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
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
Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches...Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches.While the study represents a valuable methodological step forward,it remains limited by singlecenter design,lack of quantitative calibration,and insufficient control for contamination and inter-laboratory variability.This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized,consensus-driven workflows to ensure reproducibility and clinical reliability.The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration,particularly for recurrence prediction,treatment-response monitoring,and perioperative complication risk assessment.By addressing these methodological,economic,and ethical challenges,the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.展开更多
This study establishes and validates a method for the precise quantification of aquatic microbial loads using microbial diversity absolute quantitative sequencing.By adding synthetic spike-in DNA to water samples from...This study establishes and validates a method for the precise quantification of aquatic microbial loads using microbial diversity absolute quantitative sequencing.By adding synthetic spike-in DNA to water samples from the Dahei River prior to DNA extraction and 16S rRNA gene sequencing,it generates standard curves to convert sequencing data into absolute microbial copy numbers.The method,which is proved highly accurate(R^(2)>0.99),reveals a clear contrast between the river sites:the upstream community has not only a significantly higher total microbial load but also a completely different makeup of species compared to the downstream site.This approach effectively overcomes the limitations of relative abundance analysis,providing a powerful tool for environmental monitoring,and proposes key steps for future standardization to ensure data comparability and integration.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
Breast cancer is a malignant tumor originating from breast epithelial tissue.In essence,breast epithelial cells undergo gene mutation under the influence of carcinogenic factors,leading to abnormal cell proliferation ...Breast cancer is a malignant tumor originating from breast epithelial tissue.In essence,breast epithelial cells undergo gene mutation under the influence of carcinogenic factors,leading to abnormal cell proliferation and loss of organism regulation,ultimately leading to the formation of tumors with invasive and metastatic capabilities.Carcinogenic factors of breast cancer involve multiple cellular and molecular mechanisms.Among them,disseminated tumor cells(DTCs)are considered important for treating breast cancer.However,traditional bulk sequencing techniques have limitations,such as the inability to distinguish individual cell differences and dilution of information from key cell subpopulations(such as cancer stem cells and rare immune cells).Single-cell sequencing(scRNA-seq)overcomes the heterogeneity of tumors that traditional sequencing cannot capture by analysing the molecular characteristics of single cells,providing a highresolution perspective for precise typing of breast cancer,exploration of the mechanism of the microenvironment,and personalized treatment.Through this technology,researchers can identify specific gene expression profiles of different cell subpopulations,thus providing a new basis for the molecular typing and personalized treatment of breast cancer.This article explains how single-cell sequencing is used to describe the origin of disseminated tumor cells(DTCs),analyse tumor heterogeneity,metastasis,etc.,and review the current literature on the use of scRNA-seq in breast cancer treatment.In the future,cell separation and processing steps in single-cell sequencing will be further improved to ensure the accuracy of the results and broader application in clinical diagnosis and treatment.展开更多
We are sorry for the mistakes of Affiliation,"a State Key Laboratory of Advanced Fiber Materials,Center for Advanced Low-Dimension Materials,Donghua University,Shanghai 201620,China"should be replaced by&quo...We are sorry for the mistakes of Affiliation,"a State Key Laboratory of Advanced Fiber Materials,Center for Advanced Low-Dimension Materials,Donghua University,Shanghai 201620,China"should be replaced by"a State Key Laboratory of Advanced Fiber Materials,Center for Advanced Low-Dimension Materials,College of Materials Science and Engineering,Donghua University,Shanghai 201620,China".We apologized for the inconvenience caused by this error.展开更多
