Ongoing encroachment is driving recent alpine shrubline dynamics globally,but the role of shrub-shrub interactions in shaping shrublines and their relationships with stem density changes remain poorly understood.Here,...Ongoing encroachment is driving recent alpine shrubline dynamics globally,but the role of shrub-shrub interactions in shaping shrublines and their relationships with stem density changes remain poorly understood.Here,the size and age of shrubs from 26 Salix shrubline populations along a 900-km latitudinal gradient(30°-38°N)were measured and mapped across the eastern Tibetan Plateau.Point pattern analyses were used to quantify the spatial distribution patterns of juveniles and adults,and to assess spatial associations between them.Mean intensity of univariate and bivariate spatial patterns was related to biotic and abiotic variables.Bivariate mark correlation functions with a quantitative mark(shrub height,basal stem diameter,crown width)were also employed to investigate the spatial relationships between shrub traits of juveniles and adults.Structural equation models were used to explore the relationships among conspecific interactions,patterns,shrub traits and recruitment dynamics under climate change.Most shrublines showed clustered patterns,suggesting the existence of conspecific facilitation.Clustered patterns of juveniles and conspecific interactions(potentially facilitation)tended to intensify with increasing soil moisture stress.Summer warming before 2010 triggered positive effects on population interactions and spatial patterns via increased shrub recruitment.However,summer warming after2010 triggered negative effects on interactions through reduced shrub recruitment.Therefore,shrub recruitment shifts under rapid climate change could impact spatial patterns,alter conspecific interactions and modify the direction and degree of shrublines responses to climate.These changes would have profound implications for the stability of alpine woody ecosystems.展开更多
Stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is a devastating disease in wheat worldwide.Discovering and characterizing new resistance genes/QTL is crucial for wheat breeding programs.In this study,we ...Stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is a devastating disease in wheat worldwide.Discovering and characterizing new resistance genes/QTL is crucial for wheat breeding programs.In this study,we fine-mapped and characterized a stripe rust resistance gene,YRAYH,on chromosome arm 5BL in the Chinese wheat landrace Anyuehong(AYH).Evaluations of stripe rust response to prevalent Chinese Pst races in near-isogenic lines derived from a cross of Anyuehong and Taichung 29 showed that YrAYH conferred a high level of resistance at all growth stages.Fine mapping using a large segregating population of 9748 plants,narrowed the YRAYH locus to a 3.7 Mb interval on chromosome arm 5BL that included 61 annotated genes.Transcriptome analysis of two NIL pairs identified 64 upregulated differentially expressed genes(DEGs)in the resistant NILs(NILs-R).Annotations indicated that many of these genes have roles in plant disease resistance pathways.Through a combined approach of fine-mapping and transcriptome sequencing,we identified a serine/threonine-protein kinase SRPK as a candidate gene underlying YrAYH.A unique 25 bp insertion was identified in the NILs-R compared to the NILs-S and previously published wheat genomes.An InDel marker was developed and co-segregated with YrAYH.Agronomic trait evaluation of the NILs suggested that YrAYH not only reduces the impact of stripe rust but was also associated with a gene that increases plant height and spike length.展开更多
This study is thefirst attempt to assess the nature of the soil,especially on the western side of the Porali Plain in Balochistan;a new emerging agriculture hub,using weathering and pollution indices supplemented by mu...This study is thefirst attempt to assess the nature of the soil,especially on the western side of the Porali Plain in Balochistan;a new emerging agriculture hub,using weathering and pollution indices supplemented by multi-variate analysis based on geochemical data.The outcomes of this study are expected to help farmers in soil manage-ment and selecting suitable crops for the region.Twenty-five soil samples were collected,mainly from the arable land of the Porali Plain.After drying and coning-quarter-ing,soil samples were analyzed for major and trace ele-ments using the XRF technique;sieving and hydrometric methods were employed for granulometric analysis.Esti-mated data were analyzed using Excel,SPSS,and Surfer software to calculate various indices,correlation matrix,and spatial distribution.The granulometric analysis showed that 76%of the samples belonged to loam types of soil,12%to sand type,and 8%to silt type.Weathering indices:CIA,CIW,PIA,PWI,WIP,CIX,and ICV were calculated to infer the level of alteration.These indices reflect mod-erate to intense weathering;supported by K_(2)O/AI_(2)O_(3),Rb/K_(2)O,Rb/Ti,and Rb/Sr ratios.Assessment of the geo-ac-cumulation and Nemerow Pollution indices pinpoint rela-tively high concentrations of Pb,Ni,and Cr concentration in the soils.The correlation matrix and Principal Compo-nent Analysis show that the soil in this study area is mainly derived from the weathering of igneous rocks of Bela Ophiolite(Cretaceous age)and Jurassic sedimentary rocks of Mor Range having SEDEX/MVT type mineralization.Weathering may result in the undesirable accumulation of certain trace elements which adversely affects crops.展开更多
BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with poor prognosis.Previous studies have implicated the gut microbiota in CCA,but evidence for causal mechanisms is lacking.AIM To investig...BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with poor prognosis.Previous studies have implicated the gut microbiota in CCA,but evidence for causal mechanisms is lacking.AIM To investigate the causal relationship between gut microbiota and CCA risk.METHODS We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA.Genetic variants were used as instrumental variables.Multiple sensitivity analyses assessed result robustness.RESULTS Fifteen gut microbial taxa showed significant causal associations with CCA risk.Higher genetically predicted abundance of genus Eubacteriumnodatum group,genus Ruminococcustorques group,genus Coprococcus,genus Dorea,and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA.Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae,genus Alistipes,order Enterobacteriales,and phylum Firmicutes.Protective effects against CCA were suggested for genus Collinsella,genus Eisenbergiella,genus Anaerostipes,genus Paraprevotella,genus Parasutterella,and phylum Verrucomicrobia.Sensitivity analyses indicated these findings were reliable without pleiotropy.CONCLUSION This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk.Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.展开更多
A cascading failure of landslide dams caused by strong earthquakes or torrential rains in mountainous river valleys can pose great threats to people’s lives,properties,and infrastructures.In this study,based on the t...A cascading failure of landslide dams caused by strong earthquakes or torrential rains in mountainous river valleys can pose great threats to people’s lives,properties,and infrastructures.In this study,based on the three-dimensional Reynoldsaveraged Navier-Stokes equations(RANS),the renormalization group(RNG)k-εturbulence model,suspended and bed load transport equations,and the instability discriminant formula of dam breach side slope,and the explicit finite volume method(FVM),a detailed numerical simulation model for calculating the hydro-morphodynamic characteristics of cascading dam breach process has been developed.The developed numerical model can simulate the breach hydrograph and the dam breach morphology evolution during the cascading failure process of landslide dams.A model test of the breaches of two cascading landslide dams has been used as the validation case.The comparison of the calculated and measured results indicates that the breach hydrograph and the breach morphology evolution process of the upstream and downstream dams are generally consistent with each other,and the relative errors of the key breaching parameters,i.e.,the peak breach flow and the time to peak of each dam,are less than±5%.Further,the comparison of the breach hydrographs of the upstream and downstream dams shows that there is an amplification effect of the breach flood on the cascading landslide dam failures.Three key parameters,i.e.,the distance between the upstream and the downstream dams,the river channel slope,and the downstream dam height,have been used to study the flood amplification effect.The parameter sensitivity analyses show that the peak breach flow at the downstream dam decreases with increasing distance between the upstream and the downstream dams,and the downstream dam height.Further,the peak breach flow at the downstream dam first increases and then decreases with steepening of the river channel slope.When the flood caused by the upstream dam failure flows to the downstream dam,it can produce a surge wave that overtops and erodes the dam crest,resulting in a lowering of the dam crest elevation.This has an impact on the failure occurrence time and the peak breach flow of the downstream dam.The influence of the surge wave on the downstream dam failure process is related to the volume of water that overtops the dam crest and the erosion characteristics of dam material.Moreover,the cascading failure case of the Xiaogangjian and Lower Xiaogangjian landslide dams has also been used as the representative case for validating the model.In comparisons of the calculated and measured breach hydrographs and final breach morphologies,the relative errors of the key dam breaching parameters are all within±10%,which verify the rationality of the model is applicable to real-world cases.Overall,the numerical model developed in this study can provide important technical support for the risk assessment and emergency treatment of failures of cascading landslide dams.展开更多
BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling ...BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling tissue function and regeneration.Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases.However,the lack of vasculature limits the utility of dental pulp organoids.AIM To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM.The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids.The biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were studied.RESULTS The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and function.Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis.The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids.CONCLUSION In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies.展开更多
Lithium-sulfur battery(LSB)has brought much attention and concern because of high theoretical specific capacity and energy density as one of main competitors for next-generation energy storage systems.The widely comme...Lithium-sulfur battery(LSB)has brought much attention and concern because of high theoretical specific capacity and energy density as one of main competitors for next-generation energy storage systems.The widely commercial application and development of LSB is mainly hindered by serious“shuttle effect”of lithium polysulfides(Li PSs),slow reaction kinetics,notorious lithium dendrites,etc.In various structures of LSB materials,array structured materials,possessing the composition of ordered micro units with the same or similar characteristics of each unit,present excellent application potential for various secondary cells due to some merits such as immobilization of active substances,high specific surface area,appropriate pore sizes,easy modification of functional material surface,accommodated huge volume