Nicotiana tabacum(2n=4x=48),an economically important non-food crop and a model plant for genetic studies,faces challenges in efficient genotyping of novel germplasm.To address this,we developed the Ta-LD-SC,a 20K SNP...Nicotiana tabacum(2n=4x=48),an economically important non-food crop and a model plant for genetic studies,faces challenges in efficient genotyping of novel germplasm.To address this,we developed the Ta-LD-SC,a 20K SNP Affymetrix Axiom array,based on resequencing data from 150 tobacco accessions.A total of 20,213 unique SNPs were carefully selected,achieving coverage of over 90%of the tobacco genome(Nitab4.5 and NtaSR1)with a uniform probe distribution,limiting density to no more than 5 SNPs per 200 kb.The array underwent extensive validation using 866 tobacco accessions(NP panel)and 288 F2 individuals from a cross between K326 and Oxford 26(GP panel).Performance metrics demonstrated its robustness,with high SNP call rates(93.6%-99.8%),a low technical error rate(<1%),and a superior PolyHighResolution SNP rate(79.79%)compared to other crop SNP arrays.Population structure analysis of the NP panel revealed two major introductions of foreign germplasm that have significantly influenced the genetic diversity of Chinese tobacco resources.Using the array,a genome-wide association study(GWAS)identified 62 genes linked to eight agronomic traits,and a high-density genetic map encompassing 4553 SNPs across 6606.08 cM was constructed.The Ta-LD-SC array provides a valuable tool for rapid,high-quality genotyping offering supporting marker annotations that may benefit genetic research and breeding of tobacco.展开更多
Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs ...Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs and widely use of haploidentical-related donor HSCT(e.g. Beijing Protocol) make everyone can have a donor(1), and the novel, reduced-toxicity transplant regimens help elderly patients receive HSCT safely(2).展开更多
Objective:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the only potentially curative method for treating myelodysplastic syndrome(MDS).Post-HSCT measurable residual disease(post-HSCT MRD)is associat...Objective:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the only potentially curative method for treating myelodysplastic syndrome(MDS).Post-HSCT measurable residual disease(post-HSCT MRD)is associated with inferior transplant outcomes.In this prospective study,we aimed to investigate the prognostic value of post-HSCT MRD in relapse prediction in MDS.Methods:A total of 166 patients diagnosed with MDS were prospectively enrolled in this study.The KaplanMeier method was used to calculate the survival probabilities.Potential risk factors for outcomes after transplantation were evaluated through univariate and multivariate Cox regression models.Results:For patients with negative and positive post-HSCT MRD,the cumulative incidence of relapse(CIR)and disease-free survival(DFS)at 3 years were 5.9%and 69.6%(P<0.001)and 82.7%and 26.1%(P<0.001),respectively.In the multivariate analysis,post-HSCT MRD(HR=22.801,P<0.001)and Revised International Prognostic Scoring System(IPSS-R)risk stratification(HR=4.346,P=0.003)were independently correlated with relapse.A scoring system for relapse prediction was built based on post-HSCT MRD and IPSS-R stratification.The cumulative incidence of relapse at 3 years was 1.1%,15.8%,and 91.7%for patients with scores of 0,1,and 2,respectively(P<0.001).Conclusions:Our results demonstrated both post-HSCT MRD and IPSS-R scores were independent prognostic factors for OS,DFS,and relapse for MDS patients after allo-HSCT.The risk score system could better predict transplant outcomes and refine the risk stratification than alone in patients with MDS.展开更多
Rosa banksiae,known as Lady Banks'rose,is a perennial ornamental crop and a versatile herb in traditional Chinese medicine.Given the lack of genomic resources,we assembled a Hi Fi and Nanopore sequencing-derived 4...Rosa banksiae,known as Lady Banks'rose,is a perennial ornamental crop and a versatile herb in traditional Chinese medicine.Given the lack of genomic resources,we assembled a Hi Fi and Nanopore sequencing-derived 458.58 Mb gap-free telomere-to-telomere high-quality R.banksiae genome with a scaffold N50=63.90 Mb.The genome of R.banksiae exhibited no lineage-specific whole-genome duplication compared with other Rosaceae.The phylogenomic analysis of 13 Rosaceae and Arabidopsis through a comparative genomics study showed that numerous gene families were lineage-specific both before and after the diversification of Rosaceae.Some of these genes are candidates for new genes that have evolved from parental genes through fusion events.Fusion genes are divided into three types:Type-I and Type-II genes contain two parental genes that are generated by duplication,distributed in the same and different regions of the genome,respectively;and Type-III can only be detected in one parental gene.Here,Type-I genes are found to have more relaxed selection pressure and lower Ks values than Type-II,indicating that these newly evolved Type-I genes may play important roles in driving phenotypic evolution.Functional analysis exhibited that newly formed fusion genes can regulate the phenotype traits of plant growth and development,suggesting the functional significance of these genes.This study identifies new fusion genes that could be responsible for phenotype evolution and provides information on the evolutionary history of recently diverged species in the Rosa genus.Our data represents the major progress in understanding the new fusion genes evolution pattern of Rosaceae and provides an invaluable resource for phylogenomic studies in plants.展开更多
Objective:Immune effector cell-associated hematotoxicity(ICAHT),characterized by prolonged cytopenia and delayed hematopoietic recovery,is a common complication following chimeric antigen receptor T(CAR-T)cell therapy...Objective:Immune effector cell-associated hematotoxicity(ICAHT),characterized by prolonged cytopenia and delayed hematopoietic recovery,is a common complication following chimeric antigen receptor T(CAR-T)cell therapy.However,the applicability of existing predictive models,CAR-HEMATOTOX(CAR-HT)for lymphoma,acute lymphoblastic leukemia-HEMATOTOX(ALL-HT)for B-ALL,and the early ICAHT prediction model(e IPM),remains uncertain across different hematologic malignancies.Methods:We prospectively analyzed 119 patients who received CAR-T therapy between January 2022 and June2025,including B-ALL(n=62),T-ALL/non-Hodgkin's lymphoma(NHL)(n=25),and multiple myeloma(MM,n=32).The CAR-HT,ALL-HT,and e IPM models were evaluated for their ability to predict ICAHT severity and survival outcomes.Results:Grade 3 ICAHT occurred in 32.3%of B-ALL,40.0%of T-ALL/NHL,and 25.0%of MM patients,while grade 4 rates were 33.9%,20.0%,and 6.3%,respectively.CAR-HT classified 67.2%of patients as high-risk,and ALL-HT identified 56.3%of ALL/NHL patients as high-risk.In both models,high-risk groups experienced significantly more prolonged neutropenia than low-risk groups(CAR-HT:17.7 vs.5.3 d,P<0.001;ALL-HT:21.3 vs.7.7 d,P<0.001).Both e IPMpre and e IPMpost strongly correlated with grade 3-4 ICAHT(P<0.001).Importantly,survival analysis showed that e IPMpre stratification distinguished outcomes:1-year overall survival(OS)was 65%in medium+high-risk vs.84%in low-risk patients(P=0.006),and 1-year disease-free survival(DFS)was 44%vs.73%(P<0.001).Similar predictive accuracy was observed with e IPMpost.Conclusions:The CAR-HT,ALL-HT,and e IPM models consistently identify patients at high risk for severe ICAHT across B-ALL,T-ALL/NHL,and MM.Among these,the e IPM stands out as a promising universal tool for survival prediction.These models provide valuable prognostic insights that can guide supportive care and inform treatment planning in CAR-T therapy.展开更多
Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematop...Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.展开更多
We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic ste...We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before transplantation.In this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia patients.Increasing score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.展开更多
Analysis of patient＇s materials like cells or nucleic acids obtained in a minimally invasive or noninvasive manner through the sampling of blood or other body fluids serves as liquid biopsies, which has huge potentia...Analysis of patient＇s materials like cells or nucleic acids obtained in a minimally invasive or noninvasive manner through the sampling of blood or other body fluids serves as liquid biopsies, which has huge potential for numerous diagnostic applications. Circulating cell-free DNA（cfDNA） is explored as a prognostic or predictive marker of liquid biopsies with the improvements in genomic and molecular methods. DNA methylation is an important epigenetic marker known to affect gene expression. cfDNA methylation detection is a very promising approach as abnormal distribution of DNA methylation is one of the hallmarks of many cancers and methylation changes occur early during carcinogenesis. This re？view summarizes the various investigational applications of cfDNA methylation and its oxidized de？rivatives as biomarkers for cancer diagnosis, prenatal diagnosis and organ transplantation monitoring.The review also provides a brief overview of the technologies for cfDNA methylation analysis based on next generation sequencing.展开更多
Objective: Challenges remain in current practices of colorectal cancer(CRC) screening, such as low compliance,low specificities and expensive cost. This study aimed to identify high-risk groups for CRC from the genera...Objective: Challenges remain in current practices of colorectal cancer(CRC) screening, such as low compliance,low specificities and expensive cost. This study aimed to identify high-risk groups for CRC from the general population using regular health examination data.Methods: The study population consist of more than 7,000 CRC cases and more than 140,000 controls. Using regular health examination data, a model detecting CRC cases was derived by the classification and regression trees(CART) algorithm. Receiver operating characteristic(ROC) curve was applied to evaluate the performance of models. The robustness and generalization of the CART model were validated by independent datasets. In addition, the effectiveness of CART-based screening was compared with stool-based screening.Results: After data quality control, 4,647 CRC cases and 133,898 controls free of colorectal neoplasms were used for downstream analysis. The final CART model based on four biomarkers(age, albumin, hematocrit and percent lymphocytes) was constructed. In the test set, the area under ROC curve(AUC) of the CART model was 0.88 [95%confidence interval(95% CI), 0.87-0.90] for detecting CRC. At the cutoff yielding 99.0% specificity, this model’s sensitivity was 62.2%(95% CI, 58.1%-66.2%), thereby achieving a 63-fold enrichment of CRC cases. We validated the robustness of the method across subsets of test set with diverse CRC incidences, aging rates, genders ratio, distributions of tumor stages and locations, and data sources. Importantly, CART-based screening had the higher positive predictive value(1.6%) than fecal immunochemical test(0.3%).Conclusions: As an alternative approach for the early detection of CRC, this study provides a low-cost method using regular health examination data to identify high-risk individuals for CRC for further examinations. The approach can promote early detection of CRC especially in developing countries such as China, where annual health examination is popular but regular CRC-specific screening is rare.展开更多
Objective To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of“people with the five elements in t...Objective To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of“people with the five elements in traditional Chinese medicine(TCM).”Methods Data collected from the literature review,two sessions of brainstorming of experts with related experience in“people with the five elements in TCM”from October 2020 to December 2020,and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed.Triangulation was used in this study,and theming and synthesizing were used to analyze the data.Results A total of 31 experts and 30 interviewees participated in this study.The median age of the experts and interviewees were 48.0 and 38.5 years,respectively;51.66%and 54.8%of experts and interviewees,respectively,were men.The descriptors of facial diagrams of“people with the five elements in TCM”were complexion,shape,distribution state of facial bones,convergence trend of facial muscles,and facial expression.A theoretical model of“people with the five elements in TCM”was shaped based on these findings.Conclusion The study suggests a possibility for bridging the gap between personality and bodily state,identifying an avenue for personality research from the perspective of TCM.展开更多
CTR1 is a key negative regulator in ethylene signal transduction. A salt-induced CTR1 like gene （TaCTR1） was cloned from wheat, its expression under abiotic stresses, subcellular localization and the effect of overe...CTR1 is a key negative regulator in ethylene signal transduction. A salt-induced CTR1 like gene （TaCTR1） was cloned from wheat, its expression under abiotic stresses, subcellular localization and the effect of overexpression of TaCTR1 on salt tolerance in tobacco was studied. A putative CTR1 gene was cloned and characterized from wheat via rapid amplification of cDNA ends （RACE） and RT-PCR. TaCTR1 expression under stresses was analyzed using semi-quantitative RT-PCR and the effect of overexpression of TaCTR1 on salt tolerance was conducted in tobacco. The full-length cDNA of TaCTR1 is 2 635 bp which codes for a polypeptide of 759 amino acids. There is a conserved serine/threonine protein kinase domain at the carboxyl terminus containing an ATP-binding site. Southern blot analysis revealed that TaCTR1 consisted of a gene family in wheat. The amino acid homologies of CTR1 among different organisms share higher similarities. Expression analysis revealed that TaCTR1 was induced by NaC1 and drought stress but inhibited by ABA treatment. Transient expression of TaCTR1-GFP in the onion epidermal cells indicated that TaCTR1 was probably targeted to the plasma membrane. Overexpression of TaCTR1 decreased salt tolerance in transgenic tobacco （Nicotiana tabacum L.） plants compared with the control. To our knowledge, TaCTR1 is the first CTR1 gene cloned in wheat and may be involved in various abiotic stresses. Overexpression of TaCTR1 decreased the salt tolerance in tobacco suggested that TaCTR1 may act as a negative regulator of salt stress in plants.展开更多