Objective:Long non-coding RNAs have been found to play a pivotal role in breast cancer,yet the majority of these lncRNAs remain to be thoroughly investigated.This study aimed to explore the role of differentially expr...Objective:Long non-coding RNAs have been found to play a pivotal role in breast cancer,yet the majority of these lncRNAs remain to be thoroughly investigated.This study aimed to explore the role of differentially expressed long non-coding RNAs(lncRNAs)in breast cancer stemness and drug sensitivity.Methods:Database mining was performed to evaluate the expression of LINC00467 in different types of breast cancer and its association with clinical features.The function of LINC00467 was examined through colony formation assays,quantitative reverse transcription PCR(qRT-PCR),and western blotting following LINC00467 silencing in breast cancer cell lines.Results:LINC00467 was significantly upregulated in various breast cancer subtypes with spatial specificity.Silencing LINC00467 reduced clonogenic capacity and downregulated the stemness-associated factor LIN28B as well as phosphorylated RAC-alpha serine/threonine-protein kinase(p-AKT).The transcription factors specificity protein 1(SP1)and E2F transcription factor 1(E2F1)were predicted to bind to the LINC00467 promoter.Furthermore,breast cancer samples with high LINC00467 expression displayed reduced sensitivity to AKT inhibitors,and high LINC00467 expression was negatively correlated with the therapeutic response to programmed cell death 1(PD-1)antibodies.Conclusion:Our findings suggest that spatially expressed LINC00467 may promote breast cancer stemness by regulating AKT signaling and could serve as a potential new therapeutic target and indicator of drug sensitivity in breast cancer.展开更多
Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusio...Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusion genes in patients with AML.Methods A total of 85 adult AML samples previously identified as fusion gene-negative by multiplex nested reverse transcription-polymerase chain reaction(RT-PCR)were subjected to NGS analysis.Results Fusion genes were detected in 21 of 72(29.2%)patients.Among the 26 primary refractory patients,11(42.3%)exhibited fusion genes,whereas among the 18 relapsed patients,fusion genes were identified in five(27.8%).Notably,lysine methyltransferase 2A(KMT2A)and nucleoporin 98(NUP98)rearrangements were enriched in refractory/relapsed patients.Additionally,recurrent fusion transcripts involving eukaryotic translation initiation factor 4A1(EIF4A1)were identified.The identification of additional fusion genes resulted in an approximate 20.8%(11/53)reclassification of medium-risk karyotypes to the high-risk category,thereby enhancing diagnostic accuracy.Conclusions Targeted NGS may complement conventional methods for identifying novel fusions in refractory/relapsed AML;however,its prognostic value requires validation in prospective controlled trials.展开更多
AIM:To identify differentially expressed genes(DEGs)in rabbits with traumatic proliferative vitreoretinopathy(PVR)using high-throughput sequencing(HTS).METHODS:Thirty-six rabbits were randomly allocated to the control...AIM:To identify differentially expressed genes(DEGs)in rabbits with traumatic proliferative vitreoretinopathy(PVR)using high-throughput sequencing(HTS).METHODS:Thirty-six rabbits were randomly allocated to the control group and the PVR group induced by scleral puncture.On the 28th day following modeling,fundus B-ultrasound and fundus photography were performed on all rabbits,and hematoxylin-eosin(HE)staining was conducted on retinal tissues.RNA sequencing(RNA-Seq)combined with bioinformatics analysis was used to screen PVRassociated DEGs.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out for the identified DEGs.S100A6,EDNRB and CEBPD were randomly selected for quantitative reverse transcription polymerase chain reaction(RT-qPCR)validation to verify the reliability of the RNA-Seq results.RESULTS:Fundus B-ultrasound,fundus photography and retinal HE staining confirmed the successful establishment of the traumatic PVR rabbit model.A total of 1587 DEGs were screened,of which 1094 were significantly up-regulated and 493 were significantly down-regulated.GO function enrichment analysis showed that these DEGs were mainly enriched in immune response,extracellular region and inflammatory response.KEGG pathway enrichment analysis showed that DEGs were mainly involved in the cytokine-cytokine receptor interaction and hematopoietic cell lineage pathway.RT-qPCR results showed that S100A6,CEBPD and EDNRB were significantly increased in PVR group.CONCLUSION:A large number of genes exhibit significant differential expression in rabbits with traumatic PVR,among which S100A6,CEBPD and EDNRB may play an important role in traumatic PVR.展开更多
Overview of diabetic gastroparesis Diabetic gastroparesis(DGP)is a common gastrointestinal complication of diabetes mellitus,characterized primarily by delayed gastric emptying.With the rising prevalence of diabetes,t...Overview of diabetic gastroparesis Diabetic gastroparesis(DGP)is a common gastrointestinal complication of diabetes mellitus,characterized primarily by delayed gastric emptying.With the rising prevalence of diabetes,the incidence of DGP has increased annually,currently affecting approximately 50%of diabetic patients[1].Its main clinical manifestations include belching,nausea,vomiting,abdominal distension,and anorexia,which not only severely impair patients’quality of life but also trigger serious complications such as blood glucose fluctuations[2].Diagnosis primarily relies on clinical symptoms,exclusionary testing,and gastric emptying scintigraphy.展开更多
Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinic...Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinical management.Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR,often resulting in delayed therapeutic interventions.Highthroughput sequencing(HTS)technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy.In the context of TB,diverse sequencing strategies and platforms are being employed to fulfill specific research goals,ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates.This review systematically examines current progress in the application of HTS for rapid pathogen identification,comprehensive AMR profiling,epidemiological studies,advances in novel drugs,and vaccine development.Furthermore,we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.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
The triple transgenic mouse model of Alzheimer’s disease(3×Tg-AD)is a widely used model that exhibits region-dependent patterns of progressive amyloid-βand tau pathology.Although structural brain abnormalities ...The triple transgenic mouse model of Alzheimer’s disease(3×Tg-AD)is a widely used model that exhibits region-dependent patterns of progressive amyloid-βand tau pathology.Although structural brain abnormalities on magnetic resonance imaging have been observed in 3×Tg-AD mice at later disease stages(>12 months)and as early as 2 months,few studies have investigated changes in these mice during the stage with extensive amyloid-βdeposition and onset of tau pathology(around 9 months).This study aimed to assess brain morphometry and microstructure alterations in 9 month-old 3×Tg-AD mice to better understand the neural mechanisms underlying these specific pathological features.Voxel-based analyses were employed on T2-weighted and diffusion tensor imaging to identify differences between 3×Tg-AD and control mice.Compared with controls,3×Tg-AD mice exhibited lower gray matter volume in several regions including both hippocampal regions,the right thalamus,the left caudoputamen,and the cortex.Reduced white matter volume was observed in fiber tracts including the corpus callosum,internal capsule,stria terminalis,and olfactory tract.Whole-brain diffusion tensor imaging analysis revealed a significant decrease in fractional anisotropy and an increase in both radial and mean diffusivity within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei,with no significant difference in axial diffusivity.Correlation analyses demonstrated significant associations between behavioral performance measures,with both gray and white matter volumes within regions showing significant morphometric differences.Notably,behavioral performance also exhibited significant correlations with diffusion tensor imaging measures particularly within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei.Immunofluorescence analysis confirmed increased amyloid-βplaques and p-Tau protein expression in the hippocampal regions of 3×Tg-AD mice,which corroborated the magnetic resonance imaging findings.Transcriptome analysis in hippocampus tissue identified 1389 differentially expressed genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that numerous differentially expressed genes were enriched in biological processes relevant to synapse structure,cognition,learning,and memory,with particular emphasis on Wnt and mitogen-activated protein kinase signaling pathways.Collectively,these findings suggest that intricate anatomical and microstructural alterations occur in 3×Tg-AD model mice at the onset of pathology around 9 months,potentially driven by gene expression alterations.Moreover,our results support the potential utility of brain volume and diffusion metrics as biomarkers for Alzheimer’s disease pathology,which could have significant implications for clinical diagnosis of Alzheimer’s disease patients.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
OBJECTIVE:To investigate Acupuncture-herb therapy modulates gut microbiota in abdominal obesity.METHODS:A randomized controlled trial was designed in accordance with standard protocols.Abdominally obese subjects were ...OBJECTIVE:To investigate Acupuncture-herb therapy modulates gut microbiota in abdominal obesity.METHODS:A randomized controlled trial was designed in accordance with standard protocols.Abdominally obese subjects were randomized into four groups:A2(Control):double placebo,A1(Needle):press needle+placebo herb,A3(herb):herbal medicine(Huatan Lishi Fang化痰利湿方)+placebo needle,A4(Combination):press needle+herbal medicine.After 12 weeks of treatment,groups were relabeled B1-B4.Weight,waist circumference,and body mass index were measured monthly.Gut microbiota was analyzed via 16S rRNA sequencing for diversity and abundance.RESULTS:Combined needle-herb therapy significantly reduced waist circumference(P<0.05).All treatments altered gut microbiota composition.The combination group showed significant changes in diversity(Chao1,Shannon,Simpson;P<0.05).Needle therapy increased Bacteroidia;herbs reduced Lachnospiraceae and Megamonas.All results were significant(P<0.05).CONCLUSION:Combined needle-herb treatment modulated 25 key gut flora across multiple taxonomic levels in abdominal obesity.It reduced Firmicutes and Bacteroidota.Bacteroidota,Actinobacteriota,and Prevotellaceae may suppress obesity,whereas Proteobacteria,Lachnospiraceae,and Megamonas may promote it.The combination specifically altered Bacteroidaceae,Lachnospiraceae,Bacteroidia,and Megamonas.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
