Foot-and-mouth disease virus(FMDV) rapidly causes cytopathic effects in susceptible cells. Incomplete viral clearance during the acute infection leads to persistent infection. The relationship between host gene expres...Foot-and-mouth disease virus(FMDV) rapidly causes cytopathic effects in susceptible cells. Incomplete viral clearance during the acute infection leads to persistent infection. The relationship between host gene expression and the persistent infection remains unclear. In this study, we analyzed the transcriptome profiles of BHK-21 cells acutely and persistently infected with FMDV to identify differences in gene expression. GO and KEGG enrichment analyses showed that the 8,378 differentially expressed genes were significantly enriched in categories including metabolism, biosynthesis, ribosome function, and endocytosis. In persistently infected BHK-21 cells, ribosome-and translation-related genes were significantly down-regulated. There were more differentially expressed immune-related genes during persistent infection than during acute infection. Two hundred and seventy-four genes were differentially expressed in both acutely and persistently infected BHK-21 cells. Among these genes, heat shock protein family B member 1(Hspb1) knockdown significantly inhibited FMDV replication. Our research provides a basis for further research to understand the mechanisms of persistent FMDV infection including the genes involved in FMDV replication.展开更多
The variety and functionality of current clinical vaccine adjuvants remain limited.Conventional aluminum-based adjuvants predominantly induce Th2-biased humoral immunity but exhibit a limited capacity to elicit Th1-me...The variety and functionality of current clinical vaccine adjuvants remain limited.Conventional aluminum-based adjuvants predominantly induce Th2-biased humoral immunity but exhibit a limited capacity to elicit Th1-mediated cellular immune responses,particularly tumor antigen-specific cytotoxic CD8+T lymphocytes(CTLs),which are essential for effective cancer vaccine performance.Inspired by natural biomolecular condensates,we developed a versatile noncovalent protein self-assembly strategy distinct from traditional approaches requiring structural domain modifications or bifunctional crosslinkers.Our methodology employs amphiphilic molecules(sodium myristate/SMA and sodium dodecyl thiolate/SDT)as molecular bridges to mediate protein-protein interactions through hydrophobic forces and disulfide bond formation.This process generates nanoscale protein condensate(PCD)vaccines with exceptional stability.As a novel adjuvant system,these synthetic condensates significantly enhance antigen cross-presentation by optimizing key parameters:antigen loading capacity,lymph node targeting,cytosolic delivery,and lysosomal escape.Consequently,they induce robust antigen-specific CTL responses and humoral immunity,demonstrating potent antitumor efficacy.Importantly,we found that the synthetic protein condensate(PCD)alone can act as a nanoadjuvant.By increasing mitochondrial membrane permeability,PCD induces mitochondrial DNA leakage into the cytosol,activating the cGAS-STING pathway and promoting DC maturation.This safe and scalable platform eliminates the need for complex covalent modifications or genetic engineering,and it facilitates the design of diverse modular antigens,including neoantigens and viral antigens.Given its straightforward manufacturing process and superior immunogenicity,this synthetic PCD vaccine adjuvant has significant potential for clinical application and translation.展开更多
Background:Sirtuin-3(Sirt3)has been documented to protect against mitochondrial dysfunction and apoptosis.Honokiol(HKL)is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurologica...Background:Sirtuin-3(Sirt3)has been documented to protect against mitochondrial dysfunction and apoptosis.Honokiol(HKL)is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurological disorders.The present study aimed to explore the neuroprotective effects of HKL and the role of Sirt3 following intracerebral hemorrhage(ICH).Methods:An in vivo ICH model in rats was established by injecting autologous blood into the right basal ganglia.PC12 cells were stimulated with hemin.For the in vivo investigation,the modified Neurological Severity Scores and the Morris water maze test were performed to assess neurological deficits.Hematoxylin-Eosin and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to evaluate the histopathology and apoptosis.Immunohistochemical staining was used to investigate the expression of Sirt3.Adenosine triphosphate(ATP)levels were quantified to assess mitochondrial dysfunction.Cell counting kit-8,lactate dehydrogenase assay,and flow cytometry were used to analyze cell vitality and apoptosis