Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell l...Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological dysfunction.Current treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢB.Adeno-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential cures.Our group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy mice.Here,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.展开更多
Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression...Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression.Tumor-associated macrophages(TAMs)are a predominant constituent of the TME,and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer.TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype.The latter especially are crucial drivers of tumor invasion,growth,angiogenesis,metastasis,immunosuppression,and resistance to therapy.TAMs are of importance in the occurrence,development,diagnosis,prognosis,and treatment of common digestive system malignant tumors.In this review,we summarize the role of TAMs in common digestive system malignant tumors,including esophageal,gastric,colorectal,pancreatic and liver cancers.How TAMs promote the development of tumors,and how they act as potential therapeutic targets and their clinical applications are also described.展开更多
针对加工零件传统单一变量对加工误差统计分析,不能解决多关联变量之间的关系对加工误差的影响问题,提出一种多维随机变量的机械加工误差分析系统。通过分析加工零件的关联尺寸,用Matlab建立加工误差的分布规律图,分析产生有效加工误差...针对加工零件传统单一变量对加工误差统计分析,不能解决多关联变量之间的关系对加工误差的影响问题,提出一种多维随机变量的机械加工误差分析系统。通过分析加工零件的关联尺寸,用Matlab建立加工误差的分布规律图,分析产生有效加工误差的概率;用统计产品和服务解决方案(statistical product and service solution,SPSS)对测量出的关联尺寸组进行Q型聚类分析,分析加工误差易发生段;用3维点图法分析关联尺寸产生的系统误差和随机误差;建立环形轴类零件的加工误差系统分析模型。结果表明,该分析系统能提高机械加工误差分析的精确度。展开更多
Electromagnetic pulse(EMP)is a kind of transient electromagnetic phenomenon with short rise time of the leading edge and wide spectrum,which usually disrupts communications and damages electronic equipment and system....Electromagnetic pulse(EMP)is a kind of transient electromagnetic phenomenon with short rise time of the leading edge and wide spectrum,which usually disrupts communications and damages electronic equipment and system.It is challenging for an EMP sensor to measure a wideband electromagnetic pulse without distortion for the whole spectrum.Therefore,analyzing the distortion of EMP measurement is crucial to evaluating the sensor distortion characteristics and correcting the measurement results.Waveform fidelity is usually employed to evaluate the distortion of an antenna.However,this metric depends on specific signal waveforms,thus is unsuitable for evaluating and analyzing the distortion of EMP sensors.In this paper,an associated-hermite-function based distortion analysis method including system transfer matrices and distortion rates is proposed,which is general and independent from individual waveforms.The system transfer matrix and distortion rate can be straightforwardly calculated by the signal orthogonal transformation coefficients using associated-hermite functions.Distortion of a sensor vs.frequency is then visualized via the system transfer matrix,which is convenient in quantitative analysis of the distortion.Measurement of a current probe,a coaxial pulse voltage probe and a B-field sensor were performed,based on which the feasibility and effectiveness of the proposed distortion analysis method is successfully verified.展开更多
This paper generalizes the method of Ng6 and Winkler （2010, 2011） for finding rational general solutions of a first order non-autonomous algebraic ordinary differential equation （AODE） to the case of a higher orde...This paper generalizes the method of Ng6 and Winkler （2010, 2011） for finding rational general solutions of a first order non-autonomous algebraic ordinary differential equation （AODE） to the case of a higher order AODE, provided a proper parametrization of its solution hypersurface. The authors reduce the problem of finding the rational general solution of a higher order AODE to finding the rational general solution of an associated system. The rational general solutions of the original AODE and its associated system are in computable 1-1 correspondence. The authors give necessary and sufficient conditions for the associated system to have a rational solution based on proper reparametrization of invariant algebraic space curves. The authors also relate invariant space curves to first integrals and characterize rationally solvable systems by rational first integrals.展开更多
Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. He...Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online softwares; Secondly, Human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system in U937 cells. Cell proliferation and apoptosis were next evaluated in KIAA0100-knockdown U937 cells. The bioinformatic prediction showed that human KIAA0100 gene was located on 17q11.2, and human KIAA0100 protein was located in the secretory pathway. Besides, human KIAA0100 protein contained a signalpeptide, a transmembrane region, three types of secondary structures (alpha helix, extended strand, and random coil) , and four domains from mitochondrial protein 27 (FMP27). The observation on functional characterization of human KIAA0100 gene revealed that its downregulation inhibited cell proliferation, and promoted cell apoptosis in U937 cells. To summarize, these results suggest human KIAA0100 gene possibly comes within mitochondrial genome; moreover, it is a novel anti-apoptotic factor related to carcinogenesis or progression in acute monocytic leukemia, and may be a potential target for immunotherapy against acute monocytic leukemia.展开更多
Long noncoding RNA(IncRNA)urothelial carcinoma associated 1(UCA1)has been reported to be highly expressed in many kinds of cancers.This meta-analysis summarized its potential prognostic value in digestive system malig...Long noncoding RNA(IncRNA)urothelial carcinoma associated 1(UCA1)has been reported to be highly expressed in many kinds of cancers.This meta-analysis summarized its potential prognostic value in digestive system malignancies.A meta-analysis was performed through a comprehensive search in PubMed,EMBASE,the Cochrane Library,Web of Science and Chinese National Knowledge Infrastructure(CNKI)for suitable articles on the prognostic impact of UCA1 in digestive system malignancies from inception to June 27,2019.Pooled hazard ratios(HRs)with 95% confidence interval(95%CI)were calculated to summarize the effect.Sixteen studies were included in the study,with a total of 1504 patients.A significant association was observed between UCA1 abundance and poor overall survival(OS),and shorter disease-free survival(DFS)for patients with digestive system malignancies,with pooled HR of 2.07(95%CI:1.74-2.47),and of 2.50(95%CI:1.62-3.86).Subgroup analysis and sensitivity analysis suggested the reliability of our findings.It is suggested that UCA1 abundance may serve as a reliable predictive factor for poor prognosis in patients with digestive system malignancies.展开更多
文摘Mucopolysaccharidoses typeⅢB is a rare genetic disorder caused by mutations in the gene that encodes for N-acetyl-alpha-glucosaminidase.This results in the aggregation of heparan sulfate polysaccharides within cell lysosomes that leads to progressive and severe debilitating neurological dysfunction.Current treatment options are expensive,limited,and presently there are no approved cures for mucopolysaccharidoses typeⅢB.Adeno-associated virus gene therapy has significantly advanced the field forward,allowing researchers to successfully design,enhance,and improve potential cures.Our group recently published an effective treatment using a codon-optimized triple mutant adeno-associated virus 8 vector that restores N-acetyl-alpha-glucosaminidase levels,auditory function,and lifespan in the murine model for mucopolysaccharidoses typeⅢB to that seen in healthy mice.Here,we review the current state of the field in relation to the capsid landscape,adeno-associated virus gene therapy and its successes and challenges in the clinic,and how novel adenoassociated virus capsid designs have evolved research in the mucopolysaccharidoses typeⅢB field.
基金Supported by National Natural Science Foundation of China,No.82272396Suzhou Medical and Health Science and Technology Innovation Project,No.SKY2022057The Youth Medical Talent of Jiangsu Province,No.QNRC2016475.
文摘Many digestive system malignant tumors are characterized by high incidence and mortality rate.Increasing evidence has revealed that the tumor microenvironment(TME)is involved in cancer initiation and tumor progression.Tumor-associated macrophages(TAMs)are a predominant constituent of the TME,and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer.TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype.The latter especially are crucial drivers of tumor invasion,growth,angiogenesis,metastasis,immunosuppression,and resistance to therapy.TAMs are of importance in the occurrence,development,diagnosis,prognosis,and treatment of common digestive system malignant tumors.In this review,we summarize the role of TAMs in common digestive system malignant tumors,including esophageal,gastric,colorectal,pancreatic and liver cancers.How TAMs promote the development of tumors,and how they act as potential therapeutic targets and their clinical applications are also described.
文摘针对加工零件传统单一变量对加工误差统计分析,不能解决多关联变量之间的关系对加工误差的影响问题,提出一种多维随机变量的机械加工误差分析系统。通过分析加工零件的关联尺寸,用Matlab建立加工误差的分布规律图,分析产生有效加工误差的概率;用统计产品和服务解决方案(statistical product and service solution,SPSS)对测量出的关联尺寸组进行Q型聚类分析,分析加工误差易发生段;用3维点图法分析关联尺寸产生的系统误差和随机误差;建立环形轴类零件的加工误差系统分析模型。结果表明,该分析系统能提高机械加工误差分析的精确度。
基金Research Project of High-Level Talents of Jiangsu Police Institute(No.2911118010).