Metagenomic next-generation sequencing(mNGS)is a culture-independent technique that directly extracts and sequences all nucleic acids from clinical specimens.By leveraging high-throughput sequencing and bioinformatic ...Metagenomic next-generation sequencing(mNGS)is a culture-independent technique that directly extracts and sequences all nucleic acids from clinical specimens.By leveraging high-throughput sequencing and bioinformatic analysis,it characterizes the entire microbial landscape,including bacteria,fungi,viruses,and parasites.This approach significantly broadens detection coverage,improves sensitivity,and reduces turnaround time compared with conventional diagnostic methods.Since its initial application to suspected infectious uveitis by Doan et al.in 2006,mNGS has been increasingly integrated into ophthalmic practice to facilitate pathogen identification or exclusion[1].展开更多
BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prola...BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prolapse and hemorrhoids,and tissue selecting technique,are employed for treatment,they are often associated with postoperative complications,including unsatisfactory defecation,bleeding,and anal stenosis.In contrast,Xiaozhiling injection,a traditional Chinese medicine-based therapy,has emerged as a minimally invasive and effective alternative for internal hemorrhoids.This treatment offers distinct advantages,such as reduced dietary restrictions,broad applicability,and minimal induction of systemic inflammatory responses.Additionally,Xiaozhiling injection effectively eliminates hemorrhoid nuclei,prevents local tissue necrosis,preserves anal cushion integrity,and mitigates postoperative complications,including bleeding and prolapse.Despite its clinical efficacy,the molecular mechanisms underlying its therapeutic effects remain poorly understood,warranting further investigation.AIM To investigate the molecular mechanism underlying the therapeutic effect of Xiaozhiling injection in the treatment of internal hemorrhoids.METHODS An internal hemorrhoid model was established in rats,and the rats were randomly divided into a modeling group[control group(CK group)]and a treatment group.One week after injection,Stereo-seq and electron microscopy were used to study the changes in gene expression and subcellular structures in fibroblasts.RESULTS Single-cell sequencing revealed differences in the expression and transcript levels of the genes collagen 3 alpha 1,decorin,and actin alpha 2 in fibroblasts between the CK group and the treatment group.Spatial transcriptome analysis revealed that genes of the sphingosine kinase 1(Sphk1)/sphingosine-1-phosphate(S1P)pathway spatially overlapped with key genes of the transforming growth factor beta 1 pathway,namely,Sphk1,S1P receptor,and transforming growth factor beta 1,in the treatment group.The proportion of fibroblasts was lower in the treatment group than in the CK group,and Xiaozhiling treatment had a significant effect on the proportion of fibroblasts in hemorrhoidal tissue.Immunohistochemistry revealed a significant increase in the expression of a fibroblast marker.Electron microscopy showed that the endoplasmic reticulum of fibroblasts contained a large amount of glycogen,indicating cell activation.Fibroblast activation and the expression of key genes of the Sphk1-S1P pathway could be observed at the injection site,suggesting that after Xiaozhiling intervention,the Sphk1-S1P pathway could be activated to promote fibrosis.CONCLUSION Xiaozhiling injection exerts its therapeutic effects on internal hemorrhoids by promoting collagen synthesis and secretion in fibroblasts.After Xiaozhiling intervention,the Sphk1-S1P pathway can be activated to promote fibrosis.展开更多
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)。
文摘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).
文摘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(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).
文摘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.
文摘Wu et al recently applied multi-region 16S rRNA sequencing to characterize the gastric cancer microbiome,demonstrating improved taxonomic resolution and detection sensitivity over conventional single-region approaches.While the study represents a valuable methodological step forward,it remains limited by singlecenter design,lack of quantitative calibration,and insufficient control for contamination and inter-laboratory variability.This editorial critically appraises these methodological gaps and emphasizes that future efforts must focus on harmonized,consensus-driven workflows to ensure reproducibility and clinical reliability.The translational potential of multi-region 16S lies in moving from descriptive microbial profiling to actionable clinical integration,particularly for recurrence prediction,treatment-response monitoring,and perioperative complication risk assessment.By addressing these methodological,economic,and ethical challenges,the field can advance toward evidence-based and clinically deployable microbiome-guided precision oncology.
