AIM:To investigate the expression of key biomarkers in hepatoma cell lines,tumor cells from patients’blood samples,and tumor tissues.METHODS:We performed the biomarker tests in two steps.First,cells plated on coversl...AIM:To investigate the expression of key biomarkers in hepatoma cell lines,tumor cells from patients’blood samples,and tumor tissues.METHODS:We performed the biomarker tests in two steps.First,cells plated on coverslips were used to assess biomarkers,and fluorescence intensities were calculated using the NIH Image J software.The measured values were analyzed using the SPSS19.0 software to make comparisons among eight cell lines.Second,eighty-four individual samples were used to assess the biomarkers’expression.Negative enrichment of the blood samples was performed,and karyocytes were isolated and dropped onto pretreated glass slides for further analysis by immunofluorescence staining.Fluorescence intensities were compared among hepatocellular carcinoma(HCC)patients,chronic HBV-infected patients,and healthy controls following methods similar to those used for cell lines.The relationships between the expression of biomarkers and clinical pathological parameters were analyzed by Spearman rank correlation tests.In addition,we studied the distinct biomarkers’expression with three-dimensional laser confocal microscopy reconstructions,and Kaplan-Meier survival analysis was performed to understand the clinical significance of these biomarkers.RESULTS:Microscopic examination and fluorescence intensity calculations indicated that cytokeratin 8/18/19(CK)expression was significantly higher in six of the seven HCC cell lines examined than in the control cells,and the expression levels of asialoglycoprotein receptor(ASGPR)and glypican-3(GPC3)were higher in all seven HCC cell lines than in the control.Cells obtained from HCC patients’blood samples also displayed significantly higher expression levels of ASGPR,GPC3,and CK than cells from chronic HBV-infected patients or healthy controls;these proteins may be valuable surface biomarkers for identifying HCC circulating tumor cells isolated and enriched from the blood samples.The stem cell-like and epithelial-mesenchymal transition-related biomarkers could be detected on the karyocyte slides.ASGPR and GPC3 were expressed at high levels,and thus three-dimensional reconstructions were used to observe their expression in detail.This analysis indicated that GPC3 was localized in the cytoplasm and membrane,but that ASGPR had a polar localization.Survival analyses showed that expression of GPC3 and ASGPR is associated with a patient’s overall survival(OS).CONCLUSION:ASGPR,GPC3,and CK may be valuable HCC biomarkers for CTC detection;the expression of ASGPR and GPC3 might be helpful for understanding patients’OS.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
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
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 ...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 CAG 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 CAG GTC 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
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
Problems existin similarity measurement and index tree construction which affect the performance of nearest neighbor search of high-dimensional data. The equidistance problem is solved using NPsim function to calculat...Problems existin similarity measurement and index tree construction which affect the performance of nearest neighbor search of high-dimensional data. The equidistance problem is solved using NPsim function to calculate similarity. And a sequential NPsim matrix is built to improve indexing performance. To sum up the above innovations,a nearest neighbor search algorithm of high-dimensional data based on sequential NPsim matrix is proposed in comparison with the nearest neighbor search algorithms based on KD-tree or SR-tree on Munsell spectral data set. Experimental results show that the proposed algorithm similarity is better than that of other algorithms and searching speed is more than thousands times of others. In addition,the slow construction speed of sequential NPsim matrix can be increased by using parallel computing.展开更多
