A sulfated galactoftucan designated as UpG was obtained from the brown algae Undaria pinnatifida by calcium chloride extraction.Chemical analyses showed that UpG is composed of galactose and fucose at a high sulfation...A sulfated galactoftucan designated as UpG was obtained from the brown algae Undaria pinnatifida by calcium chloride extraction.Chemical analyses showed that UpG is composed of galactose and fucose at a high sulfation level.Low-molecular weight UpGP-0.5 was prepared from UpG through acid hydrolysis for structure characterization.The backbones of UpG are determined to beα-(1,3)-Fuc,α-(1,4)-Gal,α-(1,3)-Gal,andα-(1,6)-Gal by GC-MS,FT-IR,NMR,and LC-MS analyses.Sulfate groups are modified at C2 and/or C4 of fucose and C3 and/or C4 of galactose.UpG could partially lower blood sugar and serum lipid levels in type 2 diabetic mice.Moreover,UpG treatment regulates the abundance of some specific gut microbiota,such as enriching the abundance of Muribaculum and Christensenellaceae,and reducing that of Bilophila,Tannerellaceae,Candidatus Saccharimonas and Anaerotruncus.The findings characterized the detailed structure of a sulfated galactofucan and investigated its potential for the treatment of type 2 diabetes mellitus.展开更多
By using the characteristics of the new building in China, this article constructs the virtual repeat sale method to produce virtual repeat data which is similar to the repeat sale model on the house price index. Case...By using the characteristics of the new building in China, this article constructs the virtual repeat sale method to produce virtual repeat data which is similar to the repeat sale model on the house price index. Case-Shiller procedure and OFHEO method are used to calculate the house price index for new building in China. A discussion is given and furthering models are needed to take advantage of the virtual repeat sale data.展开更多
[Objectives] The purpose of this study is to dissociate endophytic fungus producing diterpenoids from Torreya fargesii tissue and examines its inhibiting effect on tumor cells. [Methods]Plant endophytes were isolated ...[Objectives] The purpose of this study is to dissociate endophytic fungus producing diterpenoids from Torreya fargesii tissue and examines its inhibiting effect on tumor cells. [Methods]Plant endophytes were isolated and purified to study their resistance to Gram-positive( G+) and Gram-negative bacteria( G-). High performance liquid chromatography( HPLC) was used for analysis of the retention time,relative peak area and percentage content of its metabolite. By liquid chromatography-mass spectrometry( HPLC-MS),the material characteristic of the ion pair information of the metabolites was measured. The bacterial strain was also classified. [Results] The results showed that the secondary metabolites produced by the strain BP6 T3 possessed double resistance to G+and G-bacteria. The strain was identified as Penicillium sp by preliminary classification. Through HPLC analysis,the retention time of fermentation extracts was 12. 8 min with almost the same as the standard of taxol. According to the chromatograph,the relative peak area was 12 887. 11,the average relative percentage was about 15. 8%,and the content of taxol analogs in fermentation broth reached 16. 59 mg/L. The material characteristic of the formation of ion fragments of taxane analogues in metabolic extracts was identical to that of the taxol standard determined by HPLC-MS. It can be initially determined that strain BP6 T3 can produce taxane compounds. Taxol substance produced by this strain had obvious inhibitory effect on Hela cells with the concentration increasing. Different precursors had a significant effect on the production of paclitaxel metabolites in this strain. L-phenylalanine was used as the precursor and the yield increased most,with an increase rate of 425. 7%. [Conclusions] The strain is expected to be used for mass production in antitumor drug taxol.展开更多
In this paper, an innovative Genetic Algorithms (GA)-based inexact non-linear programming (GAINLP) problem solving approach has been proposed for solving non-linear programming optimization problems with inexact infor...In this paper, an innovative Genetic Algorithms (GA)-based inexact non-linear programming (GAINLP) problem solving approach has been proposed for solving non-linear programming optimization problems with inexact information (inexact non-linear operation programming). GAINLP was developed based on a GA-based inexact quadratic solving method. The Genetic Algorithm Solver of the Global Optimization Toolbox (GASGOT) developed by MATLABTM was adopted as the implementation environment of this study. GAINLP was applied to a municipality solid waste management case. The results from different scenarios indicated that the proposed GA-based heuristic optimization approach was able to generate a solution for a complicated nonlinear problem, which also involved uncertainty.展开更多
Coronavirus disease 2019(COVID-19)is a global infectious disease that seriously endangers human life and health and affects normal social activities.Since the pandemic outbreak from December 2019 to February 2023,the ...Coronavirus disease 2019(COVID-19)is a global infectious disease that seriously endangers human life and health and affects normal social activities.Since the pandemic outbreak from December 2019 to February 2023,the total number of confirmed cases has exceeded 753 million,and the deaths caused by COVID-19 have reached 6.6 million(https://covid19.who.int;accessed on Feb.16,2023).展开更多