基金supported by the National Natural Science Foundation of China(Grant No.32160172)the Key Science-Technology Project of Inner Mongolia(2023KYPT0010)+1 种基金the Natural Science Foundation of Inner Mongolia Autonomous Region of China(Grant No.2025QN03006)the 2023 Inner Mongolia Public Institution High-level Talent Introduction Scientific Research Support Project.
文摘This study establishes and validates a method for the precise quantification of aquatic microbial loads using microbial diversity absolute quantitative sequencing.By adding synthetic spike-in DNA to water samples from the Dahei River prior to DNA extraction and 16S rRNA gene sequencing,it generates standard curves to convert sequencing data into absolute microbial copy numbers.The method,which is proved highly accurate(R^(2)>0.99),reveals a clear contrast between the river sites:the upstream community has not only a significantly higher total microbial load but also a completely different makeup of species compared to the downstream site.This approach effectively overcomes the limitations of relative abundance analysis,providing a powerful tool for environmental monitoring,and proposes key steps for future standardization to ensure data comparability and integration.
基金funded by grants from Guangdong Basic and Applied Basic Research Foundation (2025A1515011901)Natural Science Foundation of Guangdong Province (2024A1515012228)。
文摘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.
文摘Breast cancer is a malignant tumor originating from breast epithelial tissue.In essence,breast epithelial cells undergo gene mutation under the influence of carcinogenic factors,leading to abnormal cell proliferation and loss of organism regulation,ultimately leading to the formation of tumors with invasive and metastatic capabilities.Carcinogenic factors of breast cancer involve multiple cellular and molecular mechanisms.Among them,disseminated tumor cells(DTCs)are considered important for treating breast cancer.However,traditional bulk sequencing techniques have limitations,such as the inability to distinguish individual cell differences and dilution of information from key cell subpopulations(such as cancer stem cells and rare immune cells).Single-cell sequencing(scRNA-seq)overcomes the heterogeneity of tumors that traditional sequencing cannot capture by analysing the molecular characteristics of single cells,providing a highresolution perspective for precise typing of breast cancer,exploration of the mechanism of the microenvironment,and personalized treatment.Through this technology,researchers can identify specific gene expression profiles of different cell subpopulations,thus providing a new basis for the molecular typing and personalized treatment of breast cancer.This article explains how single-cell sequencing is used to describe the origin of disseminated tumor cells(DTCs),analyse tumor heterogeneity,metastasis,etc.,and review the current literature on the use of scRNA-seq in breast cancer treatment.In the future,cell separation and processing steps in single-cell sequencing will be further improved to ensure the accuracy of the results and broader application in clinical diagnosis and treatment.
文摘We are sorry for the mistakes of Affiliation,"a State Key Laboratory of Advanced Fiber Materials,Center for Advanced Low-Dimension Materials,Donghua University,Shanghai 201620,China"should be replaced by"a State Key Laboratory of Advanced Fiber Materials,Center for Advanced Low-Dimension Materials,College of Materials Science and Engineering,Donghua University,Shanghai 201620,China".We apologized for the inconvenience caused by this error.
基金supported by grants from the Natural Science Foundation of Hunan Province(2023JJ30879,2026JJ80914)。
文摘Objective:Long non-coding RNAs have been found to play a pivotal role in breast cancer,yet the majority of these lncRNAs remain to be thoroughly investigated.This study aimed to explore the role of differentially expressed long non-coding RNAs(lncRNAs)in breast cancer stemness and drug sensitivity.Methods:Database mining was performed to evaluate the expression of LINC00467 in different types of breast cancer and its association with clinical features.The function of LINC00467 was examined through colony formation assays,quantitative reverse transcription PCR(qRT-PCR),and western blotting following LINC00467 silencing in breast cancer cell lines.Results:LINC00467 was significantly upregulated in various breast cancer subtypes with spatial specificity.Silencing LINC00467 reduced clonogenic capacity and downregulated the stemness-associated factor LIN28B as well as phosphorylated RAC-alpha serine/threonine-protein kinase(p-AKT).The transcription factors specificity protein 1(SP1)and E2F transcription factor 1(E2F1)were predicted to bind to the LINC00467 promoter.Furthermore,breast cancer samples with high LINC00467 expression displayed reduced sensitivity to AKT inhibitors,and high LINC00467 expression was negatively correlated with the therapeutic response to programmed cell death 1(PD-1)antibodies.Conclusion:Our findings suggest that spatially expressed LINC00467 may promote breast cancer stemness by regulating AKT signaling and could serve as a potential new therapeutic target and indicator of drug sensitivity in breast cancer.