change,enough facilitated transportation for electrons/lithium ions,and special functional groups strongly adsorbing Li PSs.Thus many novel array structured materials are applied to battery for tackling thorny problems mentioned above.In this review,recent progresses and developments on array structured materials applied in LSBs including preparation ways,collaborative structural designs based on array structures,and action mechanism analyses in improving electrochemical performance and safety are summarized.Meanwhile,we also have detailed discussion for array structured materials in LSBs and constructed the structure-function relationships between array structured materials and battery performances.Lastly,some directions and prospects about preparation ways,functional modifications,and practical applications of array structured materials in LSBs are generalized.We hope the review can attract more researchers'attention and bring more studying on array structured materials for other secondary batteries including LSB.展开更多
BACKGROUND Colonization with Helicobacter pylori(H.pylori)has a strong correlation with gastric cancer,and the virulence factor CagA is implicated in carcinogenesis.Studies have been conducted using medicinal plants w...BACKGROUND Colonization with Helicobacter pylori(H.pylori)has a strong correlation with gastric cancer,and the virulence factor CagA is implicated in carcinogenesis.Studies have been conducted using medicinal plants with the aim of eliminating the pathogen;however,the possibility of blocking H.pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed.This type of study is expensive and time-consuming,requiring in vitro and/or in vivo tests,which can be solved using bioinformatics.Therefore,prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein.AIM To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H.pylori.METHODS In this in silico study,the structures of the phenolic compounds(ligands)kaempferol,myricetin,quercetin,ponciretin(flavonoids),and chlorogenic acid(phenolic acid)were selected from the PubChem database.These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H.pylori infection.The three-dimensional structure model of the CagA oncoprotein of H.pylori(receptor)was obtained through molecular modeling using computational tools from the I-Tasser platform,employing the threading methodology.The primary sequence of CagA was sourced from GenBank(BAK52797.1).A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands,utilizing the GRaSP online platform.Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4(ADT)software,and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software.Two sets of simulations were performed:One involving the central region of CagA with phenolic compounds,and another involving the carboxy-terminus region of CagA with phenolic compounds.The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software.RESULTS The structure model obtained for the CagA oncoprotein exhibited high quality(C-score=0.09)and was validated using parameters from the MolProbity platform.The GRaSP online platform identified 24 residues(phenylalanine and leucine)as potential binding sites on the CagA oncoprotein.Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein.No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds;however,all phenolic compounds interacted with the central region of the oncoprotein.Phenolic compounds and CagA exhibited significant affinity energy(-7.9 to-9.1 kcal/mol):CagA/kaempferol formed 28 chemical bonds,CagA/myricetin formed 18 chemical bonds,CagA/quercetin formed 16 chemical bonds,CagA/ponciretin formed 13 chemical bonds,and CagA/chlorogenic acid formed 17 chemical bonds.Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif,all of them bound to residues,mostly positively or negatively charged,located near this region.CONCLUSION In silico,the tested phenolic compounds formed stable complexes with CagA.Therefore,they could be tested in vitro and/or in vivo to validate the findings,and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.展开更多
基金the National Natural Science Foundation of China(42271054)the Second Tibetan Plateau Scientific Expedition and Research Program(2019QZKK0301)。
文摘Ongoing encroachment is driving recent alpine shrubline dynamics globally,but the role of shrub-shrub interactions in shaping shrublines and their relationships with stem density changes remain poorly understood.Here,the size and age of shrubs from 26 Salix shrubline populations along a 900-km latitudinal gradient(30°-38°N)were measured and mapped across the eastern Tibetan Plateau.Point pattern analyses were used to quantify the spatial distribution patterns of juveniles and adults,and to assess spatial associations between them.Mean intensity of univariate and bivariate spatial patterns was related to biotic and abiotic variables.Bivariate mark correlation functions with a quantitative mark(shrub height,basal stem diameter,crown width)were also employed to investigate the spatial relationships between shrub traits of juveniles and adults.Structural equation models were used to explore the relationships among conspecific interactions,patterns,shrub traits and recruitment dynamics under climate change.Most shrublines showed clustered patterns,suggesting the existence of conspecific facilitation.Clustered patterns of juveniles and conspecific interactions(potentially facilitation)tended to intensify with increasing soil moisture stress.Summer warming before 2010 triggered positive effects on population interactions and spatial patterns via increased shrub recruitment.However,summer warming after2010 triggered negative effects on interactions through reduced shrub recruitment.Therefore,shrub recruitment shifts under rapid climate change could impact spatial patterns,alter conspecific interactions and modify the direction and degree of shrublines responses to climate.These changes would have profound implications for the stability of alpine woody ecosystems.
