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
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
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
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
BACKGROUND Osteonecrosis of the femoral head(ONFH)is an ischaemic disorder often leading to collapse of the femoral head and severe hip dysfunction.Mesenchymal stem cells(MSCs)have a key role in bone repair,through th...BACKGROUND Osteonecrosis of the femoral head(ONFH)is an ischaemic disorder often leading to collapse of the femoral head and severe hip dysfunction.Mesenchymal stem cells(MSCs)have a key role in bone repair,through their ability to differentiate into osteoblasts and their paracrine regulation of the bone microenvironment.While altered MSCs behaviour has been reported in some secondary forms of ONFH,the proliferative and differentiation programmes of MSCs in human idiopathic ONFH have not been previously characterized.AIM To compare the proliferative capacity,differentiation potential and nuclear factor kappa B(NF-κB)pathway activation of bone marrow MSCs(BM-MSCs)from idiopathic ONFH patients with those from osteoarthritis controls.METHODS Femoral heads were collected during total hip replacement surgeries.Idiopathic ONFH was defined by imaging and histological criteria.Secondary causes were excluded.BM-MSCs were isolated from trabecular bone cylinders and expanded to passage 2 prior characterizations.Proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay at various seeding densities.Osteogenic potential was assessed by alkaline phosphatase activity,osteogenic gene expression(RUNX2,ALPL,COL1A1 and BGLAP)and Alizarin Red staining.Adipogenesis was quantified by Oil Red O staining.Expression of NF-κB target genes(IL6,NFKBIA,CCL2)was analyzed by quantitative polymerase chain reaction.RESULTS Idiopathic ONFH MSCs exhibited significantly higher proliferation rates than osteoarthritis controls.However,they showed reduced alkaline phosphatase activity and osteogenic gene expression but paradoxically,increased mineralization,suggesting non-canonical mineral deposition mechanisms.These cells also display increased adipogenic differentiation.Importantly,ONFH-MSCs expressed higher,although non-significant levels of certain NF-κB target gene genes,consistent with an activated inflammatory state.CONCLUSION Human BM-MSCs from idiopathic ONFH display a paradoxical phenotype:Hyperproliferative yet osteogenically impaired with greater adipogenesis and activation of NF-κB signalling.This functional compromise and inflammatory bias may underline the failure of bone regeneration in ONFH,highlighting the need for therapies redirecting MSCs fate and modulating the bone marrow niche.展开更多
In this letter,we comment on the article by Xuan Yuan et al,published in the recent issue of the World Journal of Gastroenterology.Mixed lineage kinase domainlike protein(MLKL)exhibits cell-type-specific functions in ...In this letter,we comment on the article by Xuan Yuan et al,published in the recent issue of the World Journal of Gastroenterology.Mixed lineage kinase domainlike protein(MLKL)exhibits cell-type-specific functions in liver parenchymal and non-parenchymal cells,playing dual roles in the pathogenesis of liver diseases.In hepatocytes,MLKL primarily mediates necroptosis and inhibits autophagy,thereby exacerbating liver injury.Conversely,in non-parenchymal liver cells,MLKL modulates inflammatory responses and promotes fibrotic processes,thereby driving disease progression.Notably,MLKL also demonstrates protective functions under specific conditions.For instance,MLKL can inhibit intracellular bacterial replication,promote endosomal trafficking,and facilitate the generation and release of extracellular vesicles,potentially exerting hepatoprotective effects.Understanding these cell-type-specific mechanisms of MLKL action,including its dual roles in promoting injury and providing protection,is crucial for elucidating the complex pathogenesis of liver diseases and developing targeted therapeutic strategies.展开更多
Although mixed lineage kinase domain-like protein(MLKL)is widely recognized as a critical effector in the necroptotic signaling pathway,MLKL plays broader regulatory roles beyond programmed necroptosis.Notably,Xuan Yu...Although mixed lineage kinase domain-like protein(MLKL)is widely recognized as a critical effector in the necroptotic signaling pathway,MLKL plays broader regulatory roles beyond programmed necroptosis.Notably,Xuan Yuan et al demonstrated that CPD4,an ATP-binding pocket inhibitor of MLKL,significantly reduces liver inflammation and improves liver function by inhibiting NF-κB signaling,suggesting its use as a potential therapeutic candidate for alcoholic liver disease.However,the pharmacokinetic properties and long-term toxicity of CPD4 require further evaluation.Moreover,a single therapeutic strategy targeting MLKL may not be sufficient.Future studies should focus on the precise regulation of MLKL and develop combination therapies to achieve dual intervention of inflammatory and cell death pathways.This paper provides an important theoretical foundation for translational research on MLKL-targeted therapy.However,its clinical translation requires overcoming existing limitations and further elucidating the regulatory network of MLKL in complex microenvironments.展开更多