Foxes are susceptible to SARS-CoV-2 in laboratory settings,and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes.In this study,we assessed the binding capacities of fox ACE2 t...Foxes are susceptible to SARS-CoV-2 in laboratory settings,and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes.In this study,we assessed the binding capacities of fox ACE2 to important sarbecoviruses,including SARS-CoV,SARS-CoV-2,and animal-origin SARS-CoV-2 related viruses.Our findings demonstrated that fox ACE2 exhibits broad binding capabilities to receptor-binding domains(RBDs)of sarbecoviruses.We further determined the cryo-EM structures of fox ACE2 complexed with RBDs of SARS-CoV,SARS-CoV-2 prototype(PT),and Omicron BF.7.Through structural analysis,we identified that the K417 mutation can weaken the ability of SARS-CoV-2 sub-variants to bind to fox ACE2,thereby reducing the susceptibility of foxes to SARS-CoV-2 sub-variants.In addition,the Y498 residue in the SARS-CoV RBD plays a crucial role in forming a vital cation-πinteraction with K353 in the fox ACE2 receptor.This interaction is the primary determinant for the higher affinity of the SARS-CoV RBD compared to that of the SARS-CoV-2 PT RBD.These results indicate that foxes serve as potential hosts for numerous sarbecoviruses,highlighting the critical importance of surveillance efforts.展开更多
Background:Androgenic alopecia(AGA)is the most common type of hair loss in men,and there are many studies on the treatment of hair loss by platelet-rich plasma(PRP).The human scalp contains a huge microbiome,but its r...Background:Androgenic alopecia(AGA)is the most common type of hair loss in men,and there are many studies on the treatment of hair loss by platelet-rich plasma(PRP).The human scalp contains a huge microbiome,but its role in the process of hair loss remains unclear,and the relationship between PRP and the microbiome needs further study.Therefore,the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition.Methods:We performed PRP treatment on 14 patients with AGA,observed their clinical efficacy,and collected scalp swab samples before and after treatment.The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial identification.Results:The results showed that PRP was effective in the treatment of AGA patients,and the hair growth increased significantly.The results of relative abundance analysis of microbiota showed that after treatment,g_Cutibacterium increased and g_Staphylococcus decreased,which played a stable role in scalp microbiota.In addition,g_Lawsonella decreased,indicating that the scalp oil production decreased after treatment.Conclusions:The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.展开更多
Nicotine is widely recognized as the primary contributor to tobacco dependence.Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area(VTA)n...Nicotine is widely recognized as the primary contributor to tobacco dependence.Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area(VTA)neurons,and accumulating evidence suggests that glia play prominent roles in nicotine addiction.However,VTA neurons and glia have yet to be characterized at the transcriptional level during the progression of nicotine self-administration.Here,a male mouse model of nicotine self-administration is established and the timing of three critical phases(pre-addiction,addicting,and post-addiction phase)is characterized.Single-nucleus RNA sequencing in the VTA at each phase is performed to comprehensively classify specific cell subtypes.Adaptive changes occurred during the addicting and post-addiction phases,with the addicting phase displaying highly dynamic neuroplasticity that profoundly impacts the transcription in each cell subtype.Furthermore,significant transcriptional changes in energy metabolism-related genes are observed,accompanied by notable structural alterations in neuronal mitochondria during the progression of nicotine self-administration.The results provide insights into mechanisms underlying the progression of nicotine addiction,serving as an important resource for identifying potential molecular targets for nicotine cessation.展开更多
Mountains are rich in biodiversity,and butterflies are species-rich and have a good ecological and evolutionary research foundation.This review addresses the potential and progress of studying mountain biodiversity us...Mountains are rich in biodiversity,and butterflies are species-rich and have a good ecological and evolutionary research foundation.This review addresses the potential and progress of studying mountain biodiversity using butterflies as a model.We discuss the uniqueness of mountain ecosystems,factors influencing the distribution of mountain butterflies,representative genetic and evolutionary models in butterfly research,and evolutionary studies of mountain biodiversity involving butterfly genetics and genomics.Finally,we demonstrate the necessity of studying mountain butterflies and propose future perspectives.This review provides insights for studying the biodiversity of mountain butterflies as well as a summary of research methods for reference.展开更多
Kallima butterflies are famous for their leaf-mimicking wing patterns.Yet the characterization of Kallima species is still under debate owing to their high phenotypic similarity.With the release of the K.inachus refer...Kallima butterflies are famous for their leaf-mimicking wing patterns.Yet the characterization of Kallima species is still under debate owing to their high phenotypic similarity.With the release of the K.inachus reference genome,phylogenetic studies based on genome-wide data have been carried out,thus improving the understanding of the evolutionary relationships of the genus Kallima.However,we noticed that there is some conflict between genome-based phylogenies and morphological classifications in butterflies.We further examined the cause of this conflict by conducting an in-depth study of the relationships among Kallima butterflies to test possible reticulate phylogenetic topologies.We constructed phylogenies based on various datasets(including SNPs in single-copy genes,coding sequences,neutral regions and all remaining sites across the genome)to compare the topologies,revealing the complex evolutionary history of Kallima butterflies.Our results suggest that the reticulate species topology may constitute a pervasive pattern present not only in species with adaptive radiations but also in gradually evolving species,with Kallima butterflies as an example.展开更多