基金supported by grants from the Major Program of National Agricultural Science and Technology of China(NK20220607)the National Natural Science Foundation of China(32272059 and 31971883)the Science and Technology Department of Sichuan Province(2021YFYZ0002,2022ZDZX0014,and 2023NSFSC1995)。
文摘Stripe rust,caused by Puccinia striiformis f.sp.tritici(Pst),is a devastating disease in wheat worldwide.Discovering and characterizing new resistance genes/QTL is crucial for wheat breeding programs.In this study,we fine-mapped and characterized a stripe rust resistance gene,YRAYH,on chromosome arm 5BL in the Chinese wheat landrace Anyuehong(AYH).Evaluations of stripe rust response to prevalent Chinese Pst races in near-isogenic lines derived from a cross of Anyuehong and Taichung 29 showed that YrAYH conferred a high level of resistance at all growth stages.Fine mapping using a large segregating population of 9748 plants,narrowed the YRAYH locus to a 3.7 Mb interval on chromosome arm 5BL that included 61 annotated genes.Transcriptome analysis of two NIL pairs identified 64 upregulated differentially expressed genes(DEGs)in the resistant NILs(NILs-R).Annotations indicated that many of these genes have roles in plant disease resistance pathways.Through a combined approach of fine-mapping and transcriptome sequencing,we identified a serine/threonine-protein kinase SRPK as a candidate gene underlying YrAYH.A unique 25 bp insertion was identified in the NILs-R compared to the NILs-S and previously published wheat genomes.An InDel marker was developed and co-segregated with YrAYH.Agronomic trait evaluation of the NILs suggested that YrAYH not only reduces the impact of stripe rust but was also associated with a gene that increases plant height and spike length.
基金supported by the Dean Faculty of Science,University of Karachi research grant.
文摘This study is thefirst attempt to assess the nature of the soil,especially on the western side of the Porali Plain in Balochistan;a new emerging agriculture hub,using weathering and pollution indices supplemented by multi-variate analysis based on geochemical data.The outcomes of this study are expected to help farmers in soil manage-ment and selecting suitable crops for the region.Twenty-five soil samples were collected,mainly from the arable land of the Porali Plain.After drying and coning-quarter-ing,soil samples were analyzed for major and trace ele-ments using the XRF technique;sieving and hydrometric methods were employed for granulometric analysis.Esti-mated data were analyzed using Excel,SPSS,and Surfer software to calculate various indices,correlation matrix,and spatial distribution.The granulometric analysis showed that 76%of the samples belonged to loam types of soil,12%to sand type,and 8%to silt type.Weathering indices:CIA,CIW,PIA,PWI,WIP,CIX,and ICV were calculated to infer the level of alteration.These indices reflect mod-erate to intense weathering;supported by K_(2)O/AI_(2)O_(3),Rb/K_(2)O,Rb/Ti,and Rb/Sr ratios.Assessment of the geo-ac-cumulation and Nemerow Pollution indices pinpoint rela-tively high concentrations of Pb,Ni,and Cr concentration in the soils.The correlation matrix and Principal Compo-nent Analysis show that the soil in this study area is mainly derived from the weathering of igneous rocks of Bela Ophiolite(Cretaceous age)and Jurassic sedimentary rocks of Mor Range having SEDEX/MVT type mineralization.Weathering may result in the undesirable accumulation of certain trace elements which adversely affects crops.
