Under the optimal norming constants, this paper studies the higher-order expansions of the distributions and densities of the powered order statistics of Maxwell sequence. As auxiliary results, the corresponding conve...Under the optimal norming constants, this paper studies the higher-order expansions of the distributions and densities of the powered order statistics of Maxwell sequence. As auxiliary results, the corresponding convergence rates are obtained. The results show that the convergence rates of distributions and densities of normalized power order statistics are related to power index in principle. Finally, we compared the accuracy of each approximations with its true values through numerical experiments.展开更多
The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The mai...The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The main distribution area of the C. angulata is located in Fujian, South China. In total, 420 C. angulata were collected from 14 natural habitats(populations) along the Fujian coast, and their genetic diversity and structure were analyzed in the mitochondrial COI and nuclear gene ITS2 sequences. Results reveal that all the 14 populations of C. angulata exhibited high levels of genetic diversity, with a total of 57(haplotype diversity: 0.811±0.016) and 124(haplotype diversity: 0.912±0.007) haplotypes revealed by COI and ITS2, respectively. Notably, significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ) population(FS T by COI: 0.035–0.142, P<0.05;FS T by ITS2: 0.078–0.123, P<0.05) with other populations were observed for the first time, which is also supported by the results of molecular variance analysis(FC T by COI: 0.105, P<0.05;FC T by ITS2: 0.086, P<0.05) and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree. Furthermore, the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations. In addition, the population dynamics analysis suggests that the C. angulata may have undergone expansion during the third ice age of the Pleistocene. These results provide a reference for the preservation and further genetic improvement of C. angulata.展开更多
To investigate the seismic response evolution of offshore bridges under the coupled effects of main-aftershock sequences and chloride-induced erosion,a time-dependent damage finite element model of a three-span,three-...To investigate the seismic response evolution of offshore bridges under the coupled effects of main-aftershock sequences and chloride-induced erosion,a time-dependent damage finite element model of a three-span,three-column simply supported bridge was established based on energy dissipation theory and static pushover analysis.Seismic time-history analysis was conducted to obtain key response indicators,including the maximum displacement and residual displacement at the pier top,as well as the proportion of cumulative hysteretic energy generated at the pier bottom during aftershocks.The results show that structural durability degradation significantly affected the seismic responses:under the same seismic excitation,the maximum pier-top displacement of long-term service bridges increased by at least 10%,with a maximum increase of up to 43%,compared with newly built bridges.When subjected to high-intensity earthquakes,the residual displacement at the pier top continuously increased with service time,rising by 66%,121%,and 163%after 50,75,and 100 a of service,respectively,compared with new bridges.Aftershocks induced noticeable cumulative damage at critical locations such as the pier bottom,with the cumulative hysteretic energy accounting for an average of 14.08%of the total energy dissipation during the main-aftershock sequence,reaching a maximum of 25.3%.Therefore,it is recommended that both the energy contribution of aftershocks and the effect of durability degradation be considered in the seismic design of offshore bridges.展开更多
Nickel-based alloy clad plate(NACP)is a promising composite structural material owing to its excellent mechanical and corrosion-resistant properties,as well as its low cost.However,the development of welding technolog...Nickel-based alloy clad plate(NACP)is a promising composite structural material owing to its excellent mechanical and corrosion-resistant properties,as well as its low cost.However,the development of welding technology for NACP has lagged behind.Herein,N08825/L360 NACP was used as the model material,and welded joints were prepared using tungsten inert gas welding to investigate the effects of different welding sequences and filler metals on the micro structure and mechanical properties of joints.The results showed that weld seams filled with mixed filler metals under the post-flyer welding seam welding sequence exhibited a uniform micro structure,and the joints performed well in tensile,bending,and impact tests.For joints filled with mixed filler metals under the post-base welding seam sequence(P-BWS)satisfactory face-bending,root-bending,and tensile properties were achieved;however,cracks formed in the side-bending specimens,and the impact toughness decreased greatly.Micro structural analysis shows that the deterioration in weld toughness is attributable to two factors:severe dimensional embrittlement and micro structural embrittlement,both caused by the formation of hardened welds in the welding seam.Under the P-BWS,using only nickel-based alloy filler metals effectively prevents the deterioration of the micro structure and properties of welding seams.展开更多
The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of ...The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.展开更多
Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macro...Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
In this paper,we introduce non-abelian cohomology groups and classify the nonabelian extensions of Rota-Baxter pre-Lie algebras in terms of non-abelian cohomology groups.Next,we explore the inducibility of pairs of au...In this paper,we introduce non-abelian cohomology groups and classify the nonabelian extensions of Rota-Baxter pre-Lie algebras in terms of non-abelian cohomology groups.Next,we explore the inducibility of pairs of automorphisms and derive the analog Wells exact sequences under the circumstance of Rota-Baxter pre-Lie algebras.Finally,we discuss the inducibility problem of pairs of automorphisms about an abelian extensions of Rota-Baxter pre-Lie algebras.展开更多