Objective:Ulcerative colitis is closely associated with intestinal stem cell(ISC)loss and impaired intestinal mucus barrier.Sinisan(SNS),a compound Chinese herbal medicine,has a long history in the treatment of intest...Objective:Ulcerative colitis is closely associated with intestinal stem cell(ISC)loss and impaired intestinal mucus barrier.Sinisan(SNS),a compound Chinese herbal medicine,has a long history in the treatment of intestinal dysfunction,yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied.Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery.Methods:Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium(DSS)-induced murine colitis model.RNA-sequencing was used to demonstrate the mechanism.Further,reverse transcription-quantitative polymerase chain reaction,immunofluorescence staining,and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS.Furthermore,potential active ingredients from SNS were predicted by network pharmacology analysis.Results:SNS dramatically suppressed DSS-induced acute colonic inflammation in mice.RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes,and upregulation of lipid metabolism and proliferation-related genes,such as Irf7,Ppara,Clspn and Hspa5.Additionally,ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids,leading to enhanced mucin expression.Furthermore,potential active ingredients from SNS that mediated inflammation,lipid metabolism,proliferation,apoptosis,stem cells and secretory cells were predicted using a network pharmacology approach.Conclusion:Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation,suggesting a of novel therapeutic strategy against colitis.展开更多
Cell lineage tracing is a key technology for describing the developmental history of individual progenitor cells and assembling them to form a lineage development tree.However,traditional methods have limitations of p...Cell lineage tracing is a key technology for describing the developmental history of individual progenitor cells and assembling them to form a lineage development tree.However,traditional methods have limitations of poor stability and insufficient reso-lution.As an efficient and flexible gene editing tool,CRISPR-Cas9 system has been widely used in biological research.Furthermore,CRISPR-Cas9 gene editing-based tracing methods can introduce fluorescent proteins,reporter genes,or DNA barcodes for high-throughput sequencing,enabling precise lineage analysis,significantly im-proving precision and resolution,and expanding its application range.In this review,we summarize applications of CRISPR-Cas9 system in cell lineage tracing,with special emphasis on its successful applications in traditional model animals(e.g.,zebrafish and mice),large animal models(pigs),and human cells or organoids.We also discussed its potential prospects and challenges in xenotransplantation and regenerative medicine.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
Unraveling the lineage relationships of all descendants from a zygote is fundamental to advancing our understanding of developmental and stem cell biology.However,existing cell barcoding technologies in zebrafish lack...Unraveling the lineage relationships of all descendants from a zygote is fundamental to advancing our understanding of developmental and stem cell biology.However,existing cell barcoding technologies in zebrafish lack the resolution to capture the majority of cell divisions during embryogenesis.A recently developed method,a substitution mutation-aided lineage-tracing system(SMALT),successfully reconstructed high-resolution cell phylogenetic trees for Drosophila melanogaster.Here,we implement the SMALT system in zebrafish,recording a median of 14 substitution mutations on a one-kilobase-pair barcoding sequence for one-day post-fertilization embryos.Leveraging this system,we reconstruct four cell lineage trees for zebrafish fin cells,encompassing both original and regenerated fin.Each tree consists of hundreds of internal nodes with a median bootstrap support of 99%.Analysis of the obtained cell lineage trees reveals that regenerated fin cells mainly originate from cells in the same part of the fins.Through multiple times sampling germ cells from the same individual,we show the stability of the germ cell pool and the early separation of germ cell and somatic cell progenitors.Our system offers the potential for reconstructing high-quality cell phylogenies across diverse tissues,providing valuable insights into development and disease in zebrafish.展开更多
