There is a large surface-groundwater exchange downstream ofwastewater treatment plants(WWTPs),and antibiotics upstream may influence sites downstream of rivers.Thus,samples from 9 effluent-receiving urban rivers(ERURs...There is a large surface-groundwater exchange downstream ofwastewater treatment plants(WWTPs),and antibiotics upstream may influence sites downstream of rivers.Thus,samples from 9 effluent-receiving urban rivers(ERURs)and 12 groundwater sites were collected in Shijiazhuang City in December 2020 and April 2021.For ERURs,8 out of 13 target quinolone antibiotics(QNs)were detected,and the total concentration of QNs in December and April were 100.6-4,398 ng/L and 8.02–2,476 ng/L,respectively.For groundwater,all target QNs were detected,and the total QNs concentration was 1.09–23.03 ng/L for December and 4.54–170.3 ng/L for April.The distribution of QNs was dissimilar between ERURs and groundwater.Most QN concentrations were weakly correlated with land use types in the system.The results of a positive matrix factorization model(PMF)indicated four potential sources of QNs in both ERURs and groundwater,and WWTP effluents were the main source of QNs.From December to April,the contribution of WWTP effluents and agricultural emissions increased,while livestock activities decreased.Singular value decomposition(SVD)results showed that the spatial variation of most QNs was mainly contributed by sites downstream(7.09%-88.86%)of ERURs.Then,a new method that combined the results of SVD and PMF was developed for a specific-source-site risk quotient(SRQ),and the SRQ for QNs was at high level,especially for the sites downstream of WWTPs.Regarding temporal variation,the SRQ for WWTP effluents,aquaculture,and agricultural emissions increased.Therefore,in order to control the antibiotic pollution,more attention should be paid to WWTP effluents,aquaculture,and agricultural emission sources for the benefit of sites downstream of WWTPs.展开更多
Wholly defined ex vivo expansion conditions for biliary tree stem cell(BTSC)organoids were established,consisting of a defined proliferative medium(DPM)used in combination with soft hyaluronan hydrogels.The DPM consis...Wholly defined ex vivo expansion conditions for biliary tree stem cell(BTSC)organoids were established,consisting of a defined proliferative medium(DPM)used in combination with soft hyaluronan hydrogels.The DPM consisted of commercially available Kubota's Medium(KM),to which a set of small molecules,particular paracrine signals,and heparan sulfate(HS)were added.The small molecules used were DNA methyltransferase inhibitor(RG108),TGF-βType I receptor inhibitor(A83-01),adenylate cyclase activator(Forskolin),and L-type Ca2+channel agonist(Bay K8644).A key paracrine signal proved to be R-spondin 1(RSPO1),a secreted protein that activates Wnts.Soluble hyaluronans,0.05%sodium hyaluronate,were used with DPM to expand monolayer cultures.Expansion of organoids was achieved by using DPM in combination with embedding organoids in Matrigel that was replaced with a defined thiol-hyaluronan triggered with PEGDA to form a hydrogel with a rheology[G*]of less than 100 Pa.The combination is called the BTSC-Expansion-Glycogel-System(BEX-gel system)for expanding BTSCs as a monolayer or as organoids.The BTSC organoids were expanded more than 3000-fold ex vivo in the BEX-gel system within 70 days while maintaining phenotypic traits indicative of stem/progenitors.Stem-cell-patch grafting of expanded BTSC organoids was performed on the livers of Fah-/-mice with tyrosinemia and resulted in the rescue of the mice and restoration of their normal liver functions.The BEX-gel system for BTSC organoid expansion provides a strategy to generate sufficient numbers of organoids for the therapeutic treatments of liver diseases.展开更多
基金This work was supported by the Natural Science Foundation of Hebei Province(No.D2019208152)the Natural Science Foundation of Higher Education Institutions of Hebei Province(No.ZD2021046).
文摘There is a large surface-groundwater exchange downstream ofwastewater treatment plants(WWTPs),and antibiotics upstream may influence sites downstream of rivers.Thus,samples from 9 effluent-receiving urban rivers(ERURs)and 12 groundwater sites were collected in Shijiazhuang City in December 2020 and April 2021.For ERURs,8 out of 13 target quinolone antibiotics(QNs)were detected,and the total concentration of QNs in December and April were 100.6-4,398 ng/L and 8.02–2,476 ng/L,respectively.For groundwater,all target QNs were detected,and the total QNs concentration was 1.09–23.03 ng/L for December and 4.54–170.3 ng/L for April.The distribution of QNs was dissimilar between ERURs and groundwater.Most QN concentrations were weakly correlated with land use types in the system.The results of a positive matrix factorization model(PMF)indicated four potential sources of QNs in both ERURs and groundwater,and WWTP effluents were the main source of QNs.From December to April,the contribution of WWTP effluents and agricultural emissions increased,while livestock activities decreased.Singular value decomposition(SVD)results showed that the spatial variation of most QNs was mainly contributed by sites downstream(7.09%-88.86%)of ERURs.Then,a new method that combined the results of SVD and PMF was developed for a specific-source-site risk quotient(SRQ),and the SRQ for QNs was at high level,especially for the sites downstream of WWTPs.Regarding temporal variation,the SRQ for WWTP effluents,aquaculture,and agricultural emissions increased.Therefore,in order to control the antibiotic pollution,more attention should be paid to WWTP effluents,aquaculture,and agricultural emission sources for the benefit of sites downstream of WWTPs.
基金Major Program of National Key Research and Development Project(2020YFA0112600,2019YFA0801502)National Natural Science Foundation of China(82173019,82270638,8220374,82300718)+1 种基金Project of Shanghai Science and Technology Commission(22ZR1451100,22Y11908500)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai,and Shanghai Engineering Research Center of Stem Cells Translational Medicine(20DZ2255100).
文摘Wholly defined ex vivo expansion conditions for biliary tree stem cell(BTSC)organoids were established,consisting of a defined proliferative medium(DPM)used in combination with soft hyaluronan hydrogels.The DPM consisted of commercially available Kubota's Medium(KM),to which a set of small molecules,particular paracrine signals,and heparan sulfate(HS)were added.The small molecules used were DNA methyltransferase inhibitor(RG108),TGF-βType I receptor inhibitor(A83-01),adenylate cyclase activator(Forskolin),and L-type Ca2+channel agonist(Bay K8644).A key paracrine signal proved to be R-spondin 1(RSPO1),a secreted protein that activates Wnts.Soluble hyaluronans,0.05%sodium hyaluronate,were used with DPM to expand monolayer cultures.Expansion of organoids was achieved by using DPM in combination with embedding organoids in Matrigel that was replaced with a defined thiol-hyaluronan triggered with PEGDA to form a hydrogel with a rheology[G*]of less than 100 Pa.The combination is called the BTSC-Expansion-Glycogel-System(BEX-gel system)for expanding BTSCs as a monolayer or as organoids.The BTSC organoids were expanded more than 3000-fold ex vivo in the BEX-gel system within 70 days while maintaining phenotypic traits indicative of stem/progenitors.Stem-cell-patch grafting of expanded BTSC organoids was performed on the livers of Fah-/-mice with tyrosinemia and resulted in the rescue of the mice and restoration of their normal liver functions.The BEX-gel system for BTSC organoid expansion provides a strategy to generate sufficient numbers of organoids for the therapeutic treatments of liver diseases.