The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains and directs oscillations through transcriptional and translational feedback loops,which modulates an approximately...The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains and directs oscillations through transcriptional and translational feedback loops,which modulates an approximately 24-h cycle of endocrine and metabolic rhythms within cells and tissues.While circadian clocks regulate metabolic processes and related physiology,emerging evidence indicates that metabolism and circadian rhythm are intimately intertwined.In this review,we highlight the concept of metabolites,including lipids and other polar metabolites generated from intestinal microbial metabolism and nutrient intake,as time cues that drive changes in circadian rhythms,which in turn influence metabolism and aging.Furthermore,we discuss the roles of functional metabolites as circadian cues,paving a new direction on potential intervention targets of circadian disruption,pathological aging,as well as metabolic diseases that are clinically important.展开更多
BACKGROUND Probiotic Acetobacter pasteurianus is used to treat diabetes,but its specific hypoglycemic substances and mechanisms remain unclear.AIM To investigate the components for lipid metabolism of A.pasteurianus a...BACKGROUND Probiotic Acetobacter pasteurianus is used to treat diabetes,but its specific hypoglycemic substances and mechanisms remain unclear.AIM To investigate the components for lipid metabolism of A.pasteurianus and its hypoglycemic effects,providing a basis for its broader application.METHODS The lipid metabolism of A.pasteurianus under different growth conditions was analyzed using lipidomics.Neutral lipid staining in A.pasteurianus cells and the formation of lipid droplet-like structures were observed using a confocal laser scanning microscope.The neutral lipid components were also analyzed using thin layer chromato-graphy.A diabetic mouse model was established to evaluate the hypoglycemic effects of the main lipid components of A.pasteurianus and their role in repairing tissues such as the pancreas.RESULTS After comparing the effects of three culture media,namely,brain heart infusion(BHI)medium with 2%glucose,chromium-rich and zinc-rich medium,and mineral salt medium,A.pasteurianus grew well in BHI containing 2%glucose and produced the most lipids.A total of 583 lipid metabolic products was identified,with higher levels of coenzyme Q9(CoQ9),oleic acid(OA),and wax ester,but no triacylglycerol was observed.It was found that the components that affected lipid metabolism in A.pasteurianus were mainly CoQ9 and OA.They exhibited hypoglycemic effects comparable to metformin in diabetic mice,repaired damaged pancreatic tissues,and did not cause damage to the liver and spleen.CONCLUSION Under high-nutrient growth conditions,A.pasteurianus contains abundant lipid components,such as CoQ9 and OA,with good hypoglycemic effects.展开更多
Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the firs...Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the first time developed a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells. Our data showed that CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels, leading to the significant suppression of HUVEC proliferation, adhesion and migration. These results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis, and CD146 siRNA can be used as a new inhibitor for anti-angiogenesis therapy.展开更多
Decades of investigation on DNA methylation have led to deeper insights into its metabolic mechanisms and biological functions.This understanding was fueled by the recent development of genome editing tools and our im...Decades of investigation on DNA methylation have led to deeper insights into its metabolic mechanisms and biological functions.This understanding was fueled by the recent development of genome editing tools and our improved capacity for analyzing the global DNA methylome in mammalian cells.This review focuses on the maintenance of DNA methylation patterns during mitotic cell division.We discuss the latest discoveries of the mechanisms for the inheritance of DNA methylation as a stable epigenetic memory.We also highlight recent evidence showing the rapid turnover of DNA methylation as a dynamic gene regulatory mechanism.A body of work has shown that altered DNA methylomes are common features in aging and disease.We discuss the potential links between methylation maintenance mechanisms and diseaseassociated methylation changes.展开更多
Modern China,similar to most developing nations,has seen a rise in the prevalence of both obesity and diesel exhaust based air pollution.The cause of obesity is multi-factorial encompassing diet,lifestyle and social f...Modern China,similar to most developing nations,has seen a rise in the prevalence of both obesity and diesel exhaust based air pollution.The cause of obesity is multi-factorial encompassing diet,lifestyle and social factors.Also there has been a reduction in the consumption of fruit,vegetables,and traditional medicinal foods such as polyphenol containing green tea.Replacing these,are high fat and carbohydrate based processed foods which are quickly displacing these wholefoods in the diet.This review paper proposes evidence that a potential cause of obesity is also linked to environmental stress stimuli such as air pollutants,particularly diesel exhaust fumes(DEF)of>2.5μm particulate matter,and discusses a role for a green tea catechin(EGCG)for use as a dietary defence against diet and environmentally induced obesity.China is now at a critical point of a public health pandemic with rising air-borne pollution(via car exhaust fumes DEF),industry pollution such as heavy metals,and the benzene hydrocarbon based‘2PM’particulate matter,now accepted as a major environmental issue for public health.Relevant data published in MEDLINE since 1995 has been gathered to formulate the following review.展开更多