Regenerating functional new neurons in the adult mammalian central nervous system has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss.Glial ce...Regenerating functional new neurons in the adult mammalian central nervous system has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss.Glial cells,on the other hand,can divide and repopulate themselves under injury or diseased conditions.We have previously reported that ectopic expression of NeuroD1 in dividing glial cells can directly convert them into neurons.Here,using astrocytic lineage-tracing reporter mice(Aldh1l1-CreERT2 mice crossing with Ai14 mice),we demonstrate that lineage-traced astrocytes can be successfully converted into NeuNpositive neurons after expressing NeuroD1 through adeno-associated viruses.Retroviral expression of NeuroD1 further confirms that dividing glial cells can be converted into neurons.Importantly,we demonstrate that for in vivo cell conversion study,using a safe level of adeno-associated virus dosage(10^10–10^12 gc/mL,1μL)in the rodent brain is critical to avoid artifacts caused by toxic dosage,such as that used in a recent bioRxiv study(2×10^13 gc/mL,1μL,mouse cortex).For therapeutic purpose under injury or diseased conditions,or for non-human primate studies,adeno-associated virus dosage needs to be optimized through a series of dose-finding experiments.Moreover,for future in vivo gliato-neuron conversion studies,we recommend that the adeno-associated virus results are further verified with retroviruses that mainly express transgenes in dividing glial cells in order to draw solid conclusions.The study was approved by the Laboratory Animal Ethics Committee of Jinan University,China(approval No.IACUC-20180330-06)on March 30,2018.展开更多
Since the generation of induced pluripotent stem cells in 2006, cellular reprogramming has attracted increasing attention as a revolutionary strategy for cell replacement therapy. Recent advances have revealed that so...Since the generation of induced pluripotent stem cells in 2006, cellular reprogramming has attracted increasing attention as a revolutionary strategy for cell replacement therapy. Recent advances have revealed that somatic cells can be directly converted into other mature cell types, which eliminates the risk of neoplasia and the generation of undesired cell types. Astrocytes become reactive and undergo proliferation, which hampers axon regeneration following injury, stroke, and neurodegenerative diseases. An emerging technique to directly reprogram astrocytes into induced neural stem cells （iNSCs） and induced neurons （iNs） by neural fate determinants brings potential hope to cell replacement therapy for the above neurological problems. Here, we discuss the development of direct reprogramming of various cell types into iNs and iNSCs, then detail astrocyte-derived iNSCs and iNs in vivo and in vitro. Finally, we highlight the unsolved challenges and opportunities for improvement.展开更多
Oligodendrocyte lineage gene 1 plays a key role in hypoxic-ischemic brain damage and myelin repair, miRNA-9 is involved in the occurrence of many related neurological disorders. Bioin- formatics analysis demonstrated ...Oligodendrocyte lineage gene 1 plays a key role in hypoxic-ischemic brain damage and myelin repair, miRNA-9 is involved in the occurrence of many related neurological disorders. Bioin- formatics analysis demonstrated that miRNA-9 complementarily, but incompletely, bound oligodendrocyte lineage gene 1, but whether miRNA-9 regulates oligodendrocyte lineage gene 1 remains poorly understood. Whole brain slices of 3-day-old Sprague-Dawley rats were cultured and divided into four groups： control group; oxygen-glucose deprivation group （treatment with 8% O2 ＋ 92% N2 and sugar-free medium for 60 minutes）; transfection control group （after oxygen and glucose deprivation for 60 minutes, transfected with control plasmid） and miRNA-9 transfection group （after oxygen and glucose deprivation for 60 minutes, transfected with miRNA-9 plasmid）. From the third day of transfection, and with increasing culture days, oligodendrocyte lineage gene 1 expression increased in each group, peaked at 14 days, and then decreased at 21 days. Real-time quantitative PCR results, however, demonstrated that oligoden- drocyte lineage gene 1 expression was lower in the miRNA-9 transfection group than that in the transfection control group at 1, 3, 7, 14, 21 and 28 days after transfection. Results suggested that miRNA-9 possibly negatively regulated oligodendrocyte lineage gene 1 in brain tissues during hypoxic-ischemic brain damage.展开更多
