The magnetic cooling utilizing magneto-caloric effect is recognized as promising energy efficiency and environmentally friendly technology.Here we report a systematical study on the microstructures,magnetic properties...The magnetic cooling utilizing magneto-caloric effect is recognized as promising energy efficiency and environmentally friendly technology.Here we report a systematical study on the microstructures,magnetic properties and cryogenic magneto-caloric performances of the Gd_(20)Ho_(20)Tm_(20)Cu_(20)Ni_(20) amorphous ribbons.It is found that the ribbons reveal a second-order phase transition and are accompanied by a table-shaped magneto-caloric effect.The calculated magneticentropy-change maximum |ΔSM|,temperature averaged entropy change(i.e.,TEC(10)),and refrigerant capacity reach 13.9 J/kg·K,13.84 J/kg-K and 740 J/kg with magnetic field change of 0-7 T,respectively,indicating that the present Gd_(20)Ho_(20)Tm_(20)Cu_(20)Ni_(20) amorphous ribbons are good candidates for magnetic cooling.展开更多
Previous approaches to Chinese zero pronoun resolution mainly use syntactic information and probabilistic methods, but the context information is ignored. To make full use of the context and semantic information, we b...Previous approaches to Chinese zero pronoun resolution mainly use syntactic information and probabilistic methods, but the context information is ignored. To make full use of the context and semantic information, we build a context-aware model. We propose a key words extraction strategy and design a classification model by using distributed representations as context feature. To our best knowledge, this is the first work using distributed representations in Chinese zero pronoun resolution. Experimental results show that our approach achieves a better performance than previous supervised methods.展开更多
The growth in biomedical data resources has raised potential privacy concerns and risks of genetic information leakage. For instance, exome sequencing aids clinical decisions by comparing data through web services, bu...The growth in biomedical data resources has raised potential privacy concerns and risks of genetic information leakage. For instance, exome sequencing aids clinical decisions by comparing data through web services, but it requires significant trust between users and providers. To alleviate privacy concerns, the most commonly used strategy is to anonymize sensitive data. Unfortunately, studies have shown that anonymization is insufficient to protect against reidentification attacks. Recently, privacy-preserving technologies have been applied to preserve application utility while protecting the privacy of biomedical data. We present the PICOTEES framework, a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants (https://birthdefectlab.cn:3000/). PICOTEES enables privacy-preserving queries of the phenotype spectrum for a single variant by utilizing trusted execution environment technology, which can protect the privacy of the user's query information, backend models, and data, as well as the final results. We demonstrate the utility and performance of PICOTEES by exploring a bioinformatics dataset. The dataset is from a cohort containing 20,909 genetic testing patients with 3,152,508 variants from the Children's Hospital of Fudan University in China, dominated by the Chinese Han population (>99.9%). Our query results yield a large number of unreported diagnostic variants and previously reported pathogenicity.展开更多
Background:Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay(NDD),but its genetic basis has not been fully characterized.This study attempted to analyze the genetic...Background:Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay(NDD),but its genetic basis has not been fully characterized.This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume(WBDV).Methods:We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years.We recruited only NDD patients without acquired etiologies or positive genetic results.Cranial magnetic resonance imaging(MRI)and clinical exome sequencing(2742 genes)data were acquired.A genetic burden test was performed,and the results were compared between patients with and without significant WBDV.Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development.Results:We recruited a total of 253 NDD patients.Among them,26 had significantly decreased WBDV(<-2 standard deviations[SDs]),and 14 had significantly increased WBDV(>+2 SDs).NDD patients with significant WBDV had higher rates of motor development delay(49.8%[106/213]vs.75.0%[30/40],P=0.003)than patients without significant WBDV.Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV.Analyses of the literature further demonstrated that these genes were not randomly identified:burden genes were more related to the brain development than background genes(P=1.656e^(-9)).In seven human brain regions related to motor development,we observed burden genes had higher expression before 37-week gestational age than postnatal stages.Functional analyses found that burden genes were enriched in embryonic brain development,with positive regulation of synaptic growth at the neuromuscular junction,positive regulation of deoxyribonucleic acid templated transcription,and response to hormone,and these genes were shown to be expressed in neural progenitors.Based on single cell sequencing analyses,we found TUBB2B gene had elevated expression levels in neural progenitor cells,interneuron,and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron.Conclusion:Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay,which could be explained by the genetic differences characterized herein.展开更多
