Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous ...Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.展开更多
The selection of power transformer is very important to power sector. Most methods are utilized according to the initial cost and don’t consider the synthetical evaluation of economy and technology. Based on previous...The selection of power transformer is very important to power sector. Most methods are utilized according to the initial cost and don’t consider the synthetical evaluation of economy and technology. Based on previous research, this paper addresses a new practical probabilistic life cycle cost model. Then, in order to demonstrate the practicability of probabilistic life cycle cost for the power transformer, illustrative investment alternatives of actual power transformers are discussed. From the result of the numerical investigation, it may be positively stated that the optimum investment alternative for the power transformer based on the probabilistic life cycle cost model proposed in this study will lead to a more rational, economical and effective procedure compared with the conventional method only considering the initial cost.展开更多
One important aspect of mesenchymal stromal cells (MSCs)-mediated immunomodulation is the recruitment and induction of regulatory T (Treg) cells. However, we do not yet know whether MSCs have similar effects on th...One important aspect of mesenchymal stromal cells (MSCs)-mediated immunomodulation is the recruitment and induction of regulatory T (Treg) cells. However, we do not yet know whether MSCs have similar effects on the other subsets of Treg cells. Herein, we studied the effects of MSCs on CD8+CD28- Treg cells and found that the MSCs could not only increase the proportion of CD8+CD28- T cells, but also enhance CD8+CD28-T cells' ability of hampering naive CD4+ T-cell proliferation and activation, decreasing the production of IFN-γ by activated CD4+ T cells and inducing the apoptosis of activated CD4+ T cells. Mechanistically, the MSCs affected the functions of the CD8+CD28- T cells partially through moderate upregulating the expression of IL-10 and FasL. The MSCs had no distinct effect on the shift from CD8+CD28+ T cells to CD8+CD28- T cells, but did increase the proportion of CD8+CD28- T cells by reducing their rate of apoptosis. In summary, this study shows that MSCs can enhance the regulatory function of CD8+CD28- Treg cells, shedding new light on MSCs-mediated immune regulation.展开更多
Serine/arginine-rich splicing factor 7(SRSF7),a known splicing factor,has been revealed to play oncogenic roles in multiple cancers.However,the mechanisms underlying its oncogenic roles have not been well addressed.He...Serine/arginine-rich splicing factor 7(SRSF7),a known splicing factor,has been revealed to play oncogenic roles in multiple cancers.However,the mechanisms underlying its oncogenic roles have not been well addressed.Here,based on N6-methyladenosine(m^(6)A)co-methylation network analysis across diverse cell lines,we find that the gene expression of SRSF7 is positively correlated with glioblastoma(GBM)cell-specific m^(6)A methylation.We then indicate that SRSF7 is a novel m^(6)A regulator,which specifically facilitates the m^(6)A methylation near its binding sites on the mRNAs involved in cell proliferation and migration,through recruiting the methyltransferase complex.Moreover,SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m^(6)A methyltransferase.The two m^(6)A sites on the mRNA for PDZ-binding kinase(PBK)are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2(IGF2BP2).Together,our discovery reveals a novel role of SRSF7 in regulating m^(6)A and validates the presence and functional importance of temporal-and spatial-specific regulation of m^(6)A mediated by RNA-binding proteins(RBPs).展开更多
Acute-on-chronic liver failure(ACLF)can be cured by liver transplantation;however,perioperative complications still affect posttransplant outcomes.In recent years,early rehabilitation for critical illness,liver diseas...Acute-on-chronic liver failure(ACLF)can be cured by liver transplantation;however,perioperative complications still affect posttransplant outcomes.In recent years,early rehabilitation for critical illness,liver disease,and surgery have significantly improved organ reserve function,surgery tolerance,and postoperative quality of life.They could also be applied in the perioperative period of liver transplantation in patients with ACLF.Therefore,the Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association,the Organ Transplant Committee of China Association Rehabilitation Medicine,and the Guangdong Medical Doctor Association of Organ Transplantation conducted a comprehensive review of rehabilitation in end-stage liver disease,critical illness and surgical patients by summarizing current evidence and best clinical practices and proposed a practice consensus on evaluation of cardiopulmonary and physical function,rehabilitation or physiotherapies,as well as the safety concerns in perioperative liver transplant recipients.It will be a valuable resource for hepatologists,transplant surgeons,and intensivists as they care for ACLF patients during transplantation.展开更多
IntroductIon Advances in acute stroke treatment and the widespread establishment of dedicated stroke units have resulted in an increase in post-stroke survival and life expectancy.However,stroke remains a leading caus...IntroductIon Advances in acute stroke treatment and the widespread establishment of dedicated stroke units have resulted in an increase in post-stroke survival and life expectancy.However,stroke remains a leading cause of long-term disability worldwide,making the improve-ment of poststroke outcomes a chief health-care goal for many countries.The current strategies strive to reduce the initial injury by acutely implementing thrombolytic and/or endovascular interventions,to better under-stand the major determinants that influence the stroke recovery and to search for inno-vative,effective and accessible recovery and rehabilitation modalities that can mitigate various poststroke deficits and enhance the quality of life.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81672261(to XH),81972151(to HZ),82372568(to JL)the Natural Science Foundation of Guangdong Province,Nos.2019A1515011106(to HZ),2023A1515030080(to JL)。
文摘Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.