in vitro.Immunofluorescence staining was performed to observe mitochondrial morphology and dynamin-related protein 1(Drp1)localization to mitochondria.Western blot was applied to quantify the expression of Sirt3,Bax,Bcl-2,cleaved-caspase-3,Drp1,phosphorylation of Drp1 at serine-616,and phosphorylation of Drp1 at serine-637 in vivo and in vitro.Results:HKL treatment alleviated neurological deficits,attenuated the histopathological damage and cell apoptosis,and restored the decreased ATP levels in ICH rats.HKL improved cell survival rate,reduced cell apoptosis,and inhibited mitochondrial fission in PC12 cells.Moreover,both in vivo and in vitro models showed increased phosphorylation of Drp1 at Ser616,and reduced phosphorylation of Drp1 at Ser637.Meanwhile,immunofluorescence co-localization analysis revealed that hemin increased the overlap of Drp1 and mitochondria in PC12 cells.The phosphorylation and mitochondrial translocation of Drp1 were effectively reversed by HKL treatment.Importantly,the selective Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl)pyridine suppressed these effects.Conclusion:Our findings demonstrated that HKL ameliorated ICH-induced apoptosis and mitochondrial fission by Sirt3,suggesting that HKL has immense prospects for the treatment of ICH.展开更多
The crop pests and diseases in agriculture is one of the most important reason for the reduction of bulk grain and oil crops and the decline of fruit and vegetable crop quality,which threaten macroeconomic stability a...The crop pests and diseases in agriculture is one of the most important reason for the reduction of bulk grain and oil crops and the decline of fruit and vegetable crop quality,which threaten macroeconomic stability and sustainable development.However,the recognition method based on manual and instruments has been unable to meet the needs of scientific research and production due to its strong subjectivity and low efficiency.The recognition method based on pattern recognition and deep learning can automatically fit image features,and use features to classify and predict images.This study introduced the improved Vision Transformer(ViT)method for crop pest image recognition.Among them,the region with the most obvious features can be effectively selected by block partition.The self-attention mechanism of the transformer can better excavate the special solution that is not an obvious lesion area.In the experiment,data with 7 classes of examples are used for verification.It can be illustrated from results that this method has high accuracy and can give full play to the advantages of image processing and recognition technology,accurately judge the crop diseases and pests category,provide method reference for agricultural diseases and pests identification research,and further optimize the crop diseases and pests control work for agricultural workers in need.展开更多
As the new generation of artificial intelligence(AI)continues to evolve,weather big data and statistical machine learning(SML)technologies complement each other and are deeply integrated to significantly improve the p...As the new generation of artificial intelligence(AI)continues to evolve,weather big data and statistical machine learning(SML)technologies complement each other and are deeply integrated to significantly improve the processing and forecasting accuracy of fishery weather.Accurate fishery weather services play a crucial role in fishery production,serving as a great safeguard for economic benefits and personal safety,enabling fishermen to carry out fishery production better,and contributing to the sustainable development of the fishery industry.The objective of this paper is to offer an understanding of the present state of research and development in SML technology for simulating and forecasting fishery weather.Specifically,we analyze the current state of research and technical features of SML in weather and summarize the applications of SML in simulation and forecasting of fishery weather,which mainly include three aspects:fishery weather scenario generation,fishery weather forecasting,and fishery extreme weather warning.We also illustrate the main technical means and principles of SML technology.Finally,we summarize the most advanced SML fields and provide an outlook on their application value in the field of fishery weather.展开更多
基金the financial support of the National Infrastructure of Natural Resources for Science and Technology Program(No.2011-572)the National Natural Sciences Foundation of China(No.31370185)+2 种基金the National Basic Research Program of China(No.2011CB504800)to Prof.Congyi Zhengthe Fundamental Research Funds for the Central Universities(2042018kf0241)the National Science and Technology Infrastructure Grants(NSTI-CR15 and NSTI-CR16)to Dr.Chao Shen.