MicroRNAs(miRNAs)are small noncoding RNA molecules ubiquitously distributed across diverse organisms,serving as pivotal regulators of genetic expression.Notably,plant-derived miRNAs have been demonstrated to have uniq...MicroRNAs(miRNAs)are small noncoding RNA molecules ubiquitously distributed across diverse organisms,serving as pivotal regulators of genetic expression.Notably,plant-derived miRNAs have been demonstrated to have unique bioactivity and certain stability in mammalian systems,thereby facilitating their capacity for cross-kingdom modulation of gene expression.While there is substantial evidence supporting the regulation of mammalian cells by plant-derived miRNAs,several questions remain unanswered.Specifically,a comprehensive investigation of the mechanisms underlying the stability and transport of plant miRNAs and their cross-kingdom regulation of gene expression in mammals remains to be done.In this review,we summarized the origin,processing,and functional mechanisms of plant miRNAs in mammalian tissues and circulation,emphasizing their greater resistance to mammalian digestion and circulation systems compared to animal miRNAs.Additionally,we introduce four well-known plant miRNAs that have been extensively studied for their functions and mechanisms in mammalian systems.By delving into these aspects,we aim to offer a fundamental understanding of this intriguing field and shed light on the complex interactions between plant miRNAs and mammalian biology.展开更多
According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting ag...According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research.展开更多
Synthetic biology provides a new paradigm for life science research(“build to learn”)and opens the future journey of biotechnology(“build to use”).Here,we discuss advances of various principles and technologies in...Synthetic biology provides a new paradigm for life science research(“build to learn”)and opens the future journey of biotechnology(“build to use”).Here,we discuss advances of various principles and technologies in the mainstream of the enabling technology of synthetic biology,including synthesis and assembly of a genome,DNA storage,gene editing,molecular evolution and de novo design of function proteins,cell and gene circuit engineering,cell-free synthetic biology,artificial intelligence(AI)-aided synthetic biology,as well as biofoundries.We also introduce the concept of quantitative synthetic biology,which is guiding synthetic biology towards increased accuracy and predictability or the real rational design.We conclude that synthetic biology will establish its disciplinary system with the iterative development of enabling technologies and the maturity of the core theory.展开更多
Histone H2A monoubiquitination is associated with transcriptional repression and needs to be removed by deubiquitinases to facilitate gene transcription in eukaryotes.However,the deubiquitinase responsible for genome-...Histone H2A monoubiquitination is associated with transcriptional repression and needs to be removed by deubiquitinases to facilitate gene transcription in eukaryotes.However,the deubiquitinase responsible for genome-wide H2A deubiquitination in plants has yet to be identified.In this study,we found that the previously identified PWWP-EPCR-ARID-TRB(PEAT)complex components interact with both the ubiquitin-specific protease UBP5 and the redundant histone acetyltransferases HAM1 and HAM2(HAM1/2)to form a larger version of PEAT complex in Arabidopsis thaliana.UBP5 functions as an H2A deubiquitinase in a nucleosome substrate-dependent manner in vitro and mediates H2A deubiquitination at the whole-genome level in vivo.HAM1/2 are shared subunits of the PEAT complex and the conserved NuA4 histone acetyltransferase com-plex,and are responsible for histone H4K5 acetylation.Within the PEAT complex,the PWWP components(PWWP1,PWWP2,and PWWP3)directly interact with UBP5 and are necessary for UBP5-mediated H2A deu-biquitination,while the EPCR components(EPCR1 and EPCR2)directly interact with HAM1/2 and are required for HAM1/2-mediated H4K5acetylation.Collectively,our study not onlyidentifies dual roles of thePEAT com-plex in H2A deubiquitination and H4K5 acetylation but also illustrates how these processes collaborate at the whole-genome level to regulate the transcription and development in plants.展开更多
