This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multis...This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.展开更多
As the world strives to reduce the impact of population growth, urbanization, agricultural expansion, and climate change on food security, energy and water shortage, resource over-exploration, biodiversity loss, envir...As the world strives to reduce the impact of population growth, urbanization, agricultural expansion, and climate change on food security, energy and water shortage, resource over-exploration, biodiversity loss, environmental pollution, and ultimately human health, timely and higher resolution land cover information is urgently needed to achieve the sustainable development goals of the United Nations.展开更多
The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,an...The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,and radiological characteristics,as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen,China.All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS).The most common laboratory abnormalities were hypoalbuminemia,lymphopenia,decreased percentage of lymphocytes (LYM) and neutrophils (NEU),elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH),and decreased CD8 count.The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity.ALB,LYM,LYM (%),LDH,NEU (%),and CRP were highly correlated to the acute lung injury.Age,viral load,lung injury score,and blood biochemistry indexes,albumin (ALB),CRP,LDH,LYM (%),LYM,and NEU (%),may be predictors of disease severity.Moreover,the Angiotensin Ⅱlevel in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury.Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.展开更多
In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a n...In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.展开更多
Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human ...Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.展开更多
Recently, the emergence of pre-trained models(PTMs) has brought natural language processing(NLP) to a new era. In this survey, we provide a comprehensive review of PTMs for NLP. We first briefly introduce language rep...Recently, the emergence of pre-trained models(PTMs) has brought natural language processing(NLP) to a new era. In this survey, we provide a comprehensive review of PTMs for NLP. We first briefly introduce language representation learning and its research progress. Then we systematically categorize existing PTMs based on a taxonomy from four different perspectives. Next,we describe how to adapt the knowledge of PTMs to downstream tasks. Finally, we outline some potential directions of PTMs for future research. This survey is purposed to be a hands-on guide for understanding, using, and developing PTMs for various NLP tasks.展开更多
This special issue of Acta Mathematica Scientia is dedicated to the celebration of the 70th birthday of Constantine M. Dafermos. Costas is the Alumni-Alumnae University Professor of Brown University, a Fellow of the A...This special issue of Acta Mathematica Scientia is dedicated to the celebration of the 70th birthday of Constantine M. Dafermos. Costas is the Alumni-Alumnae University Professor of Brown University, a Fellow of the American Academy of Arts and Sciences, a Correspondent Member of the Academy of Athens, a Foreign Member of the Academia Nazionale dei Lincei, a SIAM Fellow, and an Honorary Professor of the Chinese Academy of Sciences. He is also an Editor-in-Chief of this journal.展开更多
Using seven well-replicated Qilian juniper (Sabina przewalskii Kom.) ring-width chronologies developed at Zongwulong and Shalike Mts. in the northeastern part of the Qaidam Basin annual precipitation from previous Jul...Using seven well-replicated Qilian juniper (Sabina przewalskii Kom.) ring-width chronologies developed at Zongwulong and Shalike Mts. in the northeastern part of the Qaidam Basin annual precipitation from previous July to current June in the recent 1000 years was re- constructed for Delingha. The reconstruction can capture 63.1% of precipitation variance and the equation was stable over time. For the reconstructed precipitation, wet periods occurred in AD1520—1633 and 1933—2001, whereas dry intervals in 1429—1519 and 1634—1741. In ad- dition, the magnitude in precipitation variation was lower before 1430 with about 15 mm, but it increased to 30 mm during the period of 1430 to 1850. After 1850, the precipitation variance de- creased again. In contrast to the increase in temperature, a decrease in annual precipitation was evident since the 1990s. The agreement in low-frequency variation between the reconstruction and the glacier accumulation and particulate content in Dunde ice cores during the recent several hundred years suggested that the precipitation reconstructed in this study was rather reliable, and represented a regional signal. This 1000-year reconstruction could benefit our understanding of climatic variation in decadal to century-scale in this region, and provide basic data to climate models and to prediction of future climate in the 21st century.展开更多
