The reconstruction of demographic history using ancient and modern genomic resources reveals extensive interactions and admixture between ancient nomadic pastoralists and the social organizations of the Chinese Centra...The reconstruction of demographic history using ancient and modern genomic resources reveals extensive interactions and admixture between ancient nomadic pastoralists and the social organizations of the Chinese Central Plain.However,the extent to which Y-chromosome genetic legacies from nomadic emperor-related ancestral lineages influence the Chinese paternal gene pool remains unclear.Here,we genotype 2717 ethnolinguistically diverse samples belonging to C2a lineages,perform whole-genome sequencing on 997 representative samples,and integrate these data with ancient genomic sequences.We reconstruct the evolutionary histories of Northern Zhou-,Qing emperor-,and pastoralist-related lineages to assess their genetic impact on modern Chinese populations.This reassembled fine-scale Ychromosome phylogeny identifies deep divergence and five Neolithic expansion events contributing differently to the formation of northern Chinese populations.Phylogeographic modeling indicates that the nomadic empires of the Northern Zhou and Qing dynasties genetically originated from the Mongolian Plateau.Phylogenetic topology and shared haplotype patterns show that three upstream ancestors of Northern Zhou(C2a1a1b1a2a1b-FGC28857),Donghu tribe(C2a1a1b1-F1756),and Qing(C2a1a3a2-F10283)emperor-related lineages expanded during the middle Neolithic,contributing significantly to genetic flow between ancient northeastern Asians and modern East Asians.Notably,this study reveals limited direct contributions of Emperor Wu of Northern Zhou’s lineages to modern East Asians.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the pathogen responsible for coronavirus disease 2019(COVID-19),continues to evolve,giving rise to more variants and global reinfections.Previous research ha...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the pathogen responsible for coronavirus disease 2019(COVID-19),continues to evolve,giving rise to more variants and global reinfections.Previous research has demonstrated that barcode segments can effectively and cost-efficiently identify specific species within closely related populations.In this study,we designed and tested RNA barcode segments based on genetic evolutionary relationships to facilitate the efficient and accurate identification of SARS-CoV-2 from extensive virus samples,including human coronaviruses(HCoVs)and SARSr-CoV-2 lineages.Nucleotide sequences sourced from NCBI and GISAID were meticulously selected and curated to construct training sets,encompassing 1733 complete genome sequences of HCoVs and SARSr-CoV-2 lineages.Through genetic-level species testing,we validated the accuracy and reliability of the barcode segments for identifying SARS-CoV-2.Subsequently,75 main and subordinate species-specific barcode segments for SARS-CoV-2,located in ORF1ab,S,E,ORF7a,and N coding sequences,were intercepted and screened based on single-nucleotide polymorphism sites and weighted scores.Post-testing,these segments exhibited high recall rates(nearly 100%),specificity(almost 30%at the nucleotide level),and precision(100%)performance on identification.They were eventually visualized using one and two-dimensional combined barcodes and deposited in an online database(http://virusbarcodedatabase.top/).The successful integration of barcoding technology in SARS-CoV-2 identification provides valuable insights for future studies involving complete genome sequence polymorphism analysis.Moreover,this cost-effective and efficient identification approach also provides valuable reference for future research endeavors related to virus surveillance.展开更多
Avian infectious bronchitis(IB)is a highly contagious infectious disease caused by infectious bronchitis virus(IBV),which is prevalent in many countries worldwide and causes serious harm to the poultry industry.At pre...Avian infectious bronchitis(IB)is a highly contagious infectious disease caused by infectious bronchitis virus(IBV),which is prevalent in many countries worldwide and causes serious harm to the poultry industry.At present,many commercial IBV vaccines have been used for the prevention and control of IB;however,IB outbreaks occur frequently.In this study,two new strains of IBV,SX/2106 and SX/2204,were isolated from two flocks which were immunized with IBV H120 vaccine in central China.Phylogenetic and recombination analysis indicated that SX/2106,which was clustered into the GI-19 lineage,may be derived from recombination events of the GI-19 and GI-7 strains and the LDT3-A vaccine.Genetic analysis showed that SX/2204 belongs to the GVI-1 lineage,which may have originated from the recombination of the GI-13 and GVI-1 strains and the H120 vaccine.The virus cross-neutralization test showed that the antigenicity of SX/2106 and SX/2204 was different from H120.Animal experiments found that both SX/2106 and SX/2204 could replicate effectively in the lungs and kidneys of chickens and cause disease and death,and H120 immunization could not provide effective protection against the two IBV isolates.It is noteworthy that the pathogenicity of SX/2204 has significantly increased compared to the GVI-1 strains isolated previously,with a mortality rate up to 60%.Considering the continuous mutation and recombination of the IBV genome to produce new variant strains,it is important to continuously monitor epidemic strains and develop new vaccines for the prevention and control of IBV epidemics.展开更多
