The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKS...The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.展开更多
Dear Editor,Severe fever with thrombocytopenia syndrome(SFTS)is an emerging tick-borne infectious disease caused by a novel bunyavirus called SFTS virus(SFTSV).It was initially identified in China in 2009(Yu et al.,20...Dear Editor,Severe fever with thrombocytopenia syndrome(SFTS)is an emerging tick-borne infectious disease caused by a novel bunyavirus called SFTS virus(SFTSV).It was initially identified in China in 2009(Yu et al.,2011).Since then,the number of reported SFTS cases has rapidly increased in China,South Korea,and Japan(Li,et al.,2018;Takahashi et al.,2014;Kim et al.,2018).Sporadic SFTS cases have also been identified in several other Asian countries,such as Vietnam,Pakistan,Myanmar,and Thailand(Takahashi et al.,2014;Tran et al.,2019;Li et al.,2021).This disease is recognized as a highly lethal viral hemorrhagic fever with a mortality rate ranging from 12%to 50%(Yu et al.,2011;Li et al.,2018;Takahashi et al.,2014;Kim et al.,2013).SFTS primarily spreads to humans through bites from ticks infected with SFTSV,with the Haemaphysalis longicornis tick acting as the predominant vector for SFTSV(Zhuang et al.,2018).展开更多
发热伴血小板减少综合征(severe fever with thrombocytopenia syndrome,SFTS)是一种新发传染病,主要通过蜱虫叮咬传播,其病原体为发热伴血小板减少综合征病毒(severe fever with thrombocytopenia syndrome virus,SFTSV)。人际传播引发...发热伴血小板减少综合征(severe fever with thrombocytopenia syndrome,SFTS)是一种新发传染病,主要通过蜱虫叮咬传播,其病原体为发热伴血小板减少综合征病毒(severe fever with thrombocytopenia syndrome virus,SFTSV)。人际传播引发的SFTS聚集性疫情在国内外均有报道,人们重点关注了人际传播的感染途径,然而SFTS聚集性疫情和病毒基因型之间的相关性研究却未见报道。本文主要报道了2022~2023年河南省信阳市发生的两起SFTS聚集性疫情,探讨了SFTSV出现人际传播感染的可能途径,并对SFTS聚集性疫情与病毒基因型进行了关联分析。通过4例确诊患者的病毒序列分析,发现两起聚集性疫情中的2组SFTSV分别聚集在隶属于不同基因型的两个分支。将本研究病毒序列与GenBank中获得的SFTS聚集性疫情报道过的病毒序列进行系统发育分析,进一步发现人际传播病例报道的SFTSV涉及3种基因型,提示SFTS聚集性疫情的发生可能和病毒基因型无明显关联。本研究表明血液接触感染可能是SFTS聚集性疫情发生的主要传播途径,为揭示SFTS聚集性疫情的人际传播链提供了遗传学证据,为SFTS的人际传播防控提供了科学数据支撑。展开更多
AIM:To confirm whether exosome-mediated delivery of aptamer S58(Exo-S58) has a better antifibrotic effect than naked S58 in human conjunctival fibroblasts(HCon Fs) and a rat glaucoma filtration surgery(GFS) model.METH...AIM:To confirm whether exosome-mediated delivery of aptamer S58(Exo-S58) has a better antifibrotic effect than naked S58 in human conjunctival fibroblasts(HCon Fs) and a rat glaucoma filtration surgery(GFS) model.METHODS:To enhance the effective reaction time of aptamer S58 in vivo, we loaded aptamer S58 into exosomes derived from HEK293 T cells by PEI transfection to determine the effect of Exo-S58 in HCon Fs and a rat GFS model.RESULTS:Exo-S58 can significantly reduce cell proliferation, migration and fibrosis in TGF-β2-induced HCon Fs. In an in vivo experiment, Exo-S58 treatment prolonged filtering bleb retention and reduced fibrosis compared with naked S58 treatment in GFS rats.CONCLUSION:The exosomes are safe and valid carriers to deliver aptamers. Furthermore, Exo-S58 exhibited superior antifibrotic effect than naked S58 both in HCon Fs cells and rat GFS models.展开更多
This study investigated the molecular markers of DS-1-47,a component of an implantation-promoting traditional Chinese medicine consisting of Astragalus mongholicus,Atractylodes macrocephala,Scutellaria baicalensis and...This study investigated the molecular markers of DS-1-47,a component of an implantation-promoting traditional Chinese medicine consisting of Astragalus mongholicus,Atractylodes macrocephala,Scutellaria baicalensis and Dipsacales,in an attempt to clarify the molecular mechanism and action targets of DS-1-47.Controlled ovarian stimulation（COS） method was used to establish the implantation dysfunction models of mice.Animals were divided into normal pregnant group,COS model group and DS-1-47 group.Laser capture microdissection-double dimensional electrophoresis-mass spectrum（LCM-DE-MS） was used to analyze the uterine protein molecules that were possibly involved in the promotion of implantation.Twenty-three proteins in DS-1-47 group were significantly changed as compared to those in COS model group,with 7 proteins down-regulated and 16 proteins up-regulated.Except for some constituent proteins,the down-regulated proteins included collagen α-1（Ⅵ） chain,keratin 7,keratin 14,myosin regulatory light chain 12 B,myosin light polypeptide 9,heat shock protein β-7,and C-U-editing enzyme APOBEC-2;the up-regulated proteins included apolipoprotein A-I,calcium regulated protein-3,proliferating cell nuclear antigen,L-xylulose reductase,and calcium binding protein.These 23 proteins that were regulated by DS-1-47 represented a broad diversity of molecule functions.The down-regulated proteins were associated with stress and immune response,and those up-regulated proteins were related to proliferation.It was suggested that these proteins were important in regulating the uterine environment for the blastocyst implantation.By identification of DS-1-47 markers,proteomic analysis coupled with functional assays is demonstrated to be a promising approach to better understand the molecular mechanism of traditional Chinese medicine.展开更多
