Mycobacterium tuberculosis FabH, an essential enzyme in mycolic acids biosynthetic pathway, is an attractive target for novel anti-tuberculosis agents. Structure-based design, synthesis of novel inhibitors of mtFabH w...Mycobacterium tuberculosis FabH, an essential enzyme in mycolic acids biosynthetic pathway, is an attractive target for novel anti-tuberculosis agents. Structure-based design, synthesis of novel inhibitors of mtFabH was reported in this paper. A novel scaffold structure was designed, and 12 candidate compounds that displayed favorable binding with the active site were identified and synthesized. 2009 Song Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.展开更多
Based upon the crystal structure of a previously reported fragment hit that binds to Corresponding author. β-secretase, a novel series of non-peptidic small-molecule β-secretase inhibitors, namely hexahydropyrimidin...Based upon the crystal structure of a previously reported fragment hit that binds to Corresponding author. β-secretase, a novel series of non-peptidic small-molecule β-secretase inhibitors, namely hexahydropyrimidin-5-ols, along with two series of their analogues, were rationally designed through structural modification. The CADD study was performed and revealed good expectation. Inhibitory activities of the corresponding structural cores were tested, which provided further support for our design approach.展开更多
A series of 7-azaindol derivatives were designed based on the homologous 3D model of human acrosin.These compounds were synthesized and evaluated for their human acrosin inhibitory activities in vitro.Compounds 7a,7i,...A series of 7-azaindol derivatives were designed based on the homologous 3D model of human acrosin.These compounds were synthesized and evaluated for their human acrosin inhibitory activities in vitro.Compounds 7a,7i,7j,7k and 7n showed highly inhibitory activity against human acrosin.The three-dimensional structure-activity relationship was investigated through a CoMFA model,which provided valuable information to further study of potential human acrosin inhibitors.展开更多
The mammalian target of rapamycin(mTOR) is a critical component of the PI3K-AKT signaling pathway. It is highly activated in cervical cancer, which continues to pose an important clinical challenge with an urgent need...The mammalian target of rapamycin(mTOR) is a critical component of the PI3K-AKT signaling pathway. It is highly activated in cervical cancer, which continues to pose an important clinical challenge with an urgent need for new and improved therapeutic approaches. Herein, we describe the structure-based drug discovery and biological evaluation of a series of m TOR kinase inhibitors as potential anti-cervical cancer agents. The results of enzymatic activity assays supported C3 as a potential m TOR inhibitor, which exhibited high inhibitory activity with an IC50 of 1.57 μM. Molecular docking and dynamics simulation were conducted to predict the binding patterns, suggesting relationships between structure and activity. The anti-proliferative assay against diverse cancer cell lines was displayed subsequently, revealing that C3 exhibited significant proliferation inhibition against cervical cancer cell He La(IC50=0.38μM) compared with other cell lines. Moreover, C3 could effectively reduce the expression of phospho-ribosomal S6 protein(p-S6) in He La cells in a dose-dependent manner. Noteworthily, m TOR signaling and other cellular pathways might contribute to the significant effect of C3 against cervical cancer simultaneously. These data indicated that C3 represented a good lead molecule for further development as a therapeutic agent for cervical cancer treatment.展开更多
There is a great need for new vaccine development against influenza A viruses due to the drawbacks of traditional vaccines that are mainly prepared using embryonated eggs.The main component of the current split influe...There is a great need for new vaccine development against influenza A viruses due to the drawbacks of traditional vaccines that are mainly prepared using embryonated eggs.The main component of the current split influenza A virus vaccine is viral hemagglutinin(HA)which induces a strong antibody-mediated immune response.To develop a modern vaccine against influenza A viruses,the current research has been focused on the universal vaccines targeting viral M2,NP and HA proteins.Crystallographic studies have shown that HA forms a trimer embedded on the viral envelope surface,and each monomer consists of a globular head(HA1)and a“rod-like”stalk region(HA2),the latter being more conserved among different HA subtypes and being the primary target for universal vaccines.In this study,we rationally designed the HA head based on the crystal structure of the 2009-pandemic influenza A(H1N1)virus HA as a model,tested its immunogenicity in mice,solved its crystal structure and further examined its immunological characteristics.The results show that the HA globular head can be easily prepared by in vitro refolding in an E.coli expression system,which maintains its intact structure and allows for the stimulation of a strong immune response.Together with recent reports on some similar HA globular head preparations we conclude that structure-based rational design of the HA globular head can be used for subtype-specific vaccines against influenza viruses.展开更多