Deeper understanding of the mechanism by which wheat responds to salt stress(SS)remains a major challenge due to the scarcity of available single-cellucleus transcriptomics resources.Here,in order to uncover the trans...Deeper understanding of the mechanism by which wheat responds to salt stress(SS)remains a major challenge due to the scarcity of available single-cellucleus transcriptomics resources.Here,in order to uncover the transcriptional patterns during the late stage of SS of different wheat cells,we performed single-nucleus RNA-sequencing(snRNA-seq)on roots and leaves of wheat seedlings under NaCl treatment for 7 d.Integrating snRNA-seq with bulk RNA-seq and physiological and biochemical indices measurement,the single-cell transcriptome atlas of wheat roots and leaves was constructed,and response patterns of cell types to SS were identified based on enrichment of differentially expressed genes for osmotic stress,ion transport,and oxidative stress.Moreover,several cell-type-specific salt-tolerant candidate genes were determined based on pseudotime analysis and functional validation,such as TaWRKY75-A in root hair cells,NICOTIANAMINE SYNTHASE(NAS)genes in root stele I cells,and dehydrin(DHN)genes in leaf fiber cells.展开更多
Hypospadias is a common congenital malformation of the male external genitalia, with severe cases presenting considerable surgical and long-term challenges. Despite the clinical importance of severe hypospadias demons...Hypospadias is a common congenital malformation of the male external genitalia, with severe cases presenting considerable surgical and long-term challenges. Despite the clinical importance of severe hypospadias demonstrated by prolonged hospital stays, repeated surgeries, and substantial costs, the genetic etiology of severe hypospadias remains incompletely understood, particularly in diverse populations. To determine the molecular basis, we performed whole-exome sequencing (WES) on 30 Chinese patients from southeastern China with confirmed 46,XY karyotypes. Our analysis identified clinically relevant genetic variants, including single-nucleotide variants (SNVs) and copy number variations (CNVs), with subsequent phenotypic correlation. Clinically relevant genetic variants were identified in 33.3% (10/30) of cases, including novel SNVs in gonadal regulators (nuclear receptor subfamily 5 group A member 1 [NR5A1] c.1344dupC/c.244+1G>T and SRY-box 3 [SOX3] c.1273G>C), morphogenetic modulators (GLI family zinc finger 3 [GLI3] c.4731delA and aristaless-related homeobox [mARX] c.644C>G), and syndromic genes (patched domain containing 1 [PTCHD1] c.667G>A and euchromatic histone lysine methyltransferase 1 [EHMT1] c.3081C>T). Additionally, recurrent CNVs at 22q12.3 and a novel CNV exon 18 deletion in myelin regulatory factor (MYRF) and 18q11.2 were identified. Mutation carriers showed a significantly higher frequency of cryptorchidism (40.0% vs 5.0%, P < 0.01) and a higher prevalence of ≥3 associated malformations (80.0% vs 35.0%, P < 0.05) than non-carriers, highlighting genotype–phenotype correlations. The 33.3% diagnostic yield tripled conventional estimates, demonstrating WES efficacy in identifying SNVs and CNVs in severe phenotypes. These findings reveal the genetic heterogeneity of severe hypospadias and support WES utility in uncovering novel variants and structural genomic alterations.展开更多
Natural hybridization is known to play a vital role in speciation;however,the mechanisms underlying the early stages of natural hybridization remain unclear.Where two plant species come into contact,two driving forces...Natural hybridization is known to play a vital role in speciation;however,the mechanisms underlying the early stages of natural hybridization remain unclear.Where two plant species come into contact,two driving forces may balance the dynamic consequences of hybridization:fusion by hybridization-mediated gene flow,and separation by reproductive isolation(RI)(Ma et al.,2010a,b;Chang et al.,2022).展开更多
As an important resource in data link,time slots should be strategically allocated to enhance transmission efficiency and resist eavesdropping,especially considering the tremendous increase in the number of nodes and ...As an important resource in data link,time slots should be strategically allocated to enhance transmission efficiency and resist eavesdropping,especially considering the tremendous increase in the number of nodes and diverse communication needs.It is crucial to design control sequences with robust randomness and conflict-freeness to properly address differentiated access control in data link.In this paper,we propose a hierarchical access control scheme based on control sequences to achieve high utilization of time slots and differentiated access control.A theoretical bound of the hierarchical control sequence set is derived to characterize the constraints on the parameters of the sequence set.Moreover,two classes of optimal hierarchical control sequence sets satisfying the theoretical bound are constructed,both of which enable the scheme to achieve maximum utilization of time slots.Compared with the fixed time slot allocation scheme,our scheme reduces the symbol error rate by up to 9%,which indicates a significant improvement in anti-interference and eavesdropping capabilities.展开更多
Uncovering the underlying process of epileptogenesis is crucial for developing effective treatment strategies for epilepsy.However,the cellular and molecular changes throughout epileptogenesis are not fully understood...Uncovering the underlying process of epileptogenesis is crucial for developing effective treatment strategies for epilepsy.However,the cellular and molecular changes throughout epileptogenesis are not fully understood.In this study,single-nucleus RNA sequencing was performed on the hippocampus,temporal cortex,and thalamus across the acute,latent,and chronic phases in a pilocarpine-induced rat model and controls.We created a comprehensive single-nucleus transcriptomic atlas of rat epileptogenesis,consisting of 311,177 single nuclei.Our analysis revealed distinct transcriptional signatures across the three phases and regions,including significant gene expression changes in the acute phase and critical synaptic and neural network remodeling in the thalamus during the latent phase.Notably,we identified two novel astrocyte clusters during epileptogenesis,with the EX-Astro C3-IN pathway emerging as a potential intervention target.The dataset provides a detailed understanding of the dynamic cellular and molecular landscape of epileptogenesis.展开更多
