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
Against the backdrop of escalating global climate change and energy crises,the resource utilization of carbon dioxide(CO_(2)),a major greenhouse gas,has become a crucial pathway for achieving carbon peaking and carbon...Against the backdrop of escalating global climate change and energy crises,the resource utilization of carbon dioxide(CO_(2)),a major greenhouse gas,has become a crucial pathway for achieving carbon peaking and carbon neutrality goals.The hydrogenation of CO_(2)to methanol not only enables carbon sequestration and recycling,but also provides a route to produce high value-added fuels and basic chemical feedstocks,holding significant environmental and economic potential.However,this conversion process is thermodynamically and kinetically limited,and traditional catalyst systems(e.g.,Cu/ZnO/Al_(2)O_(3))exhibit inadequate activity,selectivity,and stability under mild conditions.Therefore,the development of novel high-performance catalysts with precisely tunable structures and functionalities is imperative.Metal-organic frameworks(MOFs),as crystalline porous materials with high surface area,tunable pore structures,and diverse metal-ligand compositions,have the great potential in CO_(2)hydrogenation catalysis.Their structural design flexibility allows for the construction of well-dispersed active sites,tailored electronic environments,and enhanced metal-support interactions.This review systematically summarizes the recent advances in MOF-based and MOF-derived catalysts for CO_(2)hydrogenation to methanol,focusing on four design strategies:(1)spatial confinement and in situ construction,(2)defect engineering and ion-exchange,(3)bimetallic synergy and hybrid structure design,and(4)MOF-derived nanomaterial synthesis.These approaches significantly improve CO_(2)conversion and methanol selectivity by optimizing metal dispersion,interfacial structures,and reaction pathways.The reaction mechanism is further explored by focusing on the three main reaction pathways:the formate pathway(HCOO*),the RWGS(Reverse Water Gas Shift reaction)+CO*hydrogenation pathway,and the trans-COOH pathway.In situ spectroscopic studies and density functional theory(DFT)calculations elucidate the formation and transformation of key intermediates,as well as the roles of active sites,metal-support interfaces,oxygen vacancies,and promoters.Additionally,representative catalytic performance data for MOFbased systems are compiled and compared,demonstrating their advantages over traditional catalysts in terms of CO_(2)conversion,methanol selectivity,and space-time yield.Future perspectives for MOF-based CO_(2)hydrogenation catalysts will prioritize two main directions:structural design and mechanistic understanding.The precise construction of active sites through multi-metallic synergy,defect engineering,and interfacial electronic modulation should be made to enhance catalyst selectivity and stability.In addition,advanced in situ characterization techniques combined with theoretical modeling are essential to unravel the detailed reaction mechanisms and intermediate behaviors,thereby guiding rational catalyst design.Moreover,to enable industrial application,challenges related to thermal/hydrothermal stability,catalyst recyclability,and cost-effective large-scale synthesis must be addressed.The development of green,scalable preparation methods and the integration of MOF catalysts into practical reaction systems(e.g.,flow reactors)will be crucial for bridging the gap between laboratory research and commercial deployment.Ultimately,multi-scale structure-performance optimization and catalytic system integration will be vital for accelerating the industrialization of MOF-based CO_(2)-to-methanol technologies.展开更多
In this study,an inverse design framework was established to find lightweight honeycomb structures(HCSs)with high impact resistance.The hybrid HCS,composed of re-entrant(RE)and elliptical annular re-entrant(EARE)honey...In this study,an inverse design framework was established to find lightweight honeycomb structures(HCSs)with high impact resistance.The hybrid HCS,composed of re-entrant(RE)and elliptical annular re-entrant(EARE)honeycomb cells,was created by constructing arrangement matrices to achieve structural lightweight.The machine learning(ML)framework consisted of a neural network(NN)forward regression model for predicting impact resistance and a multi-objective optimization algorithm for generating high-performance designs.The surrogate of the local design space was initially realized by establishing the NN in the small sample dataset,and the active learning strategy was used to continuously extended the local optimal design until the model converged in the global space.The results indicated that the active learning strategy significantly improved the inference capability of the NN model in unknown design domains.By guiding the iteration direction of the optimization algorithm,lightweight designs with high impact resistance were identified.The energy absorption capacity of the optimal design reached 94.98%of the EARE honeycomb,while the initial peak stress and mass decreased by 28.85%and 19.91%,respectively.Furthermore,Shapley Additive Explanations(SHAP)for global explanation of the NN indicated a strong correlation between the arrangement mode of HCS and its impact resistance.By reducing the stiffness of the cells at the top boundary of the structure,the initial impact damage sustained by the structure can be significantly improved.Overall,this study proposed a general lightweight design method for array structures under impact loads,which is beneficial for the widespread application of honeycomb-based protective structures.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
