BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the eff...BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.展开更多
淋巴细胞胞质蛋白2(lymphocyte cytosolic protein 2,LCP2)是一种衔接蛋白质,在T细胞受体信号通路中扮演重要角色,激活下游信号因子以完成机体的免疫应答过程。LCP2也在恶性肿瘤的发生发展与转移中发挥重要作用,其高表达会导致不良的预...淋巴细胞胞质蛋白2(lymphocyte cytosolic protein 2,LCP2)是一种衔接蛋白质,在T细胞受体信号通路中扮演重要角色,激活下游信号因子以完成机体的免疫应答过程。LCP2也在恶性肿瘤的发生发展与转移中发挥重要作用,其高表达会导致不良的预后效果,降低患者生存率,其具体作用机制涉及多条信号通路。本文不仅对LCP2的分子结构以及基本功能进行了介绍,而且重点综合评述了LCP2通过参与NF-κB、MAPK、JAK/STAT以及PD-1/PD-L1信号通路调控恶性肿瘤发生与发展的分子机制。总结了LCP2作为肿瘤治疗靶点的潜在作用,为将来用于相关疾病的诊断、治疗和标志物筛选等提供理论基础和参考依据。展开更多
Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression....Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.展开更多
The vehicle industry is always in search of breakthrough energy-saving and emission-reduction technologies.In recent years,vehicle intelligence has progressed considerably,and researchers are currently trying to take ...The vehicle industry is always in search of breakthrough energy-saving and emission-reduction technologies.In recent years,vehicle intelligence has progressed considerably,and researchers are currently trying to take advantage of these developments.Here we consider the case of many vehicles forming a queue,i.e.,vehicles traveling at a predetermined speed and distance apart.While the majority of existing studies on this subject have focused on the influence of the longitudinal vehicle spacing,vehicle speed,and the number of vehicles on aerodynamic drag and fuel economy,this study considers the lateral offset distance of the vehicle queue.The group fuel consumption savings rate is calculated and analyzed.As also demonstrated by experimental results,some aerodynamic benefits exist.Moreover,the fuel consumption saving rate of the vehicle queue decreases as the lateral offset distance increases.展开更多
基金Supported by the Hospital Research Fund,No.SDFEYBS1805,No.SDFEYGJ2013 and No.XKTJ-HRC20210015Suzhou Science and Technology Development Project,No.SYS2020105,No.SKJY2021078 and No.2022SS43+2 种基金the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLZD2021002CNNC Elite Talent Program2022 State Key Laboratory of Radiological Medicine and Radiation Protection jointly built by Province and Ministry,No.GZK1202244.
文摘BACKGROUND Current evidence shows that human induced pluripotent stem cells(hiPSCs)can effectively differentiate into keratinocytes(KCs),but its effect on skin burn healing has not been reported.AIM To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODS An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926,and GSE27186 was established.A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs.The expression of KCs marker proteins was detected using immunofluorescence staining.A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created,and then phosphate buffered saline(PBS),hiPSCs-KCs,or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface.The wound healing,re-epithelialization,engraftment of hiPSCs-KCs into wounds,proinflammatory factor level,and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining,carboxifluorescein diacetate succinimidyl ester(CFSE)fluorescence staining,enzyme linked immunosorbent assay,and Western blotting on days 3,7,and 14 after the injection,respectively.Moreover,the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry,EdU,Transwell,and damage repair assays.RESULTS HiPSCs-KCs could express the hallmark proteins of KCs.COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs.Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area,an increase in wound re-epithelialization,a decrease in proinflammatory factors content,and an inhibition of NF-κB pathway activation compared to the PBS group.The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration,providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSION In deep,second-degree burn wounds,COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.
文摘淋巴细胞胞质蛋白2(lymphocyte cytosolic protein 2,LCP2)是一种衔接蛋白质,在T细胞受体信号通路中扮演重要角色,激活下游信号因子以完成机体的免疫应答过程。LCP2也在恶性肿瘤的发生发展与转移中发挥重要作用,其高表达会导致不良的预后效果,降低患者生存率,其具体作用机制涉及多条信号通路。本文不仅对LCP2的分子结构以及基本功能进行了介绍,而且重点综合评述了LCP2通过参与NF-κB、MAPK、JAK/STAT以及PD-1/PD-L1信号通路调控恶性肿瘤发生与发展的分子机制。总结了LCP2作为肿瘤治疗靶点的潜在作用,为将来用于相关疾病的诊断、治疗和标志物筛选等提供理论基础和参考依据。
文摘Objective:Lung squamous cell carcinoma(LUSC)is associated with a low survival rate.Evidence suggests that bone morphogenetic proteins(BMPs)and their receptors(BMPRs)play crucial roles in tumorigenesis and progression.However,a comprehensive analysis of their role in LUSC is lacking.Our study aimed to explore the relationship between BMPs/BMPRs expression levels and the tumorigenesis and prognosis of LUSC.Methods:The“R/Limma”package was utilized to analyze the differential expression characteristics of BMPs/BMPRs in LUSC,using data from TCGA,GTEx,and GEO databases.Concurrently,the“survminer”packages were employed to investigate their prognostic value and correlation with clinical features in LUSC.The core gene associated with LUSC progression was further explored through weighted gene correlation network analysis(WGCNA).LASSO analysis was conducted to construct a prognostic risk model for LUSC.Clinical specimens were examined by immunohistochemical analysis to confirm the diagnostic value in LUSC.Furthermore,based on the tumor immune estimation resource database and tumor-immune system interaction database,the role of the core gene in the tumor microenvironment of LUSC was explored.Results:GDF10 had a significant correlation only with the pathological T stage of LUSC,and the protein expression level of GDF10 decreased with the tumorigenesis of LUSC.A prognostic risk model was constructed with GDF10 as the core gene and 5 hub genes(HRASLS,HIST1H2BH,FLRT3,CHEK2,and ALPL)for LUSC.GDF10 showed a significant positive correlation with immune cell infiltration and immune checkpoint expression.Conclusion:GDF10 might serve as a diagnostic biomarker reflecting the tumorigenesis of LUSC and regulating the tumor immune microenvironment to guide more effective treatment for LUSC.
基金This study was financially supported by the National Natural Science Foundation of China(52072156)the Postdoctoral Foundation of China(2020M682269).
文摘The vehicle industry is always in search of breakthrough energy-saving and emission-reduction technologies.In recent years,vehicle intelligence has progressed considerably,and researchers are currently trying to take advantage of these developments.Here we consider the case of many vehicles forming a queue,i.e.,vehicles traveling at a predetermined speed and distance apart.While the majority of existing studies on this subject have focused on the influence of the longitudinal vehicle spacing,vehicle speed,and the number of vehicles on aerodynamic drag and fuel economy,this study considers the lateral offset distance of the vehicle queue.The group fuel consumption savings rate is calculated and analyzed.As also demonstrated by experimental results,some aerodynamic benefits exist.Moreover,the fuel consumption saving rate of the vehicle queue decreases as the lateral offset distance increases.