OBJECTIVE TNF-related apoptosis-inducing ligand(TRAIL)is a promising cancer therapeutic agent due to its minimal toxicity to normal tissues and remarkable apoptotic activity in tumors.However,most breast cancer cells ...OBJECTIVE TNF-related apoptosis-inducing ligand(TRAIL)is a promising cancer therapeutic agent due to its minimal toxicity to normal tissues and remarkable apoptotic activity in tumors.However,most breast cancer cells are resistant to TRAIL-induced apoptosis.Our objectives are to investigate the underlying molecular mechanisms and to develop strategies to overcome such resistance.METHODS To identify modulators of TRAIL-induced apoptosis,we carried out a genome wide si RNA screen.To validate the screening result,we either silenced or overexpressed the identified genes in various breast cancer cells and changes in growth and TRAIL-induced cell apoptosis were determined in vitro and in an orthotopic xenograft mouse model.Finally,we investigated whether small molecules targeting the identified genes improve the effectiveness of TRAIL-therapy.RESULTS We unexpectedly identified androgen receptor(AR)to be responsible for TRAIL resistance.While AR is classically viewed as the key factor in prostate cancer progression,we found that AR expression levels were markedly elevated in human invasive breast cancer specimens including triple-negative breast cancers(TNBC)that are highly aggressive with poor prognosis.Importantly,breast cancer cell lines express different levels of AR that correlated with their TRAIL resistance.AR overexpression in MDA-MB-231 and MDA-MB-436 cells suppressed the TRAIL sensitivity whereas knockdown of AR rendered MCF-7 and MDA-MB-453 cells sensitive to TRAIL-induced apoptosis.AR overexpression also induced TRAIL resistance in breast tumors in vivo.Further,we observed an upregulation of the TRAIL receptor,death receptor 5(DR5)in breast cancer cells,following the removal or inhibition of AR by its antagonists Casodex and MDV3100.Treatment with AR antagonists also enhanced TRAIL-induced breast cancer cell apoptosis.CONCLUSION AR signaling suppresses TRAIL-induced breast cancer cell apoptosis,in part,by suppressing DR5 expression,and a combination of AR antagonists together with TRAIL may be a novel and effective therapy for TNBC.展开更多
Dear Editor,The nucleosome assembly protein 1(NAP-1),being a histone chaperone[1],primarily participates in the processes of nucleosome assembly and disassembly,histone transport,and histone eviction.
The aim of this study was to prepare camel serum albumin(CSA) nanoparticles using a self-assembly strategy to co-immobilize curcumin(CCM) and doxorubicin(Dox) which was in favor of combined chemotherapy and biomedical...The aim of this study was to prepare camel serum albumin(CSA) nanoparticles using a self-assembly strategy to co-immobilize curcumin(CCM) and doxorubicin(Dox) which was in favor of combined chemotherapy and biomedical applications of bactrian(Camelus bactrianus) CSA. The constructed CSA nanoparticles(CSA-NPs)with the size around 200 nm displayed a high degree of polydispersity and further encapsulation of CCM and Dox caused no apparent morphological changes to the nanocomposite(CCM/Dox CSA-NPs). The synergistic cytotoxic effect of CCM and Dox on cancer cell A549 was observed with the calculated combination index less than 1.0. Moreover, the release kinetic profile of encapsulated drugs showed a concentration dependence of glutathione(GSH) originating from the GSH used in nanoparticle formation to break the intramolecular disulfide bonds. In vitro cytotoxicity evaluations also revealed that CCM/Dox CSA-NPs showed higher cytotoxicity than that of single drug loaded CSA-NPs, which was also validated by high content screen assay. Taken together, the CCM/Dox CSA-NPs with redox-responsive attributes provided an integrated protein-based combinational drugdelivery matrix to exert synergistic effects.展开更多
Background:Maturity-onset diabetes of the young(MODY)is the most common monogenic diabetes.The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes(T2DM)among Chinese young adults.Metho...Background:Maturity-onset diabetes of the young(MODY)is the most common monogenic diabetes.The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes(T2DM)among Chinese young adults.Methods:From April 2015 to October 2017,this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China,newly diagnosed between 15 years and 45 years,with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory.Sequencing using a custom monogenic diabetes gene panel was performed,and variants of 14 MODY genes were interpreted as per current guidelines.Results:The survey determined 18 patients having genetic variants causing MODY(6 HNF1A,5 GCK,3 HNF4A,2 INS,1 PDX1,and 1 PAX4).The prevalence of MODY was 0.74%(95%confidence interval[CI]:0.40-1.08%).The clinical characteristics of MODY patients were not specific,72.2%(13/18)of them were diagnosed after 35 years,47.1%(8/17)had metabolic syndrome,and only 38.9%(7/18)had a family history of diabetes.No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.Conclusion:The prevalence of MODY in young adults with phenotypic T2DM was 0.74%,among which HNF1A-,GCK-,and HNF4A-MODY were the most common subtypes.Clinical features played a limited role in the recognition of MODY.展开更多