Imaging proteins with high resolution is crucial for studying cellular physiology and pathology.Fluorescence imaging is a privileged method to visualize proteins with subcellular precision in live cells.In recent year...Imaging proteins with high resolution is crucial for studying cellular physiology and pathology.Fluorescence imaging is a privileged method to visualize proteins with subcellular precision in live cells.In recent years,there has been a tremendous advance in the field of fluorescent dyes that are optically more sophisticated than genetically-encodable fluorescent proteins.In this review,we aim to discuss modern bioconjugation methods to specifically incorporate these dyes into protein-of-interests.We focus on advances in live-cell labeling strategies and fluorescent probes,especially the HaloTag,SNAP-tag,TMP-tag,and unnatural amino acid systems and their applications.These protein labeling methods,along with cutting-edge dyes and novel microscopy methods,have become the infrastructure for biological research in the era of super-resolution imaging.展开更多
Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions.Traditional tracking methods(e.g.,marking each animal with dye or surgic...Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions.Traditional tracking methods(e.g.,marking each animal with dye or surgically implanting microchips)can be invasive and may have an impact on the social behavior being measured.To overcome these shortcomings,video-based methods for tracking unmarked animals,such as fruit flies and zebrafish,have been developed.However,tracking individual mice in a group remains a challenging problem because of their flexible body and complicated interaction patterns.In this study,we report the development of a multi-object tracker for mice that uses the Faster region-based convolutional neural network(R-CNN)deep learning algorithm with geometric transformations in combination with multi-camera/multi-image fusion technology.The system successfully tracked every individual in groups of unmarked mice and was applied to investigate chasing behavior.The proposed system constitutes a step forward in the noninvasive tracking of individual mice engaged in social behavior.展开更多
It has been hypothesized that DNA damage has the potential to induce DNA hypermethylation,contributing to carcinogenesis in mammals.However,there is no sufficient evidence to support that DNA damage can cause genome-w...It has been hypothesized that DNA damage has the potential to induce DNA hypermethylation,contributing to carcinogenesis in mammals.However,there is no sufficient evidence to support that DNA damage can cause genome-wide DNA hypermethylation.In this study,we demonstrated that DNA single-strand breaks with 3′blocked ends(DNA 3′blocks)not only can reinforce DNA methylation at normally methylated loci but also can induce DNA methylation at normally nonmethylated loci in plants.The CG and CHG hypermethylation tend to localize within gene bodies,with a significant proportion being de novo generated.In contrast,the CHH hypermethylation is concentrated in centromeric and pericentromeric regions,primarily being reinforced methylation.Mechanistically,DNA 3′blocks regulate the DREAM complex to induce CG and CHG methylation.Moreover,they utilize the RdDM pathway to induce CHH hypermethylation.Intriguingly,repair of DNA damage or blocking the DNA damage response can fully abolish CHH hypermethylation and partially rescue CHG hypermethylation but rarely alter CG hypermethylation,indicating that DNA damage-induced symmetric DNA methylation can serve as a form of genetic imprinting.Collectively,these results suggest that DNA damage is an important force driving the emergence and evolution of genomic DNA methylation levels and patterns in plants.展开更多
Human leukocyte antigen(HLA)disparity between donors and recipients is a key determinant triggering intense alloreactivity,leading to a lethal complication,namely,acute graft-versus-host disease(aGVHD),after allogenei...Human leukocyte antigen(HLA)disparity between donors and recipients is a key determinant triggering intense alloreactivity,leading to a lethal complication,namely,acute graft-versus-host disease(aGVHD),after allogeneic transplantation.Moreover,aGVHD remains a cause of mortality after HLA-matched allogeneic transplantation.Protocols for HLA-haploidentical hematopoietic cell transplantation(haploHCT)have been established successfully and widely applied,further highlighting the urgency of performing panoramic screening of non-HLA variations correlated with aGVHD.On the basis of our time-consecutive large haploHCT cohort(with a homogenous discovery set and an extended confirmatory set),we first delineated the genetic landscape of 1366 samples to quantitatively model aGVHD risk by assessing the contributions of HLA and non-HLA genes together with clinical factors.In addition to identifying multiple loss-of-function(LoF)risk variations in non-HLA coding genes,our data-driven study revealed that non-HLA genetic variations,independent of HLA disparity,contributed the most to the occurrence of aGVHD.This unexpected major effect was verified in an independent cohort that received HLA-identical sibling HCT.Subsequent functional experiments further revealed the roles of a representative non-HLA LoF gene and LoF gene pair in regulating the alloreactivity of primary human T cells.Our findings highlight the importance of non-HLA genetic risk in the new era of transplantation and propose a new direction to explore the immunogenetic mechanism of alloreactivity and to optimize donor selection strategies for allogeneic transplantation.展开更多
基金supported by the Guizhou Provincial Basic Research Program(Natural Science)[(2024)648]the Program of China National Tobacco Corporation(110202101032(JY-09),110202201003(JY-03))the Program of Guizhou Branch of China National Tobacco Corporation(2023XM02,2021XM05,2022XM05,2024XM01).
文摘Nicotiana tabacum(2n=4x=48),an economically important non-food crop and a model plant for genetic studies,faces challenges in efficient genotyping of novel germplasm.To address this,we developed the Ta-LD-SC,a 20K SNP Affymetrix Axiom array,based on resequencing data from 150 tobacco accessions.A total of 20,213 unique SNPs were carefully selected,achieving coverage of over 90%of the tobacco genome(Nitab4.5 and NtaSR1)with a uniform probe distribution,limiting density to no more than 5 SNPs per 200 kb.The array underwent extensive validation using 866 tobacco accessions(NP panel)and 288 F2 individuals from a cross between K326 and Oxford 26(GP panel).Performance metrics demonstrated its robustness,with high SNP call rates(93.6%-99.8%),a low technical error rate(<1%),and a superior PolyHighResolution SNP rate(79.79%)compared to other crop SNP arrays.Population structure analysis of the NP panel revealed two major introductions of foreign germplasm that have significantly influenced the genetic diversity of Chinese tobacco resources.Using the array,a genome-wide association study(GWAS)identified 62 genes linked to eight agronomic traits,and a high-density genetic map encompassing 4553 SNPs across 6606.08 cM was constructed.The Ta-LD-SC array provides a valuable tool for rapid,high-quality genotyping offering supporting marker annotations that may benefit genetic research and breeding of tobacco.
文摘Since 1968 when the first successful hematopoietic stem cell transplantation(HSCT) was performed, transplant technique has developed rapidly for more than 50 years. In the past 20 years, the significant breakthroughs and widely use of haploidentical-related donor HSCT(e.g. Beijing Protocol) make everyone can have a donor(1), and the novel, reduced-toxicity transplant regimens help elderly patients receive HSCT safely(2).
