To unravel the genetic mechanisms of disease and physiological traits,it requires comprehensive sequencing analysis of large sample size in Chinese populations.Here,we report the primary results of the Chinese Academy...To unravel the genetic mechanisms of disease and physiological traits,it requires comprehensive sequencing analysis of large sample size in Chinese populations.Here,we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative(CASPMI)project launched by the Chinese Academy of Sciences,including the de novo assembly of a northern Han reference genome(NH1.0)and whole genome analyses of 597 healthy people coming from most areas in China.Given the two existing reference genomes for Han Chinese(YH and HX1)were both from the south,we constructed NH1.0,a new reference genome from a northern individual,by combining the sequencing strategies of PacBio,10×Genomics,and Bionano mapping.Using this integrated approach,we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1.In order to generate a genomic variation map of Chinese populations,we performed the whole-genome sequencing of 597 participants and identified 24.85 million(M)single nucleotide variants(SNVs),3.85 M small indels,and 106,382 structural variations.In the association analysis with collected phenotypes,we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males.Moreover,significant genetic diversity in MTHFR,TCN2,FADS1,and FADS2,which associate with circulating folate,vitamin B12,or lipid metabolism,was observed between northerners and southerners.Especially,for the homocysteine-increasing allele of rs1801133(MTHFR 677T),we hypothesize that there exists a “comfort”zone for a high frequency of 677T between latitudes of 35–45 degree North.Taken together,our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.展开更多
Since its initial release in 2001,the human reference genome has undergone continuous improvement in quality,and the recently released telomere-to-telomere(T2T)version-T2T-CHM13—reaches its highest level of continuit...Since its initial release in 2001,the human reference genome has undergone continuous improvement in quality,and the recently released telomere-to-telomere(T2T)version-T2T-CHM13—reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified,nearly homozygous genome of a hydatidiform mole cell line.Here,to provide an authentic complete diploid human genome reference for the Han Chinese,the largest population in the world,we assembled the genome of a male Han Chinese individual,T2T-YAO,which includes T2T assemblies of all the 22+X+M and 22+Y chromosomes in both haploids.The quality of T2T-YAO is much better than those of all currently available diploid assemblies,and its haploid version,T2T-YAO-hp,generated by selecting the better assembly for each autosome,reaches the top quality of fewer than one error per 29.5 Mb,even higher than that of T2T-CHM13.Derived from an individual living in the aboriginal region of the Han population,T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors.Each haplotype of T2TYAO possesses330-Mb exclusive sequences,3100 unique genes,and tens of thousands of nucleotide and structural variations as compared with CHM13,highlighting the necessity of a population-stratified reference genome.The construction of T2T-YAO,an accurate and authentic representative of the Chinese population,would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes,especially within the context of the unique variations of the Chinese population.展开更多
Neptunea cumingii is an important nutrition-rich economic species in China.Juveniles of N.cumingii suff er from high mortality at low temperatures,which has proved a limiting factor in raising seedlings in artifi cial...Neptunea cumingii is an important nutrition-rich economic species in China.Juveniles of N.cumingii suff er from high mortality at low temperatures,which has proved a limiting factor in raising seedlings in artifi cial habitats.Previous research has shown that N.cumingii displays aggregation behavior in response to adverse environmental changes.Therefore,we determined the eff ects of temperature,food,size of juvenile snails,substratum type,and density of juvenile snails on the aggregation behavior of N.cumingii.Results show that,at a low(4°C)or a high(22°C)temperature,juvenile snails adjusted to the inhospitable environment by exhibiting increased aggregation behavior.However,their