The performance of conventional similarity measurement methods is affected seriously by the curse of dimensionality of high-dimensional data.The reason is that data difference between sparse and noisy dimensionalities...The performance of conventional similarity measurement methods is affected seriously by the curse of dimensionality of high-dimensional data.The reason is that data difference between sparse and noisy dimensionalities occupies a large proportion of the similarity,leading to the dissimilarities between any results.A similarity measurement method of high-dimensional data based on normalized net lattice subspace is proposed.The data range of each dimension is divided into several intervals,and the components in different dimensions are mapped onto the corresponding interval.Only the component in the same or adjacent interval is used to calculate the similarity.To validate this method,three data types are used,and seven common similarity measurement methods are compared.The experimental result indicates that the relative difference of the method is increasing with the dimensionality and is approximately two or three orders of magnitude higher than the conventional method.In addition,the similarity range of this method in different dimensions is [0,1],which is fit for similarity analysis after dimensionality reduction.展开更多
Peroxisome proliferator-activated receptors （PPAR） belong to the nuclear hormone receptor superfamily of ligand-dependent transcription factors. Recent results have shown that agonists of PPARy, such as troglitazone...Peroxisome proliferator-activated receptors （PPAR） belong to the nuclear hormone receptor superfamily of ligand-dependent transcription factors. Recent results have shown that agonists of PPARy, such as troglitazone （TGZ）, can inhibit cell proliferation and promote cell differentiation independent of PPARy. In the present study, we provide evidence that TGZ may bind directly to EGFR and trigger its signaling and internalization independent of PPARγ. Detailed studies revealed that prolonged incubation with TGZ effectively attenuated EGFR signaling by targeting the receptor to the endo-lysosomal degradation machinery. Although the extracellular signal-regulated kinasesignaling pathway was transiently activated by TGZ in EGFR overexpressing cancer cells, inhibition of EGF-induced Akt phosphorylation most likely accounted for the growth arrest of tumor cells caused by TGZ at pharmacologically achievable concentrations. Therefore, we have provided a new line of evidence indicating that TGZ inhibits cell pro- liferation by promoting EGFR degradation and attenuating Akt phosphorylation.展开更多
Nanoparticles that contain magnetic materials,such as magnetite(Fe3O4),are particularly useful for imaging and separation techniques.Since these nanoparticles are generally considered to be biologically and chemically...Nanoparticles that contain magnetic materials,such as magnetite(Fe3O4),are particularly useful for imaging and separation techniques.Since these nanoparticles are generally considered to be biologically and chemically inert,they are typically coated with metal catalysts,antibodies or enzymes to increase their functionality as separation agents.Here,we report that magnetite nanoparticles in fact possess an intrinsic enzyme mimetic activity similar to that found in natural peroxidases,which are widely used to oxidize organic substrates in the treatment of wastewater or as detection tools.展开更多
The biological features of most foamy viruses(FVs) are poorly understood, including bovine foamy virus(BFV). BFV strain 3026(BFV3026) was isolated from the peripheral blood mononuclear cells of an infected cow in Zhan...The biological features of most foamy viruses(FVs) are poorly understood, including bovine foamy virus(BFV). BFV strain 3026(BFV3026) was isolated from the peripheral blood mononuclear cells of an infected cow in Zhangjiakou, China. A full-length genomic clone of BFV3026 was obtained from BFV3026-infected cells, and it exhibited more than 99% amino acid(AA) homology to another BFV strain isolated in the USA. Upon transfection into fetal canine thymus cells, the full-length BFV3026 clone produced viral structural and auxiliary proteins, typical cytopathic effects, and virus particles. These results demonstrate that the full-length BFV3026 clone is fully infectious and can be used in further BFV3026 research.展开更多
Virus identification is a prerequisite not only for the early diagnosis of viral infectious diseases but also for the effective prevention of epidemics.Successful cultivation is the gold standard for identifying a vir...Virus identification is a prerequisite not only for the early diagnosis of viral infectious diseases but also for the effective prevention of epidemics.Successful cultivation is the gold standard for identifying a virus,according to the Koch postulates.However,this requires screening for a permissive cell line,which is traditionally time-,reagent-and labor-intensive.Here,a simple and easy-to-operate microfluidic chip,formed by seeding a variety of cell lines and culturing them in parallel,is reported for use in virus cultivation and virus-permissive host-cell screening.The chip was tested by infection with two known viruses,enterovirus 71(EV71)and influenza virus H1N1.Infection with EV71 and H1N1 caused significant cytopathic effects(CPE)in RD and MDCK cells,respectively,demonstrating that virus cultivation based on this microfluidic cell chip can be used as a substitute for the traditional plate-based culture method and reproduce the typical CPE caused by virus infection.Using this microfluidic cell chip method for virus cultivation could make it possible to identify an emerging virus in a highthroughput,automatic,and unprecedentedly fast way.展开更多
