AIM: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation. METHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic f...AIM: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation. METHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor. RESULTS: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SMA, PDGFR and TGFβR. CONCLUSION: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation.展开更多
Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period...Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period.However,the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people,as well as their interaction mechanism,remain unknown.Here,we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity,admixture history,and differentiated adaptative features of geographically different TB-speaking people.We identify genetic differentiation related to geography and language among TB-speaking people,consistent with their differentiated admixture process with incoming or indigenous ancestral source populations.A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis.We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers.Adaptative signatures associated with the physical pigmentation(EDAR and SLC24A5)and metabolism(ALDH9A1)are identified in Loloish people,which differed from the high-altitude adaptative genetic architecture in Tibetan.TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.展开更多
Infertility is a pervasive issue affecting a considerable proportion of couples in their reproductive years,with a projected 10%-15% prevalence.It is characterized by the incapability to achieve conception following a...Infertility is a pervasive issue affecting a considerable proportion of couples in their reproductive years,with a projected 10%-15% prevalence.It is characterized by the incapability to achieve conception following a year of consistent,unprotected intercourse,and its far-reaching consequences can take a profound emotional,psychological,and social toll on couples,inducing feelings of melancholy,exasperation,and anxiety.The appraisal of infertile couples'cases is a multifaceted and daunting process,necessitating a holistic understanding of the intricate underlying factors contributing to their infertility.Consequently,an individualized evaluation should be conducted,considering diverse parameters,such as the couple's medical history,age,infertility duration,and other relevant criteria.This paper will provide an in-depth overview of the current approaches utilized in the evaluation of men with infertility,including the commonly employed diagnostic tools and procedures.Enhancing our comprehension of infertility assessment and management holds the promise of helping couples achieve their ultimate desire of conceiving and enriching their overall quality of life.展开更多
In order to modify the rail pre-grinding profile smoothly,non-uniform rational B-spline(NURBS)curve with weight factors is used to establish a parameterized model of the profile.A wheel-rail contact stochastic finite ...In order to modify the rail pre-grinding profile smoothly,non-uniform rational B-spline(NURBS)curve with weight factors is used to establish a parameterized model of the profile.A wheel-rail contact stochastic finite element model(FEM) is constructed by the Latin hypercube sampling method and 3 D elasto-plastic FEM,in which the wheelset's lateral displacement quantity is regarded as a random variable.The maximum values of nodal accumulated contact stress(NACS) and nodal mean contact stress(NMCS) in different pre-grinding profiles with differential weight factors are calculated and taken as the training samples to establish two Kriging models.A multi-objective optimization model of pre-grinding profile is established,in which the objective functions are the NACS and NMCS Kriging models.The optimum weight factors are sought using a non-dominated sorting genetic algorithm II(NSGA-II),and the corresponding optimum pre-grinding profile is obtained.The contact stress calculation before and after optimization indicates that the maximum values of NACS and NMCS decline significantly.展开更多
The study aims at determining the status of soil chemical fertility in four wild coffee forests of southeastern and southwestern Ethiopia. Accordingly, soil samples were collected from surface and subsurface depths at...The study aims at determining the status of soil chemical fertility in four wild coffee forests of southeastern and southwestern Ethiopia. Accordingly, soil samples were collected from surface and subsurface depths at three sites within each forest and analyzed for soil chemical properties. The results depicted that the soils at the four coffee forests did not reveal significant variations for most parameters, except Mg, CEC and C:N ratio. Significant variations were determined between the surface and subsurface soils of the four studied forests, partly indicating the impacts of anthropogenic factors on vegetation cover and soil fertility status along profile depth. At Harenna, surface soil had significantly higher total nitrogen and organic matter than sub-surface soil. The decline in available phosphorus with soil depth was also significant at the Harenna and Yayu forests. Most soil results were comparable and showed inter- and intra-forest variations, demonstrating the contributions of vegetation cover and climate gradients. The study revealed the declined soil quality parameters with increased depth, demonstrating the vulnerability of forest soils to human-induced disturbances of natural habitats and land degradation, coupled with climate changes. Overall, the results underline the need for a multi-site forest conservation and promote productivity of high quality coffee standards. This demands urgent supports for implementing community-oriented management and incentive options towards maintaining environmental sustainability and coffee genetic resources for global benefits.展开更多
基金Supported by National Institutes of Health Grant RO1 AA014891
文摘AIM: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation. METHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor. RESULTS: Genetic cluster analyses, based on expression of these 21 genes, showed similar expression profiles on days 1-3, days 5 and 6, and days 7-10, while freshly isolated cells (day Q) and day 4 cells were genotypically distinct from any of the other days. Additionally, gene expression clustering revealed strong upregulation of interleukin-6, JAK2 and STAT3 mRNA in the early stages of activation. Inhibition of the JAK/STAT signaling pathway impeded the morphological transdifferentiation of HSCs which correlated with decreased mRNA expression of several profibrotic genes including collagens, α-SMA, PDGFR and TGFβR. CONCLUSION: These data demonstrate unique clustered genetic profiles during the daily progression of HSC transdifferentiation and that JAK/STAT signaling may be critical in the early stages of transdifferentiation.