Background The two most basic properties of mesenchymal stem cells (MSCs) are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Whar...Background The two most basic properties of mesenchymal stem cells (MSCs) are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton' s Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton' s Jelly-derived MSCs to differentiate into nerve-like cells.Methods MSCs were cultured from the Wharton' s Jelly taken from human umbilical cord of babies delivered after full-term normal labor. Salvia miltiorrhiza and [3-mercaptoethanol were used to induce the human umbilical cord-derived MSCs to differentiate The expression of neural protein markers was shown by immunocytochemistry. The induction process was monitored by phase contrast microscopy, electron microscopy (EM), and laser scanning confocal microscopy (LSCM) . The pleiotrophin and nestin genes were measured by reverse transcription-polymerase chain reaction (RT-PCR).Results MSCs in the Wharton' s Jelly were easily attainable and could be maintained and expanded in culture. They were positive for markers of MSCs, but negative for markers of hematopoietic cells and graft-versus-host disease (GVHD)-related cells. Treatment with Salvia mihiorrhiza caused Wharton' s Jelly cells to undergo profound morphological changes. The induced MSCs developed rounded cell bodies with multiple neurite-like extensions. Eventually they developed processes that formed networks reminiscent of primary cultures of neurons. Salvia mihiorrhiza and β-mercaptoethanol also induced MSCs to express nestin, β-tubulin Ⅲ, neurofilament (NF) and glial fibrillary acidic protein (GFAP). It was confirmed by RT-PCR that MSCs could express pleiotrophin both before and after induction by Salvia miltiorrhiza. The expression was markedly enhanced after induction and the nestin gene was also expressed.Conclusions MSCs could be isolated from human umbilical cord Wharto展开更多
An arsenic hyperaccumulator Pteris vittata L. (Chinese brake) was first discovered in China by means of field survey and greenhouse cultivation. Field survey showed that Chinese brake had large accumulating capacity t...An arsenic hyperaccumulator Pteris vittata L. (Chinese brake) was first discovered in China by means of field survey and greenhouse cultivation. Field survey showed that Chinese brake had large accumulating capacity to arsenic; the orders of arsenic content in different parts of the fern were as follows: leaves】leafstalks】roots, which is totally different from that of ordinary plants; bioaccumulation coefficients of the above ground parts of the fern decreased as a power function of soil arsenic contents. In the control of pot trials with normal unpolluted soil containing 9mg/kg of arsenic, the bioaccumulation coefficients of the above ground parts and rhizoids of Chinese brake were as high as 71 and 80 respectively. Greenhouse cultivation in the contaminated soil from mining areas has shown that more than 1 times greater arsenic can be accumulated in the leaves of the fern than that of field samples with the largest content of 5070 mg/kg As on a dry matter basis. During greenhouse cultivation, arsenic展开更多
Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,...Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,we report a novel batorigin CoV causing severe and fatal pneumonia in humans.Methods:We collected clinical data and bronchoalveolar lavage(BAL)specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital,Hubei province,China.Nucleic acids of the BAL were extracted and subjected to next-generation sequencing.Virus isolation was carried out,and maximum-likelihood phylogenetic trees were constructed.Results:Five patients hospitalized from December 18 to December 29,2019 presented with fever,cough,and dyspnea accompanied by complications of acute respiratory distress syndrome.Chest radiography revealed diffuse opacities and consolidation.One of these patients died.Sequence results revealed the presence of a previously unknownβ-CoV strain in all five patients,with 99.8%to 99.9%nucleotide identities among the isolates.These isolates showed 79.0%nucleotide identity with the sequence of SARS-CoV(GenBank NC_004718)and 51.8%identity with the sequence of MERS-CoV(GenBank NC_019843).The virus is phylogenetically closest to a bat SARS-like CoV(SL-ZC45,GenBank MG772933)with 87.6%to 87.7%nucleotide identity,but is in a separate clade.Moreover,these viruses have a single intact open reading frame gene 8,as a further indicator of bat-origin CoVs.However,the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV,indicating that these viruses might use the same receptor.Conclusion:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.展开更多