文摘Electromagnetic pulse(EMP)is a kind of transient electromagnetic phenomenon with short rise time of the leading edge and wide spectrum,which usually disrupts communications and damages electronic equipment and system.It is challenging for an EMP sensor to measure a wideband electromagnetic pulse without distortion for the whole spectrum.Therefore,analyzing the distortion of EMP measurement is crucial to evaluating the sensor distortion characteristics and correcting the measurement results.Waveform fidelity is usually employed to evaluate the distortion of an antenna.However,this metric depends on specific signal waveforms,thus is unsuitable for evaluating and analyzing the distortion of EMP sensors.In this paper,an associated-hermite-function based distortion analysis method including system transfer matrices and distortion rates is proposed,which is general and independent from individual waveforms.The system transfer matrix and distortion rate can be straightforwardly calculated by the signal orthogonal transformation coefficients using associated-hermite functions.Distortion of a sensor vs.frequency is then visualized via the system transfer matrix,which is convenient in quantitative analysis of the distortion.Measurement of a current probe,a coaxial pulse voltage probe and a B-field sensor were performed,based on which the feasibility and effectiveness of the proposed distortion analysis method is successfully verified.
基金supported by the Austrian Science Foundation(FWF) via the Doctoral Program "Computational Mathematics" under Grant No.W1214Project DK11,the Project DIFFOP under Grant No.P20336-N18+2 种基金the SKLSDE Open Fund SKLSDE-2011KF-02the National Natural Science Foundation of China under Grant No.61173032the Natural Science Foundation of Beijing under Grant No.1102026,and the China Scholarship Council
文摘This paper generalizes the method of Ng6 and Winkler （2010, 2011） for finding rational general solutions of a first order non-autonomous algebraic ordinary differential equation （AODE） to the case of a higher order AODE, provided a proper parametrization of its solution hypersurface. The authors reduce the problem of finding the rational general solution of a higher order AODE to finding the rational general solution of an associated system. The rational general solutions of the original AODE and its associated system are in computable 1-1 correspondence. The authors give necessary and sufficient conditions for the associated system to have a rational solution based on proper reparametrization of invariant algebraic space curves. The authors also relate invariant space curves to first integrals and characterize rationally solvable systems by rational first integrals.
基金financial support from the National Natural Science Foundation of China (No. 081718110232)
文摘Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online softwares; Secondly, Human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system in U937 cells. Cell proliferation and apoptosis were next evaluated in KIAA0100-knockdown U937 cells. The bioinformatic prediction showed that human KIAA0100 gene was located on 17q11.2, and human KIAA0100 protein was located in the secretory pathway. Besides, human KIAA0100 protein contained a signalpeptide, a transmembrane region, three types of secondary structures (alpha helix, extended strand, and random coil) , and four domains from mitochondrial protein 27 (FMP27). The observation on functional characterization of human KIAA0100 gene revealed that its downregulation inhibited cell proliferation, and promoted cell apoptosis in U937 cells. To summarize, these results suggest human KIAA0100 gene possibly comes within mitochondrial genome; moreover, it is a novel anti-apoptotic factor related to carcinogenesis or progression in acute monocytic leukemia, and may be a potential target for immunotherapy against acute monocytic leukemia.
文摘Long noncoding RNA(IncRNA)urothelial carcinoma associated 1(UCA1)has been reported to be highly expressed in many kinds of cancers.This meta-analysis summarized its potential prognostic value in digestive system malignancies.A meta-analysis was performed through a comprehensive search in PubMed,EMBASE,the Cochrane Library,Web of Science and Chinese National Knowledge Infrastructure(CNKI)for suitable articles on the prognostic impact of UCA1 in digestive system malignancies from inception to June 27,2019.Pooled hazard ratios(HRs)with 95% confidence interval(95%CI)were calculated to summarize the effect.Sixteen studies were included in the study,with a total of 1504 patients.A significant association was observed between UCA1 abundance and poor overall survival(OS),and shorter disease-free survival(DFS)for patients with digestive system malignancies,with pooled HR of 2.07(95%CI:1.74-2.47),and of 2.50(95%CI:1.62-3.86).Subgroup analysis and sensitivity analysis suggested the reliability of our findings.It is suggested that UCA1 abundance may serve as a reliable predictive factor for poor prognosis in patients with digestive system malignancies.
