Objective To evaluate the clinical efficacy and safety of Zhenzhu Qingyuan Granules through a clinical randomized controlled trial and to analyze the potential action targets and pathways of this formula using network...Objective To evaluate the clinical efficacy and safety of Zhenzhu Qingyuan Granules through a clinical randomized controlled trial and to analyze the potential action targets and pathways of this formula using network pharmacology.Methods Patients with gastroesophageal reflux disease(GERD)of liver–stomach stagnant heat pattern who met the inclusion and exclusion criteria were randomly divided into the control group and the observation group.The control group received oral rabeprazole,whereas the observation group were given Zhenzhu Qingyuan Granules in addition to the rabeprazole.The treatment duration was 8 weeks.Clinical efficacy was observed in both groups after 8 weeks.Network pharmacology was used to analyze the action targets of ZhenzhuQingyuanGranules and the genes related to GERD,and core targets were inferred.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the potential mechanisms of this formula.Results The clinical research results showed that the total effective rate in the treatment group was 92.68%,compared with 70.00%in the control group,with a statistically significant difference(p<0.05).After treatment,both Chinese medicine syndrome score and endoscopic score improved in both groups compared with before treatment(p<0.05),and the treatment group showed greater improvement than the control group(p<0.05).Network pharmacology identified effective components of Zhenzhu Qingyuan Granules for treating GERD,including quercetin,luteolin,andβ-sitosterol,with potential action targets such as tumor protein 53(TP53),protein kinase B(AKT1),and tumor necrosis factor.Conclusion Zhenzhu Qingyuan Granules can significantly improve clinical symptoms in patients with GERD of liver–stomach stagnated heat pattern,enhance clinical efficacy,and have high safety.This formula may exert therapeutic effects through multiple targets and pathways.展开更多
This paper presents an analysis of the challenges in risk-based resource allocation in engineering projects.Sub-sequently,an alternative resource allocation evaluation method based on language information and informat...This paper presents an analysis of the challenges in risk-based resource allocation in engineering projects.Sub-sequently,an alternative resource allocation evaluation method based on language information and information axioms is proposed.Firstly,the evaluation team uses language information to give the evaluation information of the alternatives of risk resource allocation and provides the corresponding expected information for each resource.Secondly,according to the transformation formula of language information and fuzzy numbers,the above information is transformed into the evaluation information and expected information of the alternatives of risk-based resource allocation.Thirdly,according to the transformation formula of language information and fuzzy numbers,the above information is transformed into evalu-ation information and expectation information of alternative risk resource allocation.Finally,according to the information amount of each risk resource and the corresponding weight,the comprehensive information amount of the expected risk-based resource allocation alternatives is determined.展开更多
Based on the analysis of the evaluation problems associated with the risk control scheme for major engineering projects,the evaluation method of the risk control scheme considering the irrational behavior of evaluatio...Based on the analysis of the evaluation problems associated with the risk control scheme for major engineering projects,the evaluation method of the risk control scheme considering the irrational behavior of evaluation members in fuzzy random environment is proposed.Firstly,a maximum entropy model corresponding to any evaluation member is es-tablished by using triangular fuzzy random variables and grey correlation coefficient in order to obtain the weight of each risk factor of the member.Secondly,a nonlinear programming model is established according to the principle of minimiz-ing deviation to estimate the weight of different evaluation members on the evaluation of alternative risk control schemes.Lastly,the cumulative entropy model is used to calculate the weight of risk control schemes.Cumulative prospect theory obtains the comprehensive prospect utility value of each alternative to determine the optimal alternative.展开更多