The mitochondrial genome is a prominent research topic due to its indispensable role in organisms and its application in many research disciplines.However,few studies have investigated intraspecies mitogenomic variati...The mitochondrial genome is a prominent research topic due to its indispensable role in organisms and its application in many research disciplines.However,few studies have investigated intraspecies mitogenomic variation.In this study,69 mitogenomes of the Black-throated Tit(Aegithalos concinnus)were assembled and annotated from a large number of short reads generated using high-throughput sequencing technology.Comparative analyses revealed that mitogenomic characteristics such as length,gene and nucleotide composition,codon usage,and duplicated control regions were relatively conserved despite substantial intraspecies morphological changes.Yet,all the individuals from the subspecies A.c.iredalei had one more nucleotide in the 12S rRNA than the other studied subspecies.Phylogenetic analyses showed five distinct lineages based on the complete mitogenomes and the 13 combined protein-coding genes,whereas only four lineages were observed when using the duplicate control regions.Most interestingly,each lineage had both copies of the control regions of the comprising individuals,indicating that the paralogous control regions were more similar than the orthologous sequences from the distinct lineages.This suggested the control regions had undergone concerted evolution.The Black-throated Tit has complex evolutionary history and needs further investigating the taxonomic status of these lineages,as well as the underlying evolutionary processes.Our findings call for more research on intraspecies mitogenomic variation.展开更多
Objective To learn the rabies genome molecular characteristics and compare the difference of China rabies lineages. Methods The complete genomes of 12 strains from different China rabies lineages were amplified and se...Objective To learn the rabies genome molecular characteristics and compare the difference of China rabies lineages. Methods The complete genomes of 12 strains from different China rabies lineages were amplified and sequenced, and all the China street strain genomes （total 43）, Arctic and Arctic-like genomes were aligned using ClustalX2, the genome homologies were analyzed using MegAlign software, and the phylogenetic trees were constructed by MEGA 5. Results First Arctic-like rabies genome in China （CO, H1202D） was reported, and we supplemented the rabies genome data of China, ensuring at least one genome was available in each China lineage. The genome size of China V （11908nt） is obviously shorter than other lineages＇ （11923-11925nt） for the difference of N-P non-coding regions. Among different lineages, the genome homologies are almost under 90%. CQH1202D （China IV lineage） has close relationship with strains from South Korea and they share about 95% genome similarities. Conclusion The molecular characteristics of 6 different China rabies lineages were compared and analyzed from genome level, which benefits for continued comprehensive rabies surveillance, rabies prevention and control in China.展开更多
While Influenza B viruses currently circulating worldwide are of two distinct evolutionary hemagglutinin lineages, current trivalent inactivated influenza virus vaccines (TIV) contain only a single component. Single d...While Influenza B viruses currently circulating worldwide are of two distinct evolutionary hemagglutinin lineages, current trivalent inactivated influenza virus vaccines (TIV) contain only a single component. Single doses of TIV containing B antigen of B/Florida/4/2006 (Yamagata-like) or B/Brisbane/60/2008 (Victoria-like) were administered during 2008/2009 and 2009/2010 influenza seasons, respectively. The objective of this study was to evaluate the immunological response against different lineages of B antigens in school-aged children. A non-randomized sero-epidemiological study was conducted and the immunogenicity responses based on sero-protection rate and geometric mean titre ratio (GMTR) of hemagglutination inhibition (HI) antibodies were measured before and after immunization as well as post-influenza season. Our results suggested that school-aged children under the age of 9 years receiving TIV vaccination induced and retained higher level of sero-protection rate (66.7% and 69% for the 2008-09 and 2009-10 season, respectively) to the homologous lineage than the heterologous lineage post-vaccination (19.4% and 27.6% for the 2008-09 and 2009-10 season, respectively). The need for the quadrivalent TIV by including both lineages of influenza B viruses is recommended in this study, particularly for children under the age of 9 years.展开更多
Human embryonic development is orchestrated by a sophisticated network of cell-cell communication and molecular interactions.Intercellular crosstalk and specific signal stimuli play crucial roles in shaping distinct c...Human embryonic development is orchestrated by a sophisticated network of cell-cell communication and molecular interactions.Intercellular crosstalk and specific signal stimuli play crucial roles in shaping distinct cell lineages,essential for cell fate determination and lineage identity maintenance[1].Here,to address challenges posed by the scarcity and potential ethical concerns of human embryo resources.展开更多
