Klinefelter syndrome （KS） is the set of symptoms that result from the presence of an extra X chromosome in males. Postnatal population-based KS screening will enable timely diagnosis of this common chromosomal disea...Klinefelter syndrome （KS） is the set of symptoms that result from the presence of an extra X chromosome in males. Postnatal population-based KS screening will enable timely diagnosis of this common chromosomal disease, providing the opportunity for early intervention and therapy at the time point when they are most effective and may prevent later symptoms or complications. Therefore, through this study, we introduced a simple high-resolution melting （HRM） assay for KS screening and evaluated its clinical sensitivity and specificity in three medical centers using 1373 clinical blood samples. The HRM assay utilized a single primer pair to simultaneously amplify specific regions in zinc finger protein, X-linked （ZFX） and zinc finger protein, Y-linked （ZFY）. In cases of KS, the ratios of ZFX/ZFYare altered compared to those in normal males. As a result, the specific melting profiles differ and can be differentiated during data analysis. This HRM assay displayed high analytical specificity over a wide range of template DNA amounts （5 ng-50 ng） and reproducibility, high resolution for detecting KS mosaicism, and high clinical sensitivity （100%） and specificity （98.1%）. Moreover, the HRM assay was rapid （2 h per run）, inexpensive （0.2 USD per sample）, easy to perform and automatic, and compatible with both whole blood samples and dried blood spots. Therefore, this HRM assay is an ideal postnatal population-based KS screening tool that can be used for different age groups.展开更多
Klinefelter syndrome(KS)is one of the most frequent genetic abnormalities and the leading genetic cause of nonobstructive azoospermia.The breeding and study of KS mouse models are essential to advancing our knowledge ...Klinefelter syndrome(KS)is one of the most frequent genetic abnormalities and the leading genetic cause of nonobstructive azoospermia.The breeding and study of KS mouse models are essential to advancing our knowledge of the underlying pathological mechanism.Karyotyping and fluorescence in situ hybridization are reliable methods for identifying chromosomal contents.However,technical issues associated with these methods can decrease the efficiency of breeding KS mouse models and limit studies that require rapid identification of target mice.To overcome these limitations,we developed three polymerase chain reaction-based assays to measure specific genetic information,including presence or absence of the sex determining region of chromosome Y(Sry),copy number of amelogenin,X-linked(Amelx),and inactive X specific transcripts(Xist)levels.Through a combined analysis of the assay results,we can infer the karyotype of target mice.We confirmed the utility of our assays with the successful generation of KS mouse models.Our assays are rapid,inexpensive,high capacity,easy to perform,and only require small sample amounts.Therefore,they facilitate the breeding and study of KS mouse models and help advance our knowledge of the pathological mechanism underlying KS.展开更多
As one of the typical less-mobility parallel mechanisms, the spherical parallel mechanism Up.s with two degrees of freedom （2-DOF） possess high order overconstraints, and the calculation of its stiffness is partly d...As one of the typical less-mobility parallel mechanisms, the spherical parallel mechanism Up.s with two degrees of freedom （2-DOF） possess high order overconstraints, and the calculation of its stiffness is partly different with general parallel mechanisms owing to the bars in each branch are assumed to be arc-shaped. By means of small deformation superposition principle, the relationship between the angle displacement and line displacement of moving platform and the forces acted on the branches were derived out. Based on the results of static analysis, the relationship between the applied force, the line displacement and the angle displacement of the mechanism was set up. And then the stiffness matrix was obtained. The six principal stiffness of the mechanism and the corresponding directions were achieved by the orthogonal transformation. The numerical calculation was performed and the results showed that the principal stiffness and directions are varied with the pose-position of the mechanism, and the principal stiffness is gradually enlarged when it is far away from the anigin. In addition, the torsion stiffness is much greater and the line deformation stiffness is smaller, the difference between the two parts is huge. The research content of this paper supplies the theoretical foundation for the further engineering design and application of the spherical parallel mechanism.展开更多
