Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxymatrine,a...Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxymatrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mechanism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological prediction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-kB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in acceleratingMKdifferentiation and thrombopoiesis via the STING/NF-kB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.展开更多
We studied seed germination and seedling growth performance in an economically and socially important fruit tree species <em>Vitellaria paradoxa</em> C.F. Gaertn. subsp. <em>nilotica</em> (shea...We studied seed germination and seedling growth performance in an economically and socially important fruit tree species <em>Vitellaria paradoxa</em> C.F. Gaertn. subsp. <em>nilotica</em> (shea tree) in Uganda. The study aimed at determining variations in germination among five shea tree seed provenances and seedling growth performance based on five growth traits (total height, root collar diameter, leaf length, leaf width and leaf petiole length). Five populations were considered from four agroecological zones comprising of 180 candidate “plus” trees. The seed trees consisted of 16 ethnovarieties selected based on their traits for fast growth and high oil yield. A total of 1,204 biological seeds were collected and sown in a tree nursery at Ngetta Zonal Agricultural Research and Development Institute during the month of June 2018 in a randomized incomplete block design with three replications. Significant variation (χ = 708;p < 0.01) was observed in seedling phenotypic traits within and between populations. Regression equation for height growth and leaf size index were given as y = 0.3787 + 12.671x and y = 0.6483 + 15.413x respectively. Root collar diameter was more correlated to leaf size index (0.425) than to height growth (0.30). Clustering of shea tree seedlings based on phenotypic growth traits revealed one aggregated cluster indicating that most of the seedlings from the five populations were similar (Jaccard index 0.92, p < 0.01). However, clustering based on SNP markers revealed three different populations. We recorded higher growth (χ = 708;p < 0.001) in Arua shea population. Red seeded;thin pulped and hairy fruited shea tree ethnovarieties recorded faster growth than the rest. The results reveal useful traits in selection for tree growth and further identified shea tree ethnovarieties that could be selected for fast growth.展开更多
Background:Human brucellosis is prevalent in both rural and urban Uganda,yet most cases of the disease in humans go unnoticed and untreated because of inaccurate diagnosis,which is often due to the disease not manifes...Background:Human brucellosis is prevalent in both rural and urban Uganda,yet most cases of the disease in humans go unnoticed and untreated because of inaccurate diagnosis,which is often due to the disease not manifesting in any symptoms.This study was undertaken to describe trends in laboratory-confirmed human brucellosis cases at three health facilities in pastoralist communities in South-western,Uganda.Methods:Data were collected retrospectively to describe trends of brucellosis over a 10-year period(2003–2012),and supplemented with a prospective study,which was conducted from January to December 2013.Two public health facilities and a private clinic that have diagnostic laboratories were selected for these studies.Annual prevalence was calculated and linearly plotted to observe trends of the disease at the health facilities.A modified Poisson regression model was used to estimate the risk ratio(RR)and 95%confidence intervals(CIs)to determine the association between brucellosis and independent variables using the robust error variance.Results:A total of 9,177 persons with suspected brucellosis were identified in the retrospective study,of which 1,318(14.4%)were confirmed cases.Brucellosis cases peaked during the months of April and June,as observed in nearly all of the years of the study,while the most noticeable annual increase(11–23%)was observed from 2010 to 2012.In the prospective study,there were 610 suspected patients at two public health facilities.Of these,194(31.8%)were positive for brucellosis.Respondents aged 45–60 years(RR=0.50;CI:0.29–0.84)and those that tested positive for typhoid(RR=0.68;CI:0.52–0.89)were less likely to have brucellosis.Conclusions:With the noticeable increase in prevalence from 2010 to 2012,diagnosis of both brucellosis and typhoid is important for early detection,and for raising public awareness on methods for preventing brucellosis in this setting.展开更多
Understanding the hydromechanical behavior and permeability stress sensitivity of hydraulic fractures is fundamental for geotechnical applications associated with fluid injection.This paper presents a three-dimensiona...Understanding the hydromechanical behavior and permeability stress sensitivity of hydraulic fractures is fundamental for geotechnical applications associated with fluid injection.This paper presents a three-dimensional(3D)benchmark model of a laboratory experiment on graywacke to examine the dynamic hydraulic fracturing process under a polyaxial stress state.In the numerical model,injection pressures after breakdown(postbreakdown)are varied to study the impact on fracture growth.The fluid pressure front and crack front are identified in the numerical model to analyze the dynamic relationship between fluid diffusion and fracture propagation.Following the hydraulic fracturing test,the polyaxial stresses are rotated to investigate the influence of the stress field rotation on the fracture slip behavior and permeability.The results show that fracture propagation guides fluid diffusion under a high postbreakdown injection pressure.The crack front runs ahead of the fluid pressure front.Under a low postbreakdown injection pressure,the fluid pressure front gradually reaches the crack front,and fluid diffusion is the main driving factor of fracture propagation.Under polyaxial stress conditions,fluid injection not only opens tensile fractures but also induces hydroshearing.When the polyaxial stress is rotated,the fracture slip direction of a fully extended fracture is consistent with the shear stress direction.The fracture slip direction of a partly extended fracture is influenced by the increase in shear stress.Normal stress affects the permeability evolution by changing the average mechanical aperture.Shear stress can induce shearing and sliding on the fracture plane,thereby increasing permeability.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.:82074129,82004073,82204666,and 82374073)the Science and Technology Planning Project of Sichuan Province,China(Grant Nos.:2022JDJQ0061,2022ZYD0087,2022YFS0607,2022YFS0635,and 2022YFS0635-B1)+1 种基金the Joint Project of Xuzhou District People's Government and Southwest Medical University,China(Grant No.:2021XZXNYD01)Science and Technology Planning Project of Yibin City,China(Grant Nos.:2022NY020,2021ZYY009,and 2021ZYY005).