To ensure an uninterrupted power supply,mobile power sources(MPS)are widely deployed in power grids during emergencies.Comprising mobile emergency generators(MEGs)and mobile energy storage systems(MESS),MPS are capabl...To ensure an uninterrupted power supply,mobile power sources(MPS)are widely deployed in power grids during emergencies.Comprising mobile emergency generators(MEGs)and mobile energy storage systems(MESS),MPS are capable of supplying power to critical loads and serving as backup sources during grid contingencies,offering advantages such as flexibility and high resilience through electricity delivery via transportation networks.This paper proposes a design method for a 400 V–10 kV Dual-Winding Induction Generator(DWIG)intended for MEG applications,employing an improved particle swarmoptimization(PSO)algorithmbased on a back-propagation neural network(BPNN).A parameterized finite element(FE)model of the DWIG is established to derive constraints on its dimensional parameters,thereby simplifying the optimization space.Through sensitivity analysis between temperature rise and electromagnetic loss of the DWIG,the main factors influencing the machine’s temperature are identified,and electromagnetic loss is determined as the optimization objective.To obtain an accurate fitting function between electromagnetic loss and dimensional parameters,the BPNN is employed to predict the nonlinear relationship between the optimization objective and the parameters.The Latin hypercube sampling(LHS)method is used for random sampling in the FE model analysis for training,testing,and validation,which is then applied to compute the cost function in the PSO.Based on the relationships obtained by the BPNN,the PSO algorithm evaluates the fitness and cost functions to determine the optimal design point.The proposed optimization method is validated by comparing simulation results between the initial design and the optimized design.展开更多
Automation and intelligence have become the primary trends in the design of investment casting processes.However,the design of gating and riser systems still lacks precise quantitative evaluation criteria.Numerical si...Automation and intelligence have become the primary trends in the design of investment casting processes.However,the design of gating and riser systems still lacks precise quantitative evaluation criteria.Numerical simulation plays a significant role in quantitatively evaluating current processes and making targeted improvements,but its limitations lie in the inability to dynamically reflect the formation outcomes of castings under varying process conditions,making real-time adjustments to gating and riser designs challenging.In this study,an automated design model for gating and riser systems based on integrated parametric 3D modeling-simulation framework is proposed,which enhances the flexibility and usability of evaluating the casting process by simulation.Firstly,geometric feature extraction technology is employed to obtain the geometric information of the target casting.Based on this information,an automated design framework for gating and riser systems is established,incorporating multiple structural parameters for real-time process control.Subsequently,the simulation results for various structural parameters are analyzed,and the influence of these parameters on casting formation is thoroughly investigated.Finally,the optimal design scheme is generated and validated through experimental verification.Simulation analysis and experimental results show that using a larger gate neck(24 mm in side length) and external risers promotes a more uniform temperature distribution and a more stable flow state,effectively eliminating shrinkage cavities and enhancing process yield by 15%.展开更多
Subcritical reactors(SCRs)or subcritical assemblies(SCAs)are the main infrastructure for designing power reactors.These reactors are widely used for training and research because of their high level of inherent safety...Subcritical reactors(SCRs)or subcritical assemblies(SCAs)are the main infrastructure for designing power reactors.These reactors are widely used for training and research because of their high level of inherent safety.The objective of this study is to design a subcritical reactor using a pressurized water reactor(PWR)conventional fuel following two safety points.In the first approach,deeply placed SCR cores with an infinite multiplication factor(k_(∞))of less than unity were identified using the DRAGON lattice code.In the second approach,subcritical reactor cores with an effective multiplication factor(k_(eff))of less than unity were determined by coupling the cell calculations of the DRAGON lattice code and core calculations of the DONJON code.For the deeply subcritical reactor design,it was found that the reactor would remain inherently subcritical while using fuel rods with ^(235)U enrichment of up to 0.9%,regardless of the pitch of the fuel rods.In the second approach,the optimal pitches(1.3 to 2.3 cm)were determined for different fuel enrichment values from 1 to 5%.Subsequently,the k_(eff) was obtained for a fuel rod arrangement of 8×8 to 80×80,and the states in which the reactor would be subcritical were determined for different fuel enrichments at the corresponding optimal pitch.To validate the models used in the DRAGON and DONJON codes,the k_(eff) of the Isfahan Light Water Subcritical Reactor(LWSCR)was experimentally measured and compared with the results of the calculations.Finally,the effects of fuel and moderator temperature changes were investigated to ensure that the designed assemblies remained in the subcritical state at all operational temperatures.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
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 National Key Research and Development Program of China(2023YFB4104500,2023YFB4104502)the National Natural Science Foundation of China(22138013)the Taishan Scholar Project(ts201712020).