The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson＇s disease ...The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson＇s disease model mice and in the hippocampal zone of young epileptic rats. However, it remains unclear whether EGb761 enhances proliferation of endogenous neural stem cells in the brain of rats with vascular dementia. In this study, a vascular dementia model was established by repeatedly clipping and reperfusing the bilateral common carotid arteries of rats in combination with an intraperitoneal injection of a sodium nitroprusside solution. Seven days after establishing the model, rats were intragastrically given EGb761 at 50 mg/kg per day. Learning and memory abilities were assessed using the Morris water maze and proliferation of endogenous neural stem cells in the subventricular zone and dentate gyrus were labeled by 5-bromo-2-deoxyuridine immunofluorescence in all rats at 15 days, and 1, 2, and 4 months after model establishment. The escape latencies in Morris water maze tests of rats with vascular dementia after EGb761 treatment were significantly shorter than the model group. Immunofluorescence staining showed that the number and proliferation of 5-bromo-2-deoxyuridine-positive cells in the subventricular zone and dentate gyrus of the EGb761-treated group were significantly higher than in the model group. These experimental findings suggest that EGb761 enhances proliferation of neural stem cells in the subventricular zone and dentate gyrus, and significantly improves learning and memory in rats with vascular dementia.展开更多
We investigated the effects of graphene on the model herb Artemisia annua,which is renowned for produc-ing artemisinin,a widely used pharmacological compound.Seedling growth and biomass were promoted when A.annua was ...We investigated the effects of graphene on the model herb Artemisia annua,which is renowned for produc-ing artemisinin,a widely used pharmacological compound.Seedling growth and biomass were promoted when A.annua was cultivated with low concentrations of graphene,an effect which was attributed to a 1.4-fold increase in nitrogen uptake,a 15%–22%increase in chlorophyllfluorescence,and greater abun-dance of carbon cycling–related bacteria.Exposure to 10 or 20 mg/L graphene resulted in a�60%increase in H2O2,and graphene could act as a catalyst accelerator,leading to a 9-fold increase in catalase(CAT)ac-tivity in vitro and thereby maintaining reactive oxygen species(ROS)homeostasis.Importantly,graphene exposure led to an 80%increase in the density of glandular secreting trichomes(GSTs),in which artemisinin is biosynthesized and stored.This contributed to a 5%increase in artemisinin content inmature leaves.Inter-estingly,expression of miR828 was reduced by both graphene and H2O2 treatments,resulting in induction of its target gene AaMYB17,a positive regulator of GST initiation.Subsequent molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA(miRNA)biogenesis through Dicers and regulates the miR828–AaMYB17 module,thus affecting GST density.Our results suggest that graphene may contribute to yield improvement in A.annua via dynamic physiological processes together with miRNA regulation,and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.展开更多
Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-m...Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemi- sinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on compre- hensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the chal- lenge of increasing global demand of artemisinin.展开更多
Regulatory T cells(Tregs)are fundamentally important for maintaining systemic immune homeostasis and are also required for immune tolerance at the maternal-fetal interface during pregnancy.Recent studies have suggeste...Regulatory T cells(Tregs)are fundamentally important for maintaining systemic immune homeostasis and are also required for immune tolerance at the maternal-fetal interface during pregnancy.Recent studies have suggested that epigenetic regulation is critically involved in Treg development and function.However,the role of H3K36me has not yet been investigated.Here,we found that the H3K36me2 methyltransferase Nsd2 was highly expressed in Tregs.Although loss of Nsd2 did not impair systemic Treg development or function,the level of Tregs at the maternal-fetal interface was significantly decreased in pregnant Nsd2 conditional knockout mice.Consequently,maternal-fetal immune tolerance was disrupted in the absence of Nsd2 in Tregs,and the pregnant mice showed severe fetal loss.Mechanistically,Nsd2 was found to upregulate CXCR4 expression via H3K36me2 modification to promote Treg cell recruitment into the decidua and suppress the anti-fetal immune response.Overall,our data identified Nsd2 as a critical epigenetic regulator of Treg recruitment for maternal-fetal tolerance.展开更多