Aging is closely related to redox regulation.In our previous work,we proposed a new concept,“redox-stress response capacity(RRC),”and found that the decline in RRC was a dynamic characteristic of aging.However,the m...Aging is closely related to redox regulation.In our previous work,we proposed a new concept,“redox-stress response capacity(RRC),”and found that the decline in RRC was a dynamic characteristic of aging.However,the mechanism of RRC decline during aging remains unknown.In this study,using the senescent human fibroblast cell model and Caenorhabditis elegans model,we identified that peroxiredoxin 2(PRDX2),as a hydrogen peroxide(H_(2)O_(2))sensor,was involved in mediating RRC.PRDX2 knockdown led to a decline of RRC and accelerated senescence in fibroblasts and prdx-2 mutant C.elegans also showed decreased RRC.The mechanism study showed that the decreased sensor activity of PRDX2 was related to the increase in hyperoxidation of PRDX2 in senescent cells.Moreover,the level of PRDX2 hyperoxidation also increased in old C.elegans.Simultaneous overexpression of both PRDX2 and sulfiredoxin(SRX)rescued the reduced RRC and delayed senescence.The increase in PRDX2 hyperoxidation in senescent cells led to a decrease in its sensor activity,resulting in the decreased cellular response to H_(2)O_(2),which is similar to the mechanism of insulin resistance due to the lower insulin receptor sensitivity.Treatment of young cells with a high level of H_(2)O_(2)to induce a higher level of PRDX2-SO_(3) resulted in mimicking the RRC decline in senescent cells,which is also similar to a model of insulin resistance induced by high levels of insulin.All these results thrillingly indicate that there is an insulin-resistance-like phenomenon in senescent cells,we named it redox-stress response resistance,RRR.RRR in senescent cells is an important new discovery that explains RRC decline during aging and reveals the internal relationship between redox regulation and aging from a new perspective.展开更多
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.METHODS:We performed the biomarker tests in two steps.First,cells plated on coverslips were used to assess biomarkers,and fluorescence intensities were calculated using the NIH Image J software.The measured values were analyzed using the SPSS19.0 software to make comparisons among eight cell lines.Second,eighty-four individual samples were used to assess the biomarkers’expression.Negative enrichment of the blood samples was performed,and karyocytes were isolated and dropped onto pretreated glass slides for further analysis by immunofluorescence staining.Fluorescence intensities were compared among hepatocellular carcinoma(HCC)patients,chronic HBV-infected patients,and healthy controls following methods similar to those used for cell lines.The relationships between the expression of biomarkers and clinical pathological parameters were analyzed by Spearman rank correlation tests.In addition,we studied the distinct biomarkers’expression with three-dimensional laser confocal microscopy reconstructions,and Kaplan-Meier survival analysis was performed to understand the clinical significance of these biomarkers.RESULTS:Microscopic examination and fluorescence intensity calculations indicated that cytokeratin 8/18/19(CK)expression was significantly higher in six of the seven HCC cell lines examined than in the control cells,and the expression levels of asialoglycoprotein receptor(ASGPR)and glypican-3(GPC3)were higher in all seven HCC cell lines than in the control.Cells obtained from HCC patients’blood samples also displayed significantly higher expression levels of ASGPR,GPC3,and CK than cells from chronic HBV-infected patients or healthy controls;these proteins may be valuable surface biomarkers for identifying HCC circulating tumor cells isolated and enriched from the blood samples.The stem cell-like and epithelial-mesenchymal transition-related biomarkers could be detected on the karyocyte slides.ASGPR and GPC3 were expressed at high levels,and thus three-dimensional reconstructions were used to observe their expression in detail.This analysis indicated that GPC3 was localized in the cytoplasm and membrane,but that ASGPR had a polar localization.Survival analyses showed that expression of GPC3 and ASGPR is associated with a patient’s overall survival(OS).CONCLUSION:ASGPR,GPC3,and CK may be valuable HCC biomarkers for CTC detection;the expression of ASGPR and GPC3 might be helpful for understanding patients’OS.
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.
