV for a better visual function(Exo-L: 0.346, Exo-M: 3.382, Exo-H: 8.571; P〈0.05). CONCLUSION: MSCs-derived exosomes ameliorate blue light stimulation in RPE cells and laser-induced retin
基金Supported by the Youth Fund of the First Affiliated Hospital of Xinxiang Medical University(Type A-4)
文摘AIM To investigate the potential role of micro RNA-30 a(mi R-30 a) in esophageal squamous cell carcinoma(ESCC).METHODS Expression of mi R-30 a-3 p/5 p was analyzed using microarray data and fresh ESCC tissue samples. Both in vitro and in vivo assays were used to investigate the effects of mi R-30 a-3 p/5 p on ESCC cell proliferation. Furthermore,Kyoto Encyclopedia of Genes and Genomes analysis was performed to explore underlying mechanisms involved in ESCC,and then,assays were carried out to verify the potential molecular mechanism of mi R-30 a in ESCC.RESULTS Low expression of mi R-30 a-3 p/5 p was closely associated with advanced ESCC progression and poor prognosis of patients with ESCC. Knock-down of mi R-30 a-3 p/5 p promoted ESCC cell proliferation. Increased mi R-30 a-3 p/5 p expression inhibited the Wnt signaling pathway by targeting Wnt2 and Fzd2.CONCLUSION Down-regulation of mi R-30 a-3 p/5 p promotes ESCC cell proliferation by activating the Wnt signaling pathway through inhibition of Wnt2 and Fzd2.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the main causes of human death.It is usually already in middle or advanced stage when diagnosed due to its hidden symptoms in early stage.Therefore,patients have already lost the best surgical timing when diagnosed.Radiotherapy and chemotherapy are standard treatment methods for ESCC clinically,but the efficacy and prognosis of patients from them are still unsatisfactory.Therefore,it is of great clinical significance to seek for biomarkers that can predict the radiotherapy and chemotherapy response and prognosis of ESCC patients.AIM To explore the clinical value of plasma miR-21 and miR-93 in ESCC.METHODS A total of 128 ESCC patients admitted to the First Affiliated Hospital of Zhenzhou University were enrolled as a study group and treated with concurrent radiotherapy and chemotherapy,and other 45 healthy people during the same period were enrolled as a control group.The expression of plasma miR-21 and miR-93 was determined using quantitative real-time polymerase chain reaction,and the correlation of expression of plasma miR-21 and miR-93 with clinical pathological parameters about the patients was analyzed.The receiver operating characteristic(ROC)curve was adopted to assess the diagnostic value of plasma miR-21 and miR-93 for clinical pathological features of ESCC patients,the Logistic regression analysis adopted to analyze the risk factors for radiotherapy and chemotherapy efficacy in ESCC patients,and the Cox regression analysis to identify the prognostic factors for ESCC patients.RESULTS The study group showed significantly higher relative expression of plasma miR-21 and miR-93 than the control group(P<0.01).The area under the ROC curve(AUC)of plasma miR-21 for diagnosing T stage,N stage,M stage,and pathological differentiation of ESCC was 0.819,0.758,0.824,and 0.725,respectively,and that of plasma miR-93 for diagnosing T stage,N stage,and M stage of ESCC was 0.827,0.815,and 0.814,respectively.The AUC of combined plasma miR-21 and miR-93 for predic
基金the National Natural Science Foundation of China,No.81602792 and No.81602802Project of State Key Laboratory of Radiation Medicine and Protection,Soochow University,No.GZK1202101+1 种基金Suzhou Science and Technology Development Plan Project,No.KJXW2020008BOXI Natural Science Cultivation Foundation of China of the First Affiliated Hospital of Soochow University,No.BXQN202107.
文摘BACKGROUND Cervical cancer is one of the most common gynecological malignant tumors.Radiation enteritis(RE)leads to radiotherapy intolerance or termination of radiotherapy,which negatively impacts the therapeutic effect and seriously affects the quality of life of patients.If the incidence of RE in patients can be predicted in advance,and targeted clinical preventive treatment can be carried out,the side effects of radiotherapy in cervical cancer patients can be significantly reduced.Furthermore,accurate prediction of RE is essential for the selection of individualized radiation dose and the optimization of the radiotherapy plan.AIM To analyze the relationships between severe acute RE(SARE)of cervical cancer radiotherapy and clinical factors and dose-volume parameters retrospectively.METHODS We included 50 cervical cancer patients who received volumetric modulated arc therapy(VMAT)from September 2017 to June 2018 in the Department of Radiotherapy at The First Affiliated Hospital Soochow University.Clinical and dose-volume histogram factors of patients were collected.Logistic regression analysis was used to evaluate the predictive value of each factor for SARE.A nomogram to predict SARE was developed(SARE scoring system≥3 points)based on the multiple regression coefficients;validity was verified by an internal verification method.RESULTS Gastrointestinal and hematological toxicity of cervical cancer VMAT gradually increased with radiotherapy and reached the peak at the end of radiotherapy.The main adverse reactions were diarrhea,abdominal pain,colitis,anal swelling,and blood in the stool.There was no significant difference in the incidence of gastrointestinal toxicity between the radical and postoperative adjuvant radiotherapy groups(P>0.05).There were significant differences in the small intestine V_(20),V_(30),V_(40),and rectal V40 between adjuvant radiotherapy and radical radiotherapy after surgery(P<0.05).Univariate and multivariate analyses revealed anal bulge rating(OR:14.779,95%CI:1.281-170.547,P=0.031)an
文摘Vascular cell functionality is critical to blood vessel homeostasis. Constitutive NF-κB activation in vascular cells results in chronic vascular inflammation, leading to various cardiovascular diseases. However, how NF-κB regulates human blood vessel homeostasis remains largely elusive. Here, using CRISPR/Cas9-mediated gene editing, we generated RelA knockout human embryonic stem cells (hESCs) and differentiated them into various vascular cell derivatives to study how NF- KS modulates human vascular cells under basal and inflammatory conditions. Multi-dimensional phenotypic assessments and transcriptomic analyses revealed that RelA deficiency affected vascular cells via modulatinginflammation, survival, vasculogenesis, cell differentia- tion and extracellular matrix organization in a cell type- specific manner under basal condition, and that RelA protected vascular cells against apoptosis and modu- lated vascular inflammatory response upon tumor necrosis factor a (TNFa) stimulation. Lastly, further evaluation of gene expression patterns in IKBo knockout vascular cells demonstrated that IKBa acted largely independent of RelA signaling. Taken together, our data reveal a protective role of NF-κB/ReiA in modulating human blood vessel homeostasis and map the human vascular transcriptomic landscapes for the discovery of novel therapeutic targets.