Mixed hemorrhoids,especially ring-shaped mixed hemorrhoid,is still a headache for anorectal surgeons due to its post-operative complications.In recent years,clinicians have been studying and exploring to avoid and all...Mixed hemorrhoids,especially ring-shaped mixed hemorrhoid,is still a headache for anorectal surgeons due to its post-operative complications.In recent years,clinicians have been studying and exploring to avoid and alleviate these complications.In the Chinese medicine industry,the application of traditional Chinese medicine nursing technology has good and unique effect in prevent local pain,perianal edema,promote wound healing,relieve urinary retention,improve constipation,relieve anxiety,and so on.This article summarized the evidences of investigated the role of traditional Chinese medicine nursing technique in preventing and treating mixed hemorrhoid so that practitioners can make decision based on the best available evidences.展开更多
Objective:To explore the clinical application effect of self-designed automatic constant temperature moxibustion box.Methods:From June 2016 to January 2017,150 patients with neck,shoulder,back and leg pain admitted to...Objective:To explore the clinical application effect of self-designed automatic constant temperature moxibustion box.Methods:From June 2016 to January 2017,150 patients with neck,shoulder,back and leg pain admitted to our hospital were treated with moxibustion under the informed consent of the patients.The patients were randomly divided into control group and observation group,75 cases each.The group used traditional moxibustion box for moxibustion treatment,and the observation group used automatic constant temperature moxibustion box for moxibustion treatment for 15 days.After the treatment,the patient's safety,comfort,satisfaction and adverse reactions were compared,and the results were analyzed using SPSS 20 statistical software.Results:The comfort and satisfaction in study group were all superior to that of control group,with statistically significant difference(P<0.01).For patient's safety,the ratio of patients suffered from scald in study and control groups was 5.3/100 and 0,respectively.Conclusions:It is of great significance for improving clinical efficacy and preventing medical risks.It is worthy of clinical application.展开更多
基金supported by the National Nature Science Foundation of China,No.32101020(to JL)the Natural Science Foundation of Shandong Province,Nos.ZR2020MC071(to JL),ZR2023MH327(to HZ)+1 种基金the Integrated Project of Major Research Plan of National Natural Science Foundation of China,No.92249303(to PL)the Natural Science Foundation of Qingdao,No.23-2-1-193-zyyd-jch(to HZ)。
文摘The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.
基金funded by the National Nature Science Foundation of China(81,825,019 and 82,330,103)performed with approval from the Ethical Committee of Beijing Institute of Microbiology and Epidemiology(AF/SC-08/02.128).
文摘Dear Editor,Severe fever with thrombocytopenia syndrome(SFTS)is an emerging tick-borne infectious disease caused by a novel bunyavirus called SFTS virus(SFTSV).It was initially identified in China in 2009(Yu et al.,2011).Since then,the number of reported SFTS cases has rapidly increased in China,South Korea,and Japan(Li,et al.,2018;Takahashi et al.,2014;Kim et al.,2018).Sporadic SFTS cases have also been identified in several other Asian countries,such as Vietnam,Pakistan,Myanmar,and Thailand(Takahashi et al.,2014;Tran et al.,2019;Li et al.,2021).This disease is recognized as a highly lethal viral hemorrhagic fever with a mortality rate ranging from 12%to 50%(Yu et al.,2011;Li et al.,2018;Takahashi et al.,2014;Kim et al.,2013).SFTS primarily spreads to humans through bites from ticks infected with SFTSV,with the Haemaphysalis longicornis tick acting as the predominant vector for SFTSV(Zhuang et al.,2018).
