Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma(PRP)

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.

Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs.identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia

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.

The Psychosomatic Traits of“People with the Five Elements in Traditional Chinese Medicine”:A Qualitative Study

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.

Disease Risk Comorbidity Index for Patients Receiving Haploidentical Allogeneic Hematopoietic Transplantation

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.

An enrichment model using regular health examination data for early detection of colorectal cancer

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.

Cloning and Characterization of a Putative CTR1 Gene from Wheat

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.

Crystal structures of RNA-dependent RNA polymerases from Jingmen tick virus and Alongshan virus

Jingmenviruses are a group of flavi-like viruses with segmented genome and have been found in various types of hosts,including humans,cattle,monkeys,bats,rodents,sheep,ticks,mosquitoes and nematodes.Jingmenviruses,including the Jingmen tick virus(JMTV)and Alongshan virus(ALSV),have been associated with febrile illness and flu-like symptoms in humans.Viral polymerase plays critical roles in genome replication and transcription and is an ideal target for antiviral drugs.Here,we determined the crystal structures of RNA-dependent RNA polymerase(RdRp)domains of JMTV and ALSV at 2.6Åand 3.2Åresolutions,respectively.The overall structures of JMTV and ALSV RdRp domains are similar to those from the typical unsegmented viruses in Flaviviridae family,especially the Flavivirus genus.JMTV and ALSV RdRps can be divided into three subdomains and the catalytical Motif A-G are conserved like the typical flaviviruses,whereas the zinc-binding pockets are absent from the JMTV and ALSV RdRps.The 50-ends of jingmenvirus genomes are varied in length and sequence,and a highly conserved 8-nucleotide element located on the tip of stem loop A was identified and shown to be required for binding with RdRp and performing de novo replication activity.These findings provide important structural insights into RdRp of segmented flavivirus and reveal the key region of virus genome responsible for replication initiation,which would promote molecular understanding of segmented flavivirus replication and the structure-based design of antiviral drugs against flaviviruses.

The binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses

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.

Evolution of Monkeypox C9L RNA G-Quadruplex Elevates the Translation of Its Only Kelch-like Protein by Accelerating G-Quadruplex Unfolding Kinetics

Genomic surveillance of monkeypox virus(MPXV)is essential to explore the reason of its unusual outbreak.Current phylogenomic analysis of the MPXV genome mainly focuses on the effect of amino acid mutations.Herein,we explore the evolutionary variation of RNA G-quadruplex(RG4)of MPXV and find that the genome evolution of MPXV can also produce new effects through changes in the RG4 structure.This RG4 is located in MPXV’s only Kelch-like C9L gene,which encodes for an antagonist of the innate immune response.The evolution of this virus increases the unfolding kinetic constant of C9L RG4 and promotes the C9 protein level in living cells.Importantly,all reported MPXV genomes in 2022 carry the C9L-RG4-5 pattern with the highest unfolding kinetic constant.Additionally,the RG4 ligand,RGB-1,can impede the unfolding of C9L-RG4-5 and thereby reduce the C9 protein level.These findings carve out a new path to comprehensively understanding MPXV virology.

Potential and progress of studying mountain biodiversity by means of butterfly genetics and genomics

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.

Coordinate-wise monotonic transformations enable privacy-preserving age estimation with 3D face point cloud

The human face is a valuable biomarker of aging,but the collection and use of its image raise significant privacy concerns.Here we present an approach for facial data masking that preserves age-related features using coordinate-wise monotonic transformations.We first develop a deep learning model that estimates age directly from non-registered face point clouds with high accuracy and generalizability.We show that the model learns a highly indistinguishable mapping using faces treated with coordinate-wise monotonic transformations,indicating that the relative positioning of facial information is a low-level biomarker of facial aging.Through visual perception tests and computational3D face verification experiments,we demonstrate that transformed faces are significantly more difficult to perceive for human but not for machines,except when only the face shape information is accessible.Our study leads to a facial data protection guideline that has the potential to broaden public access to face datasets with minimized privacy risks.

