The recent emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)caused serious harm to human health and struck a blow to global economic development.Research on SARS-CoV-2 has greatly benefited from...The recent emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)caused serious harm to human health and struck a blow to global economic development.Research on SARS-CoV-2 has greatly benefited from the use of reverse genetics systems,which have been established to artificially manipulate the viral genome,generating recombinant and reporter infectious viruses or biosafety level 2(BSL-2)-adapted non-infectious replicons with desired modifications.These tools have been instrumental in studying the molecular biological characteristics of the virus,investigating antiviral therapeutics,and facilitating the development of attenuated vaccine candidates.Here,we review the construction strategies,development,and applications of reverse genetics systems for SARS-CoV-2,which may be applied to other CoVs as well.展开更多
Cracking furnace is the core device for ethylene production. In practice, multiple ethylene furnaces are usually run in parallel. The scheduling of the entire cracking furnace system has great significance when multip...Cracking furnace is the core device for ethylene production. In practice, multiple ethylene furnaces are usually run in parallel. The scheduling of the entire cracking furnace system has great significance when multiple feeds are simultaneously processed in multiple cracking furnaces with the changing of operating cost and yield of product. In this paper, given the requirements of both profit and energy saving in actual production process, a multi-objective optimization model contains two objectives, maximizing the average benefits and minimizing the average coking amount was proposed. The model can be abstracted as a multi-objective mixed integer non- linear programming problem. Considering the mixed integer decision variables of this multi-objective problem, an improved hybrid encoding non-dominated sorting genetic algorithm with mixed discrete variables （MDNSGA-II） is used to solve the Pareto optimal front of this model, the algorithm adopted crossover and muta- tion strategy with multi-operators, which overcomes the deficiency that normal genetic algorithm cannot handle the optimization problem with mixed variables. Finally, using an ethylene plant with multiple cracking furnaces as an example to illustrate the effectiveness of the scheduling results by comparing the optimization results of multi-objective and single objective model.展开更多
The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer’s disease(AD)research.Here,we present PI4AD,a computational medicine...The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer’s disease(AD)research.Here,we present PI4AD,a computational medicine framework that integrates multi-omics data,systems biology,and arti-ficial neural networks for therapeutic discovery.This framework leverages multi-omic and network evidence to deliver three core functionalities:clinical target prioritisation;self-organising prioritisation map construction,distinguishing AD-specific targets from those linked to neuropsychiatric disorders;and pathway crosstalk-informed therapeutic discovery.PI4AD successfully recovers clinically validated targets like APP and ESR1,confirming its prioritisation efficacy.Its artificial neural network component identifies disease-specific molecular signatures,while pathway crosstalk analysis reveals critical nodal genes(e.g.,HRAS and MAPK1),drug repurposing candidates,and clinically relevant network modules.By validating targets,elucidating disease-specific therapeutic potentials,and exploring crosstalk mechanisms,PI4AD bridges genetic insights with pathway-level biology,establishing a systems genetics foundation for rational therapeutic development.Importantly,its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation―provides a strategy to disrupt AD progression,complementing conventional amyloid/tau-focused paradigms,with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.展开更多
Genome-wide association studies （GWASs） have identified thousands of genes and genetic variants （mainly SNPs） that contribute to complex diseases in humans. Functional characterization and mechanistic elucidation ...Genome-wide association studies （GWASs） have identified thousands of genes and genetic variants （mainly SNPs） that contribute to complex diseases in humans. Functional characterization and mechanistic elucidation of these SNPs and genes action are the next major challenge. It has been well established that SNPs altering the amino acids of protein-coding genes can drastically impact protein function, and play an important role in molecular pathogenesis. Functions of regulatory SNPs can be complex and elusive, and involve gene expression regulation through the effect on RNA splicing, transcription factor binding, DNA metbylation and miRNA recruitment. In the present review, we summarize the recent progress in our understanding of functional consequences of GWAS-associated non-coding regulatory SNPs, and discuss the application of systems genetics and network biology in the interpretation of GWAS findings.展开更多