文摘The selection of power transformer is very important to power sector. Most methods are utilized according to the initial cost and don’t consider the synthetical evaluation of economy and technology. Based on previous research, this paper addresses a new practical probabilistic life cycle cost model. Then, in order to demonstrate the practicability of probabilistic life cycle cost for the power transformer, illustrative investment alternatives of actual power transformers are discussed. From the result of the numerical investigation, it may be positively stated that the optimum investment alternative for the power transformer based on the probabilistic life cycle cost model proposed in this study will lead to a more rational, economical and effective procedure compared with the conventional method only considering the initial cost.
基金This study was supported by the National Basic Research Program of China (2012CBA01302, 2010CB945400), the National Natural Science Foundation of China (31171398, 81271265, 81425016), the Key Scientific and Technological Projects of Guangdong Province (2007A032100003), the Natural Science Foundation of Guangdong Province ( S2013030013305 ), the Key Scientific and Technological Program of Guangzhou City (201400000003-3, 201300000089, 2010U1-E00551 ) and Guangdong Department of Science & Technology Translational Medicine Center grant (2011A080300002).
文摘One important aspect of mesenchymal stromal cells (MSCs)-mediated immunomodulation is the recruitment and induction of regulatory T (Treg) cells. However, we do not yet know whether MSCs have similar effects on the other subsets of Treg cells. Herein, we studied the effects of MSCs on CD8+CD28- Treg cells and found that the MSCs could not only increase the proportion of CD8+CD28- T cells, but also enhance CD8+CD28-T cells' ability of hampering naive CD4+ T-cell proliferation and activation, decreasing the production of IFN-γ by activated CD4+ T cells and inducing the apoptosis of activated CD4+ T cells. Mechanistically, the MSCs affected the functions of the CD8+CD28- T cells partially through moderate upregulating the expression of IL-10 and FasL. The MSCs had no distinct effect on the shift from CD8+CD28+ T cells to CD8+CD28- T cells, but did increase the proportion of CD8+CD28- T cells by reducing their rate of apoptosis. In summary, this study shows that MSCs can enhance the regulatory function of CD8+CD28- Treg cells, shedding new light on MSCs-mediated immune regulation.
基金supported by the National Key R&D Program of China(Grant No.2018YFA0107200)to JWthe National Natural Science Foundation of China(Grant Nos.81830082,82030078,and 81621004 to JL+1 种基金Grant Nos.31771446 and 31970594 to JWGrant No.32100452 to XS).
文摘Serine/arginine-rich splicing factor 7(SRSF7),a known splicing factor,has been revealed to play oncogenic roles in multiple cancers.However,the mechanisms underlying its oncogenic roles have not been well addressed.Here,based on N6-methyladenosine(m^(6)A)co-methylation network analysis across diverse cell lines,we find that the gene expression of SRSF7 is positively correlated with glioblastoma(GBM)cell-specific m^(6)A methylation.We then indicate that SRSF7 is a novel m^(6)A regulator,which specifically facilitates the m^(6)A methylation near its binding sites on the mRNAs involved in cell proliferation and migration,through recruiting the methyltransferase complex.Moreover,SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m^(6)A methyltransferase.The two m^(6)A sites on the mRNA for PDZ-binding kinase(PBK)are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2(IGF2BP2).Together,our discovery reveals a novel role of SRSF7 in regulating m^(6)A and validates the presence and functional importance of temporal-and spatial-specific regulation of m^(6)A mediated by RNA-binding proteins(RBPs).
基金This work was supported by the Guangdong Provincial Natural Science Foundation(2019A1515011106,2021A1515012382,2022A1515011919)National Natural Science Foundation of China(81972286,81770648,81972151)+2 种基金Guangdong Provincial Transplantation Medicine Engineering Laboratory(A04097)Guangdong Provincial Key Research and Development Project(2019B020236003)The Third Affiliated Hospital of Sun Yat-sen University Five Five-Year Engineering Projects-National Bioengineering Research Institute Development Platform(WW201905(2021)).
文摘Acute-on-chronic liver failure(ACLF)can be cured by liver transplantation;however,perioperative complications still affect posttransplant outcomes.In recent years,early rehabilitation for critical illness,liver disease,and surgery have significantly improved organ reserve function,surgery tolerance,and postoperative quality of life.They could also be applied in the perioperative period of liver transplantation in patients with ACLF.Therefore,the Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association,the Organ Transplant Committee of China Association Rehabilitation Medicine,and the Guangdong Medical Doctor Association of Organ Transplantation conducted a comprehensive review of rehabilitation in end-stage liver disease,critical illness and surgical patients by summarizing current evidence and best clinical practices and proposed a practice consensus on evaluation of cardiopulmonary and physical function,rehabilitation or physiotherapies,as well as the safety concerns in perioperative liver transplant recipients.It will be a valuable resource for hepatologists,transplant surgeons,and intensivists as they care for ACLF patients during transplantation.
基金We thank Dr Pratik Chhatbar for his assistance on generating the figure 1,and Drs James Sawers and Alexandra Parashos for their generous comments and edits on the manuscript.Dr WF acknowledges his grant supports from National Institute of Health(P20GM109040)American Heart Association(14SDG1829003).
文摘IntroductIon Advances in acute stroke treatment and the widespread establishment of dedicated stroke units have resulted in an increase in post-stroke survival and life expectancy.However,stroke remains a leading cause of long-term disability worldwide,making the improve-ment of poststroke outcomes a chief health-care goal for many countries.The current strategies strive to reduce the initial injury by acutely implementing thrombolytic and/or endovascular interventions,to better under-stand the major determinants that influence the stroke recovery and to search for inno-vative,effective and accessible recovery and rehabilitation modalities that can mitigate various poststroke deficits and enhance the quality of life.