Yunnan Province has long served as a key nexus facilitating economic and cultural exchanges between East Asia,Southeast Asia,and Qinghai-Xizang Plateau.However,previous genetic studies were largely limited by sparse m...Yunnan Province has long served as a key nexus facilitating economic and cultural exchanges between East Asia,Southeast Asia,and Qinghai-Xizang Plateau.However,previous genetic studies were largely limited by sparse marker density,low sequencing depth,or single-population designs,leaving the population genetic structure and demographic history insufficiently resolved.Here,we conduct a high-resolution population genetic study based on 366 high-depth whole-genome sequencing samples from 6 ethnic groups,including Bai,Dai,Hani,Miao,Tibetan,and Han.We identify approximately 3.51 million novel variants and reveal fine-scale population structure and complex demographic histories among Yunnan ethnic groups.Beyond the three ancestries proposed by the tri-genealogy hypothesis,we detect a Han Chinese-related lineage,Yan-Huang,within multiple Yunnan populations.We further demonstrate that Yunnan represents a major gene-flow hotspot across East and Southeast Asia despite geographic barriers.Finally,we identify genomic loci under positive selection with candidate genes enriched in immune regulation,energy metabolism,cardiac development,and dietary adaptation,highlighting the role of local environmental pressures in shaping the genetic diversity of Yunnan populations.展开更多
This study investigates the role of ERBB2 mutations in promoting recurrence and metastasis of non-muscle-invasive bladder cancer(NMIBC).Analysis of whole exome sequencing(WES)data from The Cancer Genome Atlas(TCGA)and...This study investigates the role of ERBB2 mutations in promoting recurrence and metastasis of non-muscle-invasive bladder cancer(NMIBC).Analysis of whole exome sequencing(WES)data from The Cancer Genome Atlas(TCGA)and the International Cancer Genome Consortium(ICGC)databases revealed a significant association between ERBB2 mutations and immune cell infiltration.To validate these findings,formalin-fixed,paraffin-embedded tumor tissues from patients with recurrent NMIBC were analyzed,with a focus on ERBB2 mutations.In addition,bladder cancer cell lines carrying wild type or mutant ERBB2 were established using clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(CRISPR/Cas9)technology.Functional experiments,including Western blotting,protein stability assays,and ubiquitination analyses,demonstrated that ERBB2 mutations promote hypoxia-inducible factor-1(HIF-1)phosphorylation,leading to its stabilization and enhancing the proliferative,migratory,and invasive capacities of tumor cells.Furthermore,flow cytometry,5-ethynyl-2′-deoxyuridine(EdU),Cell Counting Kit-8(CCK-8),and Transwell assays confirmed the impact of these mutations on cellular behavior,while drug sensitivity assays indicated increased susceptibility of ERBB2-mutant cells to therapeutic agents.In vivo studies using mouse models further supported these findings,showing that ERBB2 mutations promote tumor growth,metastasis,and macrophage infiltration.Collectively,these results suggest that ERBB2 mutations drive NMIBC progression by stabilizing HIF-1 through phosphorylation,thereby facilitating tumor development and immune modulation,and underscore the potential of ERBB2 as a therapeutic target for preventing NMIBC recurrence and metastasis.展开更多
The Ordos Basin is a large superimposed hydrocarbon-bearing basin in China,and further research on the sedimentary characteristics and sedimentary evolution of the sequence framework of target layers is of great theor...The Ordos Basin is a large superimposed hydrocarbon-bearing basin in China,and further research on the sedimentary characteristics and sedimentary evolution of the sequence framework of target layers is of great theoretical and practical significance for guiding oil and gas exploration.The sedimentary facies and sedimentary evolution of the high-resolution sequence framework of the Carboniferous Taiyuan Formation in the Hangjinqi area have been systematically analyzed for the first time by drilling,logging and seismic data.The results show that four types of sequence interfaces can be identified in the Taiyuan Formation:regional unconformity surfaces,scour surfaces,lithologic-lithofacies transformation surfaces and flooding surfaces.According to the sedimentary response caused by the upward and downward movements of the base level at different levels,the Taiyuan Formation can be divided into 2 long-term cycles(LSC1-LSC2),4 mid-term cycles(MSC1-MSC4)and 7 short-term cycles(SSC1-SSC7).The long-and mid-term cycles correspond to members T1and T2and layers T1-1,T1-2,T2-1,and T2-2,respectively.Long-term cycles are dominated by C1;mid-term cycles are dominated by C1and C2,followed by A2;and short-term cycles are dominated by C1,C2,A1 and A2.Under the high-resolution sequence stratigraphic framework,the Hangjinqi area underwent a transformation of fan delta and tidal flat depositional systems during the Taiyuan Formation sedimentary period.In the MSC1-MSC2stage,owing to a large-scale paleocontinent,the fan delta sedimentary body,which was limited in scale and scope,developed only in the southeastern corner and gradually transitioned basinward to tidal flat facies.In the MSC3-MSC4 stage,as the paleocontinent continuously decreased and the sedimentary range expanded,fan-delta plain sedimentation began in the study area.Several braided distributary channels with poor connectivity developed on the fan-delta plain,and between them were floodplains and peat swamps.展开更多