Objective To investigate the associations between eight serum per-and polyfluoroalkyl substances(PFASs)and regional fat depots,we analyzed the data from the National Health and Nutrition Examination Survey(NHANES)2011...Objective To investigate the associations between eight serum per-and polyfluoroalkyl substances(PFASs)and regional fat depots,we analyzed the data from the National Health and Nutrition Examination Survey(NHANES)2011-2018 cycles.Methods Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions.The associations between structurally grouped PFASs and fat distribution were assessed,and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk.Results Among females aged 39-59 years,trunk fat mass was positively associated with perfluorooctane sulfonate(PFOS).Higher concentrations of PFOS,perfluorohexane sulfonate(PFHxS),perfluorodecanoate(PFDeA),perfluorononanoate(PFNA),and n-perfluorooctanoate(n-PFOA)were linked to greater visceral adipose tissue in this group.In men,exposure to total perfluoroalkane sulfonates(PFSAs)and long-chain PFSAs was associated with reductions in abdominal fat,while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs.The prediction model demonstrated high accuracy,with an area under the curve(AUC)of 0.9925 for predicting obesity risk.Conclusion PFAS exposure is associated with regional fat distribution,with varying effects based on age,sex,and PFAS structure.The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk,with significant implications for public health.The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.展开更多
Recent years have witnessed transformative changes brought about by artificial intelligence(AI)techniques with billions of parameters for the realization of high accuracy,proposing high demand for the advanced and AI ...Recent years have witnessed transformative changes brought about by artificial intelligence(AI)techniques with billions of parameters for the realization of high accuracy,proposing high demand for the advanced and AI chip to solve these AI tasks efficiently and powerfully.Rapid progress has been made in the field of advanced chips recently,such as the development of photonic computing,the advancement of the quantum processors,the boost of the biomimetic chips,and so on.Designs tactics of the advanced chips can be conducted with elaborated consideration of materials,algorithms,models,architectures,and so on.Though a few reviews present the development of the chips from their unique aspects,reviews in the view of the latest design for advanced and AI chips are few.Here,the newest development is systematically reviewed in the field of advanced chips.First,background and mechanisms are summarized,and subsequently most important considerations for co-design of the software and hardware are illustrated.Next,strategies are summed up to obtain advanced and AI chips with high excellent performance by taking the important information processing steps into consideration,after which the design thought for the advanced chips in the future is proposed.Finally,some perspectives are put forward.展开更多
Targeting RIPK1 is a promising strategy for the treatment or alleviation of acute lung injury(ALI).SZM594,a benzothiazole compound previously developed by our research group,possessed good dual-targeting receptor-inte...Targeting RIPK1 is a promising strategy for the treatment or alleviation of acute lung injury(ALI).SZM594,a benzothiazole compound previously developed by our research group,possessed good dual-targeting receptor-interacting protein kinase 1(RIPK1)and RIPK3 activity and anti-necroptosis activity as well as acceptable in vivo efficacy.In this study,the cyclopropyl moiety of SZM594 was modified based on a structure-based design strategy.The resulting cyclohexanone-containing analogue 41 improved the selectivity toward RIPK1 over RIPK3 and the anti-necroptosis activity was also increased compared with those of SZM594.More importantly,compound 41 could inhibit the tumor necrosis factor-α(TNF-α)ex-pression in lipopolysaccharide(LPS)-induced peritoneal macrophage cell model,and significantly allevi-ate LPS-induced ALI in a mouse model.This compound could significantly inhibit the expressions of the phosphorylation of RIPK1 and down-stream RIPK3 and mixed lineage kinase domain-like protein(MLKL).Thus,these cyclohexanone-containing benzothiazole analogues represent promising lead structures for the discovery of novel protective agents of ALI.展开更多
The hybrid atomistic structure-based model has been validated to be effective in investigation of G-quadruplex folding.In this study,we performed large-scale conventional all-atom simulations to complement the folding...The hybrid atomistic structure-based model has been validated to be effective in investigation of G-quadruplex folding.In this study,we performed large-scale conventional all-atom simulations to complement the folding mechanism of human telomeric sequence Htel24 revealed by a multi-basin hybrid atomistic structure-based model.Firstly,the real time-scale of folding rate,which cannot be obtained from the structure-based simulations,was estimated directly by constructing a Markov state model.The results show that Htel24 may fold as fast as on the order of milliseconds when only considering the competition between the hybrid-1 and hybrid-2 G-quadruplex conformations.Secondly,in comparison with the results of structure-based simulations,more metastable states were identified to participate in the formation of hybrid-1 and hybrid-2 conformations.These findings suggest that coupling the hybrid atomistic structure-based model and the conventional all-atom model can provide more insights into the folding dynamics of DNA G-quadruplex.As a result,the multiscale computational framework adopted in this study may be useful to study complex processes of biomolecules involving large conformational changes.展开更多