基金supported by the National Natural Science Foundation of China(No.82100164,82302692)the Capital Medical University Research Cultivation Fund(No.PYZ22099)the Guangdong Provincial Medical Science and Technology Research Fund Project(No.A2024190).
文摘Background Fusion genes play a crucial role in the pathogenesis of acute myeloid leukemia(AML).This study investigated the utility of targeted next-generation sequencing(NGS)of RNA for detecting rare and unknown fusion genes in patients with AML.Methods A total of 85 adult AML samples previously identified as fusion gene-negative by multiplex nested reverse transcription-polymerase chain reaction(RT-PCR)were subjected to NGS analysis.Results Fusion genes were detected in 21 of 72(29.2%)patients.Among the 26 primary refractory patients,11(42.3%)exhibited fusion genes,whereas among the 18 relapsed patients,fusion genes were identified in five(27.8%).Notably,lysine methyltransferase 2A(KMT2A)and nucleoporin 98(NUP98)rearrangements were enriched in refractory/relapsed patients.Additionally,recurrent fusion transcripts involving eukaryotic translation initiation factor 4A1(EIF4A1)were identified.The identification of additional fusion genes resulted in an approximate 20.8%(11/53)reclassification of medium-risk karyotypes to the high-risk category,thereby enhancing diagnostic accuracy.Conclusions Targeted NGS may complement conventional methods for identifying novel fusions in refractory/relapsed AML;however,its prognostic value requires validation in prospective controlled trials.
基金Supported by the National Natural Science Foundation of China(No.82260210)the Natural Science Foundation of Jiangxi Province(No.20252BAC250122)+2 种基金the Science and Technology Planning Project of Jiangxi Provincial Health Commission(No.202510055)Jiangxi Province Graduate Innovation Special Fund(No.YC2025-B211)Jiangxi Association for Science Education(No.2025KXJYS019).
文摘AIM:To identify differentially expressed genes(DEGs)in rabbits with traumatic proliferative vitreoretinopathy(PVR)using high-throughput sequencing(HTS).METHODS:Thirty-six rabbits were randomly allocated to the control group and the PVR group induced by scleral puncture.On the 28th day following modeling,fundus B-ultrasound and fundus photography were performed on all rabbits,and hematoxylin-eosin(HE)staining was conducted on retinal tissues.RNA sequencing(RNA-Seq)combined with bioinformatics analysis was used to screen PVRassociated DEGs.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out for the identified DEGs.S100A6,EDNRB and CEBPD were randomly selected for quantitative reverse transcription polymerase chain reaction(RT-qPCR)validation to verify the reliability of the RNA-Seq results.RESULTS:Fundus B-ultrasound,fundus photography and retinal HE staining confirmed the successful establishment of the traumatic PVR rabbit model.A total of 1587 DEGs were screened,of which 1094 were significantly up-regulated and 493 were significantly down-regulated.GO function enrichment analysis showed that these DEGs were mainly enriched in immune response,extracellular region and inflammatory response.KEGG pathway enrichment analysis showed that DEGs were mainly involved in the cytokine-cytokine receptor interaction and hematopoietic cell lineage pathway.RT-qPCR results showed that S100A6,CEBPD and EDNRB were significantly increased in PVR group.CONCLUSION:A large number of genes exhibit significant differential expression in rabbits with traumatic PVR,among which S100A6,CEBPD and EDNRB may play an important role in traumatic PVR.
基金supported by the Yunnan Provincial Department of Education University-Hospital Joint Special Project(Grant No.XYLH202338)the National Health Commission Capacity Building and Continuing Education Center Project(Grant No.GWJJMB202510024141).
文摘Overview of diabetic gastroparesis Diabetic gastroparesis(DGP)is a common gastrointestinal complication of diabetes mellitus,characterized primarily by delayed gastric emptying.With the rising prevalence of diabetes,the incidence of DGP has increased annually,currently affecting approximately 50%of diabetic patients[1].Its main clinical manifestations include belching,nausea,vomiting,abdominal distension,and anorexia,which not only severely impair patients’quality of life but also trigger serious complications such as blood glucose fluctuations[2].Diagnosis primarily relies on clinical symptoms,exclusionary testing,and gastric emptying scintigraphy.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-038 and 2023-I2M-2-001)the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT310029 and 2023-PT310-04).