Chinese medicine (CM) is the most typical conventional therapy compared with any other traditional or alternative medicine systems. The active components of CMs are either primary or secondary metabolites generated ...Chinese medicine (CM) is the most typical conventional therapy compared with any other traditional or alternative medicine systems. The active components of CMs are either primary or secondary metabolites generated by metabolic and biosynthetic enzymes in plants, protecting the plants from environmental stress. The characteristics of these metabolites are diverse, complicated and unique. In this paper, current approaches for quality assessment were extensively reviewed, a new concept of quality marker (Q-marker) was then proposed for CM quality assessment. Additionally, definition of the Q-marker, as well as the relevant methods, were discussed, on the basis of the biosynthetic pathways of secondary metabolites and source of biological active components. Study design of Q-marker is complex system for quality assessment and production process control of CM products with transitivity and traceability. Therefore, the system with characteristics of transmission and traceability is expected to be established for regulation of quality. Upon the concept which the transitivity and traceability in the quality assessment and production process control covered the entire process, such as raw materials, decoction slices, processing, extraction and production can be further enhanced. The transitivity and traceability will inevitably require close attention to "who, what, where, when, and why" details at each stage of Q-markers of CM production form raw materials to patent product. The establishing quality standards are enablers of many and various transitivity and traceability solutions, not a solution in them. It means that the transitivity and traceability system is readily link between products and across borders in quality. According to the thinking mode and methods of investigation on quality assessment of CM product, we focus on the entire process, in terms of safety and effectiveness and quality control. The standard preparation of CM or CM decoction is not only the basis for study of Q-marker, but also the展开更多
ENSO induces coherent climate anomalies over the Indo-western Pacific, but these anomalies outlast SST anomalies of the equatorial Pacific by a season, with major effects on the Asian summer monsoon. This review provi...ENSO induces coherent climate anomalies over the Indo-western Pacific, but these anomalies outlast SST anomalies of the equatorial Pacific by a season, with major effects on the Asian summer monsoon. This review provides historical accounts of major milestones and synthesizes recent advances in the endeavor to understand summer variability over the Indo-Northwest Pacific region. Specifically, a large-scale anomalous anticyclone (AAC) is a recurrent pattern in post-E1 Nifio summers, spanning the tropical Northwest Pacific and North Indian oceans. Regarding the ocean memory that anchors the summer AAC, competing hypotheses emphasize either SST cooling in the easterly trade wind regime of the Northwest Pacific or SST warming in the westerly monsoon regime of the North Indian Ocean. Our synthesis reveals a coupled ocean- atmosphere mode that builds on both mechanisms in a two-stage evolution. In spring, when the northeast trades prevail, the AAC and Northwest Pacific cooling are coupled via wind-evaporation-SST feedback. The Northwest Pacific cooling persists to trigger a summer feedback that arises from the interaction of the AAC and North Indian Ocean warming, enabled by the westerly monsoon wind regime. This Indo-western Pacific ocean capacitor (IPOC) effect explains why E1 Nifio stages its last act over the monsoonal Indo-Northwest Pacific and casts the Indian Ocean warming and AAC in leading roles. The IPOC displays interdecadal modulations by the ENSO variance cycle, significantly correlated with ENSO at the turn of the 20th century and after the 1970s, but not in between. Outstanding issues, including future climate projections, are also discussed.展开更多
Recent years havecomputer Go, imagelearning technologiesdevelopment of deepobserved a number of big breakthroughs in artificial intelligence, including self-driving cars,recognition, speech recognition, and machine tr...Recent years havecomputer Go, imagelearning technologiesdevelopment of deepobserved a number of big breakthroughs in artificial intelligence, including self-driving cars,recognition, speech recognition, and machine translation, and in almost all the cases deephave played a vital role. Indeed, significant progresses have been made in research andlearning and their applications into robotics, computer vision, soeech orocessing.展开更多
In a survey on the Yellow Sea and the East China Sea on August 20-30 of 1999,we found a hypoxic zone(<2 mg/L)of 13700 km2 with an average thickness of 20m at the bottom of the Changjiang(Yangtze River)Estuary,with ...In a survey on the Yellow Sea and the East China Sea on August 20-30 of 1999,we found a hypoxic zone(<2 mg/L)of 13700 km2 with an average thickness of 20m at the bottom of the Changjiang(Yangtze River)Estuary,with an oxygen minimum value of 1 mg/L.The extension of the dissolved oxygen deficiency extended to the 100m isobath in a southeastward direction along the bottom of the continental shelf of the East China Sea.During the last two decades,the minimum dissolved oxygen values in the low oxygen region of the Changjiang Estuary have decreased from 2.85 mg/L to 1 mg/L.In the hypoxic zone,the apparent oxygen utilization(AOU)was 5.8 mg/L and the total oxygen depletion approximately 1.59×10^(6) t.The strong halocline above the hypoxic zone,as a result of affluent water from the Changjiang,Taiwan Warm Current(TWC),and the high concentrations of particle organic carbon(POC)and nitrogen(PON)are the major factors causing the formation of the hypoxic zone.The POC:PON ratios and nutrient concentration distributions in the hypoxic zone suggest that the oxygen deficiency in the bottom water during the summer in the East China Sea off the Changjiang is the result of organic carbon production enhanced by nutrients from the Changjiang and fluvial organic matter input,followed by a shift in regeneration of nutrients in the East China Sea.展开更多