Single-cell immune landscape of measurable residual disease in acute myeloid leukemia

Measurable residual disease(MRD)is a powerful prognostic factor of relapse in acute myeloid leukemia(AML).We applied the single-cell RNA sequencing to bone marrow(BM)samples from patients with(n=20)and without(n=12)MRD after allogeneic hematopoietic stem cell transplantation.A comprehensive immune landscape with 184,231 cells was created.Compared with CD8+T cells enriched in the MRDnegative group(MRD‒_CD8),those enriched in the MRD-positive group(MRD+_CD8)showed lower expression levels of cytotoxicity-related genes.Three monocyte clusters(i.e.,MRD+_M)and three B-cell clusters(i.e.,MRD+_B)were enriched in the MRD-positive group.Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD‒_CD8 clusters and vice versa.MRDenriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD‒_CD8 clusters.These findings revealed the characteristics of the immune cell landscape in MRD positivity,which will allow for a better understanding of the immune mechanisms for MRD conversion.

Uncovering the functional basis of mantids that resemble plants

Convergent evolution frequently causes one species to look like another to increase its survival.This“adaptive resemblance”takes many forms:edible species mimic noxious ones to avoid predation;camouflaged patterns allow an organism to blend into its environment;and being mistaken for an inedible object allows a prey species to masquerade as a twig or dead leaf.Adaptive resemblance is relatively common in insects,which comprise around 60%of known species.

Plerixafor-based mobilization and mononuclear cell counts in graft increased the risk of engraftment syndrome after autologous hematopoietic stem cell transplantation

Engraftment syndrome(ES)is one of the most common complications in the early phase after autologous hematopoietic stem cell transplantation(ASCT),and we aimed to evaluate the incidence and risk factors for ES patients receiving ASCT in the era of plerixafor-based mobilization.A total of 294 were enrolled,and 16.0%(n=47)experienced ES after ASCT.The main clinical manifestations were fever(100%),diarrhea(78.7%),skin rash(23.4%),and hypoxemia/pulmonary edema(12.8%).Plerixafor-based mobilization was associated with higher counts of CD3^(+)cells,CD4^(+)cells,and CD8^(+)cells in grafts.In univariate analysis of the total cohort,age≥60 years,receiving ASCT at complete remission(CR),higher number of mononuclear cell(MNC),CD3^(+)cell counts,CD4^(+)cells as well as CD8^(+)cells transfused and plerixafor-based mobilization were associated with ES after ASCT.Multivariate analysis showed that age≥60 years(P=0.0014),receiving ASCT at CR(P=0.002),and higher number of MNC transfused(P=0.026)were associated with ES in total cohort.In plasma cell disease subgroup,age≥60 years(P=0.013),plerixafor-based mobilization(P=0.036),and receiving ASCT at CR(P=0.002)were associated with ES.Patients with more risk factors had a higher risk of ES.The 1-year probabilities of relapse,non-relapse mortality,and survival were comparable between patients with and without ES.Thus,plerixafor-based mobilization may influence the composition of T lymphocytes in grafts and increase the risk of ES,particularly in patients with plasma cell disease.

High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the study.As soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP patients.On the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells.In contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets.Taking a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune profiles.Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of ITP.In conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP.They may offer novel targets to develop personalized immunotherapies.