We successfully conduct the label-free and real-time detection of the interactions between epoxy groups and rabbit IgG and 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ oligonucleotide, and between the hybridization of 5＇ CTT C...We successfully conduct the label-free and real-time detection of the interactions between epoxy groups and rabbit IgG and 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ oligonucleotide, and between the hybridization of 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ and its complementary 3＇ GAA GTC CAC TAC TCG GAC TA 5＇ oligonucleotide, by the oblique-incidence reflectivity difference （OI-RD） method. The dynamic curves of OI-RD signals, corresponding to the kinetic processes of biomolecular combination or hybridization, are acquired. In our case, the combination of epoxy groups with rabbit IgG and 5＇ CTT CAC CTC ATG AGC CTG AT 3＇ oligonucleotide need almost one and a half hours and about two hundred seconds, respectively; and the hybridization of the two oligonucleotides needs about five hundred seconds. The experimental results show that the OI-RD is a promising method for the real-time and label-free detection of biomolecular interactions.展开更多
SARS-CoV-2 variants are constantly emerging,hampering public health measures in controlling the number of infections.While it is well established that mutations in spike proteins observed for the different variants di...SARS-CoV-2 variants are constantly emerging,hampering public health measures in controlling the number of infections.While it is well established that mutations in spike proteins observed for the different variants directly affect virus entry into host cells,there remains a need for further expansion of systematic and multifaceted comparisons.Here,we comprehensively studied the effect of spike protein mutations on spike expression and proteolytic activation,binding affinity,viral entry efficiency and host cell tropism of eight variants of concern(VOC)and variants of interest(VOI).We found that both the full-length spike and its receptor-binding domain(RBD)of Omicron bind to hACE2 with an affinity similar to that of the wild-type.In addition,Alpha,Beta,Delta and Lambda pseudoviruses gained significantly enhanced cell entry ability compared to the wild-type,while the Omicron pseudoviruses showed a slightly increased cell entry,suggesting the vastly increased rate of transmission observed for Omicron variant is not associated with its affinity to hACE2.We also found that the spikes of Omicron and Mu showed lower S1/S2 cleavage efficiency and inefficiently utilized TMPRSS2 to enter host cells than others,suggesting that they prefer the endocytosis pathway to enter host cells.Furthermore,all variants'pseudoviruses we tested gained the ability to enter the animal ACE2-expressing cells.Especially the infection potential of rats and mice showed significantly increased,strongly suggesting that rodents possibly become a reservoir for viral evolution.The insights gained from this study provide valuable guidance for a targeted approach to epidemic control,and contribute to a better understanding of SARS-CoV-2 evolution.展开更多
Dear Editor,Mitochondria acts as a cellular organelle that produces ATP and buffers Ca2+,and plays an important role in neuronal growth,survival and function[1].Loss of mitochondria will make the ATP supply insufficie...Dear Editor,Mitochondria acts as a cellular organelle that produces ATP and buffers Ca2+,and plays an important role in neuronal growth,survival and function[1].Loss of mitochondria will make the ATP supply insufficient,resulting in synaptic transmission dysfunction[2].Further,presynaptic mitochondrial dysfunctions are often associated with severe neurological diseases[3].Abnormal mitochondrial function can also lead to neurodegenerative diseases because of the degeneration of synapse transmission,such as Alzheimer’s disease[4]and Parkinson’s disease[5].In neurons,mitochondria have a wide range of size,shape and number,which can be constantly changed through fission and fusion events to form a highly dynamic and organized network[6]and also a way of mitochondrial quality control.展开更多
Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection,the protection period of vaccination and the possibility of bui...Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection,the protection period of vaccination and the possibility of building an active herd immunity.This retrospective cohort study included 172 COVID-19 patients who were hospitalized in Wuhan.A total of404 serum samples were obtained over six months from hospitalization to convalescence.Antibodies in the specimens were quantitatively analyzed by the capture chemiluminescence immunoassays(CLIA).All patients were positive for the anti-SARS-Co V-2 Ig M/Ig G at the onset of COVID-19 symptoms,and the Ig G antibody persisted in all the patients during the convalescence.However,only approximately 25%of patients can detect the Ig M antibodies,Ig M against N protein(NIg M)and receptor binding domain of S protein(RBD-Ig M)at the 27 th week.The titers of Ig M,N-Ig M and RBD-Ig M reduced to 16.7%,17.6%and 15.2%of their peak values respectively.In contrast,the titers of Ig G,N-Ig G and RBD-Ig G peaked at 4–5 th week and reduced to 85.9%,62.6%and 87.2%of their peak values respectively at the end of observation.Dynamic behavior of antibodies and their correlation in age,gender and severity groups were investigated.In general,the COVID-19 antibody was sustained at high levels for over six months in most of the convalescent patients.Only a few patients with antibody reducing to an undetectable level which needs further attention.The humoral immune response against SARS-Co V-2 infection in COVID-19 patients exhibits a typical dynamic of acquired immunity.展开更多