Effects of elevated O_3 on the yields of rice and winter wheat were studied by using open-top chambers(OTCs). Results showed that compared to the control treatment, 200 ppb, 100 ppb, 50 ppb treatments caused a 80.4%, ...Effects of elevated O_3 on the yields of rice and winter wheat were studied by using open-top chambers(OTCs). Results showed that compared to the control treatment, 200 ppb, 100 ppb, 50 ppb treatments caused a 80.4%, 58.6% and 10.5% decrease in grain yields per winter wheat plant and a 49.1%, 26.1% and 8.2% decrease in grain yield per rice plant, respectively. According to the dose-response relation educed from OTCs experiment and the monitor data of O_3 concentrations in spots, it was estimated that the yield losses of rice and winter wheat resulted by O_3 pollution in the Yangtze River Delta region in 1999 were 0.599 million ton and 0.669 million ton, economic losses were 0.539 billion RMB Yuan and 0.936 billion RMB Yuan, respectively.展开更多
基金supported by the National Health Commission of the People’s Republic of China (201302002,Clinical Trial NCT02200679)。
文摘This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.
基金partially supported by the National Key Research and Development Program of China(2016YFA0600103)Delos Living LLCthe Cyrus Tang Foundation
文摘As the world strives to reduce the impact of population growth, urbanization, agricultural expansion, and climate change on food security, energy and water shortage, resource over-exploration, biodiversity loss, environmental pollution, and ultimately human health, timely and higher resolution land cover information is urgently needed to achieve the sustainable development goals of the United Nations.
基金This work was supported by the National Science and Technology Major Project(2017ZX10103011 and 2017ZX10204401)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2017-I2M-1-009)+1 种基金Shenzhen Science and Technology Research and Development Project(JCYJ20180504165549581 and JCYJ20170413141236903)China Postdoctoral Science Foundation(2019T120147).
文摘The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,and radiological characteristics,as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen,China.All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS).The most common laboratory abnormalities were hypoalbuminemia,lymphopenia,decreased percentage of lymphocytes (LYM) and neutrophils (NEU),elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH),and decreased CD8 count.The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity.ALB,LYM,LYM (%),LDH,NEU (%),and CRP were highly correlated to the acute lung injury.Age,viral load,lung injury score,and blood biochemistry indexes,albumin (ALB),CRP,LDH,LYM (%),LYM,and NEU (%),may be predictors of disease severity.Moreover,the Angiotensin Ⅱlevel in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury.Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.
基金supported(in part)by the Entrusted Project of National Center for Medical Service Administration,National Health and Family Planning Commission China(No.[2019]099)the First Level Funding of the Second Medical Leading Talent Project in Hubei Provincethe Special Project for Emergency of the Ministry of Science and Technology(2020YFC0841300)。
文摘In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.
基金This study was supported by the National Basic Research Program (973 Program) (Nos. 2010CB945401 and 2012CB911201), the National Natural Science Foundation of China (Grant Nos. 91019020, 81330055, and 31371508).
文摘Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.
基金the National Natural Science Foundation of China(Grant Nos.61751201 and 61672162)the Shanghai Municipal Science and Technology Major Project(Grant No.2018SHZDZX01)and ZJLab。
文摘Recently, the emergence of pre-trained models(PTMs) has brought natural language processing(NLP) to a new era. In this survey, we provide a comprehensive review of PTMs for NLP. We first briefly introduce language representation learning and its research progress. Then we systematically categorize existing PTMs based on a taxonomy from four different perspectives. Next,we describe how to adapt the knowledge of PTMs to downstream tasks. Finally, we outline some potential directions of PTMs for future research. This survey is purposed to be a hands-on guide for understanding, using, and developing PTMs for various NLP tasks.