Incomplete lineage sorting and introgression are 2 major and nonexclusive causes of specieslevel non-monophyly.Distinguishing between these 2 processes is notoriously difficult because they can generate similar geneti...Incomplete lineage sorting and introgression are 2 major and nonexclusive causes of specieslevel non-monophyly.Distinguishing between these 2 processes is notoriously difficult because they can generate similar genetic signatures.Previous studies have suggested that 2 closely related duck species,the Chinese spot-billed duck Anas zonorhyncha and the mallard A.platyrhynchosvjere polyphyletically intermixed.Here,we utilized a wide geographical sampling,multilocus data and a coalescent-based model to revisit this system.Our study confirms the finding that Chinese spot-billed ducks and Mallards are not monophyletic.There was no apparent interspecific differentiation across loci except those at the mitochondrial DNA(mtDNA)control region and the Z chromosome(CHD1Z).Based on an isolation-with-migration model and the geographical distribution of lineages,we suggest that both introgression and incomplete lineage sorting might contribute to the observed non-monophyly of the 2 closely related duck species.The mtDNA introgression was asymmetric,with high gene flow from Chinese spot-billed ducks to Mallards and negligible gene flow in the opposite direction.Given that the 2 duck species are phenotypically distinctive but weakly genetically differentiated,future work based on genomescale data is necessary to uncover genomic regions that are involved in divergence,and this work may provide further insights into the evolutionary histories of the 2 species and other waterfowls.展开更多
Since first isolation in 1947 from the Zika forest in Uganda, Zika virus(ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. Howeve...Since first isolation in 1947 from the Zika forest in Uganda, Zika virus(ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. However, during 2015–2016,an Asian lineage of ZIKV caused an unprecedentedly large outbreak in the Americas and sizeable numbers of exported cases across the globe. In this review, we critically appraise the recent advances in molecular epidemiological studies of ZIKV performed to date, and we highlight the pivotal role played by genomic surveillance in elucidating the origins,dissemination and evolution of the Asian lineage of ZIKV in Asia and in the Americas.展开更多
Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose ...Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies.展开更多
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 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.
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.
文摘BACKGROUND Osteonecrosis of the femoral head(ONFH)is an ischaemic disorder often leading to collapse of the femoral head and severe hip dysfunction.Mesenchymal stem cells(MSCs)have a key role in bone repair,through their ability to differentiate into osteoblasts and their paracrine regulation of the bone microenvironment.While altered MSCs behaviour has been reported in some secondary forms of ONFH,the proliferative and differentiation programmes of MSCs in human idiopathic ONFH have not been previously characterized.AIM To compare the proliferative capacity,differentiation potential and nuclear factor kappa B(NF-κB)pathway activation of bone marrow MSCs(BM-MSCs)from idiopathic ONFH patients with those from osteoarthritis controls.METHODS Femoral heads were collected during total hip replacement surgeries.Idiopathic ONFH was defined by imaging and histological criteria.Secondary causes were excluded.BM-MSCs were isolated from trabecular bone cylinders and expanded to passage 2 prior characterizations.Proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay at various seeding densities.Osteogenic potential was assessed by alkaline phosphatase activity,osteogenic gene expression(RUNX2,ALPL,COL1A1 and BGLAP)and Alizarin Red staining.Adipogenesis was quantified by Oil Red O staining.Expression of NF-κB target genes(IL6,NFKBIA,CCL2)was analyzed by quantitative polymerase chain reaction.RESULTS Idiopathic ONFH MSCs exhibited significantly higher proliferation rates than osteoarthritis controls.However,they showed reduced alkaline phosphatase activity and osteogenic gene expression but paradoxically,increased mineralization,suggesting non-canonical mineral deposition mechanisms.These cells also display increased adipogenic differentiation.Importantly,ONFH-MSCs expressed higher,although non-significant levels of certain NF-κB target gene genes,consistent with an activated inflammatory state.CONCLUSION Human BM-MSCs from idiopathic ONFH display a paradoxical phenotype:Hyperproliferative yet osteogenically impaired with greater adipogenesis and activation of NF-κB signalling.This functional compromise and inflammatory bias may underline the failure of bone regeneration in ONFH,highlighting the need for therapies redirecting MSCs fate and modulating the bone marrow niche.