To the Editor: Genetic diseases contribute to 35% of deaths during the first year of life and are a significant cause of intensive care.[1] A previous study based on the China Neonatal Genomes Project investigated the...To the Editor: Genetic diseases contribute to 35% of deaths during the first year of life and are a significant cause of intensive care.[1] A previous study based on the China Neonatal Genomes Project investigated the genetic causes of early infant deaths and found that >25% of deceased neonates with genetic diagnoses can be cured if diagnosed in time.[2] Therefore, it is crucial to target and diagnose neonates with genetic diseases as early as possible. According to our experience, the typical phenotypes, such as special facial features or multiple congenital anomalies (MCAs), indicate a high risk of genetic disease and lead physicians to perform genetic testing in neonates as early as possible. However, in practice, infants without typical phenotypes typically undergo a long and costly diagnostic process before genetic diagnoses are confirmed. Moreover, a recent survey by the American College of Medical Genetics and Genomics (ACMG) and other national professional organizations indicated that there are insufficient numbers of qualified geneticists to fulfil genetic service needs.[3] The ACMG published the general clinical features for genetic testing indications. For example, patients with phenotypes or family history data that strongly implicate a genetic cause may undergo genetic testing.[1] However, the study indicated that many genetic conditions arise de novo or are inherited with no family history.[1] A previous study attempted to apply the non-phenotype-driven panel approach in neonates admitted to the neonate intensive care unit (NICU).[4] However, at present, the diagnostic yield is only 3.45% (1/29).[4] In addition, the economic and ethical issues associated with genomic screening remain challenging. Therefore, the available indications for genetic testing may improve the management of genetic diseases.展开更多
After the rapid spread of SARS-CoV-2 in Wuhan,China,at the beginning of 2020,about 1.5 million confirmed cases and over 80,000 deaths have been reported around 200 countries and territories all over the world and the ...After the rapid spread of SARS-CoV-2 in Wuhan,China,at the beginning of 2020,about 1.5 million confirmed cases and over 80,000 deaths have been reported around 200 countries and territories all over the world and the number continues to increase.However,we still have limited knowledge of this new coronavirus,especially the interaction between SARS-CoV-2 and our immune system.展开更多
CHD8 is a candidate gene for autism spectrum disorders and neurological development delay.It has been reported to be essential for neurogenesis in the cerebral cortex,but the function of CHD8 in cerebellum has not bee...CHD8 is a candidate gene for autism spectrum disorders and neurological development delay.It has been reported to be essential for neurogenesis in the cerebral cortex,but the function of CHD8 in cerebellum has not been comprehensively investigated.The potential relationship of cerebellum dysplasia with psychiatric disorders in patients with CHD8 mutations is still not clear.In this study,we establish different conditional knockout mouse models to investigate the roles of CHD8 in cerebellar development.Mice with neural stem cell-specific Chd8 deletion exhibit significant reduction of cerebellum volume and no layering structure is detected.Genetic deletion of Chd8 in cerebellar granule neuron progenitors(GNPs)leads to cerebellar hypoplasia,absent of proliferation layer and ectopic of Purkinje neuron.However,no substantial cerebellar dysplasia is detected in mice with Purkinje neuron-or oligodendrocyte-specific Chd8 ablation.Single-cell RNA sequencing indicates that ribosome-related genes and pathways are most significantly disrupted in GNPs,indicating the potential mechanism.Importantly,in addition to the ataxia phenotype,mice with GNPspecific Chd8 ablation present a neuropsychiatric phenotype in three-chamber and light/dark tests.Taken together,our results provide insights not only into the function of CHD8 in cerebellar development,but also the pathogenesis of neuropsychiatric disorders in patients with CHD8 mutations.展开更多
Although ultra-small nanoclusters(USNCs,<2 nm)have immense application capabilities in biomedicine,the investigation on body-wide organ responses towards USNCs is scant.Here,applying a novel strategy of single-cell...Although ultra-small nanoclusters(USNCs,<2 nm)have immense application capabilities in biomedicine,the investigation on body-wide organ responses towards USNCs is scant.Here,applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues,we systematically evaluate the interactions between the host and calcium phosphate(CaP)USNCs at the organism level.Combining single-cell mass cytometry,and magnetic luminex assay results,we identify dynamic immune responses to CaP USNCs at the single cell resolution.The innate immune is initially activated and followed by adaptive immune activation,as evidenced by dynamic immune cells proportions.Furthermore,using Nano Genome Atlas of multi-tissues,we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney.Moreover,based on the immunological response profiles,histological evaluation of major organs and local tissue,and a body-wide transcriptomics,we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection.Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.展开更多