Objective Adaptive immune responses play a critical role in the pathogenesis of amyotrophic lateral sclerosis(ALS).In this study,we investigated the functional mechanisms of T cell subtypes and assessed the causal lin...Objective Adaptive immune responses play a critical role in the pathogenesis of amyotrophic lateral sclerosis(ALS).In this study,we investigated the functional mechanisms of T cell subtypes and assessed the causal links between CD4+cytotoxic T cell-related genes and ALS risk.Methods Single-cell RNA sequencing(scRNA-seq)of peripheral blood mononuclear cells(PBMCs)from patients with ALS and healthy controls(HC)was used to identify differentially expressed genes(DEGs)in CD4+cytotoxic T cells.Comprehensive analyses of CD4+cytotoxic T cells,including pseudotemporal trajectory,intercellular communication,and metabolic pathway analysis,were performed.Mendelian randomization(MR)analysis evaluated the causal effects of DEGs on ALS risk,with validation using independent genome-wide association study(GWAS)data.Expression patterns of the causal genes were further verified using scRNA-seq,bulk-seq,and clinical samples.Results CD4+cytotoxic T cells were significantly expanded in patients with ALS.The upregulated genes S100A6,SERPINB6,SMAD7,and TPST2 were positively correlated with ALS susceptibility,whereas DIP2A showed a protective association.Conclusion S100A6,SERPINB6,SMAD7,TPST2,and DIP2A were identified as causal genes and potential therapeutic targets in ALS,implicating CD4+cytotoxic T cells in the disease mechanisms.Further studies targeting these genes and neuroinflammatory pathways are warranted.展开更多
Nocardia is an aerobic,gram-positive,and opportunistic bacillus widely distributed in the environment.Nocardia cyriacigeorgica(N.cyriacigeorgica) was first isolated in 2001 from a chronic bronchitis patient,[1] and...Nocardia is an aerobic,gram-positive,and opportunistic bacillus widely distributed in the environment.Nocardia cyriacigeorgica(N.cyriacigeorgica) was first isolated in 2001 from a chronic bronchitis patient,[1] and has since been reported as an emerging clinically relevant pathogen worldwide.The diagnosis of nocardial infections remains challenging due to nonspecific symptoms and low culture sensitivity,resulting in high mortality.[2] Herein,we report a case of N.cyriacigeorgica brain abscess in an immunosuppressed patient who was successfully treated with antibiotics and surgery.展开更多
Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we use...Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we used a single-cell RNA sequencing dataset to create a comprehensive profile of the diverse cell types in the dorsal root ganglia and spinal cord of a mid-thoracic contusion injury model in cynomolgus monkeys.Cell communication analysis indicated that specific signaling events among various dorsal root ganglia cell types occur in response to spinal cord injury.Single-cell analysis using dimensionality reduction clustering identified distinct molecular signatures for nine cell types,including macrophage subpopulations,and differential gene expression profiles between dorsal root ganglia cells and spinal cord cells following spinal cord injury.The macrophage subpopulations were categorized into 11 clusters(MC0-MC10)based on differentially expressed genes,with the top 10 genes being ABCA6,RBMS3,EBF1,LAMA4,ANTXR2,LAMA2,SOX5,FOXP2,GHR,and APOD.MC0,MC1,and MC2 constituted the predominant macrophage populations.MC4,MC6,and MC9 were nearly absent in the spinal cord,but exhibited significant increases in the dorsal root ganglia post-spinal cord injury.Notably,these subpopulations possess a strong capacity for regulating axonal regeneration.The developmental progression of dorsal root ganglia macrophages after spinal cord injury was elucidated using cell trajectory and pseudo-time analyses.Genes such as EBF1(MC6 and MC9 marker),RBMS3(MC6 and MC9 marker),and ABCA6(MC6 marker)showed high expression levels in the critical pathways of macrophage function.Through ligand-receptor pair analysis,we determined that the effects of macrophages on microglia are predominantly mediated through interaction pairs(e.g.,SPP1-CD44,LAMC1-CD44,and FN1-CD44),potentially facilitating specific cellular communications within the immune microenvironment.The single-cell RNA sequencing dataset used in this study represents the first comprehensive transcriptional analysis of the dorsal root ganglia after spinal cord injury in cynomolgus monkeys,encompassing nearly all cell types within the dorsal root ganglia region.Using this dataset,we evaluated diverse subtypes of macrophages in the post-spinal cord injury dorsal root ganglia area and examined the signaling pathways that facilitate interactions among immune response-related macrophages in the dorsal root ganglia.Findings from this study provide a theoretical basis for understanding how the immune microenvironment influences the regenerative capacity of dorsal root ganglia neurons after spinal cord injury and offer novel insights into the complex processes underlying the pathobiology of spinal cord injury.展开更多
基金Supported by National Natural Science Foundation of China (Grant No. 12301594)Science and Technology Research Program of Chongqing Municipal Education Commission (Grant Nos. KJQN202400509and KJQN202300555)+5 种基金Natural Science Foundation of Chongqing of China (Grant No. CSTB2025NSCGPX1033)Chongqing Normal University Foundation Project (Grant No. 23XLB013)Fundamental Research Funds of China West Normal University (Grant No. 25kc008)the Initiative Projects for Ph.D. in China West Normal University (Grant No. 25KE025)Young Doctor Fundation Program of Gansu Province (Grant No.2026QB-083)Research Project of Tianshui Normal University (Grant No. TDJ2023-02)。
摘要Under the optimal norming constants, this paper studies the higher-order expansions of the distributions and densities of the powered order statistics of Maxwell sequence. As auxiliary results, the corresponding convergence rates are obtained. The results show that the convergence rates of distributions and densities of normalized power order statistics are related to power index in principle. Finally, we compared the accuracy of each approximations with its true values through numerical experiments.