文摘Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxymatrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mechanism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological prediction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-kB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in acceleratingMKdifferentiation and thrombopoiesis via the STING/NF-kB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.
文摘We studied seed germination and seedling growth performance in an economically and socially important fruit tree species <em>Vitellaria paradoxa</em> C.F. Gaertn. subsp. <em>nilotica</em> (shea tree) in Uganda. The study aimed at determining variations in germination among five shea tree seed provenances and seedling growth performance based on five growth traits (total height, root collar diameter, leaf length, leaf width and leaf petiole length). Five populations were considered from four agroecological zones comprising of 180 candidate “plus” trees. The seed trees consisted of 16 ethnovarieties selected based on their traits for fast growth and high oil yield. A total of 1,204 biological seeds were collected and sown in a tree nursery at Ngetta Zonal Agricultural Research and Development Institute during the month of June 2018 in a randomized incomplete block design with three replications. Significant variation (χ = 708;p < 0.01) was observed in seedling phenotypic traits within and between populations. Regression equation for height growth and leaf size index were given as y = 0.3787 + 12.671x and y = 0.6483 + 15.413x respectively. Root collar diameter was more correlated to leaf size index (0.425) than to height growth (0.30). Clustering of shea tree seedlings based on phenotypic growth traits revealed one aggregated cluster indicating that most of the seedlings from the five populations were similar (Jaccard index 0.92, p < 0.01). However, clustering based on SNP markers revealed three different populations. We recorded higher growth (χ = 708;p < 0.001) in Arua shea population. Red seeded;thin pulped and hairy fruited shea tree ethnovarieties recorded faster growth than the rest. The results reveal useful traits in selection for tree growth and further identified shea tree ethnovarieties that could be selected for fast growth.
基金The authors are grateful for the financial support from the International Development Research Centre(IDRC),Canada,and the participating laboratories for granting access to the records.
文摘Background:Human brucellosis is prevalent in both rural and urban Uganda,yet most cases of the disease in humans go unnoticed and untreated because of inaccurate diagnosis,which is often due to the disease not manifesting in any symptoms.This study was undertaken to describe trends in laboratory-confirmed human brucellosis cases at three health facilities in pastoralist communities in South-western,Uganda.Methods:Data were collected retrospectively to describe trends of brucellosis over a 10-year period(2003–2012),and supplemented with a prospective study,which was conducted from January to December 2013.Two public health facilities and a private clinic that have diagnostic laboratories were selected for these studies.Annual prevalence was calculated and linearly plotted to observe trends of the disease at the health facilities.A modified Poisson regression model was used to estimate the risk ratio(RR)and 95%confidence intervals(CIs)to determine the association between brucellosis and independent variables using the robust error variance.Results:A total of 9,177 persons with suspected brucellosis were identified in the retrospective study,of which 1,318(14.4%)were confirmed cases.Brucellosis cases peaked during the months of April and June,as observed in nearly all of the years of the study,while the most noticeable annual increase(11–23%)was observed from 2010 to 2012.In the prospective study,there were 610 suspected patients at two public health facilities.Of these,194(31.8%)were positive for brucellosis.Respondents aged 45–60 years(RR=0.50;CI:0.29–0.84)and those that tested positive for typhoid(RR=0.68;CI:0.52–0.89)were less likely to have brucellosis.Conclusions:With the noticeable increase in prevalence from 2010 to 2012,diagnosis of both brucellosis and typhoid is important for early detection,and for raising public awareness on methods for preventing brucellosis in this setting.
基金supported by the Knowledge Innovation Program of Wuhan-Basic Research (Grant No.2022010801010159)support from the Helmholtz Association's Initiative and Networking Fund for the Helmholtz Young Investigator Group ARES (Contract number VH-NG-1516)supported by the Swedish Radiation Safety Authority (Project SSM2020-2758).
文摘Understanding the hydromechanical behavior and permeability stress sensitivity of hydraulic fractures is fundamental for geotechnical applications associated with fluid injection.This paper presents a three-dimensional(3D)benchmark model of a laboratory experiment on graywacke to examine the dynamic hydraulic fracturing process under a polyaxial stress state.In the numerical model,injection pressures after breakdown(postbreakdown)are varied to study the impact on fracture growth.The fluid pressure front and crack front are identified in the numerical model to analyze the dynamic relationship between fluid diffusion and fracture propagation.Following the hydraulic fracturing test,the polyaxial stresses are rotated to investigate the influence of the stress field rotation on the fracture slip behavior and permeability.The results show that fracture propagation guides fluid diffusion under a high postbreakdown injection pressure.The crack front runs ahead of the fluid pressure front.Under a low postbreakdown injection pressure,the fluid pressure front gradually reaches the crack front,and fluid diffusion is the main driving factor of fracture propagation.Under polyaxial stress conditions,fluid injection not only opens tensile fractures but also induces hydroshearing.When the polyaxial stress is rotated,the fracture slip direction of a fully extended fracture is consistent with the shear stress direction.The fracture slip direction of a partly extended fracture is influenced by the increase in shear stress.Normal stress affects the permeability evolution by changing the average mechanical aperture.Shear stress can induce shearing and sliding on the fracture plane,thereby increasing permeability.