文摘BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with poor prognosis.Previous studies have implicated the gut microbiota in CCA,but evidence for causal mechanisms is lacking.AIM To investigate the causal relationship between gut microbiota and CCA risk.METHODS We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA.Genetic variants were used as instrumental variables.Multiple sensitivity analyses assessed result robustness.RESULTS Fifteen gut microbial taxa showed significant causal associations with CCA risk.Higher genetically predicted abundance of genus Eubacteriumnodatum group,genus Ruminococcustorques group,genus Coprococcus,genus Dorea,and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA.Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae,genus Alistipes,order Enterobacteriales,and phylum Firmicutes.Protective effects against CCA were suggested for genus Collinsella,genus Eisenbergiella,genus Anaerostipes,genus Paraprevotella,genus Parasutterella,and phylum Verrucomicrobia.Sensitivity analyses indicated these findings were reliable without pleiotropy.CONCLUSION This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk.Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.
基金supported by the Nursing Project of Jiangsu Cancer Hospital(ZH202001)General program of Jiangsu Provincial Health Commission Medical Research(M2021114)Project of Jiangsu Provincial Hospital Management Association(JSYGY-3-2021-284)。
基金financially supported by the National Natural Science Foundation of China(Grant Nos.U22A20602,U2040221).
文摘A cascading failure of landslide dams caused by strong earthquakes or torrential rains in mountainous river valleys can pose great threats to people’s lives,properties,and infrastructures.In this study,based on the three-dimensional Reynoldsaveraged Navier-Stokes equations(RANS),the renormalization group(RNG)k-εturbulence model,suspended and bed load transport equations,and the instability discriminant formula of dam breach side slope,and the explicit finite volume method(FVM),a detailed numerical simulation model for calculating the hydro-morphodynamic characteristics of cascading dam breach process has been developed.The developed numerical model can simulate the breach hydrograph and the dam breach morphology evolution during the cascading failure process of landslide dams.A model test of the breaches of two cascading landslide dams has been used as the validation case.The comparison of the calculated and measured results indicates that the breach hydrograph and the breach morphology evolution process of the upstream and downstream dams are generally consistent with each other,and the relative errors of the key breaching parameters,i.e.,the peak breach flow and the time to peak of each dam,are less than±5%.Further,the comparison of the breach hydrographs of the upstream and downstream dams shows that there is an amplification effect of the breach flood on the cascading landslide dam failures.Three key parameters,i.e.,the distance between the upstream and the downstream dams,the river channel slope,and the downstream dam height,have been used to study the flood amplification effect.The parameter sensitivity analyses show that the peak breach flow at the downstream dam decreases with increasing distance between the upstream and the downstream dams,and the downstream dam height.Further,the peak breach flow at the downstream dam first increases and then decreases with steepening of the river channel slope.When the flood caused by the upstream dam failure flows to the downstream dam,it can produce a surge wave that overtops and erodes the dam crest,resulting in a lowering of the dam crest elevation.This has an impact on the failure occurrence time and the peak breach flow of the downstream dam.The influence of the surge wave on the downstream dam failure process is related to the volume of water that overtops the dam crest and the erosion characteristics of dam material.Moreover,the cascading failure case of the Xiaogangjian and Lower Xiaogangjian landslide dams has also been used as the representative case for validating the model.In comparisons of the calculated and measured breach hydrographs and final breach morphologies,the relative errors of the key dam breaching parameters are all within±10%,which verify the rationality of the model is applicable to real-world cases.Overall,the numerical model developed in this study can provide important technical support for the risk assessment and emergency treatment of failures of cascading landslide dams.
基金Supported by the Science and Technology Programme of Guangzhou City,No.202201020341.
文摘BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine.Stem cells can self-organise into microsized organ units,partially modelling tissue function and regeneration.Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases.However,the lack of vasculature limits the utility of dental pulp organoids.AIM To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM.The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids.The biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were studied.RESULTS The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and function.Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis.The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids.CONCLUSION In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies.
基金This work was supported by the National Natural Science Foundation of China(52203066,51973157,61904123)the Tianjin Natural Science Foundation(18JCQNJC02900)+3 种基金the National innovation and entrepreneurship training program for college students(202310058007)the Tianjin Municipal college students’innovation and entrepreneurship training program(202310058088)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2018KJ196)the State Key Laboratory of Membrane and Membrane Separation,Tiangong University.