There are mainly two different ways of learning for animals and humans： trying on yourself through interactions or imitating/copying others through communication/observation. How these two learning strategies differ ...There are mainly two different ways of learning for animals and humans： trying on yourself through interactions or imitating/copying others through communication/observation. How these two learning strategies differ and what roles they are playing in achieving coordination among individuals are two challenging problems for researchers from various disciplines. In multiagent systems, most existing work simply focuses on individual learning for achieving coordination among agents. The social learning perspective has been largely neglected. Against this background, this article contributes by proposing an integrated solution to decision making between social learning and individual learning in multiagent systems. Two integration modes have been proposed that enable agents to choose in between these two learning strategies, either in a t＇Lxed or in an adaptive manner. Experimental evaluations have shown that these two kinds of leaning strategies have different roles in maintaining efficient coordination among agents. These differences can reveal some significant insights into the manipulation and control of agent behaviors in multiagent systems, and also shed light on understanding the social factors in shaping coordinated behaviors in humans and animals.展开更多
Metabolomics has been rapidly developed as an important field in plant sciences and natural products chemistry.As the only natural source for a diversity of monoterpenoid indole alkaloids(MIAs),especially the low-abun...Metabolomics has been rapidly developed as an important field in plant sciences and natural products chemistry.As the only natural source for a diversity of monoterpenoid indole alkaloids(MIAs),especially the low-abundance antitumor agents vinblastine and vincristine,Catharanthus roseus is highly valued and has been studied extensively as a model for medicinal plants improvement.Due to multistep enzymatic biosynthesis and complex regulation,genetic modification in the MIA pathway has resulted in complicated changes of both secondary and primary metabolism in C.roseus,affecting not only the MIA pathway but also other pathways.Research at the metabolic level is necessary to increase knowledge on the genetic regulation of the whole metabolic network connected to MIA biosynthesis.Nuclear magnetic resonance(NMR)is a very suitable and powerful complementary technique for the identification and quantification of metabolites in the plant matrix.NMR-based metabolomics has been used in studies of C.roseus for pathway elucidation,understanding stress responses,classification among different cultivars,safety and quality controls of transgenic plants,cross talk between pathways,and diversion of carbon fluxes,with the aim of fully unravelling MIA biosynthesis,its regulation and the function of the alkaloids in the plant from a systems biology point of view.展开更多
基金National Administration of Traditional Chinese Medicine Evidence-Based Capacity Building Project(2019XZZXXH005)Special Project on Traditional Chinese Medicine Scientific Research of Health Commission of Henan Province(2022ZY2022)+1 种基金Henan Provincial Top Talents Cultivation Project in Traditional Chinese Medicine Discipline of Henan Provincial Traditional Chinese Medicine Inheritance and Innovation Talents Project(Zhongjing Project)(Henan Health TraditionalMedicine Letter[2021]No.15)Special Project on Traditional Chinese Medicine Scientific Research of Health Commission of Henan Province(2023ZY2062).
文摘Objective To evaluate the clinical efficacy and safety of Zhenzhu Qingyuan Granules through a clinical randomized controlled trial and to analyze the potential action targets and pathways of this formula using network pharmacology.Methods Patients with gastroesophageal reflux disease(GERD)of liver–stomach stagnant heat pattern who met the inclusion and exclusion criteria were randomly divided into the control group and the observation group.The control group received oral rabeprazole,whereas the observation group were given Zhenzhu Qingyuan Granules in addition to the rabeprazole.The treatment duration was 8 weeks.Clinical efficacy was observed in both groups after 8 weeks.Network pharmacology was used to analyze the action targets of ZhenzhuQingyuanGranules and the genes related to GERD,and core targets were inferred.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the potential mechanisms of this formula.Results The clinical research results showed that the total effective rate in the treatment group was 92.68%,compared with 70.00%in the control group,with a statistically significant difference(p<0.05).After treatment,both Chinese medicine syndrome score and endoscopic score improved in both groups compared with before treatment(p<0.05),and the treatment group showed greater improvement than the control group(p<0.05).Network pharmacology identified effective components of Zhenzhu Qingyuan Granules for treating GERD,including quercetin,luteolin,andβ-sitosterol,with potential action targets such as tumor protein 53(TP53),protein kinase B(AKT1),and tumor necrosis factor.Conclusion Zhenzhu Qingyuan Granules can significantly improve clinical symptoms in patients with GERD of liver–stomach stagnated heat pattern,enhance clinical efficacy,and have high safety.This formula may exert therapeutic effects through multiple targets and pathways.