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 CAG 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 CAG GTC 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 Natural Science Foundation of China(No.61300078)the Importation and Development of High-Caliber Talents Project of Beijing Municipal Institutions(No.CIT&TCD201504039)+1 种基金Funding Project for Academic Human Resources Development in Beijing Union University(No.BPHR2014A03,Rk100201510)"New Start"Academic Research Projects of Beijing Union University(No.Hzk10201501)
文摘Problems existin similarity measurement and index tree construction which affect the performance of nearest neighbor search of high-dimensional data. The equidistance problem is solved using NPsim function to calculate similarity. And a sequential NPsim matrix is built to improve indexing performance. To sum up the above innovations,a nearest neighbor search algorithm of high-dimensional data based on sequential NPsim matrix is proposed in comparison with the nearest neighbor search algorithms based on KD-tree or SR-tree on Munsell spectral data set. Experimental results show that the proposed algorithm similarity is better than that of other algorithms and searching speed is more than thousands times of others. In addition,the slow construction speed of sequential NPsim matrix can be increased by using parallel computing.
基金supported by grants from the Ministry of Science and Technology of the People’s Republic of China(2018YFA0507101,2021YFA1300301)the Beijing Natural Science Foundation(5215016)。
文摘MicroRNAs(miRNAs)are small noncoding RNA molecules ubiquitously distributed across diverse organisms,serving as pivotal regulators of genetic expression.Notably,plant-derived miRNAs have been demonstrated to have unique bioactivity and certain stability in mammalian systems,thereby facilitating their capacity for cross-kingdom modulation of gene expression.While there is substantial evidence supporting the regulation of mammalian cells by plant-derived miRNAs,several questions remain unanswered.Specifically,a comprehensive investigation of the mechanisms underlying the stability and transport of plant miRNAs and their cross-kingdom regulation of gene expression in mammals remains to be done.In this review,we summarized the origin,processing,and functional mechanisms of plant miRNAs in mammalian tissues and circulation,emphasizing their greater resistance to mammalian digestion and circulation systems compared to animal miRNAs.Additionally,we introduce four well-known plant miRNAs that have been extensively studied for their functions and mechanisms in mammalian systems.By delving into these aspects,we aim to offer a fundamental understanding of this intriguing field and shed light on the complex interactions between plant miRNAs and mammalian biology.
基金Acknowledgments
We would like to thank our colleagues, Prof Hong Tang for providing pCTAP-A expression vector and Dr Li Zheng for valuable discussion. This work is supported by the National Natural Science Foundation of China （NO. 30630020）, the National Basic Research Program of China （2004CB720000）, and the CAS Proj- ect （KSCX 1-YW-02-1）.
基金supported by a grant from the National Natural Science Foundation of China (No.30870683)
文摘According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29050100,XDB29050500,XDA24020102)to X.E.Zhang,C.Liu and C.Gao,respectivelythe National Natural Science Foundation of China(31725002,31861143017,32022044,62050152 and 32071428)to J.Dai,Y.Yuan,C.You,and X.Wang,respectivelythe National Key Research and Development Program of China(2020YFA0907700,2018YFA0901600,2019YFA09004500)to Y.Feng and P.Wei。
文摘Synthetic biology provides a new paradigm for life science research(“build to learn”)and opens the future journey of biotechnology(“build to use”).Here,we discuss advances of various principles and technologies in the mainstream of the enabling technology of synthetic biology,including synthesis and assembly of a genome,DNA storage,gene editing,molecular evolution and de novo design of function proteins,cell and gene circuit engineering,cell-free synthetic biology,artificial intelligence(AI)-aided synthetic biology,as well as biofoundries.We also introduce the concept of quantitative synthetic biology,which is guiding synthetic biology towards increased accuracy and predictability or the real rational design.We conclude that synthetic biology will establish its disciplinary system with the iterative development of enabling technologies and the maturity of the core theory.
基金supported by the National Natural Science Foundation of China(grant number:32025003).
