An accurate assessment of host and pathogen gene expression during infection is critical for understanding the molecular aspects of host-pathogen interactions.Often,pathogen-derived transcripts are difficult to ascert...An accurate assessment of host and pathogen gene expression during infection is critical for understanding the molecular aspects of host-pathogen interactions.Often,pathogen-derived transcripts are difficult to ascertain at early infection stages owing to the unfavourable transcript representation compared to the host genes.In this study,we compare two sequencing techniques,RNAseq and enrichment sequencing(RenSeq and PenSeq)of cDNA,to investigate gene expression patterns in the doubled monoploid potato(DM)infected with the late blight pathogen Phytophthora infestans.Our results reveal distinct advantages of cDNA RenSeq and PenSeq over traditional RNAseq in terms of target gene representation and transcriptional quantification at early infection stages.Throughout the infection time course,cDNA enrichment sequencing enables transcriptomic analyses for more targeted host and pathogen genes.For highly expressed genes that were sampled in parallel by both cDNA enrichment and RNAseq,a high level of concordance in expression profiles is observed,indicative of at least semi-quantitative gene expression representation following enrichment.展开更多
BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,ot...BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,other genes,such as POLE,POLD1,NTHL1,MBD4,MSH3 and MLH3,have recently been associated with polyposis phenotypes,conferring heterogeneity in terms of the clinical,etiological and heritable aspects of patients with polyposis.AIM To investigate the underlying variant landscape in patients with suspected polyposis who lack variants in the APC and MUTYH genes using whole-exome sequencing.METHODS Twenty-seven participants were included in the study and subjected to germline whole-exome sequencing.In addition,their clinical-pathological,personal,and family history data were collected.RESULTS The mean age at diagnosis was 51 years,and most participants had attenuated forms of polyposis(88.9%),with 63.0%diagnosed with a primary tumor,mostly colorectal cancer(76.5%).Among the variants identified,17 were classified as pathogenic or likely pathogenic(in 12 participants),including variants in genes involved in the Wnt/β-catenin signaling pathway,such as ST7 L,A1CF,and DKK4,and variants in DNA-repair genes,such as NTHL1,PNKP,and PMS2,as well as a variant found at the FRK gene identified in a patient with classic polyposis at age 19 and with a family history of polyps.CONCLUSION This study identified novel genes potentially associated with polyposis in patients lacking germline pathogenic variants in the APC and MUTYH genes.These findings support the use of next-generation sequencing for screening,expanding the scope of polyposis-related variants beyond these two genes.展开更多
The Internet of Things(IoT)and mobile technology have significantly transformed healthcare by enabling real-time monitoring and diagnosis of patients.Recognizing Medical-Related Human Activities(MRHA)is pivotal for he...The Internet of Things(IoT)and mobile technology have significantly transformed healthcare by enabling real-time monitoring and diagnosis of patients.Recognizing Medical-Related Human Activities(MRHA)is pivotal for healthcare systems,particularly for identifying actions critical to patient well-being.However,challenges such as high computational demands,low accuracy,and limited adaptability persist in Human Motion Recognition(HMR).While some studies have integrated HMR with IoT for real-time healthcare applications,limited research has focused on recognizing MRHA as essential for effective patient monitoring.This study proposes a novel HMR method tailored for MRHA detection,leveraging multi-stage deep learning techniques integrated with IoT.The approach employs EfficientNet to extract optimized spatial features from skeleton frame sequences using seven Mobile Inverted Bottleneck Convolutions(MBConv)blocks,followed by Convolutional Long Short Term Memory(ConvLSTM)to capture spatio-temporal patterns.A classification module with global average pooling,a fully connected layer,and a dropout layer generates the final predictions.The model is evaluated on the NTU RGB+D 120 and HMDB51 datasets,focusing on MRHA such as sneezing,falling,walking,sitting,etc.It achieves 94.85%accuracy for cross-subject evaluations and 96.45%for cross-view evaluations on NTU RGB+D 120,along with 89.22%accuracy on HMDB51.Additionally,the system integrates IoT capabilities using a Raspberry Pi and GSM module,delivering real-time alerts via Twilios SMS service to caregivers and patients.This scalable and efficient solution bridges the gap between HMR and IoT,advancing patient monitoring,improving healthcare outcomes,and reducing costs.展开更多
In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology bas...In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.展开更多
BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alte...BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alterations,mechanisms,and signaling pathways underlying gallbladder NEC remain unclear.CASE SUMMARY This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient,who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V.Targeted gene sequencing and bioinformatics analysis tools,including STRING,GeneMANIA,Metascape,TRRUST,Sangerbox,cBioPortal and GSCA,were used to analyze the biological functions and features of mutated genes in gallbladder NEC.Twelve mutations(APC,ARID2,IFNA6,KEAP1,RB1,SMAD4,TP53,BTK,GATA1,GNAS,and PRDM3)were identified,and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing.A protein-protein interaction network showed significant interactions among the twelve mutated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and pathways.The results revealed 40 tumor-related pathways.A key regulatory factor for gallbladder NEC-related genes was identified,and its biological functions and features were compared with those of gallbladder carcinoma.CONCLUSION Gallbladder NEC requires standardized treatment.Comparisons with other gallbladder carcinomas revealed clinical phenotypes,molecular alterations,functional characteristics,and enriched pathways.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
Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocyt...Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.展开更多
Along with process control,perception represents the main function performed by the Edge Layer of an Internet of Things(IoT)network.Many of these networks implement various applications where the response time does no...Along with process control,perception represents the main function performed by the Edge Layer of an Internet of Things(IoT)network.Many of these networks implement various applications where the response time does not represent an important parameter.However,in critical applications,this parameter represents a crucial aspect.One important sensing device used in IoT designs is the accelerometer.In most applications,the response time of the embedded driver software handling this device is generally not analysed and not taken into account.In this paper,we present the design and implementation of a predictable real-time driver stack for a popular accelerometer and gyroscope device family.We provide clear justifications for why this response time is extremely important for critical applications in the acquisition process of such data.We present extensive measurements and experimental results that demonstrate the predictability of our solution,making it suitable for critical real-time systems.展开更多
AIM:To estimate if nanopore targeted sequencing(NTS)could identify pathogens causing postoperative endophthalmitis and further determine the feasibility of clinical application of NTS.METHODS:A total of 55 patients(55...AIM:To estimate if nanopore targeted sequencing(NTS)could identify pathogens causing postoperative endophthalmitis and further determine the feasibility of clinical application of NTS.METHODS:A total of 55 patients(55 eyes)with postoperative endophthalmitis were retrospectively included in this study with their medical records.Intraocular fluid samples were examined by NTS and microbial culture.All included patients had undergone examinations including measurement of best corrected visual acuity(BCVA)and intraocular pressure(IOP),slit-lamp biomicroscopy,and indirect ophthalmoscopy;additionally,they underwent B-ultrasound,anterior segment photography,and fundus photography if necessary.RESULTS:Among 55 patients with postoperative endophthalmitis,the age was 65.25±15.04y and there were 30 female(54.54%)patients.Forty-one(74.54%)vitreous humor samples and fourteen(25.45%)aqueous humor samples were sent for both NTS and microbial culture.NTS had a notable higher detection rate than microbial culture in detecting pathogens(90.91%vs 38.18%,χ^(2)=33.409,P<0.001).NTS exhibited high sensitivity of pathogen detection in both microbial culture positive and negative samples(100%and 85.29%,respectively).In 16 of 21(76.19%)patients who showed culture-positivity,their results corresponded with those of NTS.Moreover,in two patients(9.52%),NTS showed a better species resolution than microbial culture;in three patients(14.28%),NTS identified additional pathogens.As for fungus,the positive detection rate of NTS was significantly higher than that of microbial culture(20%vs 3.64%,χ^(2)=7.066,P=0.008).Also,NTS could detect multi-infection by bacteria and fungi than microbial culture(32.73%vs 0,χ^(2)=21.522,P<0.001).NTS could detect bacteria as well as fungi simultaneously within 48h in all patients.Meanwhile,NTS had a shorter detection time than microbial culture(1.13±0.34 vs 2.67±0.55d,Z=-9.218,P<0.001).After the NTS results were obtained,15 patients received additional intravitreal/intracameral anti-infection treatment.At follow-up,there was a statistically significant improvement in the visual acuity relative to the baseline(Z=−5.222,P<0.001).CONCLUSION:NTS can provide rapid identification and highly sensitive detection of pathogens among patients with postoperative endophthalmitis,which can guide anti-infection treatment and improve visual prognosis.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