文摘This paper presents an analysis of the challenges in risk-based resource allocation in engineering projects.Sub-sequently,an alternative resource allocation evaluation method based on language information and information axioms is proposed.Firstly,the evaluation team uses language information to give the evaluation information of the alternatives of risk resource allocation and provides the corresponding expected information for each resource.Secondly,according to the transformation formula of language information and fuzzy numbers,the above information is transformed into the evaluation information and expected information of the alternatives of risk-based resource allocation.Thirdly,according to the transformation formula of language information and fuzzy numbers,the above information is transformed into evalu-ation information and expectation information of alternative risk resource allocation.Finally,according to the information amount of each risk resource and the corresponding weight,the comprehensive information amount of the expected risk-based resource allocation alternatives is determined.
文摘Based on the analysis of the evaluation problems associated with the risk control scheme for major engineering projects,the evaluation method of the risk control scheme considering the irrational behavior of evaluation members in fuzzy random environment is proposed.Firstly,a maximum entropy model corresponding to any evaluation member is es-tablished by using triangular fuzzy random variables and grey correlation coefficient in order to obtain the weight of each risk factor of the member.Secondly,a nonlinear programming model is established according to the principle of minimiz-ing deviation to estimate the weight of different evaluation members on the evaluation of alternative risk control schemes.Lastly,the cumulative entropy model is used to calculate the weight of risk control schemes.Cumulative prospect theory obtains the comprehensive prospect utility value of each alternative to determine the optimal alternative.
基金financially sponsored by the Natural Science Foundation of Shandong Province,No.Y2008C32Scientific Research Funds of Shandong Provincial Education Ministry,No.J01K09
文摘The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson＇s disease model mice and in the hippocampal zone of young epileptic rats. However, it remains unclear whether EGb761 enhances proliferation of endogenous neural stem cells in the brain of rats with vascular dementia. In this study, a vascular dementia model was established by repeatedly clipping and reperfusing the bilateral common carotid arteries of rats in combination with an intraperitoneal injection of a sodium nitroprusside solution. Seven days after establishing the model, rats were intragastrically given EGb761 at 50 mg/kg per day. Learning and memory abilities were assessed using the Morris water maze and proliferation of endogenous neural stem cells in the subventricular zone and dentate gyrus were labeled by 5-bromo-2-deoxyuridine immunofluorescence in all rats at 15 days, and 1, 2, and 4 months after model establishment. The escape latencies in Morris water maze tests of rats with vascular dementia after EGb761 treatment were significantly shorter than the model group. Immunofluorescence staining showed that the number and proliferation of 5-bromo-2-deoxyuridine-positive cells in the subventricular zone and dentate gyrus of the EGb761-treated group were significantly higher than in the model group. These experimental findings suggest that EGb761 enhances proliferation of neural stem cells in the subventricular zone and dentate gyrus, and significantly improves learning and memory in rats with vascular dementia.
基金supported by the National Natural Science Foundation of China (82274047 and 52071192)the National Key R&D Program of China (2018YFA0900600)+3 种基金the Engineering Research Center of Coal-Based Ecological Carbon Sequestration Technology of the Ministry of Education (MJST2023-3)the China Postdoctoral Science Foundation (2023M732232)SJTU Trans-med Awards Research (20190104)supported in part by the Bill&Melinda Gates Foundation (OPP1199872 and INV-027291).
文摘We investigated the effects of graphene on the model herb Artemisia annua,which is renowned for produc-ing artemisinin,a widely used pharmacological compound.Seedling growth and biomass were promoted when A.annua was cultivated with low concentrations of graphene,an effect which was attributed to a 1.4-fold increase in nitrogen uptake,a 15%–22%increase in chlorophyllfluorescence,and greater abun-dance of carbon cycling–related bacteria.Exposure to 10 or 20 mg/L graphene resulted in a�60%increase in H2O2,and graphene could act as a catalyst accelerator,leading to a 9-fold increase in catalase(CAT)ac-tivity in vitro and thereby maintaining reactive oxygen species(ROS)homeostasis.Importantly,graphene exposure led to an 80%increase in the density of glandular secreting trichomes(GSTs),in which artemisinin is biosynthesized and stored.This contributed to a 5%increase in artemisinin content inmature leaves.Inter-estingly,expression of miR828 was reduced by both graphene and H2O2 treatments,resulting in induction of its target gene AaMYB17,a positive regulator of GST initiation.Subsequent molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA(miRNA)biogenesis through Dicers and regulates the miR828–AaMYB17 module,thus affecting GST density.Our results suggest that graphene may contribute to yield improvement in A.annua via dynamic physiological processes together with miRNA regulation,and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.