Kidney disease is manifested in a wide variety of phenotypes,many of which have an important hereditary component.To delineate the genotypic and phenotypic spectrum of pediatric nephropathy,a multicenter registration ...Kidney disease is manifested in a wide variety of phenotypes,many of which have an important hereditary component.To delineate the genotypic and phenotypic spectrum of pediatric nephropathy,a multicenter registration system is being imple-mented based on the Chinese Children Genetic Kidney Disease Database(CCGKDD).In this study,all the patients with kidney and urological diseases were recruited from 2014 to 2020.Genetic analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal features.The genetic diagnosis was confirmed in 883 of 2256(39.1%)patients from 23 provinces in China.Phenotypic profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome(SRNS,23.5%),glomerulonephritis(GN,32.2%),congenital anomalies of the kidney and urinary tract(CAKUT,21.2%),cystic renal disease(3.9%),renal calcinosis/stone(3.6%),tubulopathy(9.7%),and chronic kidney disease of unknown etiology(CKDu,5.8%).The pathogenic variants of 105 monogenetic disorders were identified.Ten distinct genomic disorders were identified as pathogenic copy number variants(CNVs)in 11 patients.The diagnostic yield differed by subgroups,and was highest in those with cystic renal disease(66.3%),followed by tubulopathy(58.4%),GN(57.7%),CKDu(43.5%),SRNS(29.2%),renal calcinosis/stone(29.3%)and CAKUT(8.6%).Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic conditions.We present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was performed.Our data demonstrate the utility of family-based exome sequencing,and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease.展开更多
From the mid 1800s,modern Lebanon began to emerge as a state.Lebanon,as“the eternal homeland”,had been accepted by the Maronites,the Sunnis and the Druze as a general principle and the foundation of nation-state con...From the mid 1800s,modern Lebanon began to emerge as a state.Lebanon,as“the eternal homeland”,had been accepted by the Maronites,the Sunnis and the Druze as a general principle and the foundation of nation-state construction.The Shi'ite sectarian identity based on the leading role of the traditional feudal zu'ama was challenged by Arab nationalism in the mid 1900s,and was replaced by a new sectarian identity,based on the Shi'ite political organizations and sectarian militias.This new Lebanese Shi'ite collective identity is featured by a pro-Iranian and pro-Syrian position,and has become a big challenge to the nation-state construction of Lebanon.展开更多
The development of secularism and secularization is a major issue in the Arab world in the intellectual,cultural and social dimensions.A general survey of the development of secularism and secularization in the Arab w...The development of secularism and secularization is a major issue in the Arab world in the intellectual,cultural and social dimensions.A general survey of the development of secularism and secularization in the Arab world is a premise to understand modern Arab politics,society and culture.展开更多
Infertility affects around 8%-12%of couples globally,and in about 50%of these cases,male factors are either the primary cause or contribute significantly to infertility.Any defects during spermiogenesis may result in ...Infertility affects around 8%-12%of couples globally,and in about 50%of these cases,male factors are either the primary cause or contribute significantly to infertility.Any defects during spermiogenesis may result in male subfertility or complete infertility in mammals.1 Previously,we found that CFAP53 is localized in the manchette and sperm tail,and it plays an essential role in sperm flagellum biogenesis.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant No.52071197)the Science and Technology Committee of Shanghai(Grant No.19ZR1418300)+2 种基金the Independent Research and Development Project of State Key Laboratory of Advanced Special SteelShanghai Key Laboratory of Advanced Ferrometallurgy,Shanghai University(Grant No.SKLASS 2019-Z003)the Science and Technology Commission of Shanghai Municipality(Grant No.19DZ2270200)。
文摘The magnetic cooling utilizing magneto-caloric effect is recognized as promising energy efficiency and environmentally friendly technology.Here we report a systematical study on the microstructures,magnetic properties and cryogenic magneto-caloric performances of the Gd_(20)Ho_(20)Tm_(20)Cu_(20)Ni_(20) amorphous ribbons.It is found that the ribbons reveal a second-order phase transition and are accompanied by a table-shaped magneto-caloric effect.The calculated magneticentropy-change maximum |ΔSM|,temperature averaged entropy change(i.e.,TEC(10)),and refrigerant capacity reach 13.9 J/kg·K,13.84 J/kg-K and 740 J/kg with magnetic field change of 0-7 T,respectively,indicating that the present Gd_(20)Ho_(20)Tm_(20)Cu_(20)Ni_(20) amorphous ribbons are good candidates for magnetic cooling.