Centromeres are chromosomal loci marked by histone variant Cen H3(centromeric histone H3)and essential for genomic stability and cell division.The budding yeast E3 ubiquitin ligase Psh1 selectively recognizes the yeas...Centromeres are chromosomal loci marked by histone variant Cen H3(centromeric histone H3)and essential for genomic stability and cell division.The budding yeast E3 ubiquitin ligase Psh1 selectively recognizes the yeast Cen H3(Cse4)for ubiquitination and controls the cellular level of Cse4 for proteolysis,but the underlying mechanism remains largely unknown.Here,we show that Psh1 uses a Cse4-binding domain(CBD,residues 1-211)to interact with Cse4-H4 instead of H3-H4,yielding a dissociation constant(Kd)of 27 nM.Psh1 recognizes Cse4-specific residues in the L1 loop and a2 helix to ensure Cse4 binding and ubiquitination.We map the Psh1-binding region of Cse4-H4 and identify a wide range of Cse4-specific residues required for the Psh1-mediated Cse4 recognition and ubiquitination.Further analyses reveal that histone chaperone Scm3 can impair Cse4 ubiquitination by abrogating Psh1-Cse4 binding.Together,our study reveals a novel Cse4-binding mode distinct from those of known Cen H3 chaperones and elucidates the mechanism by which Scm3 competes with Psh1 for Cse4 binding.展开更多
Belonging to the immunoglobulin superfamily of cell adhesion molecules,carcinoembryonic antigen related cell adhesion molecules(CEACAMs)have been found associated with various types of cancers,particularly colorectal ...Belonging to the immunoglobulin superfamily of cell adhesion molecules,carcinoembryonic antigen related cell adhesion molecules(CEACAMs)have been found associated with various types of cancers,particularly colorectal carcinoma,and developed to be tumor targets for cancer therapy.In present study,by immunizing mice with colorectal cancer LS174T cells,we generated a novel monoclonal antibody,namely CC4,recognizing an evolutionarily conserved epitope within the N-terminal IgV-like domain of CEACAMs.展开更多
Human immunodeficiency virus-1 （HIV-1）encodes 15 viral proteins. Protein-protein interactions play a large role in the function of these proteins. In this study, we attempted to identify novel interactions between t...Human immunodeficiency virus-1 （HIV-1）encodes 15 viral proteins. Protein-protein interactions play a large role in the function of these proteins. In this study, we attempted to identify novel interactions between the HIV-1 proteins to better understand the role played by viral protein-protein interactions in the life cycle of HIV-I. Genes encoding the 15 viral proteins from the HIV-1 strain AD8 were inserted into the plasmids of a yeast two-hybrid system. By screening 120 pairs of proteins, interactions between seven pairs were found. This led to the discovery of an interaction between the HIV-1 proteins integrase （IN） and glycoprotein 41 （gp41）, which was confirmed by both co-immunoprecipitation （Co-IP） assays and fluorescence resonance energy transfer （FRET） imaging in live cells. In addition, it was found that the amino acids at positions 76-100 of gp41 are required for it to bind to IN. Deletion of this region from gp41 prevented its interaction with IN and reduced the production of HIV-1 in 293T cells. This study provides new information on HIV-1 protein-protein interactions which improves the understanding of the biological functions of gp41 and IN during the virus life cycle.展开更多
The goal of our study was to raise tumor-suppressing monoclonal antibodies(mAbs)against colonic carcinoma.Here,we described the generation and intensive characterization of an anti-sTn mAb,namely 3P9,which exhibited p...The goal of our study was to raise tumor-suppressing monoclonal antibodies(mAbs)against colonic carcinoma.Here,we described the generation and intensive characterization of an anti-sTn mAb,namely 3P9,which exhibited promising capability of specifically targeting and markedly suppressing colorectal tumor.In our study,mAb 3P9 showed remarkably restricted immunoreactivity and high sensitivity and specificity in recognizing colonic adenocarcinoma.展开更多
CD146 molecule,the surface marker of tumor vascular,plays a key role in the proliferation and migration of vascular endothelial cell.However,due to lack of suitable animal model,the research about the role of CD146 in...CD146 molecule,the surface marker of tumor vascular,plays a key role in the proliferation and migration of vascular endothelial cell.However,due to lack of suitable animal model,the research about the role of CD146 in angiogenesis has been limited to molecular and cellular biological level,which could not be deepened in vivo.To solve this problem,we generated the CD146 conditional knock out mouse using the Cre-LoxP system,in which the promoter region and the first exon were flanked by two LoxP site.展开更多
基金supported by grants from the Chinese Academy of Sciences(XDB39050800)the Major Project of Guangzhou National Laboratory(GZNL2024A03013)the National Natural Science Foundation of China(92357308 and 32321004)。
文摘The circadian clock is a highly hierarchical network of endogenous pacemakers that primarily maintains and directs oscillations through transcriptional and translational feedback loops,which modulates an approximately 24-h cycle of endocrine and metabolic rhythms within cells and tissues.While circadian clocks regulate metabolic processes and related physiology,emerging evidence indicates that metabolism and circadian rhythm are intimately intertwined.In this review,we highlight the concept of metabolites,including lipids and other polar metabolites generated from intestinal microbial metabolism and nutrient intake,as time cues that drive changes in circadian rhythms,which in turn influence metabolism and aging.Furthermore,we discuss the roles of functional metabolites as circadian cues,paving a new direction on potential intervention targets of circadian disruption,pathological aging,as well as metabolic diseases that are clinically important.
