Advanced brain organoids provide promising platforms for deciphering the cellular and molecular processes of human neural development and diseases.Although various studies and reviews have described developments and a...Advanced brain organoids provide promising platforms for deciphering the cellular and molecular processes of human neural development and diseases.Although various studies and reviews have described developments and advancements in brain organoids,few studies have comprehensively summarized and analyzed the global trends in this area of neuroscience.To identify and further facilitate the development of cerebral organoids,we utilized bibliometrics and visualization methods to analyze the global trends and evolution of brain organoids in the last 10 years.First,annual publications,countries/regions,organizations,journals,authors,co-citations,and keywords relating to brain organoids were identified.The hotspots in this field were also systematically identified.Subsequently,current applications for brain organoids in neuroscience,including human neural development,neural disorders,infectious diseases,regenerative medicine,drug discovery,and toxicity assessment studies,are comprehensively discussed.Towards that end,several considerations regarding the current challenges in brain organoid research and future strategies to advance neuroscience will be presented to further promote their application in neurological research.展开更多
Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis(NASH)have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated.Inactive rhomboid p...Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis(NASH)have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated.Inactive rhomboid protein 2(IRHOM2),a promising target for treatment of inflammation-related diseases,contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis(NASH)progression.However,the molecular mechanism underlying Irhom2 regulation is still not completely understood.In this work,we identify the ubiquitin-specific protease 13(USP13)as a critical and novel endogenous blocker of IRHOM2,and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes.Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis,followed by glycometabolic disorder,lipid deposition,increased inflammation,and markedly promotes NASH development.Conversely,transgenic mice with Usp13 overexpression,lentivirus(LV)-or adeno-associated virus(AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent.Mechanistically,in response to metabolic stresses,USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N(UBC13),a ubiquitin E2 conjugating enzyme,and thus prevents its activation of downstream cascade pathway.USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.展开更多
Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding,separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration,however,this treatment guided...Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding,separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration,however,this treatment guided with endoscopic catheter in most cases.Here,we developed an oral keratin hydrogel to accelerate the ulcer healing without endoscopic guidance,which can specially adhere to the ulcer because of the high-viscosity gel formation on the wound surface in vivo.Approximately 50%of the ulcer-adhesive keratin hydrogel can resident in ethanol-treated rat stomach within 12 h,while approximately 18%of them maintained in health rat stomach in the same amount of time.Furthermore,Keratin hydrogels accelerated the ethanol-induced gastric ulcer healing by stopping the bleeding,preventing the epithelium cells from gastric acid damage,suppressing inflammation and promoting re-epithelization.The oral administration of keratin hydrogel in gastric ulcer treatment can enhance the patient compliance and reduce the gastroscopy complications.Our research findings reveal a promising biomaterial-based approach for treating gastrointestinal ulcers.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82204083(to ML)and 12372303(to BW)the Natural Science Foundation of Chongqing,No.cstc2021jcy-jmsxmX0171(to ML).
文摘Advanced brain organoids provide promising platforms for deciphering the cellular and molecular processes of human neural development and diseases.Although various studies and reviews have described developments and advancements in brain organoids,few studies have comprehensively summarized and analyzed the global trends in this area of neuroscience.To identify and further facilitate the development of cerebral organoids,we utilized bibliometrics and visualization methods to analyze the global trends and evolution of brain organoids in the last 10 years.First,annual publications,countries/regions,organizations,journals,authors,co-citations,and keywords relating to brain organoids were identified.The hotspots in this field were also systematically identified.Subsequently,current applications for brain organoids in neuroscience,including human neural development,neural disorders,infectious diseases,regenerative medicine,drug discovery,and toxicity assessment studies,are comprehensively discussed.Towards that end,several considerations regarding the current challenges in brain organoid research and future strategies to advance neuroscience will be presented to further promote their application in neurological research.
基金supported by National Natural Science Foundation of China(NSFC Grant Nos.81703527 and 82200652)Chongqing Research Program of Basic Research and Frontier Technology(Grant Nos.cstc2017jcyjAX0356,cstc2018jcyjA3686,cstc2018jcyjAX0784,cstc2018jcyjA1472,cstc2018jcyjAX0811,cstc2018jcyjA3533,and KJZD-M201801601,China)+4 种基金School-level Research Program of Chongqing University of Education(Grant Nos.KY201710B and 17GZKP01,China)Advanced Programs of Post-doctor of Chongqing(Grant No.2017LY39,China)Science and Technology Research Program of Chongqing Education Commission of China(Grant Nos.KJQN201901608,KJQN201901615,KJ1601402,and KJZDK202001603)Children's Research Institute of National Center for Schooling Development Programme and Chongqing University of Education(Grant No.CSDP19FSO1108,China)Chongqing Professional Talents Plan for Innovation and Entrepreneurship Demonstration Team(CQCY201903258,China).
文摘Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis(NASH)have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated.Inactive rhomboid protein 2(IRHOM2),a promising target for treatment of inflammation-related diseases,contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis(NASH)progression.However,the molecular mechanism underlying Irhom2 regulation is still not completely understood.In this work,we identify the ubiquitin-specific protease 13(USP13)as a critical and novel endogenous blocker of IRHOM2,and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes.Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis,followed by glycometabolic disorder,lipid deposition,increased inflammation,and markedly promotes NASH development.Conversely,transgenic mice with Usp13 overexpression,lentivirus(LV)-or adeno-associated virus(AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent.Mechanistically,in response to metabolic stresses,USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N(UBC13),a ubiquitin E2 conjugating enzyme,and thus prevents its activation of downstream cascade pathway.USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.
基金The authors acknowledge the financial assistance provided by the National Natural Science Foundation of China(11972099 and 31600770)the Venture&Innovation Support Program for Chongqing Overseas Returnees(cx2020079)+2 种基金the Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology(Chongqing University),Ministry of Education(CQKLBST-2017-008)the research and development talent base subject of advantageous traditional Chinese medicine in Bijie City,Guizhou Province(RCJD2020-21)the projects in the National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(2015BAI05B03).
文摘Hydrogel has been used for in suit gastric ulcer therapy by stopping bleeding,separating from ulcer from gastric fluids and providing extracellular matrix scaffold for tissue regeneration,however,this treatment guided with endoscopic catheter in most cases.Here,we developed an oral keratin hydrogel to accelerate the ulcer healing without endoscopic guidance,which can specially adhere to the ulcer because of the high-viscosity gel formation on the wound surface in vivo.Approximately 50%of the ulcer-adhesive keratin hydrogel can resident in ethanol-treated rat stomach within 12 h,while approximately 18%of them maintained in health rat stomach in the same amount of time.Furthermore,Keratin hydrogels accelerated the ethanol-induced gastric ulcer healing by stopping the bleeding,preventing the epithelium cells from gastric acid damage,suppressing inflammation and promoting re-epithelization.The oral administration of keratin hydrogel in gastric ulcer treatment can enhance the patient compliance and reduce the gastroscopy complications.Our research findings reveal a promising biomaterial-based approach for treating gastrointestinal ulcers.