基金partly supported by grants from the Beijing Municipal Science and Technology Commission(No.Z221100007422008)。
文摘Objective:Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is the only potentially curative method for treating myelodysplastic syndrome(MDS).Post-HSCT measurable residual disease(post-HSCT MRD)is associated with inferior transplant outcomes.In this prospective study,we aimed to investigate the prognostic value of post-HSCT MRD in relapse prediction in MDS.Methods:A total of 166 patients diagnosed with MDS were prospectively enrolled in this study.The KaplanMeier method was used to calculate the survival probabilities.Potential risk factors for outcomes after transplantation were evaluated through univariate and multivariate Cox regression models.Results:For patients with negative and positive post-HSCT MRD,the cumulative incidence of relapse(CIR)and disease-free survival(DFS)at 3 years were 5.9%and 69.6%(P<0.001)and 82.7%and 26.1%(P<0.001),respectively.In the multivariate analysis,post-HSCT MRD(HR=22.801,P<0.001)and Revised International Prognostic Scoring System(IPSS-R)risk stratification(HR=4.346,P=0.003)were independently correlated with relapse.A scoring system for relapse prediction was built based on post-HSCT MRD and IPSS-R stratification.The cumulative incidence of relapse at 3 years was 1.1%,15.8%,and 91.7%for patients with scores of 0,1,and 2,respectively(P<0.001).Conclusions:Our results demonstrated both post-HSCT MRD and IPSS-R scores were independent prognostic factors for OS,DFS,and relapse for MDS patients after allo-HSCT.The risk score system could better predict transplant outcomes and refine the risk stratification than alone in patients with MDS.
基金supported by the National Natural Science Foundation of China(Grant Nos.32201602,82304680)the Natural Science Fund of Hubei Province(Grant No.2023AFB1036)+5 种基金the Program for Excellent Sci-tech Innovation Teams of Universities in Anhui Province(Grant No.2022AH010074)Anhui Provincial Natural Science Foundation(Grant No.2308085QH295)Natural Science Research Project of Anhui Educational Committee(Grant No.2023AH040259)the Talent Scientific Research Startup Foundation,Wannan Medical College(Grant No.YR20230110)the Anhui Provincial Department of Education Young Backbone Teachers Overseas Visiting and Training Funding Program(Grant No.JWFX2023033)Beijing Life Science Academy Project(Grant No.2023200CC0270)。
文摘Rosa banksiae,known as Lady Banks'rose,is a perennial ornamental crop and a versatile herb in traditional Chinese medicine.Given the lack of genomic resources,we assembled a Hi Fi and Nanopore sequencing-derived 458.58 Mb gap-free telomere-to-telomere high-quality R.banksiae genome with a scaffold N50=63.90 Mb.The genome of R.banksiae exhibited no lineage-specific whole-genome duplication compared with other Rosaceae.The phylogenomic analysis of 13 Rosaceae and Arabidopsis through a comparative genomics study showed that numerous gene families were lineage-specific both before and after the diversification of Rosaceae.Some of these genes are candidates for new genes that have evolved from parental genes through fusion events.Fusion genes are divided into three types:Type-I and Type-II genes contain two parental genes that are generated by duplication,distributed in the same and different regions of the genome,respectively;and Type-III can only be detected in one parental gene.Here,Type-I genes are found to have more relaxed selection pressure and lower Ks values than Type-II,indicating that these newly evolved Type-I genes may play important roles in driving phenotypic evolution.Functional analysis exhibited that newly formed fusion genes can regulate the phenotype traits of plant growth and development,suggesting the functional significance of these genes.This study identifies new fusion genes that could be responsible for phenotype evolution and provides information on the evolutionary history of recently diverged species in the Rosa genus.Our data represents the major progress in understanding the new fusion genes evolution pattern of Rosaceae and provides an invaluable resource for phylogenomic studies in plants.
基金supported by National Key Research and Development Plan of China(No.2022YFC2502606,2021YFA1100902)Beijing Nova Program of Science and Technology(No.20230484446)+2 种基金Peking University People’s Hospital(No.RZ2024-01)Joint Research Project of the Shijiazhuang-Peking University Cooperation Program,Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0501200)National Natural Science Foundation of China(No.82350105,82270228)。
文摘Objective:Immune effector cell-associated hematotoxicity(ICAHT),characterized by prolonged cytopenia and delayed hematopoietic recovery,is a common complication following chimeric antigen receptor T(CAR-T)cell therapy.However,the applicability of existing predictive models,CAR-HEMATOTOX(CAR-HT)for lymphoma,acute lymphoblastic leukemia-HEMATOTOX(ALL-HT)for B-ALL,and the early ICAHT prediction model(e IPM),remains uncertain across different hematologic malignancies.Methods:We prospectively analyzed 119 patients who received CAR-T therapy between January 2022 and June2025,including B-ALL(n=62),T-ALL/non-Hodgkin's lymphoma(NHL)(n=25),and multiple myeloma(MM,n=32).The CAR-HT,ALL-HT,and e IPM models were evaluated for their ability to predict ICAHT severity and survival outcomes.Results:Grade 3 ICAHT occurred in 32.3%of B-ALL,40.0%of T-ALL/NHL,and 25.0%of MM patients,while grade 4 rates were 33.9%,20.0%,and 6.3%,respectively.CAR-HT classified 67.2%of patients as high-risk,and ALL-HT identified 56.3%of ALL/NHL patients as high-risk.In both models,high-risk groups experienced significantly more prolonged neutropenia than low-risk groups(CAR-HT:17.7 vs.5.3 d,P<0.001;ALL-HT:21.3 vs.7.7 d,P<0.001).Both e IPMpre and e IPMpost strongly correlated with grade 3-4 ICAHT(P<0.001).Importantly,survival analysis showed that e IPMpre stratification distinguished outcomes:1-year overall survival(OS)was 65%in medium+high-risk vs.84%in low-risk patients(P=0.006),and 1-year disease-free survival(DFS)was 44%vs.73%(P<0.001).Similar predictive accuracy was observed with e IPMpost.Conclusions:The CAR-HT,ALL-HT,and e IPM models consistently identify patients at high risk for severe ICAHT across B-ALL,T-ALL/NHL,and MM.Among these,the e IPM stands out as a promising universal tool for survival prediction.These models provide valuable prognostic insights that can guide supportive care and inform treatment planning in CAR-T therapy.