aggregation behaviors diff ered at these two temperatures.There was no signifi cant diff erence in the aggregation rate,but the typical aggregation size was larger at 4°C than at 22°C.At 10°C or 16°C,aggregation behavior of juvenile snails reduced.Aggregation increased in the satiation treatment at 10°C and 16°C.Small-sized juveniles tended to have higher aggregation rates(92.22%)and a larger typical aggregation size.More juveniles were distributed in the bottom of shaded substrata.A larger typical aggregation size or higher density signifi cantly reduced the mortality of juvenile snails at a low temperature(4°C).These results broaden our understanding of gastropod aggregation behavior and can be used to develop and improve commercial breeding strategies and resource recovery for N.cumingii.展开更多
Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of...Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.展开更多
Neuroinflammation plays a vital role in cerebral ischemic stroke(IS).In the acute phase of IS,microglia are activated toward the pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.Argon,an inert gas,can reduce ne...Neuroinflammation plays a vital role in cerebral ischemic stroke(IS).In the acute phase of IS,microglia are activated toward the pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.Argon,an inert gas,can reduce neuroinflammation and alleviate ischemia/reperfusion(I/R)injury.However,whether argon regulates M1/M2 polarization to protect against I/R injury as well as the underlying mechanism has not been reported.In this study,we analyzed the activation and polarization of microglia after I/R injury with or without argon administration and explored the effects of argon on NLRP3 inflammasome-mediated inflammation in microglia in vitro and in vivo.The results showed that argon application inhibited the activation of M1 microglia/macrophage in the ischemic penumbra and the expression of proteins related to NLRP3 inflammasome and pyroptosis in microglia.Argon administration also inhibited the expression and processing of IL-1β,a primary pro-inflammatory cytokine.Thus,argon alleviates I/R injury by inhibiting pro-inflammatory reactions via suppressing microglial polarization toward M1 phenotype and inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.More importantly,we showed that argon worked better than the specific NLRP3 inflammasome inhibitor MCC950 in suppressing neuroinflammation and protecting against cerebral I/R injury,suggesting the therapeutic potential of argon in neuroinflammation-related neurodegeneration diseases as a potent gas inhibitor of the NLRP3 inflammasome signaling pathway.展开更多
The Yellow River Delta(YRD)has China's largest artificial Robinia pseudoacacia forest,which was planted in the late 1970s and suffered extensive dieback in the 1990s.The health grade of the R.pseudoacacia forest(n...The Yellow River Delta(YRD)has China's largest artificial Robinia pseudoacacia forest,which was planted in the late 1970s and suffered extensive dieback in the 1990s.The health grade of the R.pseudoacacia forest(named canopy vigor grade,CVG)could be achieved by using high-resolution images and canopy vigor indicators(CVIs).However,a previous study showed that there was no significant correlation between CVG and the field-estimated aboveground biomass(AGB)of R.pseudoacacia forest.Therefore,this study aims to construct forest health indicators(FHIs)based on canopy spatial structure parameters extracted from LiDAR.The FHIs included Weibull_α(the scale parameter of the Weibull density function that reflects the shape of the tree canopy),VCI(vertical complexity index),sdCC(the standard deviation of canopy cover),H99(the 99th percentile height)and cvLAD(the coefficient of variation of leaf area density),and could significantly distinguish three forest health grades(FHG)(p<0.05).The FHG was positively correlated with forest AGB(rs=0.51,p=0.004),and the similarity value with CVG was 63.33%.The results of this study confirmed that the FHIs can reflect both canopy vigor and tree productivity,and distinguish forest health status without prior classification information.展开更多