Turner syndrome （TS）, characterized by the complete or partial absence of an X chromosome, is the only known viable chromosomal monosomy. It is one of the most common sex chromosome abnormalities in women, but it ca...Turner syndrome （TS）, characterized by the complete or partial absence of an X chromosome, is the only known viable chromosomal monosomy. It is one of the most common sex chromosome abnormalities in women, but it can also occur in men, with diverse chimeric phenotypes.展开更多
Background Newborn screening(NBS)through disease biomarkers has significantly reduced severe outcomes of congenital disorders.Moreover,exploratory newborn genetic screening programs are increasingly being implemented....Background Newborn screening(NBS)through disease biomarkers has significantly reduced severe outcomes of congenital disorders.Moreover,exploratory newborn genetic screening programs are increasingly being implemented.This consensus,developed by multidisciplinary experts,aims to standardize the combined screening of genes and biomarkers for neonatal diseases in China,balancing ethical,technical,and clinical considerations.Data sources This consensus synthesizes evidence from peer-reviewed literature(PubMed,CNKI,etc.)up to 2024 and integrates clinical experiences from multidisciplinary experts in neonatology,genetics,and laboratory medicine,focusing on disease biomarker-based NBS,newborn genetic screening,and the clinical utility of combined screening.Results The consensus defines principles for combined screening:(1)disease/gene selection:154 disease-causing genes covering 67 inherited metabolic disorders(e.g.,amino acid metabolism disorders,organic acid metabolism disorders),prioritized by treatability,onset age(<5 years),and cost-effectiveness;(2)methodology:integrating dried blood spot biomarker analysis with next-generation sequencing-based targeted capture(coverage>300×),validated by MLPA/Sanger and longrange sequencing for complex variants(e.g.,CYP21A2,SLC25A13);and(3)operational workflow:standardized workflows for informed consent,sample collection/delivery,and result interpretation,with dual reporting of marker and genetic findings within 15 days.Positive cases require family verification and/or other genetic sequencing techniques.Conclusions This consensus establishes a practical framework for integrating marker and genetic screening,aiming to improve diagnostic accuracy and achieve rapid and effective interventions,thereby saving lives and reducing the occurrence of severe complications.Implementation requires interdisciplinary collaboration and ongoing quality control to maximize clinical utility.展开更多
In this paper the general finite difference schemes with intrinsic parallelism for the boundary value problem of the semilinear parabolic system of divergence type with bounded coefficients are constructed, and the ex...In this paper the general finite difference schemes with intrinsic parallelism for the boundary value problem of the semilinear parabolic system of divergence type with bounded coefficients are constructed, and the existence and uniqueness of the difference solution for the general schemes are proved. And the convergence of the solutions of the difference schemes to the generalized solution of the original boundary value problem of the semilinear parabolic system is obtained. The multidimensional problems are also studied.展开更多
Multifunctional materials with proton conduction,circularly polarized luminescence(CPL)and a magneto-optical Faraday effect would provide a great opportunity for applications in luminescent,electrical,magneto-optical ...Multifunctional materials with proton conduction,circularly polarized luminescence(CPL)and a magneto-optical Faraday effect would provide a great opportunity for applications in luminescent,electrical,magneto-optical and optical-electronic smart devices.However,such types of multifunctional systems have rarely been reported.Herein,by introducing a chiral amine-phenol ligand,a pair of Cd(Ⅱ)-Tb(Ⅲ)enantiomers,[Cd_(2)Tb(RR/SS-H_(2)L)_(2)(H_(2)O)_(6)](ClO_(4))_(3)·2H_(2)O(R-1 and S-1)[H_(2)L=((SS/RR)-cyclohexane-1,2-diylbis(azanediyl)-bis(methylene)-bis(2-methoxyphenol))],were obtained.R-1 and S-1 feature the homochiral molecules of trinuclear Cd2Tb structures,which contain abundant H-bonds to form threedimensional(3D)supermolecular frameworks.They are chiral multifunctional materials showing strong Tb(Ⅲ)characteristic emissions,a moderate proton conductivity of 1.17×10^(-4) S cm^(-1) at 333 K and 100%RH for R-1,CPL with a luminescence dissymmetry factor value of over 10^(-3) for R-1 and S-1 and a strong magneto-optical Faraday effect,and they are the first known materials simultaneously showing CPL,proton conduction and the Faraday effect.展开更多