基金supported by the Key Program of the National Natural Science Foundation of China(No.81930004)the National Natural Science Foundation of China(No.82170208)+2 种基金Tongzhou District Distinguished Young Scholars(No.JCQN2023009)Plan Project of Tongzhou Municipal Science and Technology(No.KJ2024CX045)Beijing Natural Science Foundation(No.Z230016)。
文摘Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT.
基金This work was supported by the National Key Research and Development Program of China(2017YFA0104500)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81621001)+6 种基金the Key Program of the National Natural Science Foundation of China(81930004)Capital’s Funds for Health Improvement and Research(2018-4-4089)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-034)the Science and Technology Project of Guangdong Province of China(2016B030230003)the Project of Health Collaborative Innovation of Guangzhou City(201704020214)Peking University Clinical Scientist Program(BMU2019LCKXJ003)supported by the Fundamental Research Funds for the Central Universities.
文摘We aimed to develop a disease risk comorbidity index(DRCI)based on disease risk index(DRI)and Hematopoietic Cell Transplantation-Specific Comorbidity Index(HCT-CI)in patients receiving haploidentical hematopoietic stem cell transplantation(haplo-HSCT).We identified the prognostic factors of disease-free survival(DFS)in a training subset(n=593),then assigned a weighted score using these factors to the remaining patients(validation subset;n=296).The multivariable model identified two independent predictors of DFS:DRI and HCT-CI before transplantation.In this scoring system,we assigned a weighted score of 2 to very high-risk DRI,and assigned a weighted score of 1 to high-risk DRI and intermediate-and high-risk HCT-CI(i.e.,haplo-DRCI).In the validation cohort,the three-year DFS rate was 65.2%(95%confidence interval(CI),58.2%–72.2%),55.8%(95%CI,44.9%–66.7%),and 32.0%(95%CI,5.8%–58.2%)for the low-,intermediate-,and high-risk group,respectively(P=0.005).Haplo-DRCI can also predict DFS in disease-specific subgroups,particularly in acute leukemia patients.Increasing score was also significantly predictive of increased relapse,increased non-relapse mortality(NRM),decreased DFS,and decreased overall survival(OS)in an independent historical cohort(n=526).These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.
基金supported by grants from the National Basic Research Program of China(MOST2016YFC0900301 and 2014CB964900)the National Natural Science Foundation of China(No. 91519325)the Beijing Natural Science Foundation (No. 5162012)
文摘Analysis of patient＇s materials like cells or nucleic acids obtained in a minimally invasive or noninvasive manner through the sampling of blood or other body fluids serves as liquid biopsies, which has huge potential for numerous diagnostic applications. Circulating cell-free DNA（cfDNA） is explored as a prognostic or predictive marker of liquid biopsies with the improvements in genomic and molecular methods. DNA methylation is an important epigenetic marker known to affect gene expression. cfDNA methylation detection is a very promising approach as abnormal distribution of DNA methylation is one of the hallmarks of many cancers and methylation changes occur early during carcinogenesis. This re？view summarizes the various investigational applications of cfDNA methylation and its oxidized de？rivatives as biomarkers for cancer diagnosis, prenatal diagnosis and organ transplantation monitoring.The review also provides a brief overview of the technologies for cfDNA methylation analysis based on next generation sequencing.
基金supported by funding from Beijing Municipal Science & Technology Commission, Clinical Application and Development of Capital Characteristic (No. Z161100000516003)National Natural Science Foundation of China (No. 31871266)
文摘Objective: Challenges remain in current practices of colorectal cancer(CRC) screening, such as low compliance,low specificities and expensive cost. This study aimed to identify high-risk groups for CRC from the general population using regular health examination data.Methods: The study population consist of more than 7,000 CRC cases and more than 140,000 controls. Using regular health examination data, a model detecting CRC cases was derived by the classification and regression trees(CART) algorithm. Receiver operating characteristic(ROC) curve was applied to evaluate the performance of models. The robustness and generalization of the CART model were validated by independent datasets. In addition, the effectiveness of CART-based screening was compared with stool-based screening.Results: After data quality control, 4,647 CRC cases and 133,898 controls free of colorectal neoplasms were used for downstream analysis. The final CART model based on four biomarkers(age, albumin, hematocrit and percent lymphocytes) was constructed. In the test set, the area under ROC curve(AUC) of the CART model was 0.88 [95%confidence interval(95% CI), 0.87-0.90] for detecting CRC. At the cutoff yielding 99.0% specificity, this model’s sensitivity was 62.2%(95% CI, 58.1%-66.2%), thereby achieving a 63-fold enrichment of CRC cases. We validated the robustness of the method across subsets of test set with diverse CRC incidences, aging rates, genders ratio, distributions of tumor stages and locations, and data sources. Importantly, CART-based screening had the higher positive predictive value(1.6%) than fecal immunochemical test(0.3%).Conclusions: As an alternative approach for the early detection of CRC, this study provides a low-cost method using regular health examination data to identify high-risk individuals for CRC for further examinations. The approach can promote early detection of CRC especially in developing countries such as China, where annual health examination is popular but regular CRC-specific screening is rare.
基金financially supported by the Beijing Hospital Management Center“Dengfeng”plan[DFL20191901]。
文摘Objective To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of“people with the five elements in traditional Chinese medicine(TCM).”Methods Data collected from the literature review,two sessions of brainstorming of experts with related experience in“people with the five elements in TCM”from October 2020 to December 2020,and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed.Triangulation was used in this study,and theming and synthesizing were used to analyze the data.Results A total of 31 experts and 30 interviewees participated in this study.The median age of the experts and interviewees were 48.0 and 38.5 years,respectively;51.66%and 54.8%of experts and interviewees,respectively,were men.The descriptors of facial diagrams of“people with the five elements in TCM”were complexion,shape,distribution state of facial bones,convergence trend of facial muscles,and facial expression.A theoretical model of“people with the five elements in TCM”was shaped based on these findings.Conclusion The study suggests a possibility for bridging the gap between personality and bodily state,identifying an avenue for personality research from the perspective of TCM.