文摘Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinical management.Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR,often resulting in delayed therapeutic interventions.Highthroughput sequencing(HTS)technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy.In the context of TB,diverse sequencing strategies and platforms are being employed to fulfill specific research goals,ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates.This review systematically examines current progress in the application of HTS for rapid pathogen identification,comprehensive AMR profiling,epidemiological studies,advances in novel drugs,and vaccine development.Furthermore,we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.
文摘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supported by the National Key R&D Program of China,No.2023YFE0209500(to ZQ)the Natural Science Foundation of Guangdong Province,China,Nos.2023A1515010772(to YL),2025A1515011720(to YL)+1 种基金the Medical Science and Technology Research Foundation of Guangdong Province,No.A2024120(to YL)the National Natural Science Foundation of China,No.U22A20371(to ZQ).
文摘The triple transgenic mouse model of Alzheimer’s disease(3×Tg-AD)is a widely used model that exhibits region-dependent patterns of progressive amyloid-βand tau pathology.Although structural brain abnormalities on magnetic resonance imaging have been observed in 3×Tg-AD mice at later disease stages(>12 months)and as early as 2 months,few studies have investigated changes in these mice during the stage with extensive amyloid-βdeposition and onset of tau pathology(around 9 months).This study aimed to assess brain morphometry and microstructure alterations in 9 month-old 3×Tg-AD mice to better understand the neural mechanisms underlying these specific pathological features.Voxel-based analyses were employed on T2-weighted and diffusion tensor imaging to identify differences between 3×Tg-AD and control mice.Compared with controls,3×Tg-AD mice exhibited lower gray matter volume in several regions including both hippocampal regions,the right thalamus,the left caudoputamen,and the cortex.Reduced white matter volume was observed in fiber tracts including the corpus callosum,internal capsule,stria terminalis,and olfactory tract.Whole-brain diffusion tensor imaging analysis revealed a significant decrease in fractional anisotropy and an increase in both radial and mean diffusivity within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei,with no significant difference in axial diffusivity.Correlation analyses demonstrated significant associations between behavioral performance measures,with both gray and white matter volumes within regions showing significant morphometric differences.Notably,behavioral performance also exhibited significant correlations with diffusion tensor imaging measures particularly within the left dentate gyrus of the hippocampal region and right striatum-like amygdala nuclei.Immunofluorescence analysis confirmed increased amyloid-βplaques and p-Tau protein expression in the hippocampal regions of 3×Tg-AD mice,which corroborated the magnetic resonance imaging findings.Transcriptome analysis in hippocampus tissue identified 1389 differentially expressed genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that numerous differentially expressed genes were enriched in biological processes relevant to synapse structure,cognition,learning,and memory,with particular emphasis on Wnt and mitogen-activated protein kinase signaling pathways.Collectively,these findings suggest that intricate anatomical and microstructural alterations occur in 3×Tg-AD model mice at the onset of pathology around 9 months,potentially driven by gene expression alterations.Moreover,our results support the potential utility of brain volume and diffusion metrics as biomarkers for Alzheimer’s disease pathology,which could have significant implications for clinical diagnosis of Alzheimer’s disease patients.
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).
文摘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 National Key R&D Program of China:Clinical Evaluation Research on Intervention Technologies for Abdominal Obesitythe Role of Gut Microbiota in the Effects of Combined Acupuncture and Medication on Abdominal Obesity:an Exploration with 16S rRNA Technology(Project Code:2019YFC1710102)。
文摘OBJECTIVE:To investigate Acupuncture-herb therapy modulates gut microbiota in abdominal obesity.METHODS:A randomized controlled trial was designed in accordance with standard protocols.Abdominally obese subjects were randomized into four groups:A2(Control):double placebo,A1(Needle):press needle+placebo herb,A3(herb):herbal medicine(Huatan Lishi Fang化痰利湿方)+placebo needle,A4(Combination):press needle+herbal medicine.After 12 weeks of treatment,groups were relabeled B1-B4.Weight,waist circumference,and body mass index were measured monthly.Gut microbiota was analyzed via 16S rRNA sequencing for diversity and abundance.RESULTS:Combined needle-herb therapy significantly reduced waist circumference(P<0.05).All treatments altered gut microbiota composition.The combination group showed significant changes in diversity(Chao1,Shannon,Simpson;P<0.05).Needle therapy increased Bacteroidia;herbs reduced Lachnospiraceae and Megamonas.All results were significant(P<0.05).CONCLUSION:Combined needle-herb treatment modulated 25 key gut flora across multiple taxonomic levels in abdominal obesity.It reduced Firmicutes and Bacteroidota.Bacteroidota,Actinobacteriota,and Prevotellaceae may suppress obesity,whereas Proteobacteria,Lachnospiraceae,and Megamonas may promote it.The combination specifically altered Bacteroidaceae,Lachnospiraceae,Bacteroidia,and Megamonas.