文摘Histone H2A monoubiquitination is associated with transcriptional repression and needs to be removed by deubiquitinases to facilitate gene transcription in eukaryotes.However,the deubiquitinase responsible for genome-wide H2A deubiquitination in plants has yet to be identified.In this study,we found that the previously identified PWWP-EPCR-ARID-TRB(PEAT)complex components interact with both the ubiquitin-specific protease UBP5 and the redundant histone acetyltransferases HAM1 and HAM2(HAM1/2)to form a larger version of PEAT complex in Arabidopsis thaliana.UBP5 functions as an H2A deubiquitinase in a nucleosome substrate-dependent manner in vitro and mediates H2A deubiquitination at the whole-genome level in vivo.HAM1/2 are shared subunits of the PEAT complex and the conserved NuA4 histone acetyltransferase com-plex,and are responsible for histone H4K5 acetylation.Within the PEAT complex,the PWWP components(PWWP1,PWWP2,and PWWP3)directly interact with UBP5 and are necessary for UBP5-mediated H2A deu-biquitination,while the EPCR components(EPCR1 and EPCR2)directly interact with HAM1/2 and are required for HAM1/2-mediated H4K5acetylation.Collectively,our study not onlyidentifies dual roles of thePEAT com-plex in H2A deubiquitination and H4K5 acetylation but also illustrates how these processes collaborate at the whole-genome level to regulate the transcription and development in plants.
基金supported by National Institutes of Health(R21CA193271 and R01HL116849)National Natural Science Foundation of China(31100595 and 31300683)
文摘OBJECTIVE TNF-related apoptosis-inducing ligand(TRAIL)is a promising cancer therapeutic agent due to its minimal toxicity to normal tissues and remarkable apoptotic activity in tumors.However,most breast cancer cells are resistant to TRAIL-induced apoptosis.Our objectives are to investigate the underlying molecular mechanisms and to develop strategies to overcome such resistance.METHODS To identify modulators of TRAIL-induced apoptosis,we carried out a genome wide si RNA screen.To validate the screening result,we either silenced or overexpressed the identified genes in various breast cancer cells and changes in growth and TRAIL-induced cell apoptosis were determined in vitro and in an orthotopic xenograft mouse model.Finally,we investigated whether small molecules targeting the identified genes improve the effectiveness of TRAIL-therapy.RESULTS We unexpectedly identified androgen receptor(AR)to be responsible for TRAIL resistance.While AR is classically viewed as the key factor in prostate cancer progression,we found that AR expression levels were markedly elevated in human invasive breast cancer specimens including triple-negative breast cancers(TNBC)that are highly aggressive with poor prognosis.Importantly,breast cancer cell lines express different levels of AR that correlated with their TRAIL resistance.AR overexpression in MDA-MB-231 and MDA-MB-436 cells suppressed the TRAIL sensitivity whereas knockdown of AR rendered MCF-7 and MDA-MB-453 cells sensitive to TRAIL-induced apoptosis.AR overexpression also induced TRAIL resistance in breast tumors in vivo.Further,we observed an upregulation of the TRAIL receptor,death receptor 5(DR5)in breast cancer cells,following the removal or inhibition of AR by its antagonists Casodex and MDV3100.Treatment with AR antagonists also enhanced TRAIL-induced breast cancer cell apoptosis.CONCLUSION AR signaling suppresses TRAIL-induced breast cancer cell apoptosis,in part,by suppressing DR5 expression,and a combination of AR antagonists together with TRAIL may be a novel and effective therapy for TNBC.
基金supported by grants from the National Key Laboratory of Biomacromolecules and The National Natural Science Foundation of China (81373422)
文摘Dear Editor,The nucleosome assembly protein 1(NAP-1),being a histone chaperone[1],primarily participates in the processes of nucleosome assembly and disassembly,histone transport,and histone eviction.
基金supported by National Natural Science Foundation of China(No.U1703118)Natural Science Foundation of Jiangsu Province(No.BK20181364)+6 种基金Natural Science Foundation of Jiangsu Higher Education Institutions of China(No.19KJA310003)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Jiangsu Shuangchuang ProgramOpen Funds of the State Key Laboratory for Chemo/Biosensing and Chemometrics(No.2016015)Open Project of the National Laboratory of Biomacromolecules(No.2017KF05)the Cooperative Project between Southeast University and Nanjing Medical University(No.2018DN0004)Jiangsu Specially-Appointed Professor Project,China。
文摘The aim of this study was to prepare camel serum albumin(CSA) nanoparticles using a self-assembly strategy to co-immobilize curcumin(CCM) and doxorubicin(Dox) which was in favor of combined chemotherapy and biomedical applications of bactrian(Camelus bactrianus) CSA. The constructed CSA nanoparticles(CSA-NPs)with the size around 200 nm displayed a high degree of polydispersity and further encapsulation of CCM and Dox caused no apparent morphological changes to the nanocomposite(CCM/Dox CSA-NPs). The synergistic cytotoxic effect of CCM and Dox on cancer cell A549 was observed with the calculated combination index less than 1.0. Moreover, the release kinetic profile of encapsulated drugs showed a concentration dependence of glutathione(GSH) originating from the GSH used in nanoparticle formation to break the intramolecular disulfide bonds. In vitro cytotoxicity evaluations also revealed that CCM/Dox CSA-NPs showed higher cytotoxicity than that of single drug loaded CSA-NPs, which was also validated by high content screen assay. Taken together, the CCM/Dox CSA-NPs with redox-responsive attributes provided an integrated protein-based combinational drugdelivery matrix to exert synergistic effects.