基金Supported by the Guangxi Science and Technology Major Projects,No.AA23073012the National Natural Science Foundation of China,No.32360035 and No.32060018.
文摘BACKGROUND Probiotic Acetobacter pasteurianus is used to treat diabetes,but its specific hypoglycemic substances and mechanisms remain unclear.AIM To investigate the components for lipid metabolism of A.pasteurianus and its hypoglycemic effects,providing a basis for its broader application.METHODS The lipid metabolism of A.pasteurianus under different growth conditions was analyzed using lipidomics.Neutral lipid staining in A.pasteurianus cells and the formation of lipid droplet-like structures were observed using a confocal laser scanning microscope.The neutral lipid components were also analyzed using thin layer chromato-graphy.A diabetic mouse model was established to evaluate the hypoglycemic effects of the main lipid components of A.pasteurianus and their role in repairing tissues such as the pancreas.RESULTS After comparing the effects of three culture media,namely,brain heart infusion(BHI)medium with 2%glucose,chromium-rich and zinc-rich medium,and mineral salt medium,A.pasteurianus grew well in BHI containing 2%glucose and produced the most lipids.A total of 583 lipid metabolic products was identified,with higher levels of coenzyme Q9(CoQ9),oleic acid(OA),and wax ester,but no triacylglycerol was observed.It was found that the components that affected lipid metabolism in A.pasteurianus were mainly CoQ9 and OA.They exhibited hypoglycemic effects comparable to metformin in diabetic mice,repaired damaged pancreatic tissues,and did not cause damage to the liver and spleen.CONCLUSION Under high-nutrient growth conditions,A.pasteurianus contains abundant lipid components,such as CoQ9 and OA,with good hypoglycemic effects.
文摘Our previous study has demonstrated that CD 146 molecule is a biomarker on vascular endothelium, which is involved in angiogenesis and tumor growth. However the mechanism behind is not clear. Here we have for the first time developed a novel CD146 blockade system using CD146 siRNA to study its function on endothelial cells. Our data showed that CD146 siRNA specifically blocked the expression of CD146 on both mRNA and protein levels, leading to the significant suppression of HUVEC proliferation, adhesion and migration. These results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis, and CD146 siRNA can be used as a new inhibitor for anti-angiogenesis therapy.
基金Supported by Grants from the National High-tech R and D Pro-gram No.2012AA020206the Key Project for the Infectious Diseases No.2012ZX10002-017 and No.2013ZX10002009-001-004+2 种基金the State Key Projects for Basic Research No.2011CB910703the National Natural Science Foundation No.81372591,and No.81321091 of Chinathe Center for Marine Medicine and Rescue of Tsinghua University
文摘AIM: To investigate the expression of key biomarkers in hepatoma cell lines, tumor cells from patients’ blood samples, and tumor tissues.
基金supported by the Chinese Ministry of Science and Technology (2019YFA0801401 to B.Z.)the Chinese Academy of Sciences (XDB39000000 and QYZDY-SSW-SMC031 to B.Z.+1 种基金2019 Special Research Assistant Funding to Y.L.)the National Natural Science Foundation of China (32000559 to Y.L.)。
文摘Decades of investigation on DNA methylation have led to deeper insights into its metabolic mechanisms and biological functions.This understanding was fueled by the recent development of genome editing tools and our improved capacity for analyzing the global DNA methylome in mammalian cells.This review focuses on the maintenance of DNA methylation patterns during mitotic cell division.We discuss the latest discoveries of the mechanisms for the inheritance of DNA methylation as a stable epigenetic memory.We also highlight recent evidence showing the rapid turnover of DNA methylation as a dynamic gene regulatory mechanism.A body of work has shown that altered DNA methylomes are common features in aging and disease.We discuss the potential links between methylation maintenance mechanisms and diseaseassociated methylation changes.