基金supported by the National Key Research and Development Program of China(2018YFC2000100)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16000000)+9 种基金the National Natural Science Foundation of China(8190143281921006,82125011,92149301,92168201,91949209,92049304,92049116,32121001,82192863,82122024,82071588,81861168034,81922027,81870228,32100937,31900524,82201727)the National Key Research and Development Program of China(2020YFA0804000,2020YFA0113400,2020YFA0112200,2018YFA0107203,the STI2030-Major Projects-2021ZD0202400,2021YFF1201005,2022YFA1103700,2022YFA1103800)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation(Z190019,JQ20031)K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08)Young Elite Scientists Sponsorship Program by CAST(YESS20200012)Youth Innovation Promotion Association of CAS(EiCAZW0401)the Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(11000022T000000461062)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CASWX2022SDC-XK14)CAS Special Research Assistant(SRA)Program,and the Tencent Foundation(2021-1045).
文摘Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders,the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown.Here,we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem celis(hMSCs).Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration,increases mitochondrial reactive oxygen species(Ros)production,and accelerates cellular senescence.Mechanistically,the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes,especially several key subunits of complex III including UQCRC2.Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs.These findings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis,particularly for the mitochondrial respiration complex Il,thus providing a new potential target to counteract human stem cell senescence.
基金Supported by the National Natural Science Foundation of China(No.81700846)Tianjin Science and Technology Project of China(No.13ZCZDSY01500)
文摘AIM:To investigate the effect of the overexpression of C-X-C chemokine receptor type 4(CXCR4) on homing of mesenchymal stem cells(MSCs) in vitro and therapeutic effects of diabetic retinopathy(DR) in vivo.METHODS:MSCs were infected by lentivirus constructed with CXCR4.The expression of CXCR4 was examined by immunofluorescence,Western blot,and quantitative polymerase chain reaction.CXCR4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis,migration,and apoptotic activities.CXCR4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of DR.The histological structure of DR in rats was inspected by hematoxylin and eosin staining.The expression of rhodopsin,neuron-specific enolase(NSE),and inflammatory cytokines interleukin(IL)-6 and tumor necrosis factor(TNF)-α was examined by Western blot and immunohistochemical analyses.RESULTS:The transduction of MSCs by lentivirus was effective,and the transduced MSCs had high expression levels of CXCR4 gene and protein.Improved migration activities were observed in CXCR4-overexpressing MSCs.Further,reduced retinal damage,upregulation of rhodopsin and NSE protein,and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in vivo.CONCLUSION:The homing of MSCs can be enhanced by upregulating CXCR4 levels,possibly improving histological structures of DR.CXCR4-overexpressing MSCs can be a novel strategy for treating DR.
文摘Perleididae is a group of stem neopterygian fishes known only from the Triassic.Here,we report the discovery of a new perleidid,Teffichthys wui sp.nov.,based on six well-preserved specimens from the late Smithian(Olenekian,Early Triassic)marine deposits of Jurong,Jiangsu and Chaohu,Anhui,China.This new discovery documents the third and youngest species of Teffichthys,which is slightly younger than the Dienerian(Induan)T.elegans from Guizhou and the early Smithian T.madagascariensis from Madagascar.The new species shows diagnostic features of Teffichthys(presence of a spiracular,38-41 lateral line scales,and no more than three epaxial rays in the caudal fin)but differs from T.madagascariensis and T.elegans in some autapomorphies(e.g.,a horizontal opercle/subopercle contact and smooth scales with a nearly straight posterior margin).The diagnostic features for the genus Teffichthys and the family Perleididae are emended based on detailed comparisons of the new taxon with other perleidids.The phylogenetic relationships of perleidids with other stem neopterygians are discussed using a cladistic approach,and the results provide new insights into the phylogeny and classification of main stem neopterygian clades.
文摘Dear Editor,Myocardial infarction(MI)is the irreversible cardiomyocyte death resulting from prolonged oxygen deprivation due to obstructed blood supply(ischemia),leading to contractile dysfunction and cardiac remodeling.In recent decades,stem cell transplantation has been extensively investigated for the repair of injured heart in animal studies and clinical trials(Kanelidis et al.,2017;Gyongyosi et al.,2018).