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).
文摘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.
基金supported by the Beijing Hospitals Authority’s Ascent Programme(DFL20220301)Beijing Nova Program(20230484445)+2 种基金Capital Health Development Scientific Research Project Grant(SF 2022-2-2035 to Y.T.)Excellent Young Talent Innovation Project of Chinese Institutes for Medical Research(CX23YQA02)the Chinese Institute for Medical Research(CX23YQ03).
文摘Metagenomic next-generation sequencing(mNGS)is a culture-independent technique that directly extracts and sequences all nucleic acids from clinical specimens.By leveraging high-throughput sequencing and bioinformatic analysis,it characterizes the entire microbial landscape,including bacteria,fungi,viruses,and parasites.This approach significantly broadens detection coverage,improves sensitivity,and reduces turnaround time compared with conventional diagnostic methods.Since its initial application to suspected infectious uveitis by Doan et al.in 2006,mNGS has been increasingly integrated into ophthalmic practice to facilitate pathogen identification or exclusion[1].
基金Supported by the National Natural Science Foundation of China,No.81774118the Foreign Cooperation Project of Science and Technology Department of Fujian Province,No.2023I0021the Medical Innovation Project of Fujian Province,No.2024CXB013.
文摘BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prolapse and hemorrhoids,and tissue selecting technique,are employed for treatment,they are often associated with postoperative complications,including unsatisfactory defecation,bleeding,and anal stenosis.In contrast,Xiaozhiling injection,a traditional Chinese medicine-based therapy,has emerged as a minimally invasive and effective alternative for internal hemorrhoids.This treatment offers distinct advantages,such as reduced dietary restrictions,broad applicability,and minimal induction of systemic inflammatory responses.Additionally,Xiaozhiling injection effectively eliminates hemorrhoid nuclei,prevents local tissue necrosis,preserves anal cushion integrity,and mitigates postoperative complications,including bleeding and prolapse.Despite its clinical efficacy,the molecular mechanisms underlying its therapeutic effects remain poorly understood,warranting further investigation.AIM To investigate the molecular mechanism underlying the therapeutic effect of Xiaozhiling injection in the treatment of internal hemorrhoids.METHODS An internal hemorrhoid model was established in rats,and the rats were randomly divided into a modeling group[control group(CK group)]and a treatment group.One week after injection,Stereo-seq and electron microscopy were used to study the changes in gene expression and subcellular structures in fibroblasts.RESULTS Single-cell sequencing revealed differences in the expression and transcript levels of the genes collagen 3 alpha 1,decorin,and actin alpha 2 in fibroblasts between the CK group and the treatment group.Spatial transcriptome analysis revealed that genes of the sphingosine kinase 1(Sphk1)/sphingosine-1-phosphate(S1P)pathway spatially overlapped with key genes of the transforming growth factor beta 1 pathway,namely,Sphk1,S1P receptor,and transforming growth factor beta 1,in the treatment group.The proportion of fibroblasts was lower in the treatment group than in the CK group,and Xiaozhiling treatment had a significant effect on the proportion of fibroblasts in hemorrhoidal tissue.Immunohistochemistry revealed a significant increase in the expression of a fibroblast marker.Electron microscopy showed that the endoplasmic reticulum of fibroblasts contained a large amount of glycogen,indicating cell activation.Fibroblast activation and the expression of key genes of the Sphk1-S1P pathway could be observed at the injection site,suggesting that after Xiaozhiling intervention,the Sphk1-S1P pathway could be activated to promote fibrosis.CONCLUSION Xiaozhiling injection exerts its therapeutic effects on internal hemorrhoids by promoting collagen synthesis and secretion in fibroblasts.After Xiaozhiling intervention,the Sphk1-S1P pathway can be activated to promote fibrosis.