基金the National Natural Science Foundation of China(82202078)the Center for Archaeological Science of Sichuan University(23SASA01).
文摘Tibeto-Burman(TB)people have endeavored to adapt to the hypoxic,cold,and high-UV high-altitude environments in the Tibetan Plateau and complex disease exposures in lowland rainforests since the late Paleolithic period.However,the full landscape of genetic history and biological adaptation of geographically diverse TB-speaking people,as well as their interaction mechanism,remain unknown.Here,we generate a whole-genome meta-database of 500 individuals from 39 TB-speaking populations and present a comprehensive landscape of genetic diversity,admixture history,and differentiated adaptative features of geographically different TB-speaking people.We identify genetic differentiation related to geography and language among TB-speaking people,consistent with their differentiated admixture process with incoming or indigenous ancestral source populations.A robust genetic connection between the Tibetan-Yi corridor and the ancient Yellow River people supports their Northern China origin hypothesis.We finally report substructure-related differentiated biological adaptative signatures between highland Tibetans and Loloish speakers.Adaptative signatures associated with the physical pigmentation(EDAR and SLC24A5)and metabolism(ALDH9A1)are identified in Loloish people,which differed from the high-altitude adaptative genetic architecture in Tibetan.TB-related genomic resources provide new insights into the genetic basis of biological adaptation and better reference for the anthropologically informed sampling design in biomedical and genomic cohort research.
文摘Infertility is a pervasive issue affecting a considerable proportion of couples in their reproductive years,with a projected 10%-15% prevalence.It is characterized by the incapability to achieve conception following a year of consistent,unprotected intercourse,and its far-reaching consequences can take a profound emotional,psychological,and social toll on couples,inducing feelings of melancholy,exasperation,and anxiety.The appraisal of infertile couples'cases is a multifaceted and daunting process,necessitating a holistic understanding of the intricate underlying factors contributing to their infertility.Consequently,an individualized evaluation should be conducted,considering diverse parameters,such as the couple's medical history,age,infertility duration,and other relevant criteria.This paper will provide an in-depth overview of the current approaches utilized in the evaluation of men with infertility,including the commonly employed diagnostic tools and procedures.Enhancing our comprehension of infertility assessment and management holds the promise of helping couples achieve their ultimate desire of conceiving and enriching their overall quality of life.
基金the National Natural Science Foundation of China(No.51405516)the Doctoral Researchers Boosting Program of Xi’an Shiyou Universitythe Natural Science Foundation of Hunan Province(No.2015JJ2168)
文摘In order to modify the rail pre-grinding profile smoothly,non-uniform rational B-spline(NURBS)curve with weight factors is used to establish a parameterized model of the profile.A wheel-rail contact stochastic finite element model(FEM) is constructed by the Latin hypercube sampling method and 3 D elasto-plastic FEM,in which the wheelset's lateral displacement quantity is regarded as a random variable.The maximum values of nodal accumulated contact stress(NACS) and nodal mean contact stress(NMCS) in different pre-grinding profiles with differential weight factors are calculated and taken as the training samples to establish two Kriging models.A multi-objective optimization model of pre-grinding profile is established,in which the objective functions are the NACS and NMCS Kriging models.The optimum weight factors are sought using a non-dominated sorting genetic algorithm II(NSGA-II),and the corresponding optimum pre-grinding profile is obtained.The contact stress calculation before and after optimization indicates that the maximum values of NACS and NMCS decline significantly.
文摘The study aims at determining the status of soil chemical fertility in four wild coffee forests of southeastern and southwestern Ethiopia. Accordingly, soil samples were collected from surface and subsurface depths at three sites within each forest and analyzed for soil chemical properties. The results depicted that the soils at the four coffee forests did not reveal significant variations for most parameters, except Mg, CEC and C:N ratio. Significant variations were determined between the surface and subsurface soils of the four studied forests, partly indicating the impacts of anthropogenic factors on vegetation cover and soil fertility status along profile depth. At Harenna, surface soil had significantly higher total nitrogen and organic matter than sub-surface soil. The decline in available phosphorus with soil depth was also significant at the Harenna and Yayu forests. Most soil results were comparable and showed inter- and intra-forest variations, demonstrating the contributions of vegetation cover and climate gradients. The study revealed the declined soil quality parameters with increased depth, demonstrating the vulnerability of forest soils to human-induced disturbances of natural habitats and land degradation, coupled with climate changes. Overall, the results underline the need for a multi-site forest conservation and promote productivity of high quality coffee standards. This demands urgent supports for implementing community-oriented management and incentive options towards maintaining environmental sustainability and coffee genetic resources for global benefits.