Coxsackievirus A10(CV-A10)is one of the etiological agents associated with hand,foot and mouth disease(HFMD)and also causes a variety of illnesses in humans,including pneumonia,and myocarditis.Different people,particu...Coxsackievirus A10(CV-A10)is one of the etiological agents associated with hand,foot and mouth disease(HFMD)and also causes a variety of illnesses in humans,including pneumonia,and myocarditis.Different people,particularly young children,may have different immunological responses to infection.Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus.The characteristics of CV-A10 infection,replication,and shedding in humans remain unknown.In this study,rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans.The clinical symptoms,viral shedding,inflammatory response and pathologic changes were investigated in acute infection(1–11 day post infection)and recovery period(12–180 day post infection).All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans.Substantial inflammatory pathological damages were observed in multi-organs,including the lung,heart,liver,and kidney.During the acute period,all rhesus macaques displayed clinical signs,viral shedding,normalization of serum cytokines,and increased serum neutralizing antibodies,whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period.In addition,there were no significant differences between respiratory and digestive tract infected animals.Overall,all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.展开更多
Glycosaminoglycans(GAGs)are a class of linear polysaccharides,consisting of alternating disaccharide sequences of uronic acid and hexosamines(or galactose)with and without sulfation.They can interact with various prot...Glycosaminoglycans(GAGs)are a class of linear polysaccharides,consisting of alternating disaccharide sequences of uronic acid and hexosamines(or galactose)with and without sulfation.They can interact with various proteins,such as growth factors,receptors and cell adhesion molecules,endowing these with various biological and pharmacological activi-ties.Such activities make GAGs useful in health care products and medicines.Currently,all GAGs,with the exception of hyaluronan,are produced by extraction from animal tissues.However,limited availability,poor control of animal tissues,impurities,viruses,prions,endotoxins,contamination and other problems have increased the interest in new approaches for GAG production.These new approaches include GAGs production by chemical synthesis,chemoenzymatic synthesis and metabolic engineering.One chemically synthesized heparin pentasaccharide,fondaparinux sodium,is in clinical use.Mostly,hyaluronan today is prepared by microbial fermentation,largely replacing hyaluronan from rooster comb.The recent gram scale chemoenzymatic synthesis of a heparin dodecasaccharide suggests its potential to replace currently used animal-sourced low molecular weight heparin(LMWH).Despite these considerable successes,such high-tech approaches still cannot meet worldwide demands for GAGs.This review gives a brief introduction on the manufacturing of unfractionated and low molecular weight heparins,the chemical synthesis and chemoenzymatic synthesis of GAGs and focuses on the progress in the bioengineered preparation of GAGs,particularly heparin.展开更多
Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to severe.However,CVB3-infected mouse models mainly demonstrate viral m...Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to severe.However,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD symptoms.Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on CVB3.In this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes.The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD symptoms.Notably,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage.In the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the heart.Surprisingly,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild infections.In summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD.These models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.展开更多
基金Supported by the National Key Research and Development Program(Nos.2018YFC0311003,2017YFE0103100)the National Natural Science Foundation of China(Nos.81903534,81773628,81741165)the HighLevel Talent Special Support Plan of Zhejiang Province(No.2019R52009)。
文摘A sulfated galactoftucan designated as UpG was obtained from the brown algae Undaria pinnatifida by calcium chloride extraction.Chemical analyses showed that UpG is composed of galactose and fucose at a high sulfation level.Low-molecular weight UpGP-0.5 was prepared from UpG through acid hydrolysis for structure characterization.The backbones of UpG are determined to beα-(1,3)-Fuc,α-(1,4)-Gal,α-(1,3)-Gal,andα-(1,6)-Gal by GC-MS,FT-IR,NMR,and LC-MS analyses.Sulfate groups are modified at C2 and/or C4 of fucose and C3 and/or C4 of galactose.UpG could partially lower blood sugar and serum lipid levels in type 2 diabetic mice.Moreover,UpG treatment regulates the abundance of some specific gut microbiota,such as enriching the abundance of Muribaculum and Christensenellaceae,and reducing that of Bilophila,Tannerellaceae,Candidatus Saccharimonas and Anaerotruncus.The findings characterized the detailed structure of a sulfated galactofucan and investigated its potential for the treatment of type 2 diabetes mellitus.