Brazing filler metals are widely applied,which serve as an industrial adhesive in the joining of dissimilar structures.With the continuous emergence of new structures and materials,the demand for novel brazing filler ...Brazing filler metals are widely applied,which serve as an industrial adhesive in the joining of dissimilar structures.With the continuous emergence of new structures and materials,the demand for novel brazing filler metals is ever-increasing.It is of great significance to investigate the optimized composition design methods and to establish systematic design guidelines for brazing filler metals.This study elucidated the fundamental rules for the composition design of brazing filler metals from a three-dimensional perspective encompassing the basic properties of applied brazing filler metals,formability and processability,and overall cost.The basic properties of brazing filler metals refer to their mechanical properties,physicochemical properties,electromagnetic properties,corrosion resistance,and the wettability and fluidity during brazing.The formability and processability of brazing filler metals include the processes of smelting and casting,extrusion,rolling,drawing and ring-making,as well as the processes of granulation,powder production,and the molding of amorphous and microcrystalline structures.The cost of brazing filler metals corresponds to the sum of materials value and manufacturing cost.Improving the comprehensive properties of brazing filler metals requires a comprehensive and systematic consideration of design indicators.Highlighting the unique characteristics of brazing filler metals should focus on relevant technical indicators.Binary or ternary eutectic structures can effectively enhance the flow spreading ability of brazing filler metals,and solid solution structures contribute to the formability.By employing the proposed design guidelines,typical Ag based,Cu based,Zn based brazing filler metals,and Sn based solders were designed and successfully applied in major scientific and engineering projects.展开更多
This article explores the design of a wireless fire alarm system supported by advanced data fusion technology.It includes discussions on the basic design ideas of the wireless fire alarm system,hardware design analysi...This article explores the design of a wireless fire alarm system supported by advanced data fusion technology.It includes discussions on the basic design ideas of the wireless fire alarm system,hardware design analysis,software design analysis,and simulation analysis,all supported by data fusion technology.Hopefully,this analysis can provide some reference for the rational application of data fusion technology to meet the actual design and application requirements of the system.展开更多
With the progress of urbanization,urban landscape design has garnered increasing attention.Urban landscape design can not only reflect the construction level of a city but also has the functions of beautifying the urb...With the progress of urbanization,urban landscape design has garnered increasing attention.Urban landscape design can not only reflect the construction level of a city but also has the functions of beautifying the urban environment and enhancing the city image.Modern art enriches the expression forms of urban landscape design,and its integration with urban landscape design can greatly improve the urban landscape.This article elaborated on the connotations of modern art and urban landscape design and analyzed the application of modern art in urban landscape design.The application of modern art can help to achieve the goal of urban landscape design to the maximum extent.展开更多
A high-temperature and high-pressure valve is the key equipment of a wind tunnel system;it controls the generation of high-temperature and high-pressure gas.To reduce the adverse impact of high-temperature and high-pr...A high-temperature and high-pressure valve is the key equipment of a wind tunnel system;it controls the generation of high-temperature and high-pressure gas.To reduce the adverse impact of high-temperature and high-pressure gas on the strength of the valve body,a cooling structure is set on the valve seat.This can significantly reduce the temperature of the valve body and valve seat.The effects of its structure on the cooling characteristics and stress of the valve seat are studied,and six main parameters that can completely describe the geometry of the cooling structure are proposed.The central composite design method is used to select sample points,and the multi-objective genetic algorithm(MOGA)method is used for optimal structural design.A modification method according to the main parameters for the valve seat is proposed.The results show that the cooling structure weakens the pressure-bearing capability of the valve seat.Among the six main parameters of the valve seat,the distance from the end face of the lower hole to the Z-axis and the distance from the axis of the lower hole to the origin of the coordinates have the most obvious effects on the average stress of the valve seat.An optimum design value is proposed.This work can provide a reference for the design of high-temperature and high-pressure valves.展开更多
The security of the seed industry is crucial for ensuring national food security.Currently,developed countries in Europe and America,along with international seed industry giants,have entered the Breeding 4.0 era.This...The security of the seed industry is crucial for ensuring national food security.Currently,developed countries in Europe and America,along with international seed industry giants,have entered the Breeding 4.0 era.This era integrates biotechnology,artificial intelligence(AI),and big data information technology.In contrast,China is still in a transition period between stages 2.0 and 3.0,which primarily relies on conventional selection and molecular breeding.In the context of increasingly complex international situations,accurately identifying core issues in China's seed industry innovation and seizing the frontier of international seed technology are strategically important.These efforts are essential for