文摘This special issue of Acta Mathematica Scientia is dedicated to the celebration of the 70th birthday of Constantine M. Dafermos. Costas is the Alumni-Alumnae University Professor of Brown University, a Fellow of the American Academy of Arts and Sciences, a Correspondent Member of the Academy of Athens, a Foreign Member of the Academia Nazionale dei Lincei, a SIAM Fellow, and an Honorary Professor of the Chinese Academy of Sciences. He is also an Editor-in-Chief of this journal.
基金the National KeyBasic Research Development Project of China(Grant No.19980408)the Key Project of Knowledge Innovation of the CAs(Grant No.KZcx2-314) the National Key Project of Science and Technology(Grant No.2001-BA611B-O1).
文摘Using seven well-replicated Qilian juniper (Sabina przewalskii Kom.) ring-width chronologies developed at Zongwulong and Shalike Mts. in the northeastern part of the Qaidam Basin annual precipitation from previous July to current June in the recent 1000 years was re- constructed for Delingha. The reconstruction can capture 63.1% of precipitation variance and the equation was stable over time. For the reconstructed precipitation, wet periods occurred in AD1520—1633 and 1933—2001, whereas dry intervals in 1429—1519 and 1634—1741. In ad- dition, the magnitude in precipitation variation was lower before 1430 with about 15 mm, but it increased to 30 mm during the period of 1430 to 1850. After 1850, the precipitation variance de- creased again. In contrast to the increase in temperature, a decrease in annual precipitation was evident since the 1990s. The agreement in low-frequency variation between the reconstruction and the glacier accumulation and particulate content in Dunde ice cores during the recent several hundred years suggested that the precipitation reconstructed in this study was rather reliable, and represented a regional signal. This 1000-year reconstruction could benefit our understanding of climatic variation in decadal to century-scale in this region, and provide basic data to climate models and to prediction of future climate in the 21st century.
文摘Background The two most basic properties of mesenchymal stem cells (MSCs) are the capacities to selfrenew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton' s Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton' s Jelly-derived MSCs to differentiate into nerve-like cells.Methods MSCs were cultured from the Wharton' s Jelly taken from human umbilical cord of babies delivered after full-term normal labor. Salvia miltiorrhiza and [3-mercaptoethanol were used to induce the human umbilical cord-derived MSCs to differentiate The expression of neural protein markers was shown by immunocytochemistry. The induction process was monitored by phase contrast microscopy, electron microscopy (EM), and laser scanning confocal microscopy (LSCM) . The pleiotrophin and nestin genes were measured by reverse transcription-polymerase chain reaction (RT-PCR).Results MSCs in the Wharton' s Jelly were easily attainable and could be maintained and expanded in culture. They were positive for markers of MSCs, but negative for markers of hematopoietic cells and graft-versus-host disease (GVHD)-related cells. Treatment with Salvia mihiorrhiza caused Wharton' s Jelly cells to undergo profound morphological changes. The induced MSCs developed rounded cell bodies with multiple neurite-like extensions. Eventually they developed processes that formed networks reminiscent of primary cultures of neurons. Salvia mihiorrhiza and β-mercaptoethanol also induced MSCs to express nestin, β-tubulin Ⅲ, neurofilament (NF) and glial fibrillary acidic protein (GFAP). It was confirmed by RT-PCR that MSCs could express pleiotrophin both before and after induction by Salvia miltiorrhiza. The expression was markedly enhanced after induction and the nestin gene was also expressed.Conclusions MSCs could be isolated from human umbilical cord Wharto
基金This work was cosponsored by the National Natural Science Foundation of China (Grant Nos. 49941003 and 40071075)the Chinese Academy of Sciences (Innovation Project KZCX-401-2)the State Key Basic Research Plan of China (Grant No. 1999011808).
