Background:Mastitis seriously affects the mammary health of humans and animals.Studies have found that inflammation and oxidative stress play key roles in the occur-rence and development of mastitis.Therefore,in-depth...Background:Mastitis seriously affects the mammary health of humans and animals.Studies have found that inflammation and oxidative stress play key roles in the occur-rence and development of mastitis.Therefore,in-depth research on related molecular mechanisms is of great significance.Methods:Postpartum mice were anesthetized with pentobarbital and administered lipopolysaccharide to develop the mouse mastitis model.Proteomic analysis was per-formed to compare protein expression in mitochondria-associated endoplasmic retic-ulum membranes(MAM)from two mouse mammary gland groups.Western blot was used to detect the expression of MAM-related proteins in mitochondria.AlphaFold3 was used to predict the molecular structures of phosphofurin acidic cluster sorting protein 2(PACS2)and mitofusin 2(MFN2)and their interaction levels.The MFN2-PACS2 interaction was investigated using co-immunoprecipitation and small interfer-ing RNA.Results:The results showed that the inflammation level in the mammary gland tissue of mice with mastitis significantly increased,the total antioxidant capacity decreased,and the expression of MAM-related proteins MFN2 and PACS2 was significantly downregulated.In cell experiments,overexpression of MFN2 can inhibit inflamma-tion and oxidative stress responses,and promote the interaction between MFN2 and PACS2 to affect the formation of MAMs.Conclusion:In summary,this study suggests that mastitis can alter the expression of MAM-related proteins in mouse breast tissue.The interaction between MFN2 and PACS2 regulates the formation of MAMs.Overexpression of MFN2 can promote the formation of MAMs and inhibit inflammation and oxidative stress response in mam-mary epithelial cells.Our results provided a new theoretical basis and potential thera-peutic targets for the prevention and treatment of mastitis.展开更多
Underground space utilization is becoming increasingly essential for modern metropolitan cities such as Singapore.Mapping a soil/rock interface using traditional borehole investigation methods is expensive and difficu...Underground space utilization is becoming increasingly essential for modern metropolitan cities such as Singapore.Mapping a soil/rock interface using traditional borehole investigation methods is expensive and difficult,owing to the numerous physical constraints within a built-up city.Boreholes are often far apart,resulting in many unforeseen ground conditions during subsequent excavation.Geophysical methods are sometimes employed as possible alternatives for fast,economical,and efficient bedrock surveys.The goal of this study is to investigate the practical details of applying microtremor array measurement(MAM)as a non-invasive surface wave survey for mapping soil/rock interfaces in Singapore.Critical configurations in field data acquisition are examined,and practical recommendations for array construction are provided.In addition,30 in situ MAM tests are carried out for two major geological formations in Singapore.From the results,a standard shear wave velocity(V_(s))of 500 m/s is found to be suitable for interpreting the soil/rock interface,for the Bukit Timah Granite and Jurong formations.However,the method does not predict well when soft Kallang formation deposits are present.Other limitations are also discussed in the later parts of this paper.Conclusions and practical recommendations are discussed,providing constructive guidance to the industry.The proposed Vs-based method and associated guidelines and limitations can be used to create a digital geological database and are especially useful for rock profiling in an urban environment.展开更多
As the manufacturing mode focuses more on network and community,the orders and production processes are becoming highly dynamic and unpredictable.The traditional manufacturing system cannot handle those exceptional ev...As the manufacturing mode focuses more on network and community,the orders and production processes are becoming highly dynamic and unpredictable.The traditional manufacturing system cannot handle those exceptional events such as rush orders and machine breakdowns.Nevertheless,the multiagent manufacturing system(MAMS)becomes a critical pattern to deal with these disturbances in a real-time way.However,due to the lack of universality,MAMS is difficult to be applied to industrial sites.A new multiagent architecture and the relay cooperation model based on a positive process relation matrix are proposed to address this paper’s issue.An optimized contract net protocol(CNP)-based negotiation mechanism is developed to improve the efficiency of collaboration in the proposed architecture.Finally,a case study of self-organizing internet of things(Io T)manufacturing system is used to test the feasibility and effectiveness of the method.It is shown that the proposed self-organizing Io T manufacturing mode outperforms the traditional manufacturing system in terms of makespan and critical machine workload balancing under disturbances through comparison.展开更多
Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability o...Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome,and sustained Ca^(2+)transfer can result in mitochondrial dysfunction.We focused on KCs to explore the damage to mitochondria by EA.After EA stimulation,cells produced an oxidative stress(OS)response with a significant increase in ROS release.Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca^(2+)led to Ca^(2+)accumulation in the mitochondrial matrix via mitochondria-associated membranes(MAMs).This was accompanied by a significant release of m ROS,loss of MMP and ATP,and a significant increase in mitochondrial permeability transition pore opening,ultimately leading to mitochondrial instability.These findings confirmed the mechanism that EA induced mitochondrial Ca^(2+)imbalance in KCs via MAM,ultimately leading to mitochondrial dysfunction.Meanwhile,EA induced OS and the decrease of MMP and ATP in rat liver,and significant lesions were found in liver mitochondria.Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred,with a marked increase in lipid droplets.展开更多
Allopolyploid Brassica juncea is particularly enriched in sinigrin,a kind of 3C aliphatic glucosinolates(GSLs),giving rise to characteristic taste after picking.However,the molecular mechanism underlying 3C aliphatic ...Allopolyploid Brassica juncea is particularly enriched in sinigrin,a kind of 3C aliphatic glucosinolates(GSLs),giving rise to characteristic taste after picking.However,the molecular mechanism underlying 3C aliphatic GSLs biosynthesis in this species remains unknown.In this study,we genome-widely identified GSLs metabolic genes,indicating different evolutionary rate of GSLs metabolic genes between subgenomes of B.juncea.Eight methythioalkylmalate synthase(MAMs)homologs were identified from B.juncea,in which six MAM1s were located in chloroplast and the other two were not detected with any expression.Furthermore,BjMAM1-4,BjMAM1-5,and BjMAM1-6 displayed higher expression levels in leaves than other tissues.Silenced expression analysis revealed that BjMAM1-4 and BjMAM1-6 function in 3C and 4C aliphatic GSLs accumulation.The specificity of the substrate selection for the second cycle reaction is much lower than that of the first cycle,suggesting these genes may preferentially catalyze 3C aliphatic GSLs biosynthesis.Our study provides insights into the molecular mechanism underlying the accumulation of 3C aliphatic GSLs,thereby facilitating the manipulation of aliphatic GSLs content in B.juncea.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:32302826 and 32372961Jilin Provincial Special Project for Health Research Talents,Grant/Award Number:2020SCZ40China Postdoctoral Science Foundation,Grant/Award Number:2023M740623。
文摘Background:Mastitis seriously affects the mammary health of humans and animals.Studies have found that inflammation and oxidative stress play key roles in the occur-rence and development of mastitis.Therefore,in-depth research on related molecular mechanisms is of great significance.Methods:Postpartum mice were anesthetized with pentobarbital and administered lipopolysaccharide to develop the mouse mastitis model.Proteomic analysis was per-formed to compare protein expression in mitochondria-associated endoplasmic retic-ulum membranes(MAM)from two mouse mammary gland groups.Western blot was used to detect the expression of MAM-related proteins in mitochondria.AlphaFold3 was used to predict the molecular structures of phosphofurin acidic cluster sorting protein 2(PACS2)and mitofusin 2(MFN2)and their interaction levels.The MFN2-PACS2 interaction was investigated using co-immunoprecipitation and small interfer-ing RNA.Results:The results showed that the inflammation level in the mammary gland tissue of mice with mastitis significantly increased,the total antioxidant capacity decreased,and the expression of MAM-related proteins MFN2 and PACS2 was significantly downregulated.In cell experiments,overexpression of MFN2 can inhibit inflamma-tion and oxidative stress responses,and promote the interaction between MFN2 and PACS2 to affect the formation of MAMs.Conclusion:In summary,this study suggests that mastitis can alter the expression of MAM-related proteins in mouse breast tissue.The interaction between MFN2 and PACS2 regulates the formation of MAMs.Overexpression of MFN2 can promote the formation of MAMs and inhibit inflammation and oxidative stress response in mam-mary epithelial cells.Our results provided a new theoretical basis and potential thera-peutic targets for the prevention and treatment of mastitis.
基金Land Transport Authority Singapore to fund this research project,using the land transportation innovation fund project:non-invasive geophysical study for bedrock evaluation(Award Number:R-302-000-164-490).