基金Science and Technology Innovation Program of Hunan Province(No.2020RC4044)National Science and Technology Infrastructure Program(No.2013BAI09B12)
文摘Background:Maturity-onset diabetes of the young(MODY)is the most common monogenic diabetes.The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes(T2DM)among Chinese young adults.Methods:From April 2015 to October 2017,this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China,newly diagnosed between 15 years and 45 years,with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory.Sequencing using a custom monogenic diabetes gene panel was performed,and variants of 14 MODY genes were interpreted as per current guidelines.Results:The survey determined 18 patients having genetic variants causing MODY(6 HNF1A,5 GCK,3 HNF4A,2 INS,1 PDX1,and 1 PAX4).The prevalence of MODY was 0.74%(95%confidence interval[CI]:0.40-1.08%).The clinical characteristics of MODY patients were not specific,72.2%(13/18)of them were diagnosed after 35 years,47.1%(8/17)had metabolic syndrome,and only 38.9%(7/18)had a family history of diabetes.No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.Conclusion:The prevalence of MODY in young adults with phenotypic T2DM was 0.74%,among which HNF1A-,GCK-,and HNF4A-MODY were the most common subtypes.Clinical features played a limited role in the recognition of MODY.
基金National Basic Research Program of China from MOST,2015CB910800 to W.C. and 2014CB910202 to J. LNational Science Foundation of China,31470900 and 31522021 to W.C. and 11672317 and 31222022 to J.L.
基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39000000)the National Key Research and Development Program of China(2022YFA1303000,2022YFA1305100,2017YFA0504000)the National Natural Science Foundation of China(91849203)。
文摘Aging is closely related to redox regulation.In our previous work,we proposed a new concept,“redox-stress response capacity(RRC),”and found that the decline in RRC was a dynamic characteristic of aging.However,the mechanism of RRC decline during aging remains unknown.In this study,using the senescent human fibroblast cell model and Caenorhabditis elegans model,we identified that peroxiredoxin 2(PRDX2),as a hydrogen peroxide(H_(2)O_(2))sensor,was involved in mediating RRC.PRDX2 knockdown led to a decline of RRC and accelerated senescence in fibroblasts and prdx-2 mutant C.elegans also showed decreased RRC.The mechanism study showed that the decreased sensor activity of PRDX2 was related to the increase in hyperoxidation of PRDX2 in senescent cells.Moreover,the level of PRDX2 hyperoxidation also increased in old C.elegans.Simultaneous overexpression of both PRDX2 and sulfiredoxin(SRX)rescued the reduced RRC and delayed senescence.The increase in PRDX2 hyperoxidation in senescent cells led to a decrease in its sensor activity,resulting in the decreased cellular response to H_(2)O_(2),which is similar to the mechanism of insulin resistance due to the lower insulin receptor sensitivity.Treatment of young cells with a high level of H_(2)O_(2)to induce a higher level of PRDX2-SO_(3) resulted in mimicking the RRC decline in senescent cells,which is also similar to a model of insulin resistance induced by high levels of insulin.All these results thrillingly indicate that there is an insulin-resistance-like phenomenon in senescent cells,we named it redox-stress response resistance,RRR.RRR in senescent cells is an important new discovery that explains RRC decline during aging and reveals the internal relationship between redox regulation and aging from a new perspective.