文摘Lithium-sulfur battery(LSB)has brought much attention and concern because of high theoretical specific capacity and energy density as one of main competitors for next-generation energy storage systems.The widely commercial application and development of LSB is mainly hindered by serious“shuttle effect”of lithium polysulfides(Li PSs),slow reaction kinetics,notorious lithium dendrites,etc.In various structures of LSB materials,array structured materials,possessing the composition of ordered micro units with the same or similar characteristics of each unit,present excellent application potential for various secondary cells due to some merits such as immobilization of active substances,high specific surface area,appropriate pore sizes,easy modification of functional material surface,accommodated huge volume change,enough facilitated transportation for electrons/lithium ions,and special functional groups strongly adsorbing Li PSs.Thus many novel array structured materials are applied to battery for tackling thorny problems mentioned above.In this review,recent progresses and developments on array structured materials applied in LSBs including preparation ways,collaborative structural designs based on array structures,and action mechanism analyses in improving electrochemical performance and safety are summarized.Meanwhile,we also have detailed discussion for array structured materials in LSBs and constructed the structure-function relationships between array structured materials and battery performances.Lastly,some directions and prospects about preparation ways,functional modifications,and practical applications of array structured materials in LSBs are generalized.We hope the review can attract more researchers'attention and bring more studying on array structured materials for other secondary batteries including LSB.
文摘BACKGROUND Colonization with Helicobacter pylori(H.pylori)has a strong correlation with gastric cancer,and the virulence factor CagA is implicated in carcinogenesis.Studies have been conducted using medicinal plants with the aim of eliminating the pathogen;however,the possibility of blocking H.pylori-induced cell differentiation to prevent the onset and/or progression of tumors has not been addressed.This type of study is expensive and time-consuming,requiring in vitro and/or in vivo tests,which can be solved using bioinformatics.Therefore,prospective computational analyses were conducted to assess the feasibility of interaction between phenolic compounds from medicinal plants and the CagA oncoprotein.AIM To perform a computational prospecting of the interactions between phenolic compounds from medicinal plants and the CagA oncoprotein of H.pylori.METHODS In this in silico study,the structures of the phenolic compounds(ligands)kaempferol,myricetin,quercetin,ponciretin(flavonoids),and chlorogenic acid(phenolic acid)were selected from the PubChem database.These phenolic compounds were chosen based on previous studies that suggested medicinal plants as non-drug treatments to eliminate H.pylori infection.The three-dimensional structure model of the CagA oncoprotein of H.pylori(receptor)was obtained through molecular modeling using computational tools from the I-Tasser platform,employing the threading methodology.The primary sequence of CagA was sourced from GenBank(BAK52797.1).A screening was conducted to identify binding sites in the structure of the CagA oncoprotein that could potentially interact with the ligands,utilizing the GRaSP online platform.Both the ligands and receptor were prepared for molecular docking using AutoDock Tools 4(ADT)software,and the simulations were carried out using a combination of ADT and AutoDock Vina v.1.2.0 software.Two sets of simulations were performed:One involving the central region of CagA with phenolic compounds,and another involving the carboxy-terminus region of CagA with phenolic compounds.The receptor-ligand complexes were then analyzed using PyMol and BIOVIA Discovery Studio software.RESULTS The structure model obtained for the CagA oncoprotein exhibited high quality(C-score=0.09)and was validated using parameters from the MolProbity platform.The GRaSP online platform identified 24 residues(phenylalanine and leucine)as potential binding sites on the CagA oncoprotein.Molecular docking simulations were conducted with the three-dimensional model of the CagA oncoprotein.No complexes were observed in the simulations between the carboxy-terminus region of CagA and the phenolic compounds;however,all phenolic compounds interacted with the central region of the oncoprotein.Phenolic compounds and CagA exhibited significant affinity energy(-7.9 to-9.1 kcal/mol):CagA/kaempferol formed 28 chemical bonds,CagA/myricetin formed 18 chemical bonds,CagA/quercetin formed 16 chemical bonds,CagA/ponciretin formed 13 chemical bonds,and CagA/chlorogenic acid formed 17 chemical bonds.Although none of the phenolic compounds directly bound to the amino acid residues of the K-Xn-R-X-R membrane binding motif,all of them bound to residues,mostly positively or negatively charged,located near this region.CONCLUSION In silico,the tested phenolic compounds formed stable complexes with CagA.Therefore,they could be tested in vitro and/or in vivo to validate the findings,and to assess interference in CagA/cellular target interactions and in the oncogenic differentiation of gastric cells.