文摘An arsenic hyperaccumulator Pteris vittata L. (Chinese brake) was first discovered in China by means of field survey and greenhouse cultivation. Field survey showed that Chinese brake had large accumulating capacity to arsenic; the orders of arsenic content in different parts of the fern were as follows: leaves】leafstalks】roots, which is totally different from that of ordinary plants; bioaccumulation coefficients of the above ground parts of the fern decreased as a power function of soil arsenic contents. In the control of pot trials with normal unpolluted soil containing 9mg/kg of arsenic, the bioaccumulation coefficients of the above ground parts and rhizoids of Chinese brake were as high as 71 and 80 respectively. Greenhouse cultivation in the contaminated soil from mining areas has shown that more than 1 times greater arsenic can be accumulated in the leaves of the fern than that of field samples with the largest content of 5070 mg/kg As on a dry matter basis. During greenhouse cultivation, arsenic
基金This study was supported by grants from the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(No.2016-I2M-1-014)the National Major Science&Technology Project for Control and Prevention of Major Infectious Diseases in China(Nos.2017ZX10103004,2018ZX10305409,2017ZX10204401)the National Natural Science Foundation(No.81930063)
文摘Background:Human infections with zoonotic coronaviruses(CoVs),including severe acute respiratory syndrome(SARS)-CoV and Middle East respiratory syndrome(MERS)-CoV,have raised great public health concern globally.Here,we report a novel batorigin CoV causing severe and fatal pneumonia in humans.Methods:We collected clinical data and bronchoalveolar lavage(BAL)specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital,Hubei province,China.Nucleic acids of the BAL were extracted and subjected to next-generation sequencing.Virus isolation was carried out,and maximum-likelihood phylogenetic trees were constructed.Results:Five patients hospitalized from December 18 to December 29,2019 presented with fever,cough,and dyspnea accompanied by complications of acute respiratory distress syndrome.Chest radiography revealed diffuse opacities and consolidation.One of these patients died.Sequence results revealed the presence of a previously unknownβ-CoV strain in all five patients,with 99.8%to 99.9%nucleotide identities among the isolates.These isolates showed 79.0%nucleotide identity with the sequence of SARS-CoV(GenBank NC_004718)and 51.8%identity with the sequence of MERS-CoV(GenBank NC_019843).The virus is phylogenetically closest to a bat SARS-like CoV(SL-ZC45,GenBank MG772933)with 87.6%to 87.7%nucleotide identity,but is in a separate clade.Moreover,these viruses have a single intact open reading frame gene 8,as a further indicator of bat-origin CoVs.However,the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV,indicating that these viruses might use the same receptor.Conclusion:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
基金National Natural Science Fundantion of China(No.81430096)
文摘Chinese medicine (CM) is the most typical conventional therapy compared with any other traditional or alternative medicine systems. The active components of CMs are either primary or secondary metabolites generated by metabolic and biosynthetic enzymes in plants, protecting the plants from environmental stress. The characteristics of these metabolites are diverse, complicated and unique. In this paper, current approaches for quality assessment were extensively reviewed, a new concept of quality marker (Q-marker) was then proposed for CM quality assessment. Additionally, definition of the Q-marker, as well as the relevant methods, were discussed, on the basis of the biosynthetic pathways of secondary metabolites and source of biological active components. Study design of Q-marker is complex system for quality assessment and production process control of CM products with transitivity and traceability. Therefore, the system with characteristics of transmission and traceability is expected to be established for regulation of quality. Upon the concept which the transitivity and traceability in the quality assessment and production process control covered the entire process, such as raw materials, decoction slices, processing, extraction and production can be further enhanced. The transitivity and traceability will inevitably require close attention to "who, what, where, when, and why" details at each stage of Q-markers of CM production form raw materials to patent product. The establishing quality standards are enablers of many and various transitivity and traceability solutions, not a solution in them. It means that the transitivity and traceability system is readily link between products and across borders in quality. According to the thinking mode and methods of investigation on quality assessment of CM product, we focus on the entire process, in terms of safety and effectiveness and quality control. The standard preparation of CM or CM decoction is not only the basis for study of Q-marker, but also the