基金Supported by the Science and Technology Planning Projects of Guizhou Province,No.QKHJC-ZK[2022]YB642Health Research Project of Guizhou Province,No.gzwkj2024-324,and No.gzwkj2024-103+2 种基金WBE Liver Fibrosis Foundation,No.CFHPC2025028Beijing Liver and Gallbladder Mutual Aid Public Welfare Foundation Artificial Liver Special Fund,No.iGandanF-1082024-Rgg018Student Innovation and Entrepreneurship Training Program of Zunyi Medical University,No.S2024106612360.
文摘In this letter,we comment on the article by Xuan Yuan et al,published in the recent issue of the World Journal of Gastroenterology.Mixed lineage kinase domainlike protein(MLKL)exhibits cell-type-specific functions in liver parenchymal and non-parenchymal cells,playing dual roles in the pathogenesis of liver diseases.In hepatocytes,MLKL primarily mediates necroptosis and inhibits autophagy,thereby exacerbating liver injury.Conversely,in non-parenchymal liver cells,MLKL modulates inflammatory responses and promotes fibrotic processes,thereby driving disease progression.Notably,MLKL also demonstrates protective functions under specific conditions.For instance,MLKL can inhibit intracellular bacterial replication,promote endosomal trafficking,and facilitate the generation and release of extracellular vesicles,potentially exerting hepatoprotective effects.Understanding these cell-type-specific mechanisms of MLKL action,including its dual roles in promoting injury and providing protection,is crucial for elucidating the complex pathogenesis of liver diseases and developing targeted therapeutic strategies.
文摘Although mixed lineage kinase domain-like protein(MLKL)is widely recognized as a critical effector in the necroptotic signaling pathway,MLKL plays broader regulatory roles beyond programmed necroptosis.Notably,Xuan Yuan et al demonstrated that CPD4,an ATP-binding pocket inhibitor of MLKL,significantly reduces liver inflammation and improves liver function by inhibiting NF-κB signaling,suggesting its use as a potential therapeutic candidate for alcoholic liver disease.However,the pharmacokinetic properties and long-term toxicity of CPD4 require further evaluation.Moreover,a single therapeutic strategy targeting MLKL may not be sufficient.Future studies should focus on the precise regulation of MLKL and develop combination therapies to achieve dual intervention of inflammatory and cell death pathways.This paper provides an important theoretical foundation for translational research on MLKL-targeted therapy.However,its clinical translation requires overcoming existing limitations and further elucidating the regulatory network of MLKL in complex microenvironments.
基金supported by the National Natural Science Foundation of China(No.82322075)。
文摘Objective:Ulcerative colitis is closely associated with intestinal stem cell(ISC)loss and impaired intestinal mucus barrier.Sinisan(SNS),a compound Chinese herbal medicine,has a long history in the treatment of intestinal dysfunction,yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied.Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery.Methods:Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium(DSS)-induced murine colitis model.RNA-sequencing was used to demonstrate the mechanism.Further,reverse transcription-quantitative polymerase chain reaction,immunofluorescence staining,and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS.Furthermore,potential active ingredients from SNS were predicted by network pharmacology analysis.Results:SNS dramatically suppressed DSS-induced acute colonic inflammation in mice.RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes,and upregulation of lipid metabolism and proliferation-related genes,such as Irf7,Ppara,Clspn and Hspa5.Additionally,ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids,leading to enhanced mucin expression.Furthermore,potential active ingredients from SNS that mediated inflammation,lipid metabolism,proliferation,apoptosis,stem cells and secretory cells were predicted using a network pharmacology approach.Conclusion:Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation,suggesting a of novel therapeutic strategy against colitis.
基金supported by Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences and Comparative Medicine Center,Peking Union Medical College,Collaborative Innovation Program of the Chinese Academy of Sciences(22SH19)Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT180-01).
文摘Cell lineage tracing is a key technology for describing the developmental history of individual progenitor cells and assembling them to form a lineage development tree.However,traditional methods have limitations of poor stability and insufficient reso-lution.As an efficient and flexible gene editing tool,CRISPR-Cas9 system has been widely used in biological research.Furthermore,CRISPR-Cas9 gene editing-based tracing methods can introduce fluorescent proteins,reporter genes,or DNA barcodes for high-throughput sequencing,enabling precise lineage analysis,significantly im-proving precision and resolution,and expanding its application range.In this review,we summarize applications of CRISPR-Cas9 system in cell lineage tracing,with special emphasis on its successful applications in traditional model animals(e.g.,zebrafish and mice),large animal models(pigs),and human cells or organoids.We also discussed its potential prospects and challenges in xenotransplantation and regenerative medicine.