ensuring food security and revitalizing the seed industry.This paper systematically analyzes the characteristics of crop breeding data from artificial selection to intelligent design breeding.It explores the applications and development trends of AI and big data in modern crop breeding from several key perspectives.These include highthroughput phenotype acquisition and analysis,multiomics big data database and management system construction,AI-based multiomics integrated analysis,and the development of intelligent breeding software tools based on biological big data and AI technology.Based on an in-depth analysis of the current status and challenges of China's seed industry technology development,we propose strategic goals and key tasks for China's new generation of AI and big data-driven intelligent design breeding.These suggestions aim to accelerate the development of an intelligent-driven crop breeding engineering system that features large-scale gene mining,efficient gene manipulation,engineered variety design,and systematized biobreeding.This study provides a theoretical basis and practical guidance for the development of China's seed industry technology.展开更多
Ammonia and nitric acid,versatile industrial feedstocks,and burgeoning clean energy vectors hold immense promise for sustainable development.However,Haber–Bosch and Ostwald processes,which generates carbon dioxide as...Ammonia and nitric acid,versatile industrial feedstocks,and burgeoning clean energy vectors hold immense promise for sustainable development.However,Haber–Bosch and Ostwald processes,which generates carbon dioxide as massive by-product,contribute to greenhouse effects and pose environmental challenges.Thus,the pursuit of nitrogen fixation through carbon–neutral pathways under benign conditions is a frontier of scientific topics,with the harnessing of solar energy emerging as an enticing and viable option.This review delves into the refinement strategies for scale-up mild photocatalytic nitrogen fixation,fields ripe with potential for innovation.The narrative is centered on enhancing the intrinsic capabilities of catalysts to surmount current efficiency barriers.Key focus areas include the in-depth exploration of fundamental mechanisms underpinning photocatalytic procedures,rational element selection,and functional planning,state-of-the-art experimental protocols for understanding photo-fixation processes,valid photocatalytic activity evaluation,and the rational design of catalysts.Furthermore,the review offers a suite of forward-looking recommendations aimed at propelling the advancement of mild nitrogen photo-fixation.It scrutinizes the existing challenges and prospects within this burgeoning domain,aspiring to equip researchers with insightful perspectives that can catalyze the evolution of cutting-edge nitrogen fixation methodologies and steer the development of next-generation photocatalytic systems.展开更多
In this paper,we investigate a multi-UAV aided NOMA communication system,where multiple UAV-mounted aerial base stations are employed to serve ground users in the downlink NOMA communication,and each UAV serves its as...In this paper,we investigate a multi-UAV aided NOMA communication system,where multiple UAV-mounted aerial base stations are employed to serve ground users in the downlink NOMA communication,and each UAV serves its associated users on its own bandwidth.We aim at maximizing the overall common throughput in a finite time period.Such a problem is a typical mixed integer nonlinear problem,which involves both continuous-variable and combinatorial optimizations.To efficiently solve this problem,we propose a two-layer algorithm,which separately tackles continuous-variable and combinatorial optimization.Specifically,in the inner layer given one user association scheme,subproblems of bandwidth allocation,power allocation and trajectory design are solved based on alternating optimization.In the outer layer,a small number of candidate user association schemes are generated from an initial scheme and the best solution can be determined by comparing all the candidate schemes.In particular,a clustering algorithm based on K-means is applied to produce all candidate user association schemes,the successive convex optimization technique is adopted in the power allocation subproblem and a logistic function approximation approach is employed in the trajectory design subproblem.Simulation results show that the proposed NOMA scheme outperforms three baseline schemes in downlink common throughput,including one solution proposed in an existing literature.展开更多
基金supported by the National Basic Research Program of China(No.2004CB518908)the National High Technology Research and Development Program of China(No.2006AA020601)
文摘Mycobacterium tuberculosis FabH, an essential enzyme in mycolic acids biosynthetic pathway, is an attractive target for novel anti-tuberculosis agents. Structure-based design, synthesis of novel inhibitors of mtFabH was reported in this paper. A novel scaffold structure was designed, and 12 candidate compounds that displayed favorable binding with the active site were identified and synthesized. 2009 Song Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
基金National Natural Science Foundation of China (Grant No.20772008 and 30772650)
文摘Based upon the crystal structure of a previously reported fragment hit that binds to Corresponding author. β-secretase, a novel series of non-peptidic small-molecule β-secretase inhibitors, namely hexahydropyrimidin-5-ols, along with two series of their analogues, were rationally designed through structural modification. The CADD study was performed and revealed good expectation. Inhibitory activities of the corresponding structural cores were tested, which provided further support for our design approach.