文摘Underground space utilization is becoming increasingly essential for modern metropolitan cities such as Singapore.Mapping a soil/rock interface using traditional borehole investigation methods is expensive and difficult,owing to the numerous physical constraints within a built-up city.Boreholes are often far apart,resulting in many unforeseen ground conditions during subsequent excavation.Geophysical methods are sometimes employed as possible alternatives for fast,economical,and efficient bedrock surveys.The goal of this study is to investigate the practical details of applying microtremor array measurement(MAM)as a non-invasive surface wave survey for mapping soil/rock interfaces in Singapore.Critical configurations in field data acquisition are examined,and practical recommendations for array construction are provided.In addition,30 in situ MAM tests are carried out for two major geological formations in Singapore.From the results,a standard shear wave velocity(V_(s))of 500 m/s is found to be suitable for interpreting the soil/rock interface,for the Bukit Timah Granite and Jurong formations.However,the method does not predict well when soft Kallang formation deposits are present.Other limitations are also discussed in the later parts of this paper.Conclusions and practical recommendations are discussed,providing constructive guidance to the industry.The proposed Vs-based method and associated guidelines and limitations can be used to create a digital geological database and are especially useful for rock profiling in an urban environment.
基金supported by the National Key Research and Development Program of China(No.2018YFE0177000)National Natural Science Foundation of China(No.52075257)+1 种基金Equipment Project of Ship Assembly and Construction for the Ministry of Industry and Information Technology(No.TC190H47J)Fundamental Research Funds for the Central Universities(No.NP2020304)。
文摘As the manufacturing mode focuses more on network and community,the orders and production processes are becoming highly dynamic and unpredictable.The traditional manufacturing system cannot handle those exceptional events such as rush orders and machine breakdowns.Nevertheless,the multiagent manufacturing system(MAMS)becomes a critical pattern to deal with these disturbances in a real-time way.However,due to the lack of universality,MAMS is difficult to be applied to industrial sites.A new multiagent architecture and the relay cooperation model based on a positive process relation matrix are proposed to address this paper’s issue.An optimized contract net protocol(CNP)-based negotiation mechanism is developed to improve the efficiency of collaboration in the proposed architecture.Finally,a case study of self-organizing internet of things(Io T)manufacturing system is used to test the feasibility and effectiveness of the method.It is shown that the proposed self-organizing Io T manufacturing mode outperforms the traditional manufacturing system in terms of makespan and critical machine workload balancing under disturbances through comparison.
基金supported by fund from the National Natural Science Foundation of China(32172322)。
文摘Elaidic acid(EA)stimulation can lead to endoplasmic reticulum stress(ERS),accompanied by a large release of Ca^(2+),and ultimately the activation of NLRP3 inflammasome in Kupffer cells(KCs).Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome,and sustained Ca^(2+)transfer can result in mitochondrial dysfunction.We focused on KCs to explore the damage to mitochondria by EA.After EA stimulation,cells produced an oxidative stress(OS)response with a significant increase in ROS release.Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca^(2+)led to Ca^(2+)accumulation in the mitochondrial matrix via mitochondria-associated membranes(MAMs).This was accompanied by a significant release of m ROS,loss of MMP and ATP,and a significant increase in mitochondrial permeability transition pore opening,ultimately leading to mitochondrial instability.These findings confirmed the mechanism that EA induced mitochondrial Ca^(2+)imbalance in KCs via MAM,ultimately leading to mitochondrial dysfunction.Meanwhile,EA induced OS and the decrease of MMP and ATP in rat liver,and significant lesions were found in liver mitochondria.Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred,with a marked increase in lipid droplets.
基金The authors thank Prof.Q.Wang for GSLs analysis.This work was supported by grants from the National Natural Science Foundation of Zhejiang Province(Grant no.LZ20C150002)the National Natural Science Foundation of China(Grant no.31872095).
文摘Allopolyploid Brassica juncea is particularly enriched in sinigrin,a kind of 3C aliphatic glucosinolates(GSLs),giving rise to characteristic taste after picking.However,the molecular mechanism underlying 3C aliphatic GSLs biosynthesis in this species remains unknown.In this study,we genome-widely identified GSLs metabolic genes,indicating different evolutionary rate of GSLs metabolic genes between subgenomes of B.juncea.Eight methythioalkylmalate synthase(MAMs)homologs were identified from B.juncea,in which six MAM1s were located in chloroplast and the other two were not detected with any expression.Furthermore,BjMAM1-4,BjMAM1-5,and BjMAM1-6 displayed higher expression levels in leaves than other tissues.Silenced expression analysis revealed that BjMAM1-4 and BjMAM1-6 function in 3C and 4C aliphatic GSLs accumulation.The specificity of the substrate selection for the second cycle reaction is much lower than that of the first cycle,suggesting these genes may preferentially catalyze 3C aliphatic GSLs biosynthesis.Our study provides insights into the molecular mechanism underlying the accumulation of 3C aliphatic GSLs,thereby facilitating the manipulation of aliphatic GSLs content in B.juncea.