文摘Modern China,similar to most developing nations,has seen a rise in the prevalence of both obesity and diesel exhaust based air pollution.The cause of obesity is multi-factorial encompassing diet,lifestyle and social factors.Also there has been a reduction in the consumption of fruit,vegetables,and traditional medicinal foods such as polyphenol containing green tea.Replacing these,are high fat and carbohydrate based processed foods which are quickly displacing these wholefoods in the diet.This review paper proposes evidence that a potential cause of obesity is also linked to environmental stress stimuli such as air pollutants,particularly diesel exhaust fumes(DEF)of>2.5μm particulate matter,and discusses a role for a green tea catechin(EGCG)for use as a dietary defence against diet and environmentally induced obesity.China is now at a critical point of a public health pandemic with rising air-borne pollution(via car exhaust fumes DEF),industry pollution such as heavy metals,and the benzene hydrocarbon based‘2PM’particulate matter,now accepted as a major environmental issue for public health.Relevant data published in MEDLINE since 1995 has been gathered to formulate the following review.
基金Supported by the National Natural Science Foundation of China(No.61502475)the Importation and Development of High-Caliber Talents Project of the Beijing Municipal Institutions(No.CIT&TCD201504039)
文摘The performance of conventional similarity measurement methods is affected seriously by the curse of dimensionality of high-dimensional data.The reason is that data difference between sparse and noisy dimensionalities occupies a large proportion of the similarity,leading to the dissimilarities between any results.A similarity measurement method of high-dimensional data based on normalized net lattice subspace is proposed.The data range of each dimension is divided into several intervals,and the components in different dimensions are mapped onto the corresponding interval.Only the component in the same or adjacent interval is used to calculate the similarity.To validate this method,three data types are used,and seven common similarity measurement methods are compared.The experimental result indicates that the relative difference of the method is increasing with the dimensionality and is approximately two or three orders of magnitude higher than the conventional method.In addition,the similarity range of this method in different dimensions is [0,1],which is fit for similarity analysis after dimensionality reduction.
文摘Peroxisome proliferator-activated receptors （PPAR） belong to the nuclear hormone receptor superfamily of ligand-dependent transcription factors. Recent results have shown that agonists of PPARy, such as troglitazone （TGZ）, can inhibit cell proliferation and promote cell differentiation independent of PPARy. In the present study, we provide evidence that TGZ may bind directly to EGFR and trigger its signaling and internalization independent of PPARγ. Detailed studies revealed that prolonged incubation with TGZ effectively attenuated EGFR signaling by targeting the receptor to the endo-lysosomal degradation machinery. Although the extracellular signal-regulated kinasesignaling pathway was transiently activated by TGZ in EGFR overexpressing cancer cells, inhibition of EGF-induced Akt phosphorylation most likely accounted for the growth arrest of tumor cells caused by TGZ at pharmacologically achievable concentrations. Therefore, we have provided a new line of evidence indicating that TGZ inhibits cell pro- liferation by promoting EGFR degradation and attenuating Akt phosphorylation.
文摘Nanoparticles that contain magnetic materials,such as magnetite(Fe3O4),are particularly useful for imaging and separation techniques.Since these nanoparticles are generally considered to be biologically and chemically inert,they are typically coated with metal catalysts,antibodies or enzymes to increase their functionality as separation agents.Here,we report that magnetite nanoparticles in fact possess an intrinsic enzyme mimetic activity similar to that found in natural peroxidases,which are widely used to oxidize organic substrates in the treatment of wastewater or as detection tools.
基金supported by grants from the National Natural Science Foundation of China (31070135, 31370182)the Tianjin Research Program of Application Foundation and Advanced Technology (12JCQNJC06100)New Century Excellent Talents in University (NCET-10-0508)
文摘The biological features of most foamy viruses(FVs) are poorly understood, including bovine foamy virus(BFV). BFV strain 3026(BFV3026) was isolated from the peripheral blood mononuclear cells of an infected cow in Zhangjiakou, China. A full-length genomic clone of BFV3026 was obtained from BFV3026-infected cells, and it exhibited more than 99% amino acid(AA) homology to another BFV strain isolated in the USA. Upon transfection into fetal canine thymus cells, the full-length BFV3026 clone produced viral structural and auxiliary proteins, typical cytopathic effects, and virus particles. These results demonstrate that the full-length BFV3026 clone is fully infectious and can be used in further BFV3026 research.
基金the Scientific Instrument Developing Project of the Chinese Academy of Sciences(No.YJKYYQ20190057)the National Nature Science Foundation of China(No.81827804)+1 种基金the CAS Emergency Project of ASF Research(No.KJZDSW-L06-02)Applied Basic Research Program of Wuhan(No.2018060401011327)。
文摘Virus identification is a prerequisite not only for the early diagnosis of viral infectious diseases but also for the effective prevention of epidemics.Successful cultivation is the gold standard for identifying a virus,according to the Koch postulates.However,this requires screening for a permissive cell line,which is traditionally time-,reagent-and labor-intensive.Here,a simple and easy-to-operate microfluidic chip,formed by seeding a variety of cell lines and culturing them in parallel,is reported for use in virus cultivation and virus-permissive host-cell screening.The chip was tested by infection with two known viruses,enterovirus 71(EV71)and influenza virus H1N1.Infection with EV71 and H1N1 caused significant cytopathic effects(CPE)in RD and MDCK cells,respectively,demonstrating that virus cultivation based on this microfluidic cell chip can be used as a substitute for the traditional plate-based culture method and reproduce the typical CPE caused by virus infection.Using this microfluidic cell chip method for virus cultivation could make it possible to identify an emerging virus in a highthroughput,automatic,and unprecedentedly fast way.