Human parainfluenza viruses(HPIV)are common viral pathogens in acute respiratory infection(ARI).We aimed to describe the epidemiological and molecular characteristics of HPIV from ARI patients.This cross-sectional stu...Human parainfluenza viruses(HPIV)are common viral pathogens in acute respiratory infection(ARI).We aimed to describe the epidemiological and molecular characteristics of HPIV from ARI patients.This cross-sectional study was conducted using respiratory samples from 9,696 ARI patients between 2016 and 2020 in southern China.All samples were analyzed by quantitative real-time polymerase chain reaction to determine the presence of HPIV and other common respiratory viruses.Descriptive statistics were performed to determine the temporal and population distribution of HPIV.The fulllength hemagglutinin-neuraminidase(HN)gene of HPIV3-positive samples was sequenced for phylogenetic analysis.A total of 577(6.0%)patients tested positive for HPIV,with HPIV3 being the predominant serotype,accounting for 46.8%of cases.Notably,66.0%of these HPIV-positive cases were children aged 0-2 years.The prevalence of HPIV infections showed a decreased trend and altered peak during 2016-2020.Cough,fever,sputum production,and rhinorrhea were common respiratory symptoms in HPIV-positive patients.The majority of cases had pneumonia(63.4%).Human rhinovirus(HRV)and human coronavirus(HCoV)were the most common coinfection viruses in HPIV-positive cases,with proportions of 20.1%and 14.4%,respectively.Phylogenetic analysis revealed that the predominant lineage of HPIV3 was C3f(86.0%),followed by lineage C3a(8.0%),C3d(4.0%),and C3b(2.0%).These findings help to better understand the epidemiology of HPIV,and improve public health strategies to prevent and control HPIV infections in southern China.展开更多
Based on the study of two Early Pleistocene human skulls found in Yunxian County,Hubei Province,China,Ji et al.(2024)suggested that Homo orientalis was the common ancestor of the sapiens lineage and the longi lineage,...Based on the study of two Early Pleistocene human skulls found in Yunxian County,Hubei Province,China,Ji et al.(2024)suggested that Homo orientalis was the common ancestor of the sapiens lineage and the longi lineage,and proposed that both the two lineages originated from East Asia.We further proposed that Genus Homo should be divided into two subgenera:Subgenus Homo and Subgenus Parahomo.All members of the sapiens lineage would be assigned to Subgenus Homo,and all members of the longi lineage would be grouped into Subgenus Parahomo.Homo(Parahomo)heidelbergensis and Homo(Parahomo)neanderthalensis also were the members of the longi lineage,an evolutionary branch spreaded from East Asia to Africa and Europe more than 600,000 years ago.This paper mainly makes an introduction to the speciation,classification and phylogeny of the longi lineage.The longi lineage and the sapiens lineage are″sister group″relationship,but the longi lineage is an extinct lineage,having nothing to do with our modern people.展开更多
Decades of research asserted that the oligodendroglial lineage comprises two cell types:oligodendrocyte precursor cells and oligodendrocytes.However,recent studies employing single-cell RNA sequencing techniques have ...Decades of research asserted that the oligodendroglial lineage comprises two cell types:oligodendrocyte precursor cells and oligodendrocytes.However,recent studies employing single-cell RNA sequencing techniques have uncovered novel cell states,prompting a revision of the existing terminology.Going forward,the oligodendroglial lineage should be delineated into five distinct cell states:oligodendrocyte precursor cells,committed oligodendrocyte precursor cells,newly formed oligodendrocytes,myelin-forming oligodendrocytes,and mature oligodendrocytes.This new classification system enables a deeper understanding of the oligodendroglia in both physiological and pathological contexts.Adopting this uniform terminology will facilitate comparison and integration of data across studies.This,including the consolidation of findings from various demyelinating models,is essential to better understand the pathogenesis of demyelinating diseases.Additionally,comparing injury models across species with varying regenerative capacities can provide insights that may lead to new therapeutic strategies to overcome remyelination failure.Thus,by standardizing terminology and synthesizing data from diverse studies across different animal models,we can enhance our understanding of myelin pathology in central nervous system disorders such as multiple sclerosis,Alzheimer's disease,and amyotrophic lateral sclerosis,all of which involve oligodendroglial and myelin dysfunction.展开更多
The crosstalk between megakaryocytic lineage cells and the skeletal system has just begun to be explored but remains largely elusive.Using conditional gene knockout mouse models,we demonstrated that loss of Beclin 1(B...The crosstalk between megakaryocytic lineage cells and the skeletal system has just begun to be explored but remains largely elusive.Using conditional gene knockout mouse models,we demonstrated that loss of Beclin 1(Becn1),a major regulator of mammalian autophagy,exclusively in the megakaryocytic lineage disrupted autophagy in platelets but did not compromise megakaryopoiesis or the formation and function of platelets.Unexpectedly,conditional Becn1 deletion in male mice led to a remarkable increase in bone mass with improved bone quality,in association with a decrease in sex hormone binding globulin(SHBG)and an increase in free testosterone(FT).In vivo Becn1 overexpression in megakaryocytic lineage-specific cells reduced bone mass and quality,along with an increase in SHBG and a decrease in FT.Transplantation of wild-type bone marrow cells into megakaryocytic lineage Becn1-deficient male mice restored bone mass and normalized SHBG and FT.Furthermore,bilateral orchiectomy of Becn1^(f/f);Pf4-iCre mice,which are crippled with the production of testosterone,resulted in a reduction in bone mass and quality,whereas in vivo overexpression of SHBG,specifically in the liver of Becn1^(f/f);Pf4-iCre mice,decreased FT and reduced bone mass and quality.In addition,metformin treatment,which induces SHBG expression,reduced FT and normalized bone mass in Becn1^(f/f);Pf4-iCre mice.We thus concluded that Becn1 of the megakaryocytic lineage is dispensable locally for platelet hemostasis but limits bone mass by increasing SHBG,which in turn reduces the FT of male mice.Our findings highlight a mechanism by which Becn1 from megakaryocytic lineage cells distally balances bone growth.展开更多
Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,mar...Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.展开更多
BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the rol...BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.展开更多
Objective:Prostate cancer(PCa)is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment(TME)and high tumor heterogeneity,which challenges clinically stratified management and ...Objective:Prostate cancer(PCa)is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment(TME)and high tumor heterogeneity,which challenges clinically stratified management and reinforces the need for novel strategies to fight against castration-resistant PCa(CRPC).Methods:We performed single-cell RNA sequencing(scRNA-seq)on 10 untreated primary PCa tissues and integrated public scRNA-seq resources from three normal prostate tissues,two untreated primary PCa tissues,and six CRPC tumors to portray a comprehensive cellular and molecular interaction atlas of PCa.We further integrated the single-cell and bulk transcriptomes of PCa to establish a molecular classification system.Results:scRNA-seq profiles revealed substantial inter-and intra-tumoral heterogeneity across different cell subpopulations in untreated PCa and CRPC tumors.In the malignant epithelial reservoir,cells evolved along decoupled paths in treatment-naive PCa and CRPC tumors,and distinct transcriptional reprogramming processes were activated,highlighting anti-androgen therapy-induced lineage plasticity.Based on the specifically expressed markers of the epithelial subpopulations,we conducted unsupervised clustering analysis in The Cancer Genome Atlas prostate adenocarcinoma(TCGA-PRAD)cohort and identified three molecularly and clinically distinct subtypes.The C1 subtype,characterized by high enrichment of CRPC-enriched epithelial cells,had a high risk of rapid development of anti-androgen resistance and might require active surveillance and additional promising intervention treatments,such as integrin A3(ITGA3)+integrin B1(ITGB1)inhibition.The C2 subtype resembled the immune-modulated subtype that was most likely to benefit from anti-LAG3 immunotherapy.The C3 subtype had a favorable prognosis.Conclusions:Our study provides a comprehensive and high-resolution landscape of the intricate architecture of the PCa TME,and our trichotomic molecular taxonomy could help facilitate precision oncology.展开更多
Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomeruloneph...Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomerulonephritis may occur in rare instances.Deposition of IgA in the mesangium seems to be the underlying disease mechanism.Despite current treatment,IgA nephropathy may progress into end-stage renal disease,indicating the necessity for the development of new therapeutic agents.Lifestyle modifications and anti-proteinuric treatment are recommended,and steroids have shown to be beneficial to high risk groups.Nevertheless,other conventional immunosuppressive agents,such as cyclophosphamide and mycophenolate mofetil,may be considered,despite the lack of sufficient evidence to support their efficacy.A considerable proportion of cases remain unresponsive to these treatments,underscoring the need for novel therapeutic approaches.There are several promising immunosuppressive drugs,such as B-cell lineage depleting agents or complement system inhibitors,that are currently undergoing clinical trials.These therapies may be considered for use in selected cases.展开更多
Piezo1,a key mechanosensor in bone homeostasis,plays a crucial role in fracture healing.However,the mechanisms through which Piezo1 regulates chondrocytes and affects endochondral ossification remain poorly understood...Piezo1,a key mechanosensor in bone homeostasis,plays a crucial role in fracture healing.However,the mechanisms through which Piezo1 regulates chondrocytes and affects endochondral ossification remain poorly understood.This study aimed to investigate the regulatory mechanisms of Piezo1 in chondrocytes during endochondral ossification.Using lineage tracing,we identified chondrocyte-to-osteoblast transdifferentiation during endochondral ossification,which was impaired by chondrocyte-specific Piezo1 knockout.Piezo1 deficiency disrupted mitochondrial bioenergetics,characterized by diminished membrane potential,reduced adenosine triphosphate(ATP)synthesis,suppressed oxygen consumption rates(basal and maximal respiration),and elevated mitochondrial superoxide generation,thereby impairing endochondral ossification during fracture healing.Single-cell RNA sequencing revealed upregulated Lars2 expression in hypertrophic chondrocytes following Piezo1 knockout.Inhibition of Lars2 in chondrocytes normalized mitochondrial dynamics-related markers(MFN1,MFN2,OPA1,DRP1)and restored mitochondrial functional homeostasis.This intervention concurrently reversed Piezo1 knockout-induced suppression of osteogenic markers(Col1,ALP,OCN,OPN,RUNX2),thereby enhancing fracture repair.Protein interaction analyses confirmed direct binding betweenβ-catenin and Lars2.Mechanistically,Piezo1 governs Lars2 expression viaβ-catenin signaling.Our findings demonstrate that Piezo1 activation via Yoda1 enhances mitochondrial bioenergetics and accelerates fracture repair through theβ-catenin/Lars2 axis,offering novel insights and therapeutic avenues for fracture treatment.展开更多
基金the financial support received from the National Natural Science Foundation of China(82202078)the National Social Science Foundation of China(23&ZD203)+4 种基金support for G.H.includes National Natural Science Foundation of China(82402203)the Open Project of the Key Laboratory of Forensic Genetics of the Ministry of Public Security(2022FGKFKT05)the Center for Archaeological Science of Sichuan University(23SASA01)the 1‧3‧5 Project for Disciplines of Excellence at West China Hospital,Sichuan University(ZYJC20002)the Sichuan Science and Technology Program(2024NSFSC1518).