基金supported by the Shanghai Family Planning Commission Research Fund(No2007JG02)Shanghai Leading Academic Discipline Project(NoB906)
文摘A series of 7-azaindol derivatives were designed based on the homologous 3D model of human acrosin.These compounds were synthesized and evaluated for their human acrosin inhibitory activities in vitro.Compounds 7a,7i,7j,7k and 7n showed highly inhibitory activity against human acrosin.The three-dimensional structure-activity relationship was investigated through a CoMFA model,which provided valuable information to further study of potential human acrosin inhibitors.
基金National Natural Science Foundation of China(Grant No.21772005,81872730)the Beijing Natural Science Foundation(Grant No.7202088,7172118)。
文摘The mammalian target of rapamycin(mTOR) is a critical component of the PI3K-AKT signaling pathway. It is highly activated in cervical cancer, which continues to pose an important clinical challenge with an urgent need for new and improved therapeutic approaches. Herein, we describe the structure-based drug discovery and biological evaluation of a series of m TOR kinase inhibitors as potential anti-cervical cancer agents. The results of enzymatic activity assays supported C3 as a potential m TOR inhibitor, which exhibited high inhibitory activity with an IC50 of 1.57 μM. Molecular docking and dynamics simulation were conducted to predict the binding patterns, suggesting relationships between structure and activity. The anti-proliferative assay against diverse cancer cell lines was displayed subsequently, revealing that C3 exhibited significant proliferation inhibition against cervical cancer cell He La(IC50=0.38μM) compared with other cell lines. Moreover, C3 could effectively reduce the expression of phospho-ribosomal S6 protein(p-S6) in He La cells in a dose-dependent manner. Noteworthily, m TOR signaling and other cellular pathways might contribute to the significant effect of C3 against cervical cancer simultaneously. These data indicated that C3 represented a good lead molecule for further development as a therapeutic agent for cervical cancer treatment.
基金by the National Basic Research Program(973 Program)(Grant No.2011CB504703)We are grateful to Dr Christopher Vavricka and Dr Guangwen Lu for their help.GFG is a leading principal investigator of the Innovative Research Group of the National Natural Science Foundation of China(Grant No.81021003).
文摘There is a great need for new vaccine development against influenza A viruses due to the drawbacks of traditional vaccines that are mainly prepared using embryonated eggs.The main component of the current split influenza A virus vaccine is viral hemagglutinin(HA)which induces a strong antibody-mediated immune response.To develop a modern vaccine against influenza A viruses,the current research has been focused on the universal vaccines targeting viral M2,NP and HA proteins.Crystallographic studies have shown that HA forms a trimer embedded on the viral envelope surface,and each monomer consists of a globular head(HA1)and a“rod-like”stalk region(HA2),the latter being more conserved among different HA subtypes and being the primary target for universal vaccines.In this study,we rationally designed the HA head based on the crystal structure of the 2009-pandemic influenza A(H1N1)virus HA as a model,tested its immunogenicity in mice,solved its crystal structure and further examined its immunological characteristics.The results show that the HA globular head can be easily prepared by in vitro refolding in an E.coli expression system,which maintains its intact structure and allows for the stimulation of a strong immune response.Together with recent reports on some similar HA globular head preparations we conclude that structure-based rational design of the HA globular head can be used for subtype-specific vaccines against influenza viruses.
基金supported by the National Key R&D Program of China(No.2021YFC2700605)the National Natural Science Foundation of China(82071700 and 82101679)+4 种基金333 High-level Talent Training Project of the Jiangsu Province((2022)3-16-425)the Natural Science Foundation of Jiangsu Province(BK20220317)Jiangsu Funding Program for Excellent Postdoctoral Talent(2022ZB414)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(22KJB330001)China Postdoctoral Science Foundation(2022M711673).