N^(6)-methyladenine(6mA)is a prevalent DNA modification and is involved in a wide range of human diseases.Previous studies have indicated that 6mA is enriched in mitochondrial DNA(mtDNA)of mammals.By employing an evol...N^(6)-methyladenine(6mA)is a prevalent DNA modification and is involved in a wide range of human diseases.Previous studies have indicated that 6mA is enriched in mitochondrial DNA(mtDNA)of mammals.By employing an evolved adenine deaminase,we developed a deaminase-mediated sequencing(DM-seq)method that could achieve genome-wide mapping of 6mA in mammalian mtDNA at single-base resolution.In this study,we used an engineered adenine deaminase,known as TadA8e protein,to map 6mA in mtDNA of hepatocellular carcinoma(HCC)by DM-seq.Through high-throughput sequencing,we identified sixteen 6mA sites in both HCC and adjacent normal tissue mtDNA.The results revealed an increased overall 6mA level in mtDNA associated with HCC.Furthermore,an elevation in 6mA level was observed alongside a decrease in the m RNA levels of the corresponding genes,indicating that increased6mA level hindered transcription processes related to these genes.These findings demonstrate that 6mA in mtDNA is correlated with HCC and provide evidence supporting the inhibitory effect of elevated 6mA level on subsequent transcriptional activity.This research illuminates the intricate relationship between 6mA modification and transcriptional regulation in the context of HCC,offering valuable insights into the role of 6mA modification in HCC pathogenesis.展开更多
AIM:To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury(RIRI)to identify potential therapeutic targets.METHODS:In the bulk RNA-seq analysis,This study performed diff...AIM:To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury(RIRI)to identify potential therapeutic targets.METHODS:In the bulk RNA-seq analysis,This study performed differential gene expression analysis,weighted gene co-expression network analysis,and protein-protein interaction network analysis to identify hub genes.QuanTIseq was used to determine the composition of infiltrating immune cells.Following the identification of hub genes,single-cell RNA-seq analysis was employed to pinpoint the specific immune cell types expressing these hub genes.Cell-cell communication analysis to explore signaling pathways and interactions between immune cells was further performed.Finally,the expression of these key immune regulators in vivo using quantitative real-time polymerase chain reaction(qRT-PCR)was validated.RESULTS:Bulk RNA-seq analysis identified Stat2,Irf7,Irgm1,Igtp,Parp9,Irgm2,Nlrc5,and Tap1 as hub genes,with strong correlations to immune cell infiltration.Single-cell RNA-seq analysis further revealed six immune cell clusters,showing Irf7 predominantly in microglia and Tap1 in dendritic cells(DCs).And cell-cell communication analysis showed that microglia and DCs play central roles in coordinating immune activity.qRT-PCR validated the upregulation of these genes.CONCLUSION:In the acute phase of RIRI,Irf7 and Tap1 may be the potential therapeutic targets to reduce inflammation and promote neurological function recovery.展开更多
Real-time semantic segmentation tasks place stringent demands on network inference speed,often requiring a reduction in network depth to decrease computational load.However,shallow networks tend to exhibit degradation...Real-time semantic segmentation tasks place stringent demands on network inference speed,often requiring a reduction in network depth to decrease computational load.However,shallow networks tend to exhibit degradation in feature extraction completeness and inference accuracy.Therefore,balancing high performance with real-time requirements has become a critical issue in the study of real-time semantic segmentation.To address these challenges,this paper proposes a lightweight bilateral dual-residual network.By introducing a novel residual structure combined with feature extraction and fusion modules,the proposed network significantly enhances representational capacity while reducing computational costs.Specifically,an improved compound residual structure is designed to optimize the efficiency of information propagation and feature extraction.Furthermore,the proposed feature extraction and fusion module enables the network to better capture multi-scale information in images,improving the ability to detect both detailed and global semantic features.Experimental results on the publicly available Cityscapes dataset demonstrate that the proposed lightweight dual-branch network achieves outstanding performance while maintaining low computational complexity.In particular,the network achieved a mean Intersection over Union(mIoU)of 78.4%on the Cityscapes validation set,surpassing many existing semantic segmentation models.Additionally,in terms of inference speed,the network reached 74.5 frames per second when tested on an NVIDIA GeForce RTX 3090 GPU,significantly improving real-time performance.展开更多