We numerically investigate the effects of nonlinear time-delay on the stochastic system. With the delay time increasing, it is found that the peak of probability distribution in low steady states is decreased, and the...We numerically investigate the effects of nonlinear time-delay on the stochastic system. With the delay time increasing, it is found that the peak of probability distribution in low steady states is decreased, and the peak of probability distribution in high steady states is increased. The mean of state variable, the normalized variance, and the normalized autocorrelation function which quantifies the concentrated degree are slowly varied for small delay time. However, the mean of state variable is rapidly increased, and the normalized variance and the normalized autocorrelation function is rapidly decreased for large delay time.展开更多
In the megadiverse forests of Southeast Asia, hundreds of timber species are economically important but the population genetics of only a few taxa are known. Cross-specific amplification of microsatellite loci among c...In the megadiverse forests of Southeast Asia, hundreds of timber species are economically important but the population genetics of only a few taxa are known. Cross-specific amplification of microsatellite loci among closely related taxa could enhance our ability to study and manage previously unstudied species. We successfully utilized STMS markers in Shorea platyclados, originally developed for Shorea curtisii. The six primer pairs we tried successfully produced PCR products of expected sizes. The number of alleles observed ranged from 10 to 14 and an average of 12 alleles were detected per locus. A high expected and observed heterozygosity was observed and it ranges from 0.718 to 0.827 among all populations across all six loci tested. Microsatellite DNA markers are highly polymorphic, co-dominant, reproducible, and amenable to high throughput genetic analyses. Overall, the cross- specific amplification of microsatellite loci appears to be complicated by numerous factors. While the approach may be effective for local management and conservation ofpoorly known species, the results must be carefully interpreted.展开更多
Understanding the reproductive strategy of an organism is important in conservation ecology as it directly affects the population performance under changing environmental conditions.Chinese sturgeon(Acipenser sinensis...Understanding the reproductive strategy of an organism is important in conservation ecology as it directly affects the population performance under changing environmental conditions.Chinese sturgeon(Acipenser sinensis)are the largest anadromous fish in the Yangtze River,China.Currently,the species has only one spawning ground and has failed to spawn in recent years,leading it to the brink of extinction.To develop effective conservation measures,a further understanding of its reproductive strategy is needed.In our study,we conducted kinship analyses by using mitochondrial and microsatellite DNA data from 216 wild juveniles collected over nine years(20062013,2015)to understand the mating system,breeding interval,effective number of breeding adults,and reproductive success.The results from these analyses suggested polygynandry,with some parents contributing up to eight half-sibling juvenile genotypes.Although the spawning ground was restricted to a limited area,genetic diversity was maintained at a relatively high level(observed heterozygosity from 0.698 to 0.787 and expected heterozygosity from 0.763 to 0.787)and inbreeding coefficients in each year-class ranged from1% to 9%(low to modest detrimental effects on offspring).A parental inference analysis revealed that Chinese sturgeon have a breeding interval of 2-6 years,indicating that it has the potential to feed,accumulate nutrition in the ocean,and then migrate back to the Yangtze River for iteroparous reproduction.The annual effective number of breeders in the Yangtze River ranged from 14 to 161 during the study period,and it decreased by 62.1%from the 20112014 year-classes.This sharp population decline likely contributes to the reproduction failure.However,the ratios of effective to census population size(Ne/Nc)were all larger than 0.20 after the 2010 year-class,indicating relatively even reproductive success.Based on these results,a suggested approach to protect this species is to restock parent fish to increase the reproductive stock size and optimize the discharge of the Three Gorges Dam to reduce the unsuitable hydrological conditions and rehabilitate spawning ground habitats.展开更多
基金the Major Research Plan of the National Natural Science Foundation of China(92269105)the Zhejiang Provincial Natural Science Foundation(LZ22C180002).