文摘Foot-and-mouth disease virus(FMDV) rapidly causes cytopathic effects in susceptible cells. Incomplete viral clearance during the acute infection leads to persistent infection. The relationship between host gene expression and the persistent infection remains unclear. In this study, we analyzed the transcriptome profiles of BHK-21 cells acutely and persistently infected with FMDV to identify differences in gene expression. GO and KEGG enrichment analyses showed that the 8,378 differentially expressed genes were significantly enriched in categories including metabolism, biosynthesis, ribosome function, and endocytosis. In persistently infected BHK-21 cells, ribosome-and translation-related genes were significantly down-regulated. There were more differentially expressed immune-related genes during persistent infection than during acute infection. Two hundred and seventy-four genes were differentially expressed in both acutely and persistently infected BHK-21 cells. Among these genes, heat shock protein family B member 1(Hspb1) knockdown significantly inhibited FMDV replication. Our research provides a basis for further research to understand the mechanisms of persistent FMDV infection including the genes involved in FMDV replication.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(2023A1515012356,P.Z.)the National Natural Science Foundation of China(Grant No.82003158,Y.Z.)+5 种基金the National Natural Science Foundation of China(32371518 and 32101209,P.Z.)X.C.acknowledges financial support from the National University of Singapore(NUHSRO/2020/133/Startup/08,NUHSRO/2023/008/NUSMed/TCE/LOA,NUHSRO/2021/034/TRP/09/Nanomedicine,23-0173-A0001)National Medical Research Council(MOH-001388-00,CG21APR1005,MOH001500-00,MOH-001609-00,MOH-001740-01)Singapore Ministry of Education(MOE-000387-00,MOE-MOET32023-004)National Research Foundation(NRF000352-00)jointly supported by the National University of Singapore and Nanjing University through the NUS-Nanjing University Research Collaboration Fund 2025 Award.
文摘The variety and functionality of current clinical vaccine adjuvants remain limited.Conventional aluminum-based adjuvants predominantly induce Th2-biased humoral immunity but exhibit a limited capacity to elicit Th1-mediated cellular immune responses,particularly tumor antigen-specific cytotoxic CD8+T lymphocytes(CTLs),which are essential for effective cancer vaccine performance.Inspired by natural biomolecular condensates,we developed a versatile noncovalent protein self-assembly strategy distinct from traditional approaches requiring structural domain modifications or bifunctional crosslinkers.Our methodology employs amphiphilic molecules(sodium myristate/SMA and sodium dodecyl thiolate/SDT)as molecular bridges to mediate protein-protein interactions through hydrophobic forces and disulfide bond formation.This process generates nanoscale protein condensate(PCD)vaccines with exceptional stability.As a novel adjuvant system,these synthetic condensates significantly enhance antigen cross-presentation by optimizing key parameters:antigen loading capacity,lymph node targeting,cytosolic delivery,and lysosomal escape.Consequently,they induce robust antigen-specific CTL responses and humoral immunity,demonstrating potent antitumor efficacy.Importantly,we found that the synthetic protein condensate(PCD)alone can act as a nanoadjuvant.By increasing mitochondrial membrane permeability,PCD induces mitochondrial DNA leakage into the cytosol,activating the cGAS-STING pathway and promoting DC maturation.This safe and scalable platform eliminates the need for complex covalent modifications or genetic engineering,and it facilitates the design of diverse modular antigens,including neoantigens and viral antigens.Given its straightforward manufacturing process and superior immunogenicity,this synthetic PCD vaccine adjuvant has significant potential for clinical application and translation.