The rapa whelk Rapana venosa transforms from a phytophagous larva to a camivorous juvenile after settlement and metamorphosis.The high mortality rate and low metamorphosis rate(<1%)of larvae are among the key facto...The rapa whelk Rapana venosa transforms from a phytophagous larva to a camivorous juvenile after settlement and metamorphosis.The high mortality rate and low metamorphosis rate(<1%)of larvae are among the key factors limiting the recovery of the resources ofR.venosa.We studied these two processes and showed that the larva has the ability to settle and metamorphose in the middle and late 4 spiral whorl period,and the use of substrates(scallop shells with oysters)can significantly improve the settlement and metamorphosis rate of larvae.The presence of darkness,juvenile bivalve shellfish,and oyster polysaccharide could effectively increase the rates of larval settlement and metamorphosis.Our findings broaden the understanding of settlement and metamorphosis in gastropods and can be used to improve population control,resource recovery and commercial breeding strategies for R.venosa.展开更多
基金supported by the grants of Key Program of the Chinese Academy of Sciences(Grant No.KJZD-EW-L14 awarded to CZ)the National Key R&D Program of China from the Ministry of Science and Technology of China(Grant No.2016YFB0201702 awarded to JX,as well as Grant Nos.2016YFC0901701 and 2018YFC0910700 awarded to XF)
文摘To unravel the genetic mechanisms of disease and physiological traits,it requires comprehensive sequencing analysis of large sample size in Chinese populations.Here,we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative(CASPMI)project launched by the Chinese Academy of Sciences,including the de novo assembly of a northern Han reference genome(NH1.0)and whole genome analyses of 597 healthy people coming from most areas in China.Given the two existing reference genomes for Han Chinese(YH and HX1)were both from the south,we constructed NH1.0,a new reference genome from a northern individual,by combining the sequencing strategies of PacBio,10×Genomics,and Bionano mapping.Using this integrated approach,we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1.In order to generate a genomic variation map of Chinese populations,we performed the whole-genome sequencing of 597 participants and identified 24.85 million(M)single nucleotide variants(SNVs),3.85 M small indels,and 106,382 structural variations.In the association analysis with collected phenotypes,we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males.Moreover,significant genetic diversity in MTHFR,TCN2,FADS1,and FADS2,which associate with circulating folate,vitamin B12,or lipid metabolism,was observed between northerners and southerners.Especially,for the homocysteine-increasing allele of rs1801133(MTHFR 677T),we hypothesize that there exists a “comfort”zone for a high frequency of 677T between latitudes of 35–45 degree North.Taken together,our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.
基金supported by the Science and Technology Research Project of Henan(Grant No.232102311003)the National Natural Science Foundation of China(Grant No.U1804282)。
文摘Since its initial release in 2001,the human reference genome has undergone continuous improvement in quality,and the recently released telomere-to-telomere(T2T)version-T2T-CHM13—reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified,nearly homozygous genome of a hydatidiform mole cell line.Here,to provide an authentic complete diploid human genome reference for the Han Chinese,the largest population in the world,we assembled the genome of a male Han Chinese individual,T2T-YAO,which includes T2T assemblies of all the 22+X+M and 22+Y chromosomes in both haploids.The quality of T2T-YAO is much better than those of all currently available diploid assemblies,and its haploid version,T2T-YAO-hp,generated by selecting the better assembly for each autosome,reaches the top quality of fewer than one error per 29.5 Mb,even higher than that of T2T-CHM13.Derived from an individual living in the aboriginal region of the Han population,T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors.Each haplotype of T2TYAO possesses330-Mb exclusive sequences,3100 unique genes,and tens of thousands of nucleotide and structural variations as compared with CHM13,highlighting the necessity of a population-stratified reference genome.The construction of T2T-YAO,an accurate and authentic representative of the Chinese population,would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes,especially within the context of the unique variations of the Chinese population.