文摘Previous approaches to Chinese zero pronoun resolution mainly use syntactic information and probabilistic methods, but the context information is ignored. To make full use of the context and semantic information, we build a context-aware model. We propose a key words extraction strategy and design a classification model by using distributed representations as context feature. To our best knowledge, this is the first work using distributed representations in Chinese zero pronoun resolution. Experimental results show that our approach achieves a better performance than previous supervised methods.
基金funded by the Shanghai Hospital Development Center(SHDC2020CR6028-002 to W.Zhou)National Key R&D Program of China(2020YFC2006402 to Y.Lu)+7 种基金National Key R&D Program of China(2022ZD0116003 to X.Dong)the Science and Technology Commission of Shanghai(22002400700 to S.Wu)Shanghai Municipal Science and Technology Major Project(20Z11900600 to W.Zhou)National Key Research and Development Program(2018YFC0116903 to W.Zhou)Major Research Projects for Young and Middle-aged People of Fujian Province(2021ZQNZD017 to Y.Lu)supported by Key Lab Information Network Security,Ministry of Public Security(to H.Zheng and S.Wang)“Pioneer”and”Leading Goose”R&D Program of Zhejiang(No.2022C01126 to Q.Sun and S.Wang)National Key R&D Program of China(2021YFC2500802 and 2021YFC2500806 to H.Zheng and S.Wang).
文摘The growth in biomedical data resources has raised potential privacy concerns and risks of genetic information leakage. For instance, exome sequencing aids clinical decisions by comparing data through web services, but it requires significant trust between users and providers. To alleviate privacy concerns, the most commonly used strategy is to anonymize sensitive data. Unfortunately, studies have shown that anonymization is insufficient to protect against reidentification attacks. Recently, privacy-preserving technologies have been applied to preserve application utility while protecting the privacy of biomedical data. We present the PICOTEES framework, a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants (https://birthdefectlab.cn:3000/). PICOTEES enables privacy-preserving queries of the phenotype spectrum for a single variant by utilizing trusted execution environment technology, which can protect the privacy of the user's query information, backend models, and data, as well as the final results. We demonstrate the utility and performance of PICOTEES by exploring a bioinformatics dataset. The dataset is from a cohort containing 20,909 genetic testing patients with 3,152,508 variants from the Children's Hospital of Fudan University in China, dominated by the Chinese Han population (>99.9%). Our query results yield a large number of unreported diagnostic variants and previously reported pathogenicity.
基金grants from the Science and Technology Commission of Shanghai Municipal(No.19411964400)Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01)ZJLab.