文摘The reconstruction of demographic history using ancient and modern genomic resources reveals extensive interactions and admixture between ancient nomadic pastoralists and the social organizations of the Chinese Central Plain.However,the extent to which Y-chromosome genetic legacies from nomadic emperor-related ancestral lineages influence the Chinese paternal gene pool remains unclear.Here,we genotype 2717 ethnolinguistically diverse samples belonging to C2a lineages,perform whole-genome sequencing on 997 representative samples,and integrate these data with ancient genomic sequences.We reconstruct the evolutionary histories of Northern Zhou-,Qing emperor-,and pastoralist-related lineages to assess their genetic impact on modern Chinese populations.This reassembled fine-scale Ychromosome phylogeny identifies deep divergence and five Neolithic expansion events contributing differently to the formation of northern Chinese populations.Phylogeographic modeling indicates that the nomadic empires of the Northern Zhou and Qing dynasties genetically originated from the Mongolian Plateau.Phylogenetic topology and shared haplotype patterns show that three upstream ancestors of Northern Zhou(C2a1a1b1a2a1b-FGC28857),Donghu tribe(C2a1a1b1-F1756),and Qing(C2a1a3a2-F10283)emperor-related lineages expanded during the middle Neolithic,contributing significantly to genetic flow between ancient northeastern Asians and modern East Asians.Notably,this study reveals limited direct contributions of Emperor Wu of Northern Zhou’s lineages to modern East Asians.
基金supported by grants from Key Research&Development Project of Nanhua Biomedical Co.,Ltd.(No.H202191490139)National Natural Science Foundation of China(No.31872866)+1 种基金China Postdoctoral Science Foundation(Nos.2021M701160 and 2022M721101)Funds of Hunan university(521119400156).
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the pathogen responsible for coronavirus disease 2019(COVID-19),continues to evolve,giving rise to more variants and global reinfections.Previous research has demonstrated that barcode segments can effectively and cost-efficiently identify specific species within closely related populations.In this study,we designed and tested RNA barcode segments based on genetic evolutionary relationships to facilitate the efficient and accurate identification of SARS-CoV-2 from extensive virus samples,including human coronaviruses(HCoVs)and SARSr-CoV-2 lineages.Nucleotide sequences sourced from NCBI and GISAID were meticulously selected and curated to construct training sets,encompassing 1733 complete genome sequences of HCoVs and SARSr-CoV-2 lineages.Through genetic-level species testing,we validated the accuracy and reliability of the barcode segments for identifying SARS-CoV-2.Subsequently,75 main and subordinate species-specific barcode segments for SARS-CoV-2,located in ORF1ab,S,E,ORF7a,and N coding sequences,were intercepted and screened based on single-nucleotide polymorphism sites and weighted scores.Post-testing,these segments exhibited high recall rates(nearly 100%),specificity(almost 30%at the nucleotide level),and precision(100%)performance on identification.They were eventually visualized using one and two-dimensional combined barcodes and deposited in an online database(http://virusbarcodedatabase.top/).The successful integration of barcoding technology in SARS-CoV-2 identification provides valuable insights for future studies involving complete genome sequence polymorphism analysis.Moreover,this cost-effective and efficient identification approach also provides valuable reference for future research endeavors related to virus surveillance.
基金supported by the National Natural Science Foundation of China(32202788)the Special Research Fund of Shanxi Agricultural University for High-level Talents,China(2021XG004)+3 种基金the Fund for Shanxi“1331 Project”,China(20211331-13)the Shanxi Province Excellent Doctoral Work Award-Scientific Research Project,China(SXBYKY2021063,SXBYKY2021005,and SXBYKY 2022014)the earmarked fund for Modern Agro-industry Technology Research System of Shanxi Province,China(2023CYJSTX15-13)the Fundamental Research Program of Shanxi Province,China(202103021224156)。
文摘Avian infectious bronchitis(IB)is a highly contagious infectious disease caused by infectious bronchitis virus(IBV),which is prevalent in many countries worldwide and causes serious harm to the poultry industry.At present,many commercial IBV vaccines have been used for the prevention and control of IB;however,IB outbreaks occur frequently.In this study,two new strains of IBV,SX/2106 and SX/2204,were isolated from two flocks which were immunized with IBV H120 vaccine in central China.Phylogenetic and recombination analysis indicated that SX/2106,which was clustered into the GI-19 lineage,may be derived from recombination events of the GI-19 and GI-7 strains and the LDT3-A vaccine.Genetic analysis showed that SX/2204 belongs to the GVI-1 lineage,which may have originated from the recombination of the GI-13 and GVI-1 strains and the H120 vaccine.The virus cross-neutralization test showed that the antigenicity of SX/2106 and SX/2204 was different from H120.Animal experiments found that both SX/2106 and SX/2204 could replicate effectively in the lungs and kidneys of chickens and cause disease and death,and H120 immunization could not provide effective protection against the two IBV isolates.It is noteworthy that the pathogenicity of SX/2204 has significantly increased compared to the GVI-1 strains isolated previously,with a mortality rate up to 60%.Considering the continuous mutation and recombination of the IBV genome to produce new variant strains,it is important to continuously monitor epidemic strains and develop new vaccines for the prevention and control of IBV epidemics.
基金financially supported by the National Natural Science Foundation of China(Grant No.32060310)a grant from the Department of Education of Guangxi.