基金Supported by the National Key R&D Program of China(No.2019YFD0900800)the fund earmarked for the Modern Agro-industry Technology Research System(No.CARS-49)+5 种基金the Major Scientifi c and Technological Innovation Project of Shandong Provincial Key Research and Development Program(No.2019JZZY020708)the Industry Leading Talents Project of Taishan Scholars(to ZHANG Tao),the Double-Hundred Blue Industry Leader Team of Yantai(to ZHANG Tao)the Construction Technology and Demonstration Application of Dandong Characteristic Beach Type Marine Ranch(No.KFJ-STS-QYZD-189)the Shandong Peninsula Coastal Area Ecological Simulation Test Project:Marine Ranch Resource Evaluation and Sustainable Utilization Model ResearchNSFC-Shandong Joint Fund for Marine Science Research Centers(No.U1406403)the Creative Team Project of the Laboratory for Marine Ecology and Environmental Science,Qingdao National Laboratory for Marine Science and Technology(No.LMEES-CTSP-2018-1)。
文摘Neptunea cumingii is an important nutrition-rich economic species in China.Juveniles of N.cumingii suff er from high mortality at low temperatures,which has proved a limiting factor in raising seedlings in artifi cial habitats.Previous research has shown that N.cumingii displays aggregation behavior in response to adverse environmental changes.Therefore,we determined the eff ects of temperature,food,size of juvenile snails,substratum type,and density of juvenile snails on the aggregation behavior of N.cumingii.Results show that,at a low(4°C)or a high(22°C)temperature,juvenile snails adjusted to the inhospitable environment by exhibiting increased aggregation behavior.However,their aggregation behaviors diff ered at these two temperatures.There was no signifi cant diff erence in the aggregation rate,but the typical aggregation size was larger at 4°C than at 22°C.At 10°C or 16°C,aggregation behavior of juvenile snails reduced.Aggregation increased in the satiation treatment at 10°C and 16°C.Small-sized juveniles tended to have higher aggregation rates(92.22%)and a larger typical aggregation size.More juveniles were distributed in the bottom of shaded substrata.A larger typical aggregation size or higher density signifi cantly reduced the mortality of juvenile snails at a low temperature(4°C).These results broaden our understanding of gastropod aggregation behavior and can be used to develop and improve commercial breeding strategies and resource recovery for N.cumingii.
基金supported by the National Natural Science Foundation of China(NSFC)(No.82002312,81972069)supported in part by research grants from the National Institutes of Health,USA(No.CA226303 to TCH,No.DE030480 to RRR)+10 种基金supported by the Science and Technology Research Program of Chongqing Education Commission,China(No.KJQN202100431,KJZD-M202100401)the Top Talent Award from The First Affiliated Hospital of Chongqing Medical University,China(No.BJRC2021-04)Cultivation Program of Postdoctoral Research of The First Affiliated Hospital of Chongqing Medical University,China(No.CYYY-BSHPYXM-202202)supported by a post-doctoral fellowship from Chongqing Medical University and rewarded by China Postdoctoral Science Foundation(No.2022M720605)supported in part by research grants from the 2019 Science and Technology Project of Chongqing Education Commission,China(No.KJQN201900410)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298)the Natural Science Foundation of China(No.82102696)supported by the Medical Scientist Training Program of the National Institutes of Health,USA(No.T32 GM007281)supported in part by The University of Chicago Cancer Center Support Grant,USA(No.P30CA014599)the National Center for Advancing Translational Sciences(NCATS)of the National Institutes of Health,USA(No.5UL1TR002389)supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopedics Alumni Fund.
文摘Recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mRNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding RNAs(ncRNAs).It has been shown that ncRNAs,especially long non-coding RNAs(lncRNAs),may play crucial regulatory roles in gene expression.As one of the first isolated and reported lncRNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and metabolism.Mechanistically,H19 mediates diverse regulatory functions by serving as competing endogenous RNAs(CeRNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mRNAs or lncRNAs.Here,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic diseases.We discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of H19.Ultimately,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.
基金supported by grants from the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX20_2857 and KYCX22_3372)Senile Health Scientific Research Project of Jiangsu Province(LR2021026)+2 种基金Nantong Social Livelihood Science and Technology General Project(MS12020019)Science and Technology Planning Project of Nantong Municipality(JC2021079 and JC2020010)Natural Science Fund for Colleges and Universities in Jiangsu Province(19KJB320002).