基金supported by the National Natural Science Foundation of China (30370881, 30771348)
文摘CTR1 is a key negative regulator in ethylene signal transduction. A salt-induced CTR1 like gene （TaCTR1） was cloned from wheat, its expression under abiotic stresses, subcellular localization and the effect of overexpression of TaCTR1 on salt tolerance in tobacco was studied. A putative CTR1 gene was cloned and characterized from wheat via rapid amplification of cDNA ends （RACE） and RT-PCR. TaCTR1 expression under stresses was analyzed using semi-quantitative RT-PCR and the effect of overexpression of TaCTR1 on salt tolerance was conducted in tobacco. The full-length cDNA of TaCTR1 is 2 635 bp which codes for a polypeptide of 759 amino acids. There is a conserved serine/threonine protein kinase domain at the carboxyl terminus containing an ATP-binding site. Southern blot analysis revealed that TaCTR1 consisted of a gene family in wheat. The amino acid homologies of CTR1 among different organisms share higher similarities. Expression analysis revealed that TaCTR1 was induced by NaC1 and drought stress but inhibited by ABA treatment. Transient expression of TaCTR1-GFP in the onion epidermal cells indicated that TaCTR1 was probably targeted to the plasma membrane. Overexpression of TaCTR1 decreased salt tolerance in transgenic tobacco （Nicotiana tabacum L.） plants compared with the control. To our knowledge, TaCTR1 is the first CTR1 gene cloned in wheat and may be involved in various abiotic stresses. Overexpression of TaCTR1 decreased the salt tolerance in tobacco suggested that TaCTR1 may act as a negative regulator of salt stress in plants.
基金supported by the National Key R&D Program of China(2022YFC2303401,2021YFA1300803)National Natural Science Foundation of China(32122008)+2 种基金supported by Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)fellowships from the China Postdoctoral Science Foundation(2022T150688)the Postdoctoral Science Foundation of China(2021M700161).
文摘Foxes are susceptible to SARS-CoV-2 in laboratory settings,and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes.In this study,we assessed the binding capacities of fox ACE2 to important sarbecoviruses,including SARS-CoV,SARS-CoV-2,and animal-origin SARS-CoV-2 related viruses.Our findings demonstrated that fox ACE2 exhibits broad binding capabilities to receptor-binding domains(RBDs)of sarbecoviruses.We further determined the cryo-EM structures of fox ACE2 complexed with RBDs of SARS-CoV,SARS-CoV-2 prototype(PT),and Omicron BF.7.Through structural analysis,we identified that the K417 mutation can weaken the ability of SARS-CoV-2 sub-variants to bind to fox ACE2,thereby reducing the susceptibility of foxes to SARS-CoV-2 sub-variants.In addition,the Y498 residue in the SARS-CoV RBD plays a crucial role in forming a vital cation-πinteraction with K353 in the fox ACE2 receptor.This interaction is the primary determinant for the higher affinity of the SARS-CoV RBD compared to that of the SARS-CoV-2 PT RBD.These results indicate that foxes serve as potential hosts for numerous sarbecoviruses,highlighting the critical importance of surveillance efforts.
基金supported by the Guangdong Enterprise Joint Fund(No.2022A1515220137)The Shenzhen Science and Technology Innovation Committee(No.JCYJ20220530141615035)the Internal project of Huazhong University of Science and Technology Union Shenzhen Hospital(Nos.YN2021042 and YN2021045)。
文摘Background:Androgenic alopecia(AGA)is the most common type of hair loss in men,and there are many studies on the treatment of hair loss by platelet-rich plasma(PRP).The human scalp contains a huge microbiome,but its role in the process of hair loss remains unclear,and the relationship between PRP and the microbiome needs further study.Therefore,the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition.Methods:We performed PRP treatment on 14 patients with AGA,observed their clinical efficacy,and collected scalp swab samples before and after treatment.The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial identification.Results:The results showed that PRP was effective in the treatment of AGA patients,and the hair growth increased significantly.The results of relative abundance analysis of microbiota showed that after treatment,g_Cutibacterium increased and g_Staphylococcus decreased,which played a stable role in scalp microbiota.In addition,g_Lawsonella decreased,indicating that the scalp oil production decreased after treatment.Conclusions:The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.
基金supported by the Major Project of Tobacco Biological Effects(552022AK0070,110202102014)。
文摘Nicotine is widely recognized as the primary contributor to tobacco dependence.Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area(VTA)neurons,and accumulating evidence suggests that glia play prominent roles in nicotine addiction.However,VTA neurons and glia have yet to be characterized at the transcriptional level during the progression of nicotine self-administration.Here,a male mouse model of nicotine self-administration is established and the timing of three critical phases(pre-addiction,addicting,and post-addiction phase)is characterized.Single-nucleus RNA sequencing in the VTA at each phase is performed to comprehensively classify specific cell subtypes.Adaptive changes occurred during the addicting and post-addiction phases,with the addicting phase displaying highly dynamic neuroplasticity that profoundly impacts the transcription in each cell subtype.Furthermore,significant transcriptional changes in energy metabolism-related genes are observed,accompanied by notable structural alterations in neuronal mitochondria during the progression of nicotine self-administration.The results provide insights into mechanisms underlying the progression of nicotine addiction,serving as an important resource for identifying potential molecular targets for nicotine cessation.
基金the National Natural Science Foundation of China(32170420 and 31871271)the Beijing Natural Science Foundation(JQ19021)the Peking-Tsinghua Center for Life Science,the State Key Laboratory of Protein and Plant Gene Research,the Qidong-SLS Innovation Fund,Benyuan Charity Young Investigator Exploration Fellowship in Life Science to W.Z.,and grants from the China Postdoctoral Science Foundation(2023M730082 and BX20230026)to S.W.
文摘Mountains are rich in biodiversity,and butterflies are species-rich and have a good ecological and evolutionary research foundation.This review addresses the potential and progress of studying mountain biodiversity using butterflies as a model.We discuss the uniqueness of mountain ecosystems,factors influencing the distribution of mountain butterflies,representative genetic and evolutionary models in butterfly research,and evolutionary studies of mountain biodiversity involving butterfly genetics and genomics.Finally,we demonstrate the necessity of studying mountain butterflies and propose future perspectives.This review provides insights for studying the biodiversity of mountain butterflies as well as a summary of research methods for reference.
基金supported by grants from the National Natural Science Foundation of China(32325009,32170420)the Peking-Tsinghua Center for Life Sciences,and the State Key Laboratory of Protein and Plant Gene Research to WZ and grants from the China Postdoctoral Science Foundation(2023M730082,BX20230026)to SW.