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supported by the National Key R&D Program of China(2021YFA1302500 and 2021YFA1302501)the National Natural Science Foundation of China(32293190,32293191,31970570,and 32200492).
文摘Unraveling the lineage relationships of all descendants from a zygote is fundamental to advancing our understanding of developmental and stem cell biology.However,existing cell barcoding technologies in zebrafish lack the resolution to capture the majority of cell divisions during embryogenesis.A recently developed method,a substitution mutation-aided lineage-tracing system(SMALT),successfully reconstructed high-resolution cell phylogenetic trees for Drosophila melanogaster.Here,we implement the SMALT system in zebrafish,recording a median of 14 substitution mutations on a one-kilobase-pair barcoding sequence for one-day post-fertilization embryos.Leveraging this system,we reconstruct four cell lineage trees for zebrafish fin cells,encompassing both original and regenerated fin.Each tree consists of hundreds of internal nodes with a median bootstrap support of 99%.Analysis of the obtained cell lineage trees reveals that regenerated fin cells mainly originate from cells in the same part of the fins.Through multiple times sampling germ cells from the same individual,we show the stability of the germ cell pool and the early separation of germ cell and somatic cell progenitors.Our system offers the potential for reconstructing high-quality cell phylogenies across diverse tissues,providing valuable insights into development and disease in zebrafish.
基金This study was supported by the National Natural Science Foundation of China(No.U1801681,to GC and No.31970906,to WL)Guangdong Science and Technology Department(‘Key technologies for treatment of brain disorders’,No.2018B030332001,to GC)+2 种基金the Natural Science Foundation of Guangdong Province of China(No.2020A1515011079,to WL and No.2020A1515010854,to QW)the internal funding from Jinan University(No.21616110,to GC)the Young Scientists Fund of the National Natural Science Foundation of China(No.31701291,to WL).
文摘Regenerating functional new neurons in the adult mammalian central nervous system has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss.Glial cells,on the other hand,can divide and repopulate themselves under injury or diseased conditions.We have previously reported that ectopic expression of NeuroD1 in dividing glial cells can directly convert them into neurons.Here,using astrocytic lineage-tracing reporter mice(Aldh1l1-CreERT2 mice crossing with Ai14 mice),we demonstrate that lineage-traced astrocytes can be successfully converted into NeuNpositive neurons after expressing NeuroD1 through adeno-associated viruses.Retroviral expression of NeuroD1 further confirms that dividing glial cells can be converted into neurons.Importantly,we demonstrate that for in vivo cell conversion study,using a safe level of adeno-associated virus dosage(10^10–10^12 gc/mL,1μL)in the rodent brain is critical to avoid artifacts caused by toxic dosage,such as that used in a recent bioRxiv study(2×10^13 gc/mL,1μL,mouse cortex).For therapeutic purpose under injury or diseased conditions,or for non-human primate studies,adeno-associated virus dosage needs to be optimized through a series of dose-finding experiments.Moreover,for future in vivo gliato-neuron conversion studies,we recommend that the adeno-associated virus results are further verified with retroviruses that mainly express transgenes in dividing glial cells in order to draw solid conclusions.The study was approved by the Laboratory Animal Ethics Committee of Jinan University,China(approval No.IACUC-20180330-06)on March 30,2018.
基金supported by a grant from Department of Neurology, Zhujiang Hospital, Southern Medical Universityl, China (2014257)
文摘Since the generation of induced pluripotent stem cells in 2006, cellular reprogramming has attracted increasing attention as a revolutionary strategy for cell replacement therapy. Recent advances have revealed that somatic cells can be directly converted into other mature cell types, which eliminates the risk of neoplasia and the generation of undesired cell types. Astrocytes become reactive and undergo proliferation, which hampers axon regeneration following injury, stroke, and neurodegenerative diseases. An emerging technique to directly reprogram astrocytes into induced neural stem cells （iNSCs） and induced neurons （iNs） by neural fate determinants brings potential hope to cell replacement therapy for the above neurological problems. Here, we discuss the development of direct reprogramming of various cell types into iNs and iNSCs, then detail astrocyte-derived iNSCs and iNs in vivo and in vitro. Finally, we highlight the unsolved challenges and opportunities for improvement.