文摘Background:Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay(NDD),but its genetic basis has not been fully characterized.This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume(WBDV).Methods:We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years.We recruited only NDD patients without acquired etiologies or positive genetic results.Cranial magnetic resonance imaging(MRI)and clinical exome sequencing(2742 genes)data were acquired.A genetic burden test was performed,and the results were compared between patients with and without significant WBDV.Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development.Results:We recruited a total of 253 NDD patients.Among them,26 had significantly decreased WBDV(<-2 standard deviations[SDs]),and 14 had significantly increased WBDV(>+2 SDs).NDD patients with significant WBDV had higher rates of motor development delay(49.8%[106/213]vs.75.0%[30/40],P=0.003)than patients without significant WBDV.Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV.Analyses of the literature further demonstrated that these genes were not randomly identified:burden genes were more related to the brain development than background genes(P=1.656e^(-9)).In seven human brain regions related to motor development,we observed burden genes had higher expression before 37-week gestational age than postnatal stages.Functional analyses found that burden genes were enriched in embryonic brain development,with positive regulation of synaptic growth at the neuromuscular junction,positive regulation of deoxyribonucleic acid templated transcription,and response to hormone,and these genes were shown to be expressed in neural progenitors.Based on single cell sequencing analyses,we found TUBB2B gene had elevated expression levels in neural progenitor cells,interneuron,and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron.Conclusion:Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay,which could be explained by the genetic differences characterized herein.
基金Shanghai Municipal Science and Technology Major Project (No. 2017SHZDZX01)。
文摘To the Editor: Genetic diseases contribute to 35% of deaths during the first year of life and are a significant cause of intensive care.[1] A previous study based on the China Neonatal Genomes Project investigated the genetic causes of early infant deaths and found that >25% of deceased neonates with genetic diagnoses can be cured if diagnosed in time.[2] Therefore, it is crucial to target and diagnose neonates with genetic diseases as early as possible. According to our experience, the typical phenotypes, such as special facial features or multiple congenital anomalies (MCAs), indicate a high risk of genetic disease and lead physicians to perform genetic testing in neonates as early as possible. However, in practice, infants without typical phenotypes typically undergo a long and costly diagnostic process before genetic diagnoses are confirmed. Moreover, a recent survey by the American College of Medical Genetics and Genomics (ACMG) and other national professional organizations indicated that there are insufficient numbers of qualified geneticists to fulfil genetic service needs.[3] The ACMG published the general clinical features for genetic testing indications. For example, patients with phenotypes or family history data that strongly implicate a genetic cause may undergo genetic testing.[1] However, the study indicated that many genetic conditions arise de novo or are inherited with no family history.[1] A previous study attempted to apply the non-phenotype-driven panel approach in neonates admitted to the neonate intensive care unit (NICU).[4] However, at present, the diagnostic yield is only 3.45% (1/29).[4] In addition, the economic and ethical issues associated with genomic screening remain challenging. Therefore, the available indications for genetic testing may improve the management of genetic diseases.
基金This work was supported by the National Natural Science Foundation of China(82041015)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19000000).
文摘After the rapid spread of SARS-CoV-2 in Wuhan,China,at the beginning of 2020,about 1.5 million confirmed cases and over 80,000 deaths have been reported around 200 countries and territories all over the world and the number continues to increase.However,we still have limited knowledge of this new coronavirus,especially the interaction between SARS-CoV-2 and our immune system.
基金support by grants from the Science and Technology Commission of Shanghai Municipality(19411964400,20ZR1408400)National Natural Science Foundation of China(81741034,81720108018)+1 种基金Shanghai Municipal Science and Technology Major Project(2018SHZDZX01,2018SHZDZX05)ZJLab。
文摘CHD8 is a candidate gene for autism spectrum disorders and neurological development delay.It has been reported to be essential for neurogenesis in the cerebral cortex,but the function of CHD8 in cerebellum has not been comprehensively investigated.The potential relationship of cerebellum dysplasia with psychiatric disorders in patients with CHD8 mutations is still not clear.In this study,we establish different conditional knockout mouse models to investigate the roles of CHD8 in cerebellar development.Mice with neural stem cell-specific Chd8 deletion exhibit significant reduction of cerebellum volume and no layering structure is detected.Genetic deletion of Chd8 in cerebellar granule neuron progenitors(GNPs)leads to cerebellar hypoplasia,absent of proliferation layer and ectopic of Purkinje neuron.However,no substantial cerebellar dysplasia is detected in mice with Purkinje neuron-or oligodendrocyte-specific Chd8 ablation.Single-cell RNA sequencing indicates that ribosome-related genes and pathways are most significantly disrupted in GNPs,indicating the potential mechanism.Importantly,in addition to the ataxia phenotype,mice with GNPspecific Chd8 ablation present a neuropsychiatric phenotype in three-chamber and light/dark tests.Taken together,our results provide insights not only into the function of CHD8 in cerebellar development,but also the pathogenesis of neuropsychiatric disorders in patients with CHD8 mutations.