文摘Against the backdrop of escalating global climate change and energy crises,the resource utilization of carbon dioxide(CO_(2)),a major greenhouse gas,has become a crucial pathway for achieving carbon peaking and carbon neutrality goals.The hydrogenation of CO_(2)to methanol not only enables carbon sequestration and recycling,but also provides a route to produce high value-added fuels and basic chemical feedstocks,holding significant environmental and economic potential.However,this conversion process is thermodynamically and kinetically limited,and traditional catalyst systems(e.g.,Cu/ZnO/Al_(2)O_(3))exhibit inadequate activity,selectivity,and stability under mild conditions.Therefore,the development of novel high-performance catalysts with precisely tunable structures and functionalities is imperative.Metal-organic frameworks(MOFs),as crystalline porous materials with high surface area,tunable pore structures,and diverse metal-ligand compositions,have the great potential in CO_(2)hydrogenation catalysis.Their structural design flexibility allows for the construction of well-dispersed active sites,tailored electronic environments,and enhanced metal-support interactions.This review systematically summarizes the recent advances in MOF-based and MOF-derived catalysts for CO_(2)hydrogenation to methanol,focusing on four design strategies:(1)spatial confinement and in situ construction,(2)defect engineering and ion-exchange,(3)bimetallic synergy and hybrid structure design,and(4)MOF-derived nanomaterial synthesis.These approaches significantly improve CO_(2)conversion and methanol selectivity by optimizing metal dispersion,interfacial structures,and reaction pathways.The reaction mechanism is further explored by focusing on the three main reaction pathways:the formate pathway(HCOO*),the RWGS(Reverse Water Gas Shift reaction)+CO*hydrogenation pathway,and the trans-COOH pathway.In situ spectroscopic studies and density functional theory(DFT)calculations elucidate the formation and transformation of key intermediates,as well as the roles of active sites,metal-support interfaces,oxygen vacancies,and promoters.Additionally,representative catalytic performance data for MOFbased systems are compiled and compared,demonstrating their advantages over traditional catalysts in terms of CO_(2)conversion,methanol selectivity,and space-time yield.Future perspectives for MOF-based CO_(2)hydrogenation catalysts will prioritize two main directions:structural design and mechanistic understanding.The precise construction of active sites through multi-metallic synergy,defect engineering,and interfacial electronic modulation should be made to enhance catalyst selectivity and stability.In addition,advanced in situ characterization techniques combined with theoretical modeling are essential to unravel the detailed reaction mechanisms and intermediate behaviors,thereby guiding rational catalyst design.Moreover,to enable industrial application,challenges related to thermal/hydrothermal stability,catalyst recyclability,and cost-effective large-scale synthesis must be addressed.The development of green,scalable preparation methods and the integration of MOF catalysts into practical reaction systems(e.g.,flow reactors)will be crucial for bridging the gap between laboratory research and commercial deployment.Ultimately,multi-scale structure-performance optimization and catalytic system integration will be vital for accelerating the industrialization of MOF-based CO_(2)-to-methanol technologies.
基金the financial supports from National Key R&D Program for Young Scientists of China(Grant No.2022YFC3080900)National Natural Science Foundation of China(Grant No.52374181)+1 种基金BIT Research and Innovation Promoting Project(Grant No.2024YCXZ017)supported by Science and Technology Innovation Program of Beijing institute of technology under Grant No.2022CX01025。
文摘In this study,an inverse design framework was established to find lightweight honeycomb structures(HCSs)with high impact resistance.The hybrid HCS,composed of re-entrant(RE)and elliptical annular re-entrant(EARE)honeycomb cells,was created by constructing arrangement matrices to achieve structural lightweight.The machine learning(ML)framework consisted of a neural network(NN)forward regression model for predicting impact resistance and a multi-objective optimization algorithm for generating high-performance designs.The surrogate of the local design space was initially realized by establishing the NN in the small sample dataset,and the active learning strategy was used to continuously extended the local optimal design until the model converged in the global space.The results indicated that the active learning strategy significantly improved the inference capability of the NN model in unknown design domains.By guiding the iteration direction of the optimization algorithm,lightweight designs with high impact resistance were identified.The energy absorption capacity of the optimal design reached 94.98%of the EARE honeycomb,while the initial peak stress and mass decreased by 28.85%and 19.91%,respectively.Furthermore,Shapley Additive Explanations(SHAP)for global explanation of the NN indicated a strong correlation between the arrangement mode of HCS and its impact resistance.By reducing the stiffness of the cells at the top boundary of the structure,the initial impact damage sustained by the structure can be significantly improved.Overall,this study proposed a general lightweight design method for array structures under impact loads,which is beneficial for the widespread application of honeycomb-based protective structures.