基金Supported by the National Natural Science Foundation of China(No.32172979)the Natural Science Foundation of Fujian Province(No.2021J05159)the 2023 Special Program for Promoting High-Quality Development of Marine and Fishery Industry in Fujian Province(No.PJHYF-L-2023-2)。
摘要The Fujian oyster(Crassostrea angulata) is an economically significant shellfish species distributed mainly along the Fujian coast, Southeast China. However, its genetic diversity and structure remain unclear. The main distribution area of the C. angulata is located in Fujian, South China. In total, 420 C. angulata were collected from 14 natural habitats(populations) along the Fujian coast, and their genetic diversity and structure were analyzed in the mitochondrial COI and nuclear gene ITS2 sequences. Results reveal that all the 14 populations of C. angulata exhibited high levels of genetic diversity, with a total of 57(haplotype diversity: 0.811±0.016) and 124(haplotype diversity: 0.912±0.007) haplotypes revealed by COI and ITS2, respectively. Notably, significant intermediate level of genetic differentiations between the Ningde Zhujiang(ZJ) population(FS T by COI: 0.035–0.142, P<0.05;FS T by ITS2: 0.078–0.123, P<0.05) with other populations were observed for the first time, which is also supported by the results of molecular variance analysis(FC T by COI: 0.105, P<0.05;FC T by ITS2: 0.086, P<0.05) and the clustering of the ZJ population into distinct branches in the interpopulation genetic differentiation tree. Furthermore, the evolutionary tree and haplotype network analyses do not support the formation of a clear geographical genealogical structure among these 14 populations. In addition, the population dynamics analysis suggests that the C. angulata may have undergone expansion during the third ice age of the Pleistocene. These results provide a reference for the preservation and further genetic improvement of C. angulata.
基金National Natural Science Foundation of China(51408009)Project of Basic Research Funds for Universities in Beijing(110052971921/062)。
摘要To investigate the seismic response evolution of offshore bridges under the coupled effects of main-aftershock sequences and chloride-induced erosion,a time-dependent damage finite element model of a three-span,three-column simply supported bridge was established based on energy dissipation theory and static pushover analysis.Seismic time-history analysis was conducted to obtain key response indicators,including the maximum displacement and residual displacement at the pier top,as well as the proportion of cumulative hysteretic energy generated at the pier bottom during aftershocks.The results show that structural durability degradation significantly affected the seismic responses:under the same seismic excitation,the maximum pier-top displacement of long-term service bridges increased by at least 10%,with a maximum increase of up to 43%,compared with newly built bridges.When subjected to high-intensity earthquakes,the residual displacement at the pier top continuously increased with service time,rising by 66%,121%,and 163%after 50,75,and 100 a of service,respectively,compared with new bridges.Aftershocks induced noticeable cumulative damage at critical locations such as the pier bottom,with the cumulative hysteretic energy accounting for an average of 14.08%of the total energy dissipation during the main-aftershock sequence,reaching a maximum of 25.3%.Therefore,it is recommended that both the energy contribution of aftershocks and the effect of durability degradation be considered in the seismic design of offshore bridges.
摘要Nickel-based alloy clad plate(NACP)is a promising composite structural material owing to its excellent mechanical and corrosion-resistant properties,as well as its low cost.However,the development of welding technology for NACP has lagged behind.Herein,N08825/L360 NACP was used as the model material,and welded joints were prepared using tungsten inert gas welding to investigate the effects of different welding sequences and filler metals on the micro structure and mechanical properties of joints.The results showed that weld seams filled with mixed filler metals under the post-flyer welding seam welding sequence exhibited a uniform micro structure,and the joints performed well in tensile,bending,and impact tests.For joints filled with mixed filler metals under the post-base welding seam sequence(P-BWS)satisfactory face-bending,root-bending,and tensile properties were achieved;however,cracks formed in the side-bending specimens,and the impact toughness decreased greatly.Micro structural analysis shows that the deterioration in weld toughness is attributable to two factors:severe dimensional embrittlement and micro structural embrittlement,both caused by the formation of hardened welds in the welding seam.Under the P-BWS,using only nickel-based alloy filler metals effectively prevents the deterioration of the micro structure and properties of welding seams.
基金supported by the National Natural Science Foundation of China(81760037)Yunling Scholar Project of Yunnan Province(YNWR-YLXZ-2019-0005)+1 种基金Hunan Provincial Innovation Platform and Talent Program(2018SK4004)Hunan Provincial Natural Science Foundation(2019JJ80048).
摘要The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.
基金supported by Qingdao Key Medical and Health Discipline ProjectThe Intramural Research Program of the Affiliated Hospital of Qingdao University,No. 4910Qingdao West Coast New Area Science and Technology Project,No. 2020-55 (all to SW)。
摘要Border-associated macrophages are located at the interface between the brain and the periphery, including the perivascular spaces, choroid plexus, and meninges. Until recently, the functions of border-associated macrophages have been poorly understood and largely overlooked. However, a recent study reported that border-associated macrophages participate in stroke-induced inflammation, although many details and the underlying mechanisms remain unclear. In this study, we performed a comprehensive single-cell analysis of mouse border-associated macrophages using sequencing data obtained from the Gene Expression Omnibus(GEO) database(GSE174574 and GSE225948). Differentially expressed genes were identified, and enrichment analysis was performed to identify the transcription profile of border-associated macrophages. CellChat analysis was conducted to determine the cell communication network of border-associated macrophages. Transcription factors were predicted using the ‘pySCENIC' tool. We found that, in response to hypoxia, borderassociated macrophages underwent dynamic transcriptional changes and participated in the regulation of inflammatory-related pathways. Notably, the tumor necrosis factor pathway was activated by border-associated macrophages following ischemic stroke. The pySCENIC analysis indicated that the activity of signal transducer and activator of transcription 3(Stat3) was obviously upregulated in stroke, suggesting that Stat3 inhibition may be a promising strategy for treating border-associated macrophages-induced neuroinflammation. Finally, we constructed an animal model to investigate the effects of border-associated macrophages depletion following a stroke. Treatment with liposomes containing clodronate significantly reduced infarct volume in the animals and improved neurological scores compared with untreated animals. Taken together, our results demonstrate comprehensive changes in border-associated macrophages following a stroke, providing a theoretical basis for targeting border-associated macrophages-induced neuroinflammation in stroke treatment.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
摘要Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金Supported by the National Natural Science Foundation of China(Grant No.12161013)the School-Level Student Research Project of Guizhou University of Finance and Economics(Grant No.2024ZXSY239).