文摘The mitochondrial genome is a prominent research topic due to its indispensable role in organisms and its application in many research disciplines.However,few studies have investigated intraspecies mitogenomic variation.In this study,69 mitogenomes of the Black-throated Tit(Aegithalos concinnus)were assembled and annotated from a large number of short reads generated using high-throughput sequencing technology.Comparative analyses revealed that mitogenomic characteristics such as length,gene and nucleotide composition,codon usage,and duplicated control regions were relatively conserved despite substantial intraspecies morphological changes.Yet,all the individuals from the subspecies A.c.iredalei had one more nucleotide in the 12S rRNA than the other studied subspecies.Phylogenetic analyses showed five distinct lineages based on the complete mitogenomes and the 13 combined protein-coding genes,whereas only four lineages were observed when using the duplicate control regions.Most interestingly,each lineage had both copies of the control regions of the comprising individuals,indicating that the paralogous control regions were more similar than the orthologous sequences from the distinct lineages.This suggested the control regions had undergone concerted evolution.The Black-throated Tit has complex evolutionary history and needs further investigating the taxonomic status of these lineages,as well as the underlying evolutionary processes.Our findings call for more research on intraspecies mitogenomic variation.
基金supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2012ZX10004215)
文摘Objective To learn the rabies genome molecular characteristics and compare the difference of China rabies lineages. Methods The complete genomes of 12 strains from different China rabies lineages were amplified and sequenced, and all the China street strain genomes （total 43）, Arctic and Arctic-like genomes were aligned using ClustalX2, the genome homologies were analyzed using MegAlign software, and the phylogenetic trees were constructed by MEGA 5. Results First Arctic-like rabies genome in China （CO, H1202D） was reported, and we supplemented the rabies genome data of China, ensuring at least one genome was available in each China lineage. The genome size of China V （11908nt） is obviously shorter than other lineages＇ （11923-11925nt） for the difference of N-P non-coding regions. Among different lineages, the genome homologies are almost under 90%. CQH1202D （China IV lineage） has close relationship with strains from South Korea and they share about 95% genome similarities. Conclusion The molecular characteristics of 6 different China rabies lineages were compared and analyzed from genome level, which benefits for continued comprehensive rabies surveillance, rabies prevention and control in China.
文摘While Influenza B viruses currently circulating worldwide are of two distinct evolutionary hemagglutinin lineages, current trivalent inactivated influenza virus vaccines (TIV) contain only a single component. Single doses of TIV containing B antigen of B/Florida/4/2006 (Yamagata-like) or B/Brisbane/60/2008 (Victoria-like) were administered during 2008/2009 and 2009/2010 influenza seasons, respectively. The objective of this study was to evaluate the immunological response against different lineages of B antigens in school-aged children. A non-randomized sero-epidemiological study was conducted and the immunogenicity responses based on sero-protection rate and geometric mean titre ratio (GMTR) of hemagglutination inhibition (HI) antibodies were measured before and after immunization as well as post-influenza season. Our results suggested that school-aged children under the age of 9 years receiving TIV vaccination induced and retained higher level of sero-protection rate (66.7% and 69% for the 2008-09 and 2009-10 season, respectively) to the homologous lineage than the heterologous lineage post-vaccination (19.4% and 27.6% for the 2008-09 and 2009-10 season, respectively). The need for the quadrivalent TIV by including both lineages of influenza B viruses is recommended in this study, particularly for children under the age of 9 years.
基金supported by the National Key R&D Program of China(2024YFA1107000,2021YFA11020000,and 2022YFC2702200)the National Natural Science Foundation of China(32488101,32470843,32370842,32400662,and 32270850)+5 种基金the Chenguang and Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(24CGA22 and 22SG20)the fellowship from the China Postdoctoral Science Foundation(2023M742657 and GZB20240549)the Shanghai Post-doctoral Excellence Program(2023594)the Science and Technology Commission of Shanghai Municipality(21JC1405500)the Fundamental Research Funds for the Central Universities(22120240319 and 22120240255)the Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai.
文摘Human embryonic development is orchestrated by a sophisticated network of cell-cell communication and molecular interactions.Intercellular crosstalk and specific signal stimuli play crucial roles in shaping distinct cell lineages,essential for cell fate determination and lineage identity maintenance[1].Here,to address challenges posed by the scarcity and potential ethical concerns of human embryo resources.
基金supported by grants from the National Mega Project on Major Infectious Disease Prevention of China(2017ZX10103011)Guangdong Marine Economy Development Special Project of China(NO.GDNRC[2022]35)+1 种基金the National Natural Science Foundation of China(82171675,82101775,82071352,82341094)Guangdong Basic and Applied Basic Research Foundation of China(2022A1515011156).
文摘Human parainfluenza viruses(HPIV)are common viral pathogens in acute respiratory infection(ARI).We aimed to describe the epidemiological and molecular characteristics of HPIV from ARI patients.This cross-sectional study was conducted using respiratory samples from 9,696 ARI patients between 2016 and 2020 in southern China.All samples were analyzed by quantitative real-time polymerase chain reaction to determine the presence of HPIV and other common respiratory viruses.Descriptive statistics were performed to determine the temporal and population distribution of HPIV.The fulllength hemagglutinin-neuraminidase(HN)gene of HPIV3-positive samples was sequenced for phylogenetic analysis.A total of 577(6.0%)patients tested positive for HPIV,with HPIV3 being the predominant serotype,accounting for 46.8%of cases.Notably,66.0%of these HPIV-positive cases were children aged 0-2 years.The prevalence of HPIV infections showed a decreased trend and altered peak during 2016-2020.Cough,fever,sputum production,and rhinorrhea were common respiratory symptoms in HPIV-positive patients.The majority of cases had pneumonia(63.4%).Human rhinovirus(HRV)and human coronavirus(HCoV)were the most common coinfection viruses in HPIV-positive cases,with proportions of 20.1%and 14.4%,respectively.Phylogenetic analysis revealed that the predominant lineage of HPIV3 was C3f(86.0%),followed by lineage C3a(8.0%),C3d(4.0%),and C3b(2.0%).These findings help to better understand the epidemiology of HPIV,and improve public health strategies to prevent and control HPIV infections in southern China.