文摘Objective To investigate the associations between eight serum per-and polyfluoroalkyl substances(PFASs)and regional fat depots,we analyzed the data from the National Health and Nutrition Examination Survey(NHANES)2011-2018 cycles.Methods Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions.The associations between structurally grouped PFASs and fat distribution were assessed,and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk.Results Among females aged 39-59 years,trunk fat mass was positively associated with perfluorooctane sulfonate(PFOS).Higher concentrations of PFOS,perfluorohexane sulfonate(PFHxS),perfluorodecanoate(PFDeA),perfluorononanoate(PFNA),and n-perfluorooctanoate(n-PFOA)were linked to greater visceral adipose tissue in this group.In men,exposure to total perfluoroalkane sulfonates(PFSAs)and long-chain PFSAs was associated with reductions in abdominal fat,while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs.The prediction model demonstrated high accuracy,with an area under the curve(AUC)of 0.9925 for predicting obesity risk.Conclusion PFAS exposure is associated with regional fat distribution,with varying effects based on age,sex,and PFAS structure.The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk,with significant implications for public health.The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
基金supported by the Hong Kong Polytechnic University(1-WZ1Y,1-W34U,4-YWER).
文摘Recent years have witnessed transformative changes brought about by artificial intelligence(AI)techniques with billions of parameters for the realization of high accuracy,proposing high demand for the advanced and AI chip to solve these AI tasks efficiently and powerfully.Rapid progress has been made in the field of advanced chips recently,such as the development of photonic computing,the advancement of the quantum processors,the boost of the biomimetic chips,and so on.Designs tactics of the advanced chips can be conducted with elaborated consideration of materials,algorithms,models,architectures,and so on.Though a few reviews present the development of the chips from their unique aspects,reviews in the view of the latest design for advanced and AI chips are few.Here,the newest development is systematically reviewed in the field of advanced chips.First,background and mechanisms are summarized,and subsequently most important considerations for co-design of the software and hardware are illustrated.Next,strategies are summed up to obtain advanced and AI chips with high excellent performance by taking the important information processing steps into consideration,after which the design thought for the advanced chips in the future is proposed.Finally,some perspectives are put forward.
基金from the National Natural Science Foundation of China(Nos.82022065,81872791,82073696,81872880 and U20A20136)the Key Research and Development Program of Ningxia(No.2019BFG02017,China)the Scientific and Technological Innovation Project of Science and Technology Commission of Shanghai Municipality(No.21S11900800,China).
文摘Targeting RIPK1 is a promising strategy for the treatment or alleviation of acute lung injury(ALI).SZM594,a benzothiazole compound previously developed by our research group,possessed good dual-targeting receptor-interacting protein kinase 1(RIPK1)and RIPK3 activity and anti-necroptosis activity as well as acceptable in vivo efficacy.In this study,the cyclopropyl moiety of SZM594 was modified based on a structure-based design strategy.The resulting cyclohexanone-containing analogue 41 improved the selectivity toward RIPK1 over RIPK3 and the anti-necroptosis activity was also increased compared with those of SZM594.More importantly,compound 41 could inhibit the tumor necrosis factor-α(TNF-α)ex-pression in lipopolysaccharide(LPS)-induced peritoneal macrophage cell model,and significantly allevi-ate LPS-induced ALI in a mouse model.This compound could significantly inhibit the expressions of the phosphorylation of RIPK1 and down-stream RIPK3 and mixed lineage kinase domain-like protein(MLKL).Thus,these cyclohexanone-containing benzothiazole analogues represent promising lead structures for the discovery of novel protective agents of ALI.
基金the National Natural Science Foundation of China(Grant Nos.11504043,61671107,31670727,and 61771093)the Science Foundation of Shandong Province of China(Grant No.ZR2016JL027)+1 种基金the Taishan Young Scholars Program of Shandong Province of China(Grant No.tsqn20161049)the Youth Science and Technology Innovation Plan of Universities in Shandong,China(Grant No.2019KJE007)。
文摘The hybrid atomistic structure-based model has been validated to be effective in investigation of G-quadruplex folding.In this study,we performed large-scale conventional all-atom simulations to complement the folding mechanism of human telomeric sequence Htel24 revealed by a multi-basin hybrid atomistic structure-based model.Firstly,the real time-scale of folding rate,which cannot be obtained from the structure-based simulations,was estimated directly by constructing a Markov state model.The results show that Htel24 may fold as fast as on the order of milliseconds when only considering the competition between the hybrid-1 and hybrid-2 G-quadruplex conformations.Secondly,in comparison with the results of structure-based simulations,more metastable states were identified to participate in the formation of hybrid-1 and hybrid-2 conformations.These findings suggest that coupling the hybrid atomistic structure-based model and the conventional all-atom model can provide more insights into the folding dynamics of DNA G-quadruplex.As a result,the multiscale computational framework adopted in this study may be useful to study complex processes of biomolecules involving large conformational changes.