摘要In this paper,we introduce non-abelian cohomology groups and classify the nonabelian extensions of Rota-Baxter pre-Lie algebras in terms of non-abelian cohomology groups.Next,we explore the inducibility of pairs of automorphisms and derive the analog Wells exact sequences under the circumstance of Rota-Baxter pre-Lie algebras.Finally,we discuss the inducibility problem of pairs of automorphisms about an abelian extensions of Rota-Baxter pre-Lie algebras.
基金supported by the Construction Project of National Key Laboratory of Organic Dryland Agriculture(Preparatory)(Z135050009017-2)the Grand Science and Technology Special Project in Shanxi Province(202201140601025-2)+2 种基金the National Natural Science Foundation of China(U24A20391)the Hebei Natural Science Foundation(C2023205050)the Cultivating Young Scientific and Technological Leaders at Shanxi Agricultural University(2025QNLJ201)。
摘要Deeper understanding of the mechanism by which wheat responds to salt stress(SS)remains a major challenge due to the scarcity of available single-cellucleus transcriptomics resources.Here,in order to uncover the transcriptional patterns during the late stage of SS of different wheat cells,we performed single-nucleus RNA-sequencing(snRNA-seq)on roots and leaves of wheat seedlings under NaCl treatment for 7 d.Integrating snRNA-seq with bulk RNA-seq and physiological and biochemical indices measurement,the single-cell transcriptome atlas of wheat roots and leaves was constructed,and response patterns of cell types to SS were identified based on enrichment of differentially expressed genes for osmotic stress,ion transport,and oxidative stress.Moreover,several cell-type-specific salt-tolerant candidate genes were determined based on pseudotime analysis and functional validation,such as TaWRKY75-A in root hair cells,NICOTIANAMINE SYNTHASE(NAS)genes in root stele I cells,and dehydrin(DHN)genes in leaf fiber cells.
基金supported by National Natural Science Foundation of Fujian province(2022J01121907).
摘要Hypospadias is a common congenital malformation of the male external genitalia, with severe cases presenting considerable surgical and long-term challenges. Despite the clinical importance of severe hypospadias demonstrated by prolonged hospital stays, repeated surgeries, and substantial costs, the genetic etiology of severe hypospadias remains incompletely understood, particularly in diverse populations. To determine the molecular basis, we performed whole-exome sequencing (WES) on 30 Chinese patients from southeastern China with confirmed 46,XY karyotypes. Our analysis identified clinically relevant genetic variants, including single-nucleotide variants (SNVs) and copy number variations (CNVs), with subsequent phenotypic correlation. Clinically relevant genetic variants were identified in 33.3% (10/30) of cases, including novel SNVs in gonadal regulators (nuclear receptor subfamily 5 group A member 1 [NR5A1] c.1344dupC/c.244+1G>T and SRY-box 3 [SOX3] c.1273G>C), morphogenetic modulators (GLI family zinc finger 3 [GLI3] c.4731delA and aristaless-related homeobox [mARX] c.644C>G), and syndromic genes (patched domain containing 1 [PTCHD1] c.667G>A and euchromatic histone lysine methyltransferase 1 [EHMT1] c.3081C>T). Additionally, recurrent CNVs at 22q12.3 and a novel CNV exon 18 deletion in myelin regulatory factor (MYRF) and 18q11.2 were identified. Mutation carriers showed a significantly higher frequency of cryptorchidism (40.0% vs 5.0%, P < 0.01) and a higher prevalence of ≥3 associated malformations (80.0% vs 35.0%, P < 0.05) than non-carriers, highlighting genotype–phenotype correlations. The 33.3% diagnostic yield tripled conventional estimates, demonstrating WES efficacy in identifying SNVs and CNVs in severe phenotypes. These findings reveal the genetic heterogeneity of severe hypospadias and support WES utility in uncovering novel variants and structural genomic alterations.
基金supported by the National Natural Science Foundation of China(U23A20160,32360336)Guizhou Provincial Key Technology R&D Program(Qian KeHe ZhiCheng[2023]YiBan035).
摘要Natural hybridization is known to play a vital role in speciation;however,the mechanisms underlying the early stages of natural hybridization remain unclear.Where two plant species come into contact,two driving forces may balance the dynamic consequences of hybridization:fusion by hybridization-mediated gene flow,and separation by reproductive isolation(RI)(Ma et al.,2010a,b;Chang et al.,2022).
基金supported by the National Science Foundation of China(No.62171387)the Science and Technology Program of Sichuan Province(No.2024NSFSC0468)the China Postdoctoral Science Foundation(No.2019M663475).
摘要As an important resource in data link,time slots should be strategically allocated to enhance transmission efficiency and resist eavesdropping,especially considering the tremendous increase in the number of nodes and diverse communication needs.It is crucial to design control sequences with robust randomness and conflict-freeness to properly address differentiated access control in data link.In this paper,we propose a hierarchical access control scheme based on control sequences to achieve high utilization of time slots and differentiated access control.A theoretical bound of the hierarchical control sequence set is derived to characterize the constraints on the parameters of the sequence set.Moreover,two classes of optimal hierarchical control sequence sets satisfying the theoretical bound are constructed,both of which enable the scheme to achieve maximum utilization of time slots.Compared with the fixed time slot allocation scheme,our scheme reduces the symbol error rate by up to 9%,which indicates a significant improvement in anti-interference and eavesdropping capabilities.