文摘Based on the study of two Early Pleistocene human skulls found in Yunxian County,Hubei Province,China,Ji et al.(2024)suggested that Homo orientalis was the common ancestor of the sapiens lineage and the longi lineage,and proposed that both the two lineages originated from East Asia.We further proposed that Genus Homo should be divided into two subgenera:Subgenus Homo and Subgenus Parahomo.All members of the sapiens lineage would be assigned to Subgenus Homo,and all members of the longi lineage would be grouped into Subgenus Parahomo.Homo(Parahomo)heidelbergensis and Homo(Parahomo)neanderthalensis also were the members of the longi lineage,an evolutionary branch spreaded from East Asia to Africa and Europe more than 600,000 years ago.This paper mainly makes an introduction to the speciation,classification and phylogeny of the longi lineage.The longi lineage and the sapiens lineage are″sister group″relationship,but the longi lineage is an extinct lineage,having nothing to do with our modern people.
基金supported by KU Leuven Internal Funding(C3/21/012)the Research Foundation Flanders(FWO G092222N)(to LM)。
文摘Decades of research asserted that the oligodendroglial lineage comprises two cell types:oligodendrocyte precursor cells and oligodendrocytes.However,recent studies employing single-cell RNA sequencing techniques have uncovered novel cell states,prompting a revision of the existing terminology.Going forward,the oligodendroglial lineage should be delineated into five distinct cell states:oligodendrocyte precursor cells,committed oligodendrocyte precursor cells,newly formed oligodendrocytes,myelin-forming oligodendrocytes,and mature oligodendrocytes.This new classification system enables a deeper understanding of the oligodendroglia in both physiological and pathological contexts.Adopting this uniform terminology will facilitate comparison and integration of data across studies.This,including the consolidation of findings from various demyelinating models,is essential to better understand the pathogenesis of demyelinating diseases.Additionally,comparing injury models across species with varying regenerative capacities can provide insights that may lead to new therapeutic strategies to overcome remyelination failure.Thus,by standardizing terminology and synthesizing data from diverse studies across different animal models,we can enhance our understanding of myelin pathology in central nervous system disorders such as multiple sclerosis,Alzheimer's disease,and amyotrophic lateral sclerosis,all of which involve oligodendroglial and myelin dysfunction.
基金supported in part by grants from the National Natural Science Foundation of China(No.81673093,No.82170227,No.91649113,No.82470165,No.82000121,No.31771640)the Jiangsu Science and Technology Department(No.SBK20200191)+1 种基金the State Key Laboratory of Radiation Medicine and Protection of Soochow University(No.GZC00201)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘The crosstalk between megakaryocytic lineage cells and the skeletal system has just begun to be explored but remains largely elusive.Using conditional gene knockout mouse models,we demonstrated that loss of Beclin 1(Becn1),a major regulator of mammalian autophagy,exclusively in the megakaryocytic lineage disrupted autophagy in platelets but did not compromise megakaryopoiesis or the formation and function of platelets.Unexpectedly,conditional Becn1 deletion in male mice led to a remarkable increase in bone mass with improved bone quality,in association with a decrease in sex hormone binding globulin(SHBG)and an increase in free testosterone(FT).In vivo Becn1 overexpression in megakaryocytic lineage-specific cells reduced bone mass and quality,along with an increase in SHBG and a decrease in FT.Transplantation of wild-type bone marrow cells into megakaryocytic lineage Becn1-deficient male mice restored bone mass and normalized SHBG and FT.Furthermore,bilateral orchiectomy of Becn1^(f/f);Pf4-iCre mice,which are crippled with the production of testosterone,resulted in a reduction in bone mass and quality,whereas in vivo overexpression of SHBG,specifically in the liver of Becn1^(f/f);Pf4-iCre mice,decreased FT and reduced bone mass and quality.In addition,metformin treatment,which induces SHBG expression,reduced FT and normalized bone mass in Becn1^(f/f);Pf4-iCre mice.We thus concluded that Becn1 of the megakaryocytic lineage is dispensable locally for platelet hemostasis but limits bone mass by increasing SHBG,which in turn reduces the FT of male mice.Our findings highlight a mechanism by which Becn1 from megakaryocytic lineage cells distally balances bone growth.
基金supported by NIH grants NIH/NIA R01AG069401(to L.Q.)NIH/NHLBI U54HL165442(to K.T.)P30AR069619(to Penn Center for Musculoskeletal Disorders).
文摘Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.
基金Supported by the National Research Foundation of Korea Grant Funded by the Korea Government,No.RS-2024-00440477the Korea Institute of Science and Technology Institutional Program,No.2E33111-24-042.
文摘BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.