基金National Natural Science Foundation of China(U22A20191)。
文摘Brazing filler metals are widely applied,which serve as an industrial adhesive in the joining of dissimilar structures.With the continuous emergence of new structures and materials,the demand for novel brazing filler metals is ever-increasing.It is of great significance to investigate the optimized composition design methods and to establish systematic design guidelines for brazing filler metals.This study elucidated the fundamental rules for the composition design of brazing filler metals from a three-dimensional perspective encompassing the basic properties of applied brazing filler metals,formability and processability,and overall cost.The basic properties of brazing filler metals refer to their mechanical properties,physicochemical properties,electromagnetic properties,corrosion resistance,and the wettability and fluidity during brazing.The formability and processability of brazing filler metals include the processes of smelting and casting,extrusion,rolling,drawing and ring-making,as well as the processes of granulation,powder production,and the molding of amorphous and microcrystalline structures.The cost of brazing filler metals corresponds to the sum of materials value and manufacturing cost.Improving the comprehensive properties of brazing filler metals requires a comprehensive and systematic consideration of design indicators.Highlighting the unique characteristics of brazing filler metals should focus on relevant technical indicators.Binary or ternary eutectic structures can effectively enhance the flow spreading ability of brazing filler metals,and solid solution structures contribute to the formability.By employing the proposed design guidelines,typical Ag based,Cu based,Zn based brazing filler metals,and Sn based solders were designed and successfully applied in major scientific and engineering projects.
基金Chongqing Engineering University Undergraduate Innovation and Entrepreneurship Training Program Project:Wireless Fire Automatic Alarm System(Project No.:CXCY2024017)Chongqing Municipal Education Commission Science and Technology Research Project:Development and Research of Chongqing Wireless Fire Automatic Alarm System(Project No.:KJQN202401906)。
文摘This article explores the design of a wireless fire alarm system supported by advanced data fusion technology.It includes discussions on the basic design ideas of the wireless fire alarm system,hardware design analysis,software design analysis,and simulation analysis,all supported by data fusion technology.Hopefully,this analysis can provide some reference for the rational application of data fusion technology to meet the actual design and application requirements of the system.
文摘With the progress of urbanization,urban landscape design has garnered increasing attention.Urban landscape design can not only reflect the construction level of a city but also has the functions of beautifying the urban environment and enhancing the city image.Modern art enriches the expression forms of urban landscape design,and its integration with urban landscape design can greatly improve the urban landscape.This article elaborated on the connotations of modern art and urban landscape design and analyzed the application of modern art in urban landscape design.The application of modern art can help to achieve the goal of urban landscape design to the maximum extent.
基金supported by the National Natural Science Foundation of China(No.52175067)the Zhejiang Key Research&Development Project(No.2021C01021)+1 种基金the Natural Science Foundation of Zhejiang Province(No.LY20E050016)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(CPSF)(No.GZC20241478)。
文摘A high-temperature and high-pressure valve is the key equipment of a wind tunnel system;it controls the generation of high-temperature and high-pressure gas.To reduce the adverse impact of high-temperature and high-pressure gas on the strength of the valve body,a cooling structure is set on the valve seat.This can significantly reduce the temperature of the valve body and valve seat.The effects of its structure on the cooling characteristics and stress of the valve seat are studied,and six main parameters that can completely describe the geometry of the cooling structure are proposed.The central composite design method is used to select sample points,and the multi-objective genetic algorithm(MOGA)method is used for optimal structural design.A modification method according to the main parameters for the valve seat is proposed.The results show that the cooling structure weakens the pressure-bearing capability of the valve seat.Among the six main parameters of the valve seat,the distance from the end face of the lower hole to the Z-axis and the distance from the axis of the lower hole to the origin of the coordinates have the most obvious effects on the average stress of the valve seat.An optimum design value is proposed.This work can provide a reference for the design of high-temperature and high-pressure valves.