基金Natural Science Foundation of Hebei Province(No.H2019105137)
文摘Background:Sirtuin-3(Sirt3)has been documented to protect against mitochondrial dysfunction and apoptosis.Honokiol(HKL)is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurological disorders.The present study aimed to explore the neuroprotective effects of HKL and the role of Sirt3 following intracerebral hemorrhage(ICH).Methods:An in vivo ICH model in rats was established by injecting autologous blood into the right basal ganglia.PC12 cells were stimulated with hemin.For the in vivo investigation,the modified Neurological Severity Scores and the Morris water maze test were performed to assess neurological deficits.Hematoxylin-Eosin and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to evaluate the histopathology and apoptosis.Immunohistochemical staining was used to investigate the expression of Sirt3.Adenosine triphosphate(ATP)levels were quantified to assess mitochondrial dysfunction.Cell counting kit-8,lactate dehydrogenase assay,and flow cytometry were used to analyze cell vitality and apoptosis in vitro.Immunofluorescence staining was performed to observe mitochondrial morphology and dynamin-related protein 1(Drp1)localization to mitochondria.Western blot was applied to quantify the expression of Sirt3,Bax,Bcl-2,cleaved-caspase-3,Drp1,phosphorylation of Drp1 at serine-616,and phosphorylation of Drp1 at serine-637 in vivo and in vitro.Results:HKL treatment alleviated neurological deficits,attenuated the histopathological damage and cell apoptosis,and restored the decreased ATP levels in ICH rats.HKL improved cell survival rate,reduced cell apoptosis,and inhibited mitochondrial fission in PC12 cells.Moreover,both in vivo and in vitro models showed increased phosphorylation of Drp1 at Ser616,and reduced phosphorylation of Drp1 at Ser637.Meanwhile,immunofluorescence co-localization analysis revealed that hemin increased the overlap of Drp1 and mitochondria in PC12 cells.The phosphorylation and mitochondrial translocation of Drp1 were effectively reversed by HKL treatment.Importantly,the selective Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl)pyridine suppressed these effects.Conclusion:Our findings demonstrated that HKL ameliorated ICH-induced apoptosis and mitochondrial fission by Sirt3,suggesting that HKL has immense prospects for the treatment of ICH.
基金the National Natural Science Foundation of China under Grant 52007193 and The 2115 Talent Development Program of China Agricultural University.
文摘The crop pests and diseases in agriculture is one of the most important reason for the reduction of bulk grain and oil crops and the decline of fruit and vegetable crop quality,which threaten macroeconomic stability and sustainable development.However,the recognition method based on manual and instruments has been unable to meet the needs of scientific research and production due to its strong subjectivity and low efficiency.The recognition method based on pattern recognition and deep learning can automatically fit image features,and use features to classify and predict images.This study introduced the improved Vision Transformer(ViT)method for crop pest image recognition.Among them,the region with the most obvious features can be effectively selected by block partition.The self-attention mechanism of the transformer can better excavate the special solution that is not an obvious lesion area.In the experiment,data with 7 classes of examples are used for verification.It can be illustrated from results that this method has high accuracy and can give full play to the advantages of image processing and recognition technology,accurately judge the crop diseases and pests category,provide method reference for agricultural diseases and pests identification research,and further optimize the crop diseases and pests control work for agricultural workers in need.
基金the National Natural Science Foundation of China under Grant 52007193 and The 2115 Talent Development Program of China Agricultural University.
文摘As the new generation of artificial intelligence(AI)continues to evolve,weather big data and statistical machine learning(SML)technologies complement each other and are deeply integrated to significantly improve the processing and forecasting accuracy of fishery weather.Accurate fishery weather services play a crucial role in fishery production,serving as a great safeguard for economic benefits and personal safety,enabling fishermen to carry out fishery production better,and contributing to the sustainable development of the fishery industry.The objective of this paper is to offer an understanding of the present state of research and development in SML technology for simulating and forecasting fishery weather.Specifically,we analyze the current state of research and technical features of SML in weather and summarize the applications of SML in simulation and forecasting of fishery weather,which mainly include three aspects:fishery weather scenario generation,fishery weather forecasting,and fishery extreme weather warning.We also illustrate the main technical means and principles of SML technology.Finally,we summarize the most advanced SML fields and provide an outlook on their application value in the field of fishery weather.