文摘Neuroinflammation plays a vital role in cerebral ischemic stroke(IS).In the acute phase of IS,microglia are activated toward the pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.Argon,an inert gas,can reduce neuroinflammation and alleviate ischemia/reperfusion(I/R)injury.However,whether argon regulates M1/M2 polarization to protect against I/R injury as well as the underlying mechanism has not been reported.In this study,we analyzed the activation and polarization of microglia after I/R injury with or without argon administration and explored the effects of argon on NLRP3 inflammasome-mediated inflammation in microglia in vitro and in vivo.The results showed that argon application inhibited the activation of M1 microglia/macrophage in the ischemic penumbra and the expression of proteins related to NLRP3 inflammasome and pyroptosis in microglia.Argon administration also inhibited the expression and processing of IL-1β,a primary pro-inflammatory cytokine.Thus,argon alleviates I/R injury by inhibiting pro-inflammatory reactions via suppressing microglial polarization toward M1 phenotype and inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.More importantly,we showed that argon worked better than the specific NLRP3 inflammasome inhibitor MCC950 in suppressing neuroinflammation and protecting against cerebral I/R injury,suggesting the therapeutic potential of argon in neuroinflammation-related neurodegeneration diseases as a potent gas inhibitor of the NLRP3 inflammasome signaling pathway.
基金supported by National Natural Science Foundation of China:[Grant Number No.41471419 and No.31971579].
文摘The Yellow River Delta(YRD)has China's largest artificial Robinia pseudoacacia forest,which was planted in the late 1970s and suffered extensive dieback in the 1990s.The health grade of the R.pseudoacacia forest(named canopy vigor grade,CVG)could be achieved by using high-resolution images and canopy vigor indicators(CVIs).However,a previous study showed that there was no significant correlation between CVG and the field-estimated aboveground biomass(AGB)of R.pseudoacacia forest.Therefore,this study aims to construct forest health indicators(FHIs)based on canopy spatial structure parameters extracted from LiDAR.The FHIs included Weibull_α(the scale parameter of the Weibull density function that reflects the shape of the tree canopy),VCI(vertical complexity index),sdCC(the standard deviation of canopy cover),H99(the 99th percentile height)and cvLAD(the coefficient of variation of leaf area density),and could significantly distinguish three forest health grades(FHG)(p<0.05).The FHG was positively correlated with forest AGB(rs=0.51,p=0.004),and the similarity value with CVG was 63.33%.The results of this study confirmed that the FHIs can reflect both canopy vigor and tree productivity,and distinguish forest health status without prior classification information.
基金Supported by the National Natural Science Foundation of China(No.31572636)the Natural Science Foundation of Shandong Province(No.ZR2019BD003)+4 种基金the China Postdoctoral Science Foundation(No.2019M652498)the Earmarked Fund for Modern Agro-industry Technology Research System(No.CARS-49)the Special Funds for Talent Project of Taishan Industry Leaderthe ‘Double Hundred’ Blue Industry Leader Team of Yantaithe Creative Team Project of the Laboratory for Marine Ecology and Environmental Science,Qingdao National Laboratory for Marine Science and Technology(No.LMEES-CTSP-2018-1)
文摘The rapa whelk Rapana venosa transforms from a phytophagous larva to a camivorous juvenile after settlement and metamorphosis.The high mortality rate and low metamorphosis rate(<1%)of larvae are among the key factors limiting the recovery of the resources ofR.venosa.We studied these two processes and showed that the larva has the ability to settle and metamorphose in the middle and late 4 spiral whorl period,and the use of substrates(scallop shells with oysters)can significantly improve the settlement and metamorphosis rate of larvae.The presence of darkness,juvenile bivalve shellfish,and oyster polysaccharide could effectively increase the rates of larval settlement and metamorphosis.Our findings broaden the understanding of settlement and metamorphosis in gastropods and can be used to improve population control,resource recovery and commercial breeding strategies for R.venosa.