文摘The recent emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)caused serious harm to human health and struck a blow to global economic development.Research on SARS-CoV-2 has greatly benefited from the use of reverse genetics systems,which have been established to artificially manipulate the viral genome,generating recombinant and reporter infectious viruses or biosafety level 2(BSL-2)-adapted non-infectious replicons with desired modifications.These tools have been instrumental in studying the molecular biological characteristics of the virus,investigating antiviral therapeutics,and facilitating the development of attenuated vaccine candidates.Here,we review the construction strategies,development,and applications of reverse genetics systems for SARS-CoV-2,which may be applied to other CoVs as well.
基金Supported by the National Natural Science Foundation of China(21276078)"Shu Guang"project of Shanghai Municipal Education Commission,973 Program of China(2012CB720500)the Shanghai Science and Technology Program(13QH1401200)
文摘Cracking furnace is the core device for ethylene production. In practice, multiple ethylene furnaces are usually run in parallel. The scheduling of the entire cracking furnace system has great significance when multiple feeds are simultaneously processed in multiple cracking furnaces with the changing of operating cost and yield of product. In this paper, given the requirements of both profit and energy saving in actual production process, a multi-objective optimization model contains two objectives, maximizing the average benefits and minimizing the average coking amount was proposed. The model can be abstracted as a multi-objective mixed integer non- linear programming problem. Considering the mixed integer decision variables of this multi-objective problem, an improved hybrid encoding non-dominated sorting genetic algorithm with mixed discrete variables （MDNSGA-II） is used to solve the Pareto optimal front of this model, the algorithm adopted crossover and muta- tion strategy with multi-operators, which overcomes the deficiency that normal genetic algorithm cannot handle the optimization problem with mixed variables. Finally, using an ethylene plant with multiple cracking furnaces as an example to illustrate the effectiveness of the scheduling results by comparing the optimization results of multi-objective and single objective model.
基金supported by Noncommunicable Chronic DiseasesNational Science and Technology Major Project(2024ZD0519600 to Hai Fang,China)National Natural Science Foundation of China(32470681 and 32170663 to Hai Fang,82470220 to Zheng Wang,and 82272128 to Ming Ni)Program for Basic and Translational Research on mRNA Drugs from Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,and Innovative Research Team of High-Level Local Universities in Shanghai.
文摘The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer’s disease(AD)research.Here,we present PI4AD,a computational medicine framework that integrates multi-omics data,systems biology,and arti-ficial neural networks for therapeutic discovery.This framework leverages multi-omic and network evidence to deliver three core functionalities:clinical target prioritisation;self-organising prioritisation map construction,distinguishing AD-specific targets from those linked to neuropsychiatric disorders;and pathway crosstalk-informed therapeutic discovery.PI4AD successfully recovers clinically validated targets like APP and ESR1,confirming its prioritisation efficacy.Its artificial neural network component identifies disease-specific molecular signatures,while pathway crosstalk analysis reveals critical nodal genes(e.g.,HRAS and MAPK1),drug repurposing candidates,and clinically relevant network modules.By validating targets,elucidating disease-specific therapeutic potentials,and exploring crosstalk mechanisms,PI4AD bridges genetic insights with pathway-level biology,establishing a systems genetics foundation for rational therapeutic development.Importantly,its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation―provides a strategy to disrupt AD progression,complementing conventional amyloid/tau-focused paradigms,with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.
基金supported by the National Natural Science Foundation of China (Nos. 31371275 and 30971635)the National Basic Research Program of China (973 Program) (No. 2011CB504004)self-determined research funds of CCNU from the colleges’ basic research and operation of MOE (No. CCNU14Z01003)
文摘Genome-wide association studies （GWASs） have identified thousands of genes and genetic variants （mainly SNPs） that contribute to complex diseases in humans. Functional characterization and mechanistic elucidation of these SNPs and genes action are the next major challenge. It has been well established that SNPs altering the amino acids of protein-coding genes can drastically impact protein function, and play an important role in molecular pathogenesis. Functions of regulatory SNPs can be complex and elusive, and involve gene expression regulation through the effect on RNA splicing, transcription factor binding, DNA metbylation and miRNA recruitment. In the present review, we summarize the recent progress in our understanding of functional consequences of GWAS-associated non-coding regulatory SNPs, and discuss the application of systems genetics and network biology in the interpretation of GWAS findings.
