出行即服务(Mobilityasa Service MaaS)是近几年在全球交通运输领域逐渐流行起来的新概念.它通过单一平台、一站式的服务为用户提供量身定制的出行套餐,实现交通资源的有效整合.本文对现有的MaaS服务案例进行了总结,分析了MaaS的应用特...出行即服务(Mobilityasa Service MaaS)是近几年在全球交通运输领域逐渐流行起来的新概念.它通过单一平台、一站式的服务为用户提供量身定制的出行套餐,实现交通资源的有效整合.本文对现有的MaaS服务案例进行了总结,分析了MaaS的应用特征,并对MaaS在我国的应用前景进行了分析.结论是:理论上,MaaS服务的产生对政府、消费者和出行服务商三者都有积极的意义,但实现可持续发展的愿景需要制定合理的规划管理方案和三者之间的配合.展开更多
Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be hig...Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.展开更多
The black chokeberry is rich in polyphenols,including flavonoids with anthocyanins,flavanols and lavonols as the main components and a variety of phenolic acids represented by chlorogenic acid.Because of these polyphe...The black chokeberry is rich in polyphenols,including flavonoids with anthocyanins,flavanols and lavonols as the main components and a variety of phenolic acids represented by chlorogenic acid.Because of these polyphenols,black chokeberry has the effect of preventing and adjuvant therapy diseases.This study summarized the current research results on the types and contents of functional components in black chokeberry,and analyzed their digestion,absorption and metabolism in human body.On this basis,the disease control functions that have been proved effective in clinical research were reviewed and analyzed.These studies showed that black chokeberry have good prevention and adjuvant therapy effects on hyperlipidemia,hypertension,diabetes and inflammation.Because there are different functional components in black chokeberry,its prevention and treatment of the same disease can come from multiple pathways,which provides a more reliable effectiveness for the disease control of different populations.展开更多
Cu_(2-x)S nanostructures have been intensively studied as outstanding chemodynamic therapy(CDT)and good photothermal therapy(PTT)antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalyti...Cu_(2-x)S nanostructures have been intensively studied as outstanding chemodynamic therapy(CDT)and good photothermal therapy(PTT)antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalytic activity and good photothermal conversion property.However,they still suffer from shortage of Cu(Ⅰ)supply in the long-term and comparatively low inherent photothermal conversion efficiency.Herein,we constructed a self-enhanced synergistic PTT/CDT nanoplatform(Cu_(1.94)S@MPN)by coating Cu_(1.94)S nanoparticles with Fe(Ⅲ)/tannic acid based metal-polyphenol networks(MPN).Activated by the acidic bacterial infection microenvironment,Cu_(1.94)S@MPN could be decomposed to continuously release Cu(Ⅱ),Fe(Ⅲ)ions and tannic acid.As the result of tannic acid-involved Cu and Fe redox cycling,Cu(Ⅰ)/Fe(Ⅱ)-rich CDT could be achieved through the highly accelerated catalytic Fenton/Fenton-like reactions.More importantly,experimental results demonstrated that Cu_(1.94)S@MPN exhibited both excellent photothermal antibacterial and photothermal-enhanced CDT properties to eradicate bacteria in vitro and in vivo.Overall,this novel nanotherapeutics has great potential to become a clinic candidate for anti-infective therapy in future.展开更多
Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role i...Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.展开更多
文摘出行即服务(Mobilityasa Service MaaS)是近几年在全球交通运输领域逐渐流行起来的新概念.它通过单一平台、一站式的服务为用户提供量身定制的出行套餐,实现交通资源的有效整合.本文对现有的MaaS服务案例进行了总结,分析了MaaS的应用特征,并对MaaS在我国的应用前景进行了分析.结论是:理论上,MaaS服务的产生对政府、消费者和出行服务商三者都有积极的意义,但实现可持续发展的愿景需要制定合理的规划管理方案和三者之间的配合.
基金supported by grants from the National Key R&D Program of China(2021YFA0805700 and 2021YFA1102000)the National Natural Science Foundation of China(U2102204)the Natural Science Foundation of Yunnan Province(202001BC070001 and 202102AA100053).
文摘Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.
基金supported by National Science Foundation of China (31972090)。
文摘The black chokeberry is rich in polyphenols,including flavonoids with anthocyanins,flavanols and lavonols as the main components and a variety of phenolic acids represented by chlorogenic acid.Because of these polyphenols,black chokeberry has the effect of preventing and adjuvant therapy diseases.This study summarized the current research results on the types and contents of functional components in black chokeberry,and analyzed their digestion,absorption and metabolism in human body.On this basis,the disease control functions that have been proved effective in clinical research were reviewed and analyzed.These studies showed that black chokeberry have good prevention and adjuvant therapy effects on hyperlipidemia,hypertension,diabetes and inflammation.Because there are different functional components in black chokeberry,its prevention and treatment of the same disease can come from multiple pathways,which provides a more reliable effectiveness for the disease control of different populations.
基金financially supported by the National Natural Science Foundation of China (Nos. 81803723, 51903062)Guangdong Basic and Applied Basic Research Foundation (No. 2019B1515120006)+2 种基金Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2019), Innovation and Entrepreneurship Team Leads the Pilot Program of Zhanjiang (No. 2020LHJH005)Discipline Construction Project of Guangdong Medical University (No. 4SG22002G)Science and Technology Projects of Guangzhou (No. 202102020757)。
文摘Cu_(2-x)S nanostructures have been intensively studied as outstanding chemodynamic therapy(CDT)and good photothermal therapy(PTT)antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalytic activity and good photothermal conversion property.However,they still suffer from shortage of Cu(Ⅰ)supply in the long-term and comparatively low inherent photothermal conversion efficiency.Herein,we constructed a self-enhanced synergistic PTT/CDT nanoplatform(Cu_(1.94)S@MPN)by coating Cu_(1.94)S nanoparticles with Fe(Ⅲ)/tannic acid based metal-polyphenol networks(MPN).Activated by the acidic bacterial infection microenvironment,Cu_(1.94)S@MPN could be decomposed to continuously release Cu(Ⅱ),Fe(Ⅲ)ions and tannic acid.As the result of tannic acid-involved Cu and Fe redox cycling,Cu(Ⅰ)/Fe(Ⅱ)-rich CDT could be achieved through the highly accelerated catalytic Fenton/Fenton-like reactions.More importantly,experimental results demonstrated that Cu_(1.94)S@MPN exhibited both excellent photothermal antibacterial and photothermal-enhanced CDT properties to eradicate bacteria in vitro and in vivo.Overall,this novel nanotherapeutics has great potential to become a clinic candidate for anti-infective therapy in future.
基金supported by National Natural Science Foundation of China(Grant Nos.:81891010/81891011,81725023,82003614,82173950,31770192,32070187,32161133003 and 82003681)China Postdoctoral Science Foundation(Grant No:2022T150029).
文摘Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