基金partially supported by the Construction of Collaborative Innovation Center of Beijing Academy of Agricultural and Forestry Sciences(KJCX20240406)the Beijing Natural Science Foundation(JQ24037)+1 种基金the National Natural Science Foundation of China(32330075)the Earmarked Fund for China Agriculture Research System(CARS-02 and CARS-54)。
文摘The security of the seed industry is crucial for ensuring national food security.Currently,developed countries in Europe and America,along with international seed industry giants,have entered the Breeding 4.0 era.This era integrates biotechnology,artificial intelligence(AI),and big data information technology.In contrast,China is still in a transition period between stages 2.0 and 3.0,which primarily relies on conventional selection and molecular breeding.In the context of increasingly complex international situations,accurately identifying core issues in China's seed industry innovation and seizing the frontier of international seed technology are strategically important.These efforts are essential for ensuring food security and revitalizing the seed industry.This paper systematically analyzes the characteristics of crop breeding data from artificial selection to intelligent design breeding.It explores the applications and development trends of AI and big data in modern crop breeding from several key perspectives.These include highthroughput phenotype acquisition and analysis,multiomics big data database and management system construction,AI-based multiomics integrated analysis,and the development of intelligent breeding software tools based on biological big data and AI technology.Based on an in-depth analysis of the current status and challenges of China's seed industry technology development,we propose strategic goals and key tasks for China's new generation of AI and big data-driven intelligent design breeding.These suggestions aim to accelerate the development of an intelligent-driven crop breeding engineering system that features large-scale gene mining,efficient gene manipulation,engineered variety design,and systematized biobreeding.This study provides a theoretical basis and practical guidance for the development of China's seed industry technology.
基金financially supported by the National Natural Science Foundation of China(No.21675131)the Volkswagen Foundation(Freigeist Fellowship No.89592)+1 种基金the Natural Science Foundation of Chongqing(No.2020jcyj-zdxmX0003,CSTB2023NSCQ-MSX0924)the National Research Foundation,Singapore,and A*STAR(Agency for Science Technology and Research)under its LCER Phase 2 Programme Hydrogen&Emerging Technologies FI,Directed Hydrogen Programme(Award No.U2305D4003).
文摘Ammonia and nitric acid,versatile industrial feedstocks,and burgeoning clean energy vectors hold immense promise for sustainable development.However,Haber–Bosch and Ostwald processes,which generates carbon dioxide as massive by-product,contribute to greenhouse effects and pose environmental challenges.Thus,the pursuit of nitrogen fixation through carbon–neutral pathways under benign conditions is a frontier of scientific topics,with the harnessing of solar energy emerging as an enticing and viable option.This review delves into the refinement strategies for scale-up mild photocatalytic nitrogen fixation,fields ripe with potential for innovation.The narrative is centered on enhancing the intrinsic capabilities of catalysts to surmount current efficiency barriers.Key focus areas include the in-depth exploration of fundamental mechanisms underpinning photocatalytic procedures,rational element selection,and functional planning,state-of-the-art experimental protocols for understanding photo-fixation processes,valid photocatalytic activity evaluation,and the rational design of catalysts.Furthermore,the review offers a suite of forward-looking recommendations aimed at propelling the advancement of mild nitrogen photo-fixation.It scrutinizes the existing challenges and prospects within this burgeoning domain,aspiring to equip researchers with insightful perspectives that can catalyze the evolution of cutting-edge nitrogen fixation methodologies and steer the development of next-generation photocatalytic systems.
基金supported by Beijing Natural Science Fund–Haidian Original Innovation Joint Fund(L232040 and L232045).
文摘In this paper,we investigate a multi-UAV aided NOMA communication system,where multiple UAV-mounted aerial base stations are employed to serve ground users in the downlink NOMA communication,and each UAV serves its associated users on its own bandwidth.We aim at maximizing the overall common throughput in a finite time period.Such a problem is a typical mixed integer nonlinear problem,which involves both continuous-variable and combinatorial optimizations.To efficiently solve this problem,we propose a two-layer algorithm,which separately tackles continuous-variable and combinatorial optimization.Specifically,in the inner layer given one user association scheme,subproblems of bandwidth allocation,power allocation and trajectory design are solved based on alternating optimization.In the outer layer,a small number of candidate user association schemes are generated from an initial scheme and the best solution can be determined by comparing all the candidate schemes.In particular,a clustering algorithm based on K-means is applied to produce all candidate user association schemes,the successive convex optimization technique is adopted in the power allocation subproblem and a logistic function approximation approach is employed in the trajectory design subproblem.Simulation results show that the proposed NOMA scheme outperforms three baseline schemes in downlink common throughput,including one solution proposed in an existing literature.