文摘发热伴血小板减少综合征(severe fever with thrombocytopenia syndrome,SFTS)是一种新发传染病,主要通过蜱虫叮咬传播,其病原体为发热伴血小板减少综合征病毒(severe fever with thrombocytopenia syndrome virus,SFTSV)。人际传播引发的SFTS聚集性疫情在国内外均有报道,人们重点关注了人际传播的感染途径,然而SFTS聚集性疫情和病毒基因型之间的相关性研究却未见报道。本文主要报道了2022~2023年河南省信阳市发生的两起SFTS聚集性疫情,探讨了SFTSV出现人际传播感染的可能途径,并对SFTS聚集性疫情与病毒基因型进行了关联分析。通过4例确诊患者的病毒序列分析,发现两起聚集性疫情中的2组SFTSV分别聚集在隶属于不同基因型的两个分支。将本研究病毒序列与GenBank中获得的SFTS聚集性疫情报道过的病毒序列进行系统发育分析,进一步发现人际传播病例报道的SFTSV涉及3种基因型,提示SFTS聚集性疫情的发生可能和病毒基因型无明显关联。本研究表明血液接触感染可能是SFTS聚集性疫情发生的主要传播途径,为揭示SFTS聚集性疫情的人际传播链提供了遗传学证据,为SFTS的人际传播防控提供了科学数据支撑。
基金National Natural Science Foundation of China (No.81700836,No.81470629,No.81670860)Chongqing Natural Research Foundation (No.cstc 2018jcyj AX0034)。
文摘AIM:To confirm whether exosome-mediated delivery of aptamer S58(Exo-S58) has a better antifibrotic effect than naked S58 in human conjunctival fibroblasts(HCon Fs) and a rat glaucoma filtration surgery(GFS) model.METHODS:To enhance the effective reaction time of aptamer S58 in vivo, we loaded aptamer S58 into exosomes derived from HEK293 T cells by PEI transfection to determine the effect of Exo-S58 in HCon Fs and a rat GFS model.RESULTS:Exo-S58 can significantly reduce cell proliferation, migration and fibrosis in TGF-β2-induced HCon Fs. In an in vivo experiment, Exo-S58 treatment prolonged filtering bleb retention and reduced fibrosis compared with naked S58 treatment in GFS rats.CONCLUSION:The exosomes are safe and valid carriers to deliver aptamers. Furthermore, Exo-S58 exhibited superior antifibrotic effect than naked S58 both in HCon Fs cells and rat GFS models.
基金supported by a grant from the National Natural Science Foundation of China(No 81373873)
文摘This study investigated the molecular markers of DS-1-47,a component of an implantation-promoting traditional Chinese medicine consisting of Astragalus mongholicus,Atractylodes macrocephala,Scutellaria baicalensis and Dipsacales,in an attempt to clarify the molecular mechanism and action targets of DS-1-47.Controlled ovarian stimulation（COS） method was used to establish the implantation dysfunction models of mice.Animals were divided into normal pregnant group,COS model group and DS-1-47 group.Laser capture microdissection-double dimensional electrophoresis-mass spectrum（LCM-DE-MS） was used to analyze the uterine protein molecules that were possibly involved in the promotion of implantation.Twenty-three proteins in DS-1-47 group were significantly changed as compared to those in COS model group,with 7 proteins down-regulated and 16 proteins up-regulated.Except for some constituent proteins,the down-regulated proteins included collagen α-1（Ⅵ） chain,keratin 7,keratin 14,myosin regulatory light chain 12 B,myosin light polypeptide 9,heat shock protein β-7,and C-U-editing enzyme APOBEC-2;the up-regulated proteins included apolipoprotein A-I,calcium regulated protein-3,proliferating cell nuclear antigen,L-xylulose reductase,and calcium binding protein.These 23 proteins that were regulated by DS-1-47 represented a broad diversity of molecule functions.The down-regulated proteins were associated with stress and immune response,and those up-regulated proteins were related to proliferation.It was suggested that these proteins were important in regulating the uterine environment for the blastocyst implantation.By identification of DS-1-47 markers,proteomic analysis coupled with functional assays is demonstrated to be a promising approach to better understand the molecular mechanism of traditional Chinese medicine.
文摘Mixed hemorrhoids,especially ring-shaped mixed hemorrhoid,is still a headache for anorectal surgeons due to its post-operative complications.In recent years,clinicians have been studying and exploring to avoid and alleviate these complications.In the Chinese medicine industry,the application of traditional Chinese medicine nursing technology has good and unique effect in prevent local pain,perianal edema,promote wound healing,relieve urinary retention,improve constipation,relieve anxiety,and so on.This article summarized the evidences of investigated the role of traditional Chinese medicine nursing technique in preventing and treating mixed hemorrhoid so that practitioners can make decision based on the best available evidences.
文摘Objective:To explore the clinical application effect of self-designed automatic constant temperature moxibustion box.Methods:From June 2016 to January 2017,150 patients with neck,shoulder,back and leg pain admitted to our hospital were treated with moxibustion under the informed consent of the patients.The patients were randomly divided into control group and observation group,75 cases each.The group used traditional moxibustion box for moxibustion treatment,and the observation group used automatic constant temperature moxibustion box for moxibustion treatment for 15 days.After the treatment,the patient's safety,comfort,satisfaction and adverse reactions were compared,and the results were analyzed using SPSS 20 statistical software.Results:The comfort and satisfaction in study group were all superior to that of control group,with statistically significant difference(P<0.01).For patient's safety,the ratio of patients suffered from scald in study and control groups was 5.3/100 and 0,respectively.Conclusions:It is of great significance for improving clinical efficacy and preventing medical risks.It is worthy of clinical application.