基金supported by the National Natural Science Foundation of China,No.81241022the Beijing Municipal Natural Science Foundation in China,No.7122045,7072023
文摘Oligodendrocyte lineage gene 1 plays a key role in hypoxic-ischemic brain damage and myelin repair, miRNA-9 is involved in the occurrence of many related neurological disorders. Bioin- formatics analysis demonstrated that miRNA-9 complementarily, but incompletely, bound oligodendrocyte lineage gene 1, but whether miRNA-9 regulates oligodendrocyte lineage gene 1 remains poorly understood. Whole brain slices of 3-day-old Sprague-Dawley rats were cultured and divided into four groups： control group; oxygen-glucose deprivation group （treatment with 8% O2 ＋ 92% N2 and sugar-free medium for 60 minutes）; transfection control group （after oxygen and glucose deprivation for 60 minutes, transfected with control plasmid） and miRNA-9 transfection group （after oxygen and glucose deprivation for 60 minutes, transfected with miRNA-9 plasmid）. From the third day of transfection, and with increasing culture days, oligodendrocyte lineage gene 1 expression increased in each group, peaked at 14 days, and then decreased at 21 days. Real-time quantitative PCR results, however, demonstrated that oligoden- drocyte lineage gene 1 expression was lower in the miRNA-9 transfection group than that in the transfection control group at 1, 3, 7, 14, 21 and 28 days after transfection. Results suggested that miRNA-9 possibly negatively regulated oligodendrocyte lineage gene 1 in brain tissues during hypoxic-ischemic brain damage.
基金the National Natural Science Foundation of China(No.31401969,31772480)the Natural Science Foundation of Jiangxi Province(No.20161BAB214158).
文摘Incomplete lineage sorting and introgression are 2 major and nonexclusive causes of specieslevel non-monophyly.Distinguishing between these 2 processes is notoriously difficult because they can generate similar genetic signatures.Previous studies have suggested that 2 closely related duck species,the Chinese spot-billed duck Anas zonorhyncha and the mallard A.platyrhynchosvjere polyphyletically intermixed.Here,we utilized a wide geographical sampling,multilocus data and a coalescent-based model to revisit this system.Our study confirms the finding that Chinese spot-billed ducks and Mallards are not monophyletic.There was no apparent interspecific differentiation across loci except those at the mitochondrial DNA(mtDNA)control region and the Z chromosome(CHD1Z).Based on an isolation-with-migration model and the geographical distribution of lineages,we suggest that both introgression and incomplete lineage sorting might contribute to the observed non-monophyly of the 2 closely related duck species.The mtDNA introgression was asymmetric,with high gene flow from Chinese spot-billed ducks to Mallards and negligible gene flow in the opposite direction.Given that the 2 duck species are phenotypically distinctive but weakly genetically differentiated,future work based on genomescale data is necessary to uncover genomic regions that are involved in divergence,and this work may provide further insights into the evolutionary histories of the 2 species and other waterfowls.
基金supported by the National Key Science and Technology Projects of China (2017ZX10104001-006)the National Science and Technology Major Project (2018ZX10101004-002)supported by the Taishan Scholars program of Shandong Province (ts201511056)
文摘Since first isolation in 1947 from the Zika forest in Uganda, Zika virus(ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. However, during 2015–2016,an Asian lineage of ZIKV caused an unprecedentedly large outbreak in the Americas and sizeable numbers of exported cases across the globe. In this review, we critically appraise the recent advances in molecular epidemiological studies of ZIKV performed to date, and we highlight the pivotal role played by genomic surveillance in elucidating the origins,dissemination and evolution of the Asian lineage of ZIKV in Asia and in the Americas.
基金Supported by The National Center for Advancing Translational Sciences of the National Institutes of Health under award numbers ULl TR000454 previously awarded to Dr.Colbert and Dr.Fisher and TLlT R000456 to Dr.ColbertPancreatic Cancer Action Network(Pan-CAN)&sol American Association for Cancer Research(AACR)award 16982+1 种基金Department of Defense(DOD)/Peer Reviewed Cancer Research Program(PRCRP)award CA110535Georgia Cancer Coalition award 11072,all to Dr.Yu
文摘Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies.