文摘Klinefelter syndrome （KS） is the set of symptoms that result from the presence of an extra X chromosome in males. Postnatal population-based KS screening will enable timely diagnosis of this common chromosomal disease, providing the opportunity for early intervention and therapy at the time point when they are most effective and may prevent later symptoms or complications. Therefore, through this study, we introduced a simple high-resolution melting （HRM） assay for KS screening and evaluated its clinical sensitivity and specificity in three medical centers using 1373 clinical blood samples. The HRM assay utilized a single primer pair to simultaneously amplify specific regions in zinc finger protein, X-linked （ZFX） and zinc finger protein, Y-linked （ZFY）. In cases of KS, the ratios of ZFX/ZFYare altered compared to those in normal males. As a result, the specific melting profiles differ and can be differentiated during data analysis. This HRM assay displayed high analytical specificity over a wide range of template DNA amounts （5 ng-50 ng） and reproducibility, high resolution for detecting KS mosaicism, and high clinical sensitivity （100%） and specificity （98.1%）. Moreover, the HRM assay was rapid （2 h per run）, inexpensive （0.2 USD per sample）, easy to perform and automatic, and compatible with both whole blood samples and dried blood spots. Therefore, this HRM assay is an ideal postnatal population-based KS screening tool that can be used for different age groups.
基金This work was supported by the National Natural Science Foundation of China(Nos.52001119,51831004,52171006)the Fundamental Research Funds for the Central Universities,China.
文摘Klinefelter syndrome(KS)is one of the most frequent genetic abnormalities and the leading genetic cause of nonobstructive azoospermia.The breeding and study of KS mouse models are essential to advancing our knowledge of the underlying pathological mechanism.Karyotyping and fluorescence in situ hybridization are reliable methods for identifying chromosomal contents.However,technical issues associated with these methods can decrease the efficiency of breeding KS mouse models and limit studies that require rapid identification of target mice.To overcome these limitations,we developed three polymerase chain reaction-based assays to measure specific genetic information,including presence or absence of the sex determining region of chromosome Y(Sry),copy number of amelogenin,X-linked(Amelx),and inactive X specific transcripts(Xist)levels.Through a combined analysis of the assay results,we can infer the karyotype of target mice.We confirmed the utility of our assays with the successful generation of KS mouse models.Our assays are rapid,inexpensive,high capacity,easy to perform,and only require small sample amounts.Therefore,they facilitate the breeding and study of KS mouse models and help advance our knowledge of the pathological mechanism underlying KS.
基金Sponsored by the National Natural Science Foundation of China(Grant No.51275443 and 51005195)Key Project of Chinese Ministry of Education(Grant No.212012)+1 种基金Research Fund for the Doctoral Program of Higher Education of China(Grant No.20111333120004)Natural Science Foundationof Hebei Province(Grant No.E2012203034)
文摘As one of the typical less-mobility parallel mechanisms, the spherical parallel mechanism Up.s with two degrees of freedom （2-DOF） possess high order overconstraints, and the calculation of its stiffness is partly different with general parallel mechanisms owing to the bars in each branch are assumed to be arc-shaped. By means of small deformation superposition principle, the relationship between the angle displacement and line displacement of moving platform and the forces acted on the branches were derived out. Based on the results of static analysis, the relationship between the applied force, the line displacement and the angle displacement of the mechanism was set up. And then the stiffness matrix was obtained. The six principal stiffness of the mechanism and the corresponding directions were achieved by the orthogonal transformation. The numerical calculation was performed and the results showed that the principal stiffness and directions are varied with the pose-position of the mechanism, and the principal stiffness is gradually enlarged when it is far away from the anigin. In addition, the torsion stiffness is much greater and the line deformation stiffness is smaller, the difference between the two parts is huge. The research content of this paper supplies the theoretical foundation for the further engineering design and application of the spherical parallel mechanism.