文摘Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemi- sinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on compre- hensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the chal- lenge of increasing global demand of artemisinin.
基金supported by the National Key R&D Program of China (2018YFC1003900)the National Natural Science Foundation of China (Grant Number 82001653 to LZ and 31970828 to XW)Jiangsu Outstanding Young Investigator Program (BK20200030).
文摘Regulatory T cells(Tregs)are fundamentally important for maintaining systemic immune homeostasis and are also required for immune tolerance at the maternal-fetal interface during pregnancy.Recent studies have suggested that epigenetic regulation is critically involved in Treg development and function.However,the role of H3K36me has not yet been investigated.Here,we found that the H3K36me2 methyltransferase Nsd2 was highly expressed in Tregs.Although loss of Nsd2 did not impair systemic Treg development or function,the level of Tregs at the maternal-fetal interface was significantly decreased in pregnant Nsd2 conditional knockout mice.Consequently,maternal-fetal immune tolerance was disrupted in the absence of Nsd2 in Tregs,and the pregnant mice showed severe fetal loss.Mechanistically,Nsd2 was found to upregulate CXCR4 expression via H3K36me2 modification to promote Treg cell recruitment into the decidua and suppress the anti-fetal immune response.Overall,our data identified Nsd2 as a critical epigenetic regulator of Treg recruitment for maternal-fetal tolerance.
文摘There are mainly two different ways of learning for animals and humans： trying on yourself through interactions or imitating/copying others through communication/observation. How these two learning strategies differ and what roles they are playing in achieving coordination among individuals are two challenging problems for researchers from various disciplines. In multiagent systems, most existing work simply focuses on individual learning for achieving coordination among agents. The social learning perspective has been largely neglected. Against this background, this article contributes by proposing an integrated solution to decision making between social learning and individual learning in multiagent systems. Two integration modes have been proposed that enable agents to choose in between these two learning strategies, either in a t＇Lxed or in an adaptive manner. Experimental evaluations have shown that these two kinds of leaning strategies have different roles in maintaining efficient coordination among agents. These differences can reveal some significant insights into the manipulation and control of agent behaviors in multiagent systems, and also shed light on understanding the social factors in shaping coordinated behaviors in humans and animals.
基金National High-tech R&D Program of China(2011AA100605)Shanghai Key Discipline Cultivation and Construction Project(Horticulture)Shanghai Jiao Tong University Agri-Engineering Program.
文摘Metabolomics has been rapidly developed as an important field in plant sciences and natural products chemistry.As the only natural source for a diversity of monoterpenoid indole alkaloids(MIAs),especially the low-abundance antitumor agents vinblastine and vincristine,Catharanthus roseus is highly valued and has been studied extensively as a model for medicinal plants improvement.Due to multistep enzymatic biosynthesis and complex regulation,genetic modification in the MIA pathway has resulted in complicated changes of both secondary and primary metabolism in C.roseus,affecting not only the MIA pathway but also other pathways.Research at the metabolic level is necessary to increase knowledge on the genetic regulation of the whole metabolic network connected to MIA biosynthesis.Nuclear magnetic resonance(NMR)is a very suitable and powerful complementary technique for the identification and quantification of metabolites in the plant matrix.NMR-based metabolomics has been used in studies of C.roseus for pathway elucidation,understanding stress responses,classification among different cultivars,safety and quality controls of transgenic plants,cross talk between pathways,and diversion of carbon fluxes,with the aim of fully unravelling MIA biosynthesis,its regulation and the function of the alkaloids in the plant from a systems biology point of view.