基金Project supported by the National Basic Research Program in China(Grant No.2007CB935700)
文摘We successfully conduct the label-free and real-time detection of the interactions between epoxy groups and rabbit IgG and 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ oligonucleotide, and between the hybridization of 5＇ CTT CAG GTC ATG AGC CTG AT 3＇ and its complementary 3＇ GAA GTC CAC TAC TCG GAC TA 5＇ oligonucleotide, by the oblique-incidence reflectivity difference （OI-RD） method. The dynamic curves of OI-RD signals, corresponding to the kinetic processes of biomolecular combination or hybridization, are acquired. In our case, the combination of epoxy groups with rabbit IgG and 5＇ CTT CAC CTC ATG AGC CTG AT 3＇ oligonucleotide need almost one and a half hours and about two hundred seconds, respectively; and the hybridization of the two oligonucleotides needs about five hundred seconds. The experimental results show that the OI-RD is a promising method for the real-time and label-free detection of biomolecular interactions.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No.XDB29050100)the National Key Research and Development Program of China (Grant No.2022YFC0869900,2022YFC2303501,2020YFC0861100)the Program of the Chinese Academy of Sciences (Grant No.2020YJFK-Z-0150).
文摘SARS-CoV-2 variants are constantly emerging,hampering public health measures in controlling the number of infections.While it is well established that mutations in spike proteins observed for the different variants directly affect virus entry into host cells,there remains a need for further expansion of systematic and multifaceted comparisons.Here,we comprehensively studied the effect of spike protein mutations on spike expression and proteolytic activation,binding affinity,viral entry efficiency and host cell tropism of eight variants of concern(VOC)and variants of interest(VOI).We found that both the full-length spike and its receptor-binding domain(RBD)of Omicron bind to hACE2 with an affinity similar to that of the wild-type.In addition,Alpha,Beta,Delta and Lambda pseudoviruses gained significantly enhanced cell entry ability compared to the wild-type,while the Omicron pseudoviruses showed a slightly increased cell entry,suggesting the vastly increased rate of transmission observed for Omicron variant is not associated with its affinity to hACE2.We also found that the spikes of Omicron and Mu showed lower S1/S2 cleavage efficiency and inefficiently utilized TMPRSS2 to enter host cells than others,suggesting that they prefer the endocytosis pathway to enter host cells.Furthermore,all variants'pseudoviruses we tested gained the ability to enter the animal ACE2-expressing cells.Especially the infection potential of rats and mice showed significantly increased,strongly suggesting that rodents possibly become a reservoir for viral evolution.The insights gained from this study provide valuable guidance for a targeted approach to epidemic control,and contribute to a better understanding of SARS-CoV-2 evolution.
基金the National Key Research and Development Program of China(2017YFA0504700)The National Natural Science Foundation of China(32027901).
文摘Dear Editor,Mitochondria acts as a cellular organelle that produces ATP and buffers Ca2+,and plays an important role in neuronal growth,survival and function[1].Loss of mitochondria will make the ATP supply insufficient,resulting in synaptic transmission dysfunction[2].Further,presynaptic mitochondrial dysfunctions are often associated with severe neurological diseases[3].Abnormal mitochondrial function can also lead to neurodegenerative diseases because of the degeneration of synapse transmission,such as Alzheimer’s disease[4]and Parkinson’s disease[5].In neurons,mitochondria have a wide range of size,shape and number,which can be constantly changed through fission and fusion events to form a highly dynamic and organized network[6]and also a way of mitochondrial quality control.