文摘By using the characteristics of the new building in China, this article constructs the virtual repeat sale method to produce virtual repeat data which is similar to the repeat sale model on the house price index. Case-Shiller procedure and OFHEO method are used to calculate the house price index for new building in China. A discussion is given and furthering models are needed to take advantage of the virtual repeat sale data.
基金Supported by Provincial College Students’Innovation and Entrepreneurship Training Program of Colleges and Universities in Hubei Province in 2017(2013)"Strategic Emerging(Pillar)Industrial Talent Training Program"of Colleges and Universities in Hubei Province[Hubei Provincial Department of Education EJiao Gao(201711798030)No.11]+2 种基金Pilot Funded Project of"Comprehensive Professional Reform"of Provincial Department of Education and Provincial Department of Finance[EJiao Gao Ban(2014)No.6]Hubei Educational Science"Twelfth Five-Year Plan"Project(2014B272)School Youth Natural Science Foundation(2013dhzk003)
文摘[Objectives] The purpose of this study is to dissociate endophytic fungus producing diterpenoids from Torreya fargesii tissue and examines its inhibiting effect on tumor cells. [Methods]Plant endophytes were isolated and purified to study their resistance to Gram-positive( G+) and Gram-negative bacteria( G-). High performance liquid chromatography( HPLC) was used for analysis of the retention time,relative peak area and percentage content of its metabolite. By liquid chromatography-mass spectrometry( HPLC-MS),the material characteristic of the ion pair information of the metabolites was measured. The bacterial strain was also classified. [Results] The results showed that the secondary metabolites produced by the strain BP6 T3 possessed double resistance to G+and G-bacteria. The strain was identified as Penicillium sp by preliminary classification. Through HPLC analysis,the retention time of fermentation extracts was 12. 8 min with almost the same as the standard of taxol. According to the chromatograph,the relative peak area was 12 887. 11,the average relative percentage was about 15. 8%,and the content of taxol analogs in fermentation broth reached 16. 59 mg/L. The material characteristic of the formation of ion fragments of taxane analogues in metabolic extracts was identical to that of the taxol standard determined by HPLC-MS. It can be initially determined that strain BP6 T3 can produce taxane compounds. Taxol substance produced by this strain had obvious inhibitory effect on Hela cells with the concentration increasing. Different precursors had a significant effect on the production of paclitaxel metabolites in this strain. L-phenylalanine was used as the precursor and the yield increased most,with an increase rate of 425. 7%. [Conclusions] The strain is expected to be used for mass production in antitumor drug taxol.
文摘In this paper, an innovative Genetic Algorithms (GA)-based inexact non-linear programming (GAINLP) problem solving approach has been proposed for solving non-linear programming optimization problems with inexact information (inexact non-linear operation programming). GAINLP was developed based on a GA-based inexact quadratic solving method. The Genetic Algorithm Solver of the Global Optimization Toolbox (GASGOT) developed by MATLABTM was adopted as the implementation environment of this study. GAINLP was applied to a municipality solid waste management case. The results from different scenarios indicated that the proposed GA-based heuristic optimization approach was able to generate a solution for a complicated nonlinear problem, which also involved uncertainty.
基金supported by the Chinese Traditional Medicine Science and Technology Projects of Zhejiang Province (Nos.2021ZB002,2022ZB002,and 2020ZQ002)the National Natural Science Foundation of China (No.31702144)+1 种基金the Zhejiang Province Basic Public Welfare Research Project (No.LGF21H250002)the National Administration of Traditional Chinese Medicine and Zhejiang Province (No.GZY-ZJ-KJ-24001),China.