DEAD-box helicase 17(DDX17)protects cardiac function by promoting mitochondrial homeostasis in heart failure

DEAD-box helicase 17(DDX17)is a typical member of the DEAD-box family with transcriptional cofactor activity.Although DDX17 is abundantly expressed in the myocardium,its role in heart is not fully understood.We generated cardiomyocyte-specific Ddx17-knockout mice(Ddx17-cKO),cardiomyocyte-specific Ddx17 transgenic mice(Ddx17-Tg),and various models of cardiomyocyte injury and heart failure(HF).DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury.Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis,leading to progressive cardiac dysfunction,maladaptive remodeling and progression to heart failure.Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions.Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6(BCL6)and inhibit the expression of dynamin-related protein 1(DRP1).When DDX17 expression is reduced,transcriptional repression of BCL6 is attenuated,leading to increased DRP1 expression and mitochondrial fission,which in turn leads to impaired mitochondrial homeostasis and heart failure.We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure.These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Nicotine-induced transcriptional changes and mitochondrial dysfunction in the ventral tegmental area revealed by single-nucleus transcriptomics

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.

Chemical tags and beyond:Live-cell protein labeling technologies for modern optical imaging

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.

Expanded clinical-grade NK cells exhibit stronger effects than primary NK cells against HCMV infection

Cytomegalovirus (CMV) reactivation remains a common complication and leads to high mortality in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early natural killer (NK) cell reconstitution may protect against the development of human CMV (HCMV) infection post-HSCT. Our previous data showed that ex vivo mbIL21/4-1BBL-expanded NK cells exhibited high cytotoxicity against leukemia cells. Nevertheless, whether expanded NK cells have stronger anti-HCMV function is unknown. Herein, we compared the anti-HCMV functions of ex vivo expanded NK cells and primary NK cells. Expanded NK cells showed higher expression of activating receptors, chemokine receptors and adhesion molecules;stronger cytotoxicity against HCMV-infected fibroblasts;and better inhibition of HCMV propagation in vitro than primary NK cells. In HCMV-infected humanized mice, expanded NK cell infusion resulted in higher NK cell persistence and more effective tissue HCMV elimination than primary NK cell infusion. A clinical cohort of 20 post-HSCT patients who underwent adoptive NK cell infusion had a significantly lower cumulative incidence of HCMV infection (HR = 0.54, 95% CI = 0.32–0.93, p = 0.042) and refractory HCMV infection (HR = 0.34, 95% CI = 0.18–0.65, p = 0.009) than controls and better NK cell reconstitution on day 30 post NK cell infusion. In conclusion, expanded NK cells exhibit stronger effects than primary NK cells against HCMV infection both in vivo and in vitro.

Repair of dysfunctional bone marrow endothelial cells alleviates aplastic anemia

Aplastic anemia(AA)is a life-threatening disease characterized by bone marrow(BM)failure and pancytopenia.As an important component of the BM microenvironment,endothelial cells(ECs)play a crucial role in supporting hematopoiesis and regulating immunity.However,whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown.In this study,a classical AA mouse model and VE-cadherin blocking antibody that could antagonize the function of ECs were used to validate the role of BM ECs in the occurrence of AA.Nacetyl-L-cysteine(NAC,a reactive oxygen species scavenger)or exogenous EC infusion was administered to AA mice.Furthermore,the frequency and functions of BM ECs from AA patients and healthy donors were evaluated.BM ECs from AA patients were treated with NAC in vitro,and then the functions of BM ECs were evaluated.We found that BM ECs were significantly decreased and damaged in AA mice.Hematopoietic failure and immune imbalance became more severe when the function of BM ECs was antagonized,whereas NAC or EC infusion improved hematopoietic and immunological status by repairing BM ECs in AA mice.Consistently,BM ECs in AA patients were decreased and dysfunctional.Furthermore,dysfunctional BM ECs in AA patients led to their impaired ability to support hematopoiesis and dysregulate T cell differentiation toward proinflammatory phenotypes,which could be repaired by NAC in vitro.The reactive oxygen species pathway was activated,and hematopoiesis-and immune-related signaling pathways were enriched in BM ECs of AA patients.In conclusion,our data indicate that dysfunctional BM ECs with impaired hematopoiesis-supporting and immunomodulatory abilities are involved in the occurrence of AA,suggesting that repairing dysfunctional BM ECs may be a potential therapeutic approach for AA patients.