文摘Turner syndrome （TS）, characterized by the complete or partial absence of an X chromosome, is the only known viable chromosomal monosomy. It is one of the most common sex chromosome abnormalities in women, but it can also occur in men, with diverse chimeric phenotypes.
基金supported by grants from the"Pioneer"and"Leading Goose"R&D Program of Zhejiang Province(No.2024C03152 to H.F.).
文摘Background Newborn screening(NBS)through disease biomarkers has significantly reduced severe outcomes of congenital disorders.Moreover,exploratory newborn genetic screening programs are increasingly being implemented.This consensus,developed by multidisciplinary experts,aims to standardize the combined screening of genes and biomarkers for neonatal diseases in China,balancing ethical,technical,and clinical considerations.Data sources This consensus synthesizes evidence from peer-reviewed literature(PubMed,CNKI,etc.)up to 2024 and integrates clinical experiences from multidisciplinary experts in neonatology,genetics,and laboratory medicine,focusing on disease biomarker-based NBS,newborn genetic screening,and the clinical utility of combined screening.Results The consensus defines principles for combined screening:(1)disease/gene selection:154 disease-causing genes covering 67 inherited metabolic disorders(e.g.,amino acid metabolism disorders,organic acid metabolism disorders),prioritized by treatability,onset age(<5 years),and cost-effectiveness;(2)methodology:integrating dried blood spot biomarker analysis with next-generation sequencing-based targeted capture(coverage>300×),validated by MLPA/Sanger and longrange sequencing for complex variants(e.g.,CYP21A2,SLC25A13);and(3)operational workflow:standardized workflows for informed consent,sample collection/delivery,and result interpretation,with dual reporting of marker and genetic findings within 15 days.Positive cases require family verification and/or other genetic sequencing techniques.Conclusions This consensus establishes a practical framework for integrating marker and genetic screening,aiming to improve diagnostic accuracy and achieve rapid and effective interventions,thereby saving lives and reducing the occurrence of severe complications.Implementation requires interdisciplinary collaboration and ongoing quality control to maximize clinical utility.
文摘In this paper the general finite difference schemes with intrinsic parallelism for the boundary value problem of the semilinear parabolic system of divergence type with bounded coefficients are constructed, and the existence and uniqueness of the difference solution for the general schemes are proved. And the convergence of the solutions of the difference schemes to the generalized solution of the original boundary value problem of the semilinear parabolic system is obtained. The multidimensional problems are also studied.
基金the NSF of China(21661005,22161002 and 21761012).
文摘Multifunctional materials with proton conduction,circularly polarized luminescence(CPL)and a magneto-optical Faraday effect would provide a great opportunity for applications in luminescent,electrical,magneto-optical and optical-electronic smart devices.However,such types of multifunctional systems have rarely been reported.Herein,by introducing a chiral amine-phenol ligand,a pair of Cd(Ⅱ)-Tb(Ⅲ)enantiomers,[Cd_(2)Tb(RR/SS-H_(2)L)_(2)(H_(2)O)_(6)](ClO_(4))_(3)·2H_(2)O(R-1 and S-1)[H_(2)L=((SS/RR)-cyclohexane-1,2-diylbis(azanediyl)-bis(methylene)-bis(2-methoxyphenol))],were obtained.R-1 and S-1 feature the homochiral molecules of trinuclear Cd2Tb structures,which contain abundant H-bonds to form threedimensional(3D)supermolecular frameworks.They are chiral multifunctional materials showing strong Tb(Ⅲ)characteristic emissions,a moderate proton conductivity of 1.17×10^(-4) S cm^(-1) at 333 K and 100%RH for R-1,CPL with a luminescence dissymmetry factor value of over 10^(-3) for R-1 and S-1 and a strong magneto-optical Faraday effect,and they are the first known materials simultaneously showing CPL,proton conduction and the Faraday effect.