基金Supported by the National Natural Science Foundation of China under Grant Nos 10575041 and 90303007, and the SRFDP of the Ministry of Education of China under Project No 20040511005.
文摘We numerically investigate the effects of nonlinear time-delay on the stochastic system. With the delay time increasing, it is found that the peak of probability distribution in low steady states is decreased, and the peak of probability distribution in high steady states is increased. The mean of state variable, the normalized variance, and the normalized autocorrelation function which quantifies the concentrated degree are slowly varied for small delay time. However, the mean of state variable is rapidly increased, and the normalized variance and the normalized autocorrelation function is rapidly decreased for large delay time.
基金financially supported by Texas Tech University in the form of start-up and faculty research enhancement grants
文摘In the megadiverse forests of Southeast Asia, hundreds of timber species are economically important but the population genetics of only a few taxa are known. Cross-specific amplification of microsatellite loci among closely related taxa could enhance our ability to study and manage previously unstudied species. We successfully utilized STMS markers in Shorea platyclados, originally developed for Shorea curtisii. The six primer pairs we tried successfully produced PCR products of expected sizes. The number of alleles observed ranged from 10 to 14 and an average of 12 alleles were detected per locus. A high expected and observed heterozygosity was observed and it ranges from 0.718 to 0.827 among all populations across all six loci tested. Microsatellite DNA markers are highly polymorphic, co-dominant, reproducible, and amenable to high throughput genetic analyses. Overall, the cross- specific amplification of microsatellite loci appears to be complicated by numerous factors. While the approach may be effective for local management and conservation ofpoorly known species, the results must be carefully interpreted.
基金funded by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB31000000)the National Key R&D Program of China(2018YFD0900806)+1 种基金National Natural Science Foundation of China(31872234)the research program of China Three Gorges Corporation(201903144).
文摘Understanding the reproductive strategy of an organism is important in conservation ecology as it directly affects the population performance under changing environmental conditions.Chinese sturgeon(Acipenser sinensis)are the largest anadromous fish in the Yangtze River,China.Currently,the species has only one spawning ground and has failed to spawn in recent years,leading it to the brink of extinction.To develop effective conservation measures,a further understanding of its reproductive strategy is needed.In our study,we conducted kinship analyses by using mitochondrial and microsatellite DNA data from 216 wild juveniles collected over nine years(20062013,2015)to understand the mating system,breeding interval,effective number of breeding adults,and reproductive success.The results from these analyses suggested polygynandry,with some parents contributing up to eight half-sibling juvenile genotypes.Although the spawning ground was restricted to a limited area,genetic diversity was maintained at a relatively high level(observed heterozygosity from 0.698 to 0.787 and expected heterozygosity from 0.763 to 0.787)and inbreeding coefficients in each year-class ranged from1% to 9%(low to modest detrimental effects on offspring).A parental inference analysis revealed that Chinese sturgeon have a breeding interval of 2-6 years,indicating that it has the potential to feed,accumulate nutrition in the ocean,and then migrate back to the Yangtze River for iteroparous reproduction.The annual effective number of breeders in the Yangtze River ranged from 14 to 161 during the study period,and it decreased by 62.1%from the 20112014 year-classes.This sharp population decline likely contributes to the reproduction failure.However,the ratios of effective to census population size(Ne/Nc)were all larger than 0.20 after the 2010 year-class,indicating relatively even reproductive success.Based on these results,a suggested approach to protect this species is to restock parent fish to increase the reproductive stock size and optimize the discharge of the Three Gorges Dam to reduce the unsuitable hydrological conditions and rehabilitate spawning ground habitats.