基金supported by the National Basic Research Program of China (Grant No. 2012CB 955600)the U.S. National Science Foundation, the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDA11010103)+1 种基金the Environment Research and Technology Development Fund 2-1503 of the Japanese Ministry of Environment, the Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research 25287120 and for Young Scientists 15H05466the National Natural Science Foundation of China (Grant Nos. 41205049, 41275081, 41425019, 41525019, 41521005)
文摘ENSO induces coherent climate anomalies over the Indo-western Pacific, but these anomalies outlast SST anomalies of the equatorial Pacific by a season, with major effects on the Asian summer monsoon. This review provides historical accounts of major milestones and synthesizes recent advances in the endeavor to understand summer variability over the Indo-Northwest Pacific region. Specifically, a large-scale anomalous anticyclone (AAC) is a recurrent pattern in post-E1 Nifio summers, spanning the tropical Northwest Pacific and North Indian oceans. Regarding the ocean memory that anchors the summer AAC, competing hypotheses emphasize either SST cooling in the easterly trade wind regime of the Northwest Pacific or SST warming in the westerly monsoon regime of the North Indian Ocean. Our synthesis reveals a coupled ocean- atmosphere mode that builds on both mechanisms in a two-stage evolution. In spring, when the northeast trades prevail, the AAC and Northwest Pacific cooling are coupled via wind-evaporation-SST feedback. The Northwest Pacific cooling persists to trigger a summer feedback that arises from the interaction of the AAC and North Indian Ocean warming, enabled by the westerly monsoon wind regime. This Indo-western Pacific ocean capacitor (IPOC) effect explains why E1 Nifio stages its last act over the monsoonal Indo-Northwest Pacific and casts the Indian Ocean warming and AAC in leading roles. The IPOC displays interdecadal modulations by the ENSO variance cycle, significantly correlated with ENSO at the turn of the 20th century and after the 1970s, but not in between. Outstanding issues, including future climate projections, are also discussed.
文摘Recent years havecomputer Go, imagelearning technologiesdevelopment of deepobserved a number of big breakthroughs in artificial intelligence, including self-driving cars,recognition, speech recognition, and machine translation, and in almost all the cases deephave played a vital role. Indeed, significant progresses have been made in research andlearning and their applications into robotics, computer vision, soeech orocessing.
基金This study was made under the auspices of the National Key Basic Research Program of the Ministry of Science and Technology,P.R.China(Grant No.G1999043705)and the Shanghai Priority Academic Discipline.
文摘In a survey on the Yellow Sea and the East China Sea on August 20-30 of 1999,we found a hypoxic zone(<2 mg/L)of 13700 km2 with an average thickness of 20m at the bottom of the Changjiang(Yangtze River)Estuary,with an oxygen minimum value of 1 mg/L.The extension of the dissolved oxygen deficiency extended to the 100m isobath in a southeastward direction along the bottom of the continental shelf of the East China Sea.During the last two decades,the minimum dissolved oxygen values in the low oxygen region of the Changjiang Estuary have decreased from 2.85 mg/L to 1 mg/L.In the hypoxic zone,the apparent oxygen utilization(AOU)was 5.8 mg/L and the total oxygen depletion approximately 1.59×10^(6) t.The strong halocline above the hypoxic zone,as a result of affluent water from the Changjiang,Taiwan Warm Current(TWC),and the high concentrations of particle organic carbon(POC)and nitrogen(PON)are the major factors causing the formation of the hypoxic zone.The POC:PON ratios and nutrient concentration distributions in the hypoxic zone suggest that the oxygen deficiency in the bottom water during the summer in the East China Sea off the Changjiang is the result of organic carbon production enhanced by nutrients from the Changjiang and fluvial organic matter input,followed by a shift in regeneration of nutrients in the East China Sea.
文摘Effects of elevated O_3 on the yields of rice and winter wheat were studied by using open-top chambers(OTCs). Results showed that compared to the control treatment, 200 ppb, 100 ppb, 50 ppb treatments caused a 80.4%, 58.6% and 10.5% decrease in grain yields per winter wheat plant and a 49.1%, 26.1% and 8.2% decrease in grain yield per rice plant, respectively. According to the dose-response relation educed from OTCs experiment and the monitor data of O_3 concentrations in spots, it was estimated that the yield losses of rice and winter wheat resulted by O_3 pollution in the Yangtze River Delta region in 1999 were 0.599 million ton and 0.669 million ton, economic losses were 0.539 billion RMB Yuan and 0.936 billion RMB Yuan, respectively.