Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely unknown.Reproducible animal models mirroring...Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely unknown.Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited.Here,we describe a new mouse model of congenital hydrocephalus through knockout ofβ-catenin in Nkx2.1-expressing regional neural progenitors.Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood.Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis afterβ-catenin knockout.Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages.Thus,knockout ofβ-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.展开更多
Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically us...Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents.Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT.Herein,we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton.The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820.Furthermore,ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica(RMON)to construct nanomedicine NBD&ML@RMON,which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.展开更多
Patients with COVID-19 have revealed a massive outbreak around the world,leading to widespread concerns in global scope.Figuring out the transmission route of COVID-19 is necessary to control further spread.We analyze...Patients with COVID-19 have revealed a massive outbreak around the world,leading to widespread concerns in global scope.Figuring out the transmission route of COVID-19 is necessary to control further spread.We analyzed the data of 43 patients in Baodi Department Store(China)to supplement the transmission route and epidemiological characteristics of COVID-19 in a cluster outbreak.Incubation median was estimated to endure 5.95 days(2-13 days).Almost 76.3%of patients sought medical attention immediately upon illness onset.The median period of illness onset to hospitalization and confirmation were 3.96 days(0-14)and 5.58 days(1-21),respectively.Patients with different cluster case could demonstrate unique epidemiological characteristics due to the particularity of outbreak sites.SRAS-CoV-2 can be released into the surrounding air through patient's respiratory tract activities,and can exist for a long time for long-distance transportation.SRAS-CoV-2 RNA can be detected in aerosol in different sites,including isolation ward,general ward,outdoor,toilet,hallway,and crowded public area.Environmental factors influencing were analyzed and indicated that the SARS-CoV-2 transportation in aerosol was dependent on temperature,air humidity,ventilation rate and inactivating chemicals(ozone)content.As for the infection route of case numbers 2 to 6,10,13,16,17,18,20 and 23,we believe that aerosol transmission played a significant role in analyzing their exposure history and environmental conditions in Baodi Department Store.Aerosol transmission could occur in some cluster cases when the environmental factors are suitable,and it is an indispensable route of COVID-19 spread.展开更多
基金This work was supported by grants from the National Key Research and Development Program of China(2018YFA0108000 and 2019YFA0110300)the National Natural Science Foundation of China(8205020,32000689,31400934,31771132,31872760,31801204,and 31800858)+3 种基金the Science and Technology Commission of Shanghai Municipality(19JC1415100 and 21140902300)the Shanghai Municipal Education Commission(C120114)China Postdoctoral Science Foundation(2017M621526)the Fundamental Research Funds for the Central Universities,and the Major Program of Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(Stem Cell Strategic Biobank and Clinical Translation Platform of Stem Cell Technology,ZJ2018-ZD-004).
文摘Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mechanisms remain largely unknown.Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited.Here,we describe a new mouse model of congenital hydrocephalus through knockout ofβ-catenin in Nkx2.1-expressing regional neural progenitors.Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood.Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis afterβ-catenin knockout.Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages.Thus,knockout ofβ-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.
基金supported by National Natural Science Foundation of China(Grants 21878088,12034008,21476077,11727810)Key projects of Shanghai Science and Technology Commission(18DZ1112703)Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission,grant 2021 Sci&Tech 03-28)。
文摘Photodynamic(PDT)and photothermal therapies(PTT)are emerging treatments for tumour ablation.Organic dyes such as porphyrin,chlorin,phthalocyanine,boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents.Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT.Herein,we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton.The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820.Furthermore,ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica(RMON)to construct nanomedicine NBD&ML@RMON,which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.
基金the Key Technologies R&D Program of Tianjin(No.20ZXGBSY00100)。
文摘Patients with COVID-19 have revealed a massive outbreak around the world,leading to widespread concerns in global scope.Figuring out the transmission route of COVID-19 is necessary to control further spread.We analyzed the data of 43 patients in Baodi Department Store(China)to supplement the transmission route and epidemiological characteristics of COVID-19 in a cluster outbreak.Incubation median was estimated to endure 5.95 days(2-13 days).Almost 76.3%of patients sought medical attention immediately upon illness onset.The median period of illness onset to hospitalization and confirmation were 3.96 days(0-14)and 5.58 days(1-21),respectively.Patients with different cluster case could demonstrate unique epidemiological characteristics due to the particularity of outbreak sites.SRAS-CoV-2 can be released into the surrounding air through patient's respiratory tract activities,and can exist for a long time for long-distance transportation.SRAS-CoV-2 RNA can be detected in aerosol in different sites,including isolation ward,general ward,outdoor,toilet,hallway,and crowded public area.Environmental factors influencing were analyzed and indicated that the SARS-CoV-2 transportation in aerosol was dependent on temperature,air humidity,ventilation rate and inactivating chemicals(ozone)content.As for the infection route of case numbers 2 to 6,10,13,16,17,18,20 and 23,we believe that aerosol transmission played a significant role in analyzing their exposure history and environmental conditions in Baodi Department Store.Aerosol transmission could occur in some cluster cases when the environmental factors are suitable,and it is an indispensable route of COVID-19 spread.