基金National Natural Science Foundation of China(81673727)。
摘要Uncovering the underlying process of epileptogenesis is crucial for developing effective treatment strategies for epilepsy.However,the cellular and molecular changes throughout epileptogenesis are not fully understood.In this study,single-nucleus RNA sequencing was performed on the hippocampus,temporal cortex,and thalamus across the acute,latent,and chronic phases in a pilocarpine-induced rat model and controls.We created a comprehensive single-nucleus transcriptomic atlas of rat epileptogenesis,consisting of 311,177 single nuclei.Our analysis revealed distinct transcriptional signatures across the three phases and regions,including significant gene expression changes in the acute phase and critical synaptic and neural network remodeling in the thalamus during the latent phase.Notably,we identified two novel astrocyte clusters during epileptogenesis,with the EX-Astro C3-IN pathway emerging as a potential intervention target.The dataset provides a detailed understanding of the dynamic cellular and molecular landscape of epileptogenesis.
基金supported by the National Key R&D Program of China(2024YFA1308300)the National Natural Science Foundation of China(82460112)+5 种基金the“Xingdian Talents”Support Project of Yunnan Province(RLQB20220006)Yunnan Fundamental Research Projects(202501AS070031)the Yunnan Provincial Key Research and Development Plan(202403AC100020)the Innovative Team of Yunnan Province(202305AS350019)the Yunnan High-level Talent Training Support Program,the Technology Innovation and Talent Cultivation Project of Yunnan Province(202105AD160064)the Shenzhen Science and Technology Program(SYSPG20241211173852024).
摘要Yunnan Province has long served as a key nexus facilitating economic and cultural exchanges between East Asia,Southeast Asia,and Qinghai-Xizang Plateau.However,previous genetic studies were largely limited by sparse marker density,low sequencing depth,or single-population designs,leaving the population genetic structure and demographic history insufficiently resolved.Here,we conduct a high-resolution population genetic study based on 366 high-depth whole-genome sequencing samples from 6 ethnic groups,including Bai,Dai,Hani,Miao,Tibetan,and Han.We identify approximately 3.51 million novel variants and reveal fine-scale population structure and complex demographic histories among Yunnan ethnic groups.Beyond the three ancestries proposed by the tri-genealogy hypothesis,we detect a Han Chinese-related lineage,Yan-Huang,within multiple Yunnan populations.We further demonstrate that Yunnan represents a major gene-flow hotspot across East and Southeast Asia despite geographic barriers.Finally,we identify genomic loci under positive selection with candidate genes enriched in immune regulation,energy metabolism,cardiac development,and dietary adaptation,highlighting the role of local environmental pressures in shaping the genetic diversity of Yunnan populations.
基金supported by the Health Special Program of Jilin Provincial Department of Finance,China(Grant Nos.:ZXWSTZXEY026 and 2024WSZX-B18)the Natural Science Foundation of Jilin Provincial Department of Science and Technology Upper-level Project,China(Project No.:YDZJ202201ZYTS059).
摘要This study investigates the role of ERBB2 mutations in promoting recurrence and metastasis of non-muscle-invasive bladder cancer(NMIBC).Analysis of whole exome sequencing(WES)data from The Cancer Genome Atlas(TCGA)and the International Cancer Genome Consortium(ICGC)databases revealed a significant association between ERBB2 mutations and immune cell infiltration.To validate these findings,formalin-fixed,paraffin-embedded tumor tissues from patients with recurrent NMIBC were analyzed,with a focus on ERBB2 mutations.In addition,bladder cancer cell lines carrying wild type or mutant ERBB2 were established using clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(CRISPR/Cas9)technology.Functional experiments,including Western blotting,protein stability assays,and ubiquitination analyses,demonstrated that ERBB2 mutations promote hypoxia-inducible factor-1(HIF-1)phosphorylation,leading to its stabilization and enhancing the proliferative,migratory,and invasive capacities of tumor cells.Furthermore,flow cytometry,5-ethynyl-2′-deoxyuridine(EdU),Cell Counting Kit-8(CCK-8),and Transwell assays confirmed the impact of these mutations on cellular behavior,while drug sensitivity assays indicated increased susceptibility of ERBB2-mutant cells to therapeutic agents.In vivo studies using mouse models further supported these findings,showing that ERBB2 mutations promote tumor growth,metastasis,and macrophage infiltration.Collectively,these results suggest that ERBB2 mutations drive NMIBC progression by stabilizing HIF-1 through phosphorylation,thereby facilitating tumor development and immune modulation,and underscore the potential of ERBB2 as a therapeutic target for preventing NMIBC recurrence and metastasis.
基金supported by the Fundamental Research Funds for the Liaoning Universities(Grant No.LJ202410166012).
摘要The Ordos Basin is a large superimposed hydrocarbon-bearing basin in China,and further research on the sedimentary characteristics and sedimentary evolution of the sequence framework of target layers is of great theoretical and practical significance for guiding oil and gas exploration.The sedimentary facies and sedimentary evolution of the high-resolution sequence framework of the Carboniferous Taiyuan Formation in the Hangjinqi area have been systematically analyzed for the first time by drilling,logging and seismic data.The results show that four types of sequence interfaces can be identified in the Taiyuan Formation:regional unconformity surfaces,scour surfaces,lithologic-lithofacies transformation surfaces and flooding surfaces.According to the sedimentary response caused by the upward and downward movements of the base level at different levels,the Taiyuan Formation can be divided into 2 long-term cycles(LSC1-LSC2),4 mid-term cycles(MSC1-MSC4)and 7 short-term cycles(SSC1-SSC7).The long-and mid-term cycles correspond to members T1and T2and layers T1-1,T1-2,T2-1,and T2-2,respectively.Long-term cycles are dominated by C1;mid-term cycles are dominated by C1and C2,followed by A2;and short-term cycles are dominated by C1,C2,A1 and A2.Under the high-resolution sequence stratigraphic framework,the Hangjinqi area underwent a transformation of fan delta and tidal flat depositional systems during the Taiyuan Formation sedimentary period.In the MSC1-MSC2stage,owing to a large-scale paleocontinent,the fan delta sedimentary body,which was limited in scale and scope,developed only in the southeastern corner and gradually transitioned basinward to tidal flat facies.In the MSC3-MSC4 stage,as the paleocontinent continuously decreased and the sedimentary range expanded,fan-delta plain sedimentation began in the study area.Several braided distributary channels with poor connectivity developed on the fan-delta plain,and between them were floodplains and peat swamps.