文摘Kallima butterflies are famous for their leaf-mimicking wing patterns.Yet the characterization of Kallima species is still under debate owing to their high phenotypic similarity.With the release of the K.inachus reference genome,phylogenetic studies based on genome-wide data have been carried out,thus improving the understanding of the evolutionary relationships of the genus Kallima.However,we noticed that there is some conflict between genome-based phylogenies and morphological classifications in butterflies.We further examined the cause of this conflict by conducting an in-depth study of the relationships among Kallima butterflies to test possible reticulate phylogenetic topologies.We constructed phylogenies based on various datasets(including SNPs in single-copy genes,coding sequences,neutral regions and all remaining sites across the genome)to compare the topologies,revealing the complex evolutionary history of Kallima butterflies.Our results suggest that the reticulate species topology may constitute a pervasive pattern present not only in species with adaptive radiations but also in gradually evolving species,with Kallima butterflies as an example.
基金supported by the National Natural Science Foundation of China(Project 31971375)the Beijing Municipal Science&Technology Commission(Project Z221100003422013).
文摘Imaging proteins with high resolution is crucial for studying cellular physiology and pathology.Fluorescence imaging is a privileged method to visualize proteins with subcellular precision in live cells.In recent years,there has been a tremendous advance in the field of fluorescent dyes that are optically more sophisticated than genetically-encodable fluorescent proteins.In this review,we aim to discuss modern bioconjugation methods to specifically incorporate these dyes into protein-of-interests.We focus on advances in live-cell labeling strategies and fluorescent probes,especially the HaloTag,SNAP-tag,TMP-tag,and unnatural amino acid systems and their applications.These protein labeling methods,along with cutting-edge dyes and novel microscopy methods,have become the infrastructure for biological research in the era of super-resolution imaging.
基金supported by grants from the National Key R&D Program of China(2017YFA0105201)the National Natural Science Foundation of China(81925011,92149304,31900698,32170954,and 32100763+2 种基金the Key-Area Research and Development Program of Guangdong Province(2019B030335001)The Youth Beijing Scholars Program(015),Support Project of High-level Teachers in Beijing Municipal Universities(CIT&TCD20190334)Beijing Advanced Innovation Center for Big Data-based Precision Medicine,Capital Medical University,Beijing,China(PXM2021_014226_000026).
文摘Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions.Traditional tracking methods(e.g.,marking each animal with dye or surgically implanting microchips)can be invasive and may have an impact on the social behavior being measured.To overcome these shortcomings,video-based methods for tracking unmarked animals,such as fruit flies and zebrafish,have been developed.However,tracking individual mice in a group remains a challenging problem because of their flexible body and complicated interaction patterns.In this study,we report the development of a multi-object tracker for mice that uses the Faster region-based convolutional neural network(R-CNN)deep learning algorithm with geometric transformations in combination with multi-camera/multi-image fusion technology.The system successfully tracked every individual in groups of unmarked mice and was applied to investigate chasing behavior.The proposed system constitutes a step forward in the noninvasive tracking of individual mice engaged in social behavior.
基金supported by the National Natural Science Foundation of China(grant no.32270288 to W.Q.grant no.32400245 to J.L.)+1 种基金the China Postdoctoral Science Foundation(2024M760519 to W.L.)the Beijing Life Science Academy(2024500CA0010 to W.Q.).
文摘It has been hypothesized that DNA damage has the potential to induce DNA hypermethylation,contributing to carcinogenesis in mammals.However,there is no sufficient evidence to support that DNA damage can cause genome-wide DNA hypermethylation.In this study,we demonstrated that DNA single-strand breaks with 3′blocked ends(DNA 3′blocks)not only can reinforce DNA methylation at normally methylated loci but also can induce DNA methylation at normally nonmethylated loci in plants.The CG and CHG hypermethylation tend to localize within gene bodies,with a significant proportion being de novo generated.In contrast,the CHH hypermethylation is concentrated in centromeric and pericentromeric regions,primarily being reinforced methylation.Mechanistically,DNA 3′blocks regulate the DREAM complex to induce CG and CHG methylation.Moreover,they utilize the RdDM pathway to induce CHH hypermethylation.Intriguingly,repair of DNA damage or blocking the DNA damage response can fully abolish CHH hypermethylation and partially rescue CHG hypermethylation but rarely alter CG hypermethylation,indicating that DNA damage-induced symmetric DNA methylation can serve as a form of genetic imprinting.Collectively,these results suggest that DNA damage is an important force driving the emergence and evolution of genomic DNA methylation levels and patterns in plants.
基金supported by the Major Program of the National Natural Science Foundation of China(No.82293630)the Peking University Medicine Fund for the world’s leading discipline or discipline cluster development(No.71003Y3035)+1 种基金the National Key Research and Development Program of China(Nos.2022YFA0103300,2017YFA0104500,and 2016YFC0901603)the State Key Laboratory of Gene Function and Modulation Research and the Beijing Advanced Innovation Center for Genomics(ICG)at Peking University.
文摘Human leukocyte antigen(HLA)disparity between donors and recipients is a key determinant triggering intense alloreactivity,leading to a lethal complication,namely,acute graft-versus-host disease(aGVHD),after allogeneic transplantation.Moreover,aGVHD remains a cause of mortality after HLA-matched allogeneic transplantation.Protocols for HLA-haploidentical hematopoietic cell transplantation(haploHCT)have been established successfully and widely applied,further highlighting the urgency of performing panoramic screening of non-HLA variations correlated with aGVHD.On the basis of our time-consecutive large haploHCT cohort(with a homogenous discovery set and an extended confirmatory set),we first delineated the genetic landscape of 1366 samples to quantitatively model aGVHD risk by assessing the contributions of HLA and non-HLA genes together with clinical factors.In addition to identifying multiple loss-of-function(LoF)risk variations in non-HLA coding genes,our data-driven study revealed that non-HLA genetic variations,independent of HLA disparity,contributed the most to the occurrence of aGVHD.This unexpected major effect was verified in an independent cohort that received HLA-identical sibling HCT.Subsequent functional experiments further revealed the roles of a representative non-HLA LoF gene and LoF gene pair in regulating the alloreactivity of primary human T cells.Our findings highlight the importance of non-HLA genetic risk in the new era of transplantation and propose a new direction to explore the immunogenetic mechanism of alloreactivity and to optimize donor selection strategies for allogeneic transplantation.