基金supported by Shanghai Science and Technology Commission,China(No.21S11902100)Shanghai Municipal Health Commission Scientific Research Project(No.202140308)+3 种基金Clinical Research Project of Tongji Hospital of Tongji University[No.ITJ(ZD)2209]Shanghai Tongji Hospital National Natural Science Foundation Cultivation Project(No.GJPY2216)Shanghai Medical Innovation Research Special Foundation(No.23Y11908800)CSCO-Haosen Oncology Research Fund(No.Y-HS202301-0096).
文摘Objective:Prostate cancer(PCa)is a complex disease characterized by diverse cellular ecosystems within the tumor microenvironment(TME)and high tumor heterogeneity,which challenges clinically stratified management and reinforces the need for novel strategies to fight against castration-resistant PCa(CRPC).Methods:We performed single-cell RNA sequencing(scRNA-seq)on 10 untreated primary PCa tissues and integrated public scRNA-seq resources from three normal prostate tissues,two untreated primary PCa tissues,and six CRPC tumors to portray a comprehensive cellular and molecular interaction atlas of PCa.We further integrated the single-cell and bulk transcriptomes of PCa to establish a molecular classification system.Results:scRNA-seq profiles revealed substantial inter-and intra-tumoral heterogeneity across different cell subpopulations in untreated PCa and CRPC tumors.In the malignant epithelial reservoir,cells evolved along decoupled paths in treatment-naive PCa and CRPC tumors,and distinct transcriptional reprogramming processes were activated,highlighting anti-androgen therapy-induced lineage plasticity.Based on the specifically expressed markers of the epithelial subpopulations,we conducted unsupervised clustering analysis in The Cancer Genome Atlas prostate adenocarcinoma(TCGA-PRAD)cohort and identified three molecularly and clinically distinct subtypes.The C1 subtype,characterized by high enrichment of CRPC-enriched epithelial cells,had a high risk of rapid development of anti-androgen resistance and might require active surveillance and additional promising intervention treatments,such as integrin A3(ITGA3)+integrin B1(ITGB1)inhibition.The C2 subtype resembled the immune-modulated subtype that was most likely to benefit from anti-LAG3 immunotherapy.The C3 subtype had a favorable prognosis.Conclusions:Our study provides a comprehensive and high-resolution landscape of the intricate architecture of the PCa TME,and our trichotomic molecular taxonomy could help facilitate precision oncology.
文摘Immunoglobulin(Ig)A nephropathy is the most common type of primary glomerulonephritis globally.It typically manifests with microscopic hematuria and a spectrum of proteinuria,although rapidly progressive glomerulonephritis may occur in rare instances.Deposition of IgA in the mesangium seems to be the underlying disease mechanism.Despite current treatment,IgA nephropathy may progress into end-stage renal disease,indicating the necessity for the development of new therapeutic agents.Lifestyle modifications and anti-proteinuric treatment are recommended,and steroids have shown to be beneficial to high risk groups.Nevertheless,other conventional immunosuppressive agents,such as cyclophosphamide and mycophenolate mofetil,may be considered,despite the lack of sufficient evidence to support their efficacy.A considerable proportion of cases remain unresponsive to these treatments,underscoring the need for novel therapeutic approaches.There are several promising immunosuppressive drugs,such as B-cell lineage depleting agents or complement system inhibitors,that are currently undergoing clinical trials.These therapies may be considered for use in selected cases.
基金supported by the Key Projects of the National Natural Science Foundation of China(Grant No.32130052)the National Natural Science Youth Foundation of China(Grant No.82102584)Natural Science Foundation of Hebei Province(CN)-for Yanzhao Young Scientists Project(Grant No.H2023206519).
文摘Piezo1,a key mechanosensor in bone homeostasis,plays a crucial role in fracture healing.However,the mechanisms through which Piezo1 regulates chondrocytes and affects endochondral ossification remain poorly understood.This study aimed to investigate the regulatory mechanisms of Piezo1 in chondrocytes during endochondral ossification.Using lineage tracing,we identified chondrocyte-to-osteoblast transdifferentiation during endochondral ossification,which was impaired by chondrocyte-specific Piezo1 knockout.Piezo1 deficiency disrupted mitochondrial bioenergetics,characterized by diminished membrane potential,reduced adenosine triphosphate(ATP)synthesis,suppressed oxygen consumption rates(basal and maximal respiration),and elevated mitochondrial superoxide generation,thereby impairing endochondral ossification during fracture healing.Single-cell RNA sequencing revealed upregulated Lars2 expression in hypertrophic chondrocytes following Piezo1 knockout.Inhibition of Lars2 in chondrocytes normalized mitochondrial dynamics-related markers(MFN1,MFN2,OPA1,DRP1)and restored mitochondrial functional homeostasis.This intervention concurrently reversed Piezo1 knockout-induced suppression of osteogenic markers(Col1,ALP,OCN,OPN,RUNX2),thereby enhancing fracture repair.Protein interaction analyses confirmed direct binding betweenβ-catenin and Lars2.Mechanistically,Piezo1 governs Lars2 expression viaβ-catenin signaling.Our findings demonstrate that Piezo1 activation via Yoda1 enhances mitochondrial bioenergetics and accelerates fracture repair through theβ-catenin/Lars2 axis,offering novel insights and therapeutic avenues for fracture treatment.