基金the National Key Research and Development Program of China(2018YFC1105100)NSFC grants(T2121004,81972099,82072463,81871764)+1 种基金Zhejiang Provincial Natural Science Foundation of China(LZ22H060002,LR20H060001)Fundamental Research Funds for the Central Universities.
文摘Although ultra-small nanoclusters(USNCs,<2 nm)have immense application capabilities in biomedicine,the investigation on body-wide organ responses towards USNCs is scant.Here,applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues,we systematically evaluate the interactions between the host and calcium phosphate(CaP)USNCs at the organism level.Combining single-cell mass cytometry,and magnetic luminex assay results,we identify dynamic immune responses to CaP USNCs at the single cell resolution.The innate immune is initially activated and followed by adaptive immune activation,as evidenced by dynamic immune cells proportions.Furthermore,using Nano Genome Atlas of multi-tissues,we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney.Moreover,based on the immunological response profiles,histological evaluation of major organs and local tissue,and a body-wide transcriptomics,we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection.Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.
基金J.R.is supported by National Natural Science Foundation of China(NSFC-8182207)Shanghai Academic/Technology Research Leader(19XD1420600)Chinese Academy of Medical Sciences(2019-RC-HL_020).
文摘Kidney disease is manifested in a wide variety of phenotypes,many of which have an important hereditary component.To delineate the genotypic and phenotypic spectrum of pediatric nephropathy,a multicenter registration system is being imple-mented based on the Chinese Children Genetic Kidney Disease Database(CCGKDD).In this study,all the patients with kidney and urological diseases were recruited from 2014 to 2020.Genetic analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal features.The genetic diagnosis was confirmed in 883 of 2256(39.1%)patients from 23 provinces in China.Phenotypic profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome(SRNS,23.5%),glomerulonephritis(GN,32.2%),congenital anomalies of the kidney and urinary tract(CAKUT,21.2%),cystic renal disease(3.9%),renal calcinosis/stone(3.6%),tubulopathy(9.7%),and chronic kidney disease of unknown etiology(CKDu,5.8%).The pathogenic variants of 105 monogenetic disorders were identified.Ten distinct genomic disorders were identified as pathogenic copy number variants(CNVs)in 11 patients.The diagnostic yield differed by subgroups,and was highest in those with cystic renal disease(66.3%),followed by tubulopathy(58.4%),GN(57.7%),CKDu(43.5%),SRNS(29.2%),renal calcinosis/stone(29.3%)and CAKUT(8.6%).Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic conditions.We present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was performed.Our data demonstrate the utility of family-based exome sequencing,and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease.
文摘From the mid 1800s,modern Lebanon began to emerge as a state.Lebanon,as“the eternal homeland”,had been accepted by the Maronites,the Sunnis and the Druze as a general principle and the foundation of nation-state construction.The Shi'ite sectarian identity based on the leading role of the traditional feudal zu'ama was challenged by Arab nationalism in the mid 1900s,and was replaced by a new sectarian identity,based on the Shi'ite political organizations and sectarian militias.This new Lebanese Shi'ite collective identity is featured by a pro-Iranian and pro-Syrian position,and has become a big challenge to the nation-state construction of Lebanon.
文摘The development of secularism and secularization is a major issue in the Arab world in the intellectual,cultural and social dimensions.A general survey of the development of secularism and secularization in the Arab world is a premise to understand modern Arab politics,society and culture.
基金supported by the National Science Fund for Distinguished Young Scholars of China (No.81925015)the National Natural Science Foundation of China (No.91649202)+1 种基金the Shandong Provincial Key Research&Development Program (China) (No.2018YFJH0504)the open fund of the State Key Laboratory of Reproductive Medicine (China) (SKLRM-K202201).
文摘Infertility affects around 8%-12%of couples globally,and in about 50%of these cases,male factors are either the primary cause or contribute significantly to infertility.Any defects during spermiogenesis may result in male subfertility or complete infertility in mammals.1 Previously,we found that CFAP53 is localized in the manchette and sperm tail,and it plays an essential role in sperm flagellum biogenesis.