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funded by the Science and Technology Projects of State Grid Corporation of China(Project No.J2024136).
文摘To ensure an uninterrupted power supply,mobile power sources(MPS)are widely deployed in power grids during emergencies.Comprising mobile emergency generators(MEGs)and mobile energy storage systems(MESS),MPS are capable of supplying power to critical loads and serving as backup sources during grid contingencies,offering advantages such as flexibility and high resilience through electricity delivery via transportation networks.This paper proposes a design method for a 400 V–10 kV Dual-Winding Induction Generator(DWIG)intended for MEG applications,employing an improved particle swarmoptimization(PSO)algorithmbased on a back-propagation neural network(BPNN).A parameterized finite element(FE)model of the DWIG is established to derive constraints on its dimensional parameters,thereby simplifying the optimization space.Through sensitivity analysis between temperature rise and electromagnetic loss of the DWIG,the main factors influencing the machine’s temperature are identified,and electromagnetic loss is determined as the optimization objective.To obtain an accurate fitting function between electromagnetic loss and dimensional parameters,the BPNN is employed to predict the nonlinear relationship between the optimization objective and the parameters.The Latin hypercube sampling(LHS)method is used for random sampling in the FE model analysis for training,testing,and validation,which is then applied to compute the cost function in the PSO.Based on the relationships obtained by the BPNN,the PSO algorithm evaluates the fitness and cost functions to determine the optimal design point.The proposed optimization method is validated by comparing simulation results between the initial design and the optimized design.
基金financially supported by the National Key Research and Development Program of China (2022YFB3706802)。
文摘Automation and intelligence have become the primary trends in the design of investment casting processes.However,the design of gating and riser systems still lacks precise quantitative evaluation criteria.Numerical simulation plays a significant role in quantitatively evaluating current processes and making targeted improvements,but its limitations lie in the inability to dynamically reflect the formation outcomes of castings under varying process conditions,making real-time adjustments to gating and riser designs challenging.In this study,an automated design model for gating and riser systems based on integrated parametric 3D modeling-simulation framework is proposed,which enhances the flexibility and usability of evaluating the casting process by simulation.Firstly,geometric feature extraction technology is employed to obtain the geometric information of the target casting.Based on this information,an automated design framework for gating and riser systems is established,incorporating multiple structural parameters for real-time process control.Subsequently,the simulation results for various structural parameters are analyzed,and the influence of these parameters on casting formation is thoroughly investigated.Finally,the optimal design scheme is generated and validated through experimental verification.Simulation analysis and experimental results show that using a larger gate neck(24 mm in side length) and external risers promotes a more uniform temperature distribution and a more stable flow state,effectively eliminating shrinkage cavities and enhancing process yield by 15%.
文摘Subcritical reactors(SCRs)or subcritical assemblies(SCAs)are the main infrastructure for designing power reactors.These reactors are widely used for training and research because of their high level of inherent safety.The objective of this study is to design a subcritical reactor using a pressurized water reactor(PWR)conventional fuel following two safety points.In the first approach,deeply placed SCR cores with an infinite multiplication factor(k_(∞))of less than unity were identified using the DRAGON lattice code.In the second approach,subcritical reactor cores with an effective multiplication factor(k_(eff))of less than unity were determined by coupling the cell calculations of the DRAGON lattice code and core calculations of the DONJON code.For the deeply subcritical reactor design,it was found that the reactor would remain inherently subcritical while using fuel rods with ^(235)U enrichment of up to 0.9%,regardless of the pitch of the fuel rods.In the second approach,the optimal pitches(1.3 to 2.3 cm)were determined for different fuel enrichment values from 1 to 5%.Subsequently,the k_(eff) was obtained for a fuel rod arrangement of 8×8 to 80×80,and the states in which the reactor would be subcritical were determined for different fuel enrichments at the corresponding optimal pitch.To validate the models used in the DRAGON and DONJON codes,the k_(eff) of the Isfahan Light Water Subcritical Reactor(LWSCR)was experimentally measured and compared with the results of the calculations.Finally,the effects of fuel and moderator temperature changes were investigated to ensure that the designed assemblies remained in the subcritical state at all operational temperatures.
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.