基金supported by the National Key Research and Development Program of China(Grant No.2020YFC0861100 and 2020YFC0000)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB29050100)+2 种基金the Key Technology Development Program of Shenzhen(Grant No.JSGG20200225153042494)the Youth Innovation Promotion Association of CAS(Grant No.2014308)the Interdisciplinary Innovation Team of CAS。
文摘Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection,the protection period of vaccination and the possibility of building an active herd immunity.This retrospective cohort study included 172 COVID-19 patients who were hospitalized in Wuhan.A total of404 serum samples were obtained over six months from hospitalization to convalescence.Antibodies in the specimens were quantitatively analyzed by the capture chemiluminescence immunoassays(CLIA).All patients were positive for the anti-SARS-Co V-2 Ig M/Ig G at the onset of COVID-19 symptoms,and the Ig G antibody persisted in all the patients during the convalescence.However,only approximately 25%of patients can detect the Ig M antibodies,Ig M against N protein(NIg M)and receptor binding domain of S protein(RBD-Ig M)at the 27 th week.The titers of Ig M,N-Ig M and RBD-Ig M reduced to 16.7%,17.6%and 15.2%of their peak values respectively.In contrast,the titers of Ig G,N-Ig G and RBD-Ig G peaked at 4–5 th week and reduced to 85.9%,62.6%and 87.2%of their peak values respectively at the end of observation.Dynamic behavior of antibodies and their correlation in age,gender and severity groups were investigated.In general,the COVID-19 antibody was sustained at high levels for over six months in most of the convalescent patients.Only a few patients with antibody reducing to an undetectable level which needs further attention.The humoral immune response against SARS-Co V-2 infection in COVID-19 patients exhibits a typical dynamic of acquired immunity.
基金supported by the grants from Natural Science Foundation of China(31521002,31970621,31871318,31671344,31801070)National Key Research and Development Program of China(2019YFA0508902)Strategic Priority Research Program(XDB37010100)。
文摘Centromeres are chromosomal loci marked by histone variant Cen H3(centromeric histone H3)and essential for genomic stability and cell division.The budding yeast E3 ubiquitin ligase Psh1 selectively recognizes the yeast Cen H3(Cse4)for ubiquitination and controls the cellular level of Cse4 for proteolysis,but the underlying mechanism remains largely unknown.Here,we show that Psh1 uses a Cse4-binding domain(CBD,residues 1-211)to interact with Cse4-H4 instead of H3-H4,yielding a dissociation constant(Kd)of 27 nM.Psh1 recognizes Cse4-specific residues in the L1 loop and a2 helix to ensure Cse4 binding and ubiquitination.We map the Psh1-binding region of Cse4-H4 and identify a wide range of Cse4-specific residues required for the Psh1-mediated Cse4 recognition and ubiquitination.Further analyses reveal that histone chaperone Scm3 can impair Cse4 ubiquitination by abrogating Psh1-Cse4 binding.Together,our study reveals a novel Cse4-binding mode distinct from those of known Cen H3 chaperones and elucidates the mechanism by which Scm3 competes with Psh1 for Cse4 binding.
文摘Belonging to the immunoglobulin superfamily of cell adhesion molecules,carcinoembryonic antigen related cell adhesion molecules(CEACAMs)have been found associated with various types of cancers,particularly colorectal carcinoma,and developed to be tumor targets for cancer therapy.In present study,by immunizing mice with colorectal cancer LS174T cells,we generated a novel monoclonal antibody,namely CC4,recognizing an evolutionarily conserved epitope within the N-terminal IgV-like domain of CEACAMs.
基金supported by the National Nano Project(grant no.2011CB933600)the National Natural Science Foundation of China(grant no.31470269)supported by the Institute of Biophysics and the National Laboratory of Biomacromolecules at the Chinese Academy of Sciences(CAS)
文摘Human immunodeficiency virus-1 （HIV-1）encodes 15 viral proteins. Protein-protein interactions play a large role in the function of these proteins. In this study, we attempted to identify novel interactions between the HIV-1 proteins to better understand the role played by viral protein-protein interactions in the life cycle of HIV-I. Genes encoding the 15 viral proteins from the HIV-1 strain AD8 were inserted into the plasmids of a yeast two-hybrid system. By screening 120 pairs of proteins, interactions between seven pairs were found. This led to the discovery of an interaction between the HIV-1 proteins integrase （IN） and glycoprotein 41 （gp41）, which was confirmed by both co-immunoprecipitation （Co-IP） assays and fluorescence resonance energy transfer （FRET） imaging in live cells. In addition, it was found that the amino acids at positions 76-100 of gp41 are required for it to bind to IN. Deletion of this region from gp41 prevented its interaction with IN and reduced the production of HIV-1 in 293T cells. This study provides new information on HIV-1 protein-protein interactions which improves the understanding of the biological functions of gp41 and IN during the virus life cycle.
文摘The goal of our study was to raise tumor-suppressing monoclonal antibodies(mAbs)against colonic carcinoma.Here,we described the generation and intensive characterization of an anti-sTn mAb,namely 3P9,which exhibited promising capability of specifically targeting and markedly suppressing colorectal tumor.In our study,mAb 3P9 showed remarkably restricted immunoreactivity and high sensitivity and specificity in recognizing colonic adenocarcinoma.
文摘CD146 molecule,the surface marker of tumor vascular,plays a key role in the proliferation and migration of vascular endothelial cell.However,due to lack of suitable animal model,the research about the role of CD146 in angiogenesis has been limited to molecular and cellular biological level,which could not be deepened in vivo.To solve this problem,we generated the CD146 conditional knock out mouse using the Cre-LoxP system,in which the promoter region and the first exon were flanked by two LoxP site.