文摘Coronavirus disease 2019(COVID-19)is a global infectious disease that seriously endangers human life and health and affects normal social activities.Since the pandemic outbreak from December 2019 to February 2023,the total number of confirmed cases has exceeded 753 million,and the deaths caused by COVID-19 have reached 6.6 million(https://covid19.who.int;accessed on Feb.16,2023).
基金the Medical and Health Science and Technology Innovation Project of Chinese Academy of Medical Sciences(CIFMS,2016-I2M-2-001)National Resource Center for Non-Human Primates,Major Science and Technology Special Projects in Yunnan ProvinceKunming Science and Technology Innovation and Service Capacity Enhancement Program Key Projects(2016-2-R-07674)。
文摘Coxsackievirus A10(CV-A10)is one of the etiological agents associated with hand,foot and mouth disease(HFMD)and also causes a variety of illnesses in humans,including pneumonia,and myocarditis.Different people,particularly young children,may have different immunological responses to infection.Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus.The characteristics of CV-A10 infection,replication,and shedding in humans remain unknown.In this study,rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans.The clinical symptoms,viral shedding,inflammatory response and pathologic changes were investigated in acute infection(1–11 day post infection)and recovery period(12–180 day post infection).All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans.Substantial inflammatory pathological damages were observed in multi-organs,including the lung,heart,liver,and kidney.During the acute period,all rhesus macaques displayed clinical signs,viral shedding,normalization of serum cytokines,and increased serum neutralizing antibodies,whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period.In addition,there were no significant differences between respiratory and digestive tract infected animals.Overall,all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.
基金This study was supported by China Scholarship Council(W.J.)the National Institutes of Health(DK111958 and CA231074)(F.Z.and R.J.L.).
文摘Glycosaminoglycans(GAGs)are a class of linear polysaccharides,consisting of alternating disaccharide sequences of uronic acid and hexosamines(or galactose)with and without sulfation.They can interact with various proteins,such as growth factors,receptors and cell adhesion molecules,endowing these with various biological and pharmacological activi-ties.Such activities make GAGs useful in health care products and medicines.Currently,all GAGs,with the exception of hyaluronan,are produced by extraction from animal tissues.However,limited availability,poor control of animal tissues,impurities,viruses,prions,endotoxins,contamination and other problems have increased the interest in new approaches for GAG production.These new approaches include GAGs production by chemical synthesis,chemoenzymatic synthesis and metabolic engineering.One chemically synthesized heparin pentasaccharide,fondaparinux sodium,is in clinical use.Mostly,hyaluronan today is prepared by microbial fermentation,largely replacing hyaluronan from rooster comb.The recent gram scale chemoenzymatic synthesis of a heparin dodecasaccharide suggests its potential to replace currently used animal-sourced low molecular weight heparin(LMWH).Despite these considerable successes,such high-tech approaches still cannot meet worldwide demands for GAGs.This review gives a brief introduction on the manufacturing of unfractionated and low molecular weight heparins,the chemical synthesis and chemoenzymatic synthesis of GAGs and focuses on the progress in the bioengineered preparation of GAGs,particularly heparin.
基金supported by several key projects,the Medical and Health Science and Technology Innovation Project of the Chinese Academy of Medical Sciences(CIFMS,2016-I2M-2-001)the National Resource Center for Non-Human Primates,Major Science and Technology Special Projects in Yunnan Province,Kunming Science and Technology Innovation and Service Capacity Enhancement Program Key Projects(2016-2-R-07674)+3 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2018-I2M-3-002 and 2021-I2M-1-024)the National Key R&D Project of China(2021YFF0702804)Peking Union Medical College-Central University Basic Scientific Research Business Fee(Project number.:3332023079)Yunnan Province Applied Basic Research Special Project-General Project(project number:202401CF070048,202301AT070367).
文摘Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to severe.However,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD symptoms.Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on CVB3.In this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes.The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD symptoms.Notably,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage.In the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the heart.Surprisingly,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild infections.In summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD.These models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.