摘要Objective Adaptive immune responses play a critical role in the pathogenesis of amyotrophic lateral sclerosis(ALS).In this study,we investigated the functional mechanisms of T cell subtypes and assessed the causal links between CD4+cytotoxic T cell-related genes and ALS risk.Methods Single-cell RNA sequencing(scRNA-seq)of peripheral blood mononuclear cells(PBMCs)from patients with ALS and healthy controls(HC)was used to identify differentially expressed genes(DEGs)in CD4+cytotoxic T cells.Comprehensive analyses of CD4+cytotoxic T cells,including pseudotemporal trajectory,intercellular communication,and metabolic pathway analysis,were performed.Mendelian randomization(MR)analysis evaluated the causal effects of DEGs on ALS risk,with validation using independent genome-wide association study(GWAS)data.Expression patterns of the causal genes were further verified using scRNA-seq,bulk-seq,and clinical samples.Results CD4+cytotoxic T cells were significantly expanded in patients with ALS.The upregulated genes S100A6,SERPINB6,SMAD7,and TPST2 were positively correlated with ALS susceptibility,whereas DIP2A showed a protective association.Conclusion S100A6,SERPINB6,SMAD7,TPST2,and DIP2A were identified as causal genes and potential therapeutic targets in ALS,implicating CD4+cytotoxic T cells in the disease mechanisms.Further studies targeting these genes and neuroinflammatory pathways are warranted.
基金funded by grants from Guangdong Basic and Applied Basic Research Foundation (2025A1515011901)Natural Science Foundation of Guangdong Province (2024A1515012228)。
摘要Nocardia is an aerobic,gram-positive,and opportunistic bacillus widely distributed in the environment.Nocardia cyriacigeorgica(N.cyriacigeorgica) was first isolated in 2001 from a chronic bronchitis patient,[1] and has since been reported as an emerging clinically relevant pathogen worldwide.The diagnosis of nocardial infections remains challenging due to nonspecific symptoms and low culture sensitivity,resulting in high mortality.[2] Herein,we report a case of N.cyriacigeorgica brain abscess in an immunosuppressed patient who was successfully treated with antibiotics and surgery.
基金supported by the Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)the National Key Research andDevelopment Project of Stem Cell and Transformation Research,No.2019YFA0112100(to SF)+2 种基金Tianjin Natural Science Foundation’s Youth Project for DiverseInvestments,No.21JCQNJC01300(to BF)the National Natural Science Foundation of China(Youth Program),No.82102563(to BF)Tianjin Major Science andTechnology Special Projects and Engineering Projects,No.21ZXJBSY00080(to YR).
摘要Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we used a single-cell RNA sequencing dataset to create a comprehensive profile of the diverse cell types in the dorsal root ganglia and spinal cord of a mid-thoracic contusion injury model in cynomolgus monkeys.Cell communication analysis indicated that specific signaling events among various dorsal root ganglia cell types occur in response to spinal cord injury.Single-cell analysis using dimensionality reduction clustering identified distinct molecular signatures for nine cell types,including macrophage subpopulations,and differential gene expression profiles between dorsal root ganglia cells and spinal cord cells following spinal cord injury.The macrophage subpopulations were categorized into 11 clusters(MC0-MC10)based on differentially expressed genes,with the top 10 genes being ABCA6,RBMS3,EBF1,LAMA4,ANTXR2,LAMA2,SOX5,FOXP2,GHR,and APOD.MC0,MC1,and MC2 constituted the predominant macrophage populations.MC4,MC6,and MC9 were nearly absent in the spinal cord,but exhibited significant increases in the dorsal root ganglia post-spinal cord injury.Notably,these subpopulations possess a strong capacity for regulating axonal regeneration.The developmental progression of dorsal root ganglia macrophages after spinal cord injury was elucidated using cell trajectory and pseudo-time analyses.Genes such as EBF1(MC6 and MC9 marker),RBMS3(MC6 and MC9 marker),and ABCA6(MC6 marker)showed high expression levels in the critical pathways of macrophage function.Through ligand-receptor pair analysis,we determined that the effects of macrophages on microglia are predominantly mediated through interaction pairs(e.g.,SPP1-CD44,LAMC1-CD44,and FN1-CD44),potentially facilitating specific cellular communications within the immune microenvironment.The single-cell RNA sequencing dataset used in this study represents the first comprehensive transcriptional analysis of the dorsal root ganglia after spinal cord injury in cynomolgus monkeys,encompassing nearly all cell types within the dorsal root ganglia region.Using this dataset,we evaluated diverse subtypes of macrophages in the post-spinal cord injury dorsal root ganglia area and examined the signaling pathways that facilitate interactions among immune response-related macrophages in the dorsal root ganglia.Findings from this study provide a theoretical basis for understanding how the immune microenvironment influences the regenerative capacity of dorsal root ganglia neurons after spinal cord injury and offer novel insights into the complex processes underlying the pathobiology of spinal cord injury.