Here,a novel real-time monitoring sensor that integrates the oxidation of peroxymonosulfate(PMS)and the in situ monitoring of the pollutant degradation process is proposed.Briefly,FeCo@carbon fiber(FeCo@CF)was utilize...Here,a novel real-time monitoring sensor that integrates the oxidation of peroxymonosulfate(PMS)and the in situ monitoring of the pollutant degradation process is proposed.Briefly,FeCo@carbon fiber(FeCo@CF)was utilized as the anode electrode,while graphite rods served as the cathode electrode in assembling the galvanic cell.The FeCo@CF electrode exhibited rapid reactivity with PMS,generating reactive oxygen species that efficiently degrade organic pollutants.The degradation experiments indicate that complete bisphenol A(BPA)degradation was achieved within 10 min under optimal conditions.The real-time electrochemical signal was measured in time during the catalytic reaction,and a linear relationship between BPA concentration and the real-time charge(Q)was confirmed by the equation ln(C0/C)=4.393Q(correlation coefficients,R^(2)=0.998).Furthermore,experiments conducted with aureomycin and tetracycline further validated the effectiveness of the monitoring sensor.First-principles investigation confirmed the superior adsorption energy and improved electron transfer in FeCo@CF.The integration of pollutant degradation with in situ monitoring of catalytic reactions offers promising prospects for expanding the scope of the monitoring of catalytic processes and making significant contributions to environmental purification.展开更多
BACKGROUND Understanding the status and function of tumor-infiltrating immune cells is essential for improving immunotherapeutic effects and predicting the clinical response in human patients with carcinoma.However,li...BACKGROUND Understanding the status and function of tumor-infiltrating immune cells is essential for improving immunotherapeutic effects and predicting the clinical response in human patients with carcinoma.However,little is known about tumor-infiltrating immune cells,and the corresponding research results in hepatocellular carcinoma(HCC)are limited.AIM To investigate potential biomarker genes that are important for the development of HCC and to understand how immune cell subsets react throughout this process.METHODS Using single-cell RNA sequencing and T-cell receptor sequencing,the heterogeneity and potential functions of immune cell subpopulations from HCC tissue and normal tissue adjacent to carcinoma,as well as their possible interactions,were analyzed.RESULTS Eight T-cell clusters from patients were analyzed and identified using bioinformatics,including six typical major Tcell clusters and two newly identified T-cell clusters,among which Fc epsilon receptor 1G+T cells were characterized by the upregulation of Fc epsilon receptor 1G,tyrosine kinase binding protein,and T cell receptor delta constant,whereas metallothionein 1E+T cells proliferated significantly in tumors.Differentially expressed genes,such as regulator of cell cycle,cysteine and serine rich nuclear protein 1,SMAD7 and metallothionein 1E,were identified as significantly upregulated in tumors and have potential as biomarkers.In association with T-cell receptor analysis,we inferred the clonal expansion characteristics of each T-cell cluster in HCC patients.CONCLUSION We identified lymphocyte subpopulations and potential biomarker genes critical for HCC development and revealed the clonal amplification of infiltrating T cells.These data provide valuable resources for understanding the response of immune cell subsets in HCC.展开更多
Background:Medulloblastoma(MB)is one of the most common malignant brain tumors that mainly affect children.Various approaches have been used to model MB to facilitate investigating tumorigenesis.This study aims to com...Background:Medulloblastoma(MB)is one of the most common malignant brain tumors that mainly affect children.Various approaches have been used to model MB to facilitate investigating tumorigenesis.This study aims to compare the recapitulation of MB between subcutaneous patient-derived xenograft(sPDX),intracranial patient-derived xenograft(iPDX),and genetically engineered mouse models(GEMM)at the single-cell level.Methods:We obtained primary human sonic hedgehog(SHH)and group 3(G3)MB samples from six patients.For each patient specimen,we developed two sPDX and iPDX models,respectively.Three Patch+/-GEMM models were also included for sequencing.Single-cell RNA sequencing was performed to compare gene expression profiles,cellular composition,and functional pathway enrichment.Bulk RNA-seq deconvolution was performed to compare cellular composition across models and human samples.Results:Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single-cell level within the SHH and G3 subgroups,followed by the GEMM model and iPDX.The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment(TME)cells that can be clustered in human SHH tumors,including a higher proportion of tumor-associated astrocytes and immune cells,and an additional cluster of vascular endothelia when compared to human SHH tumors.Conclusions:This study was the first to compare experimental models for MB at the single-cell level,providing value insights into model selection for different research purposes.sPDX and iPDX are suitable for drug testing and personalized therapy screenings,whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.展开更多
In this study,a high-confining pressure and real-time large-displacement shearing-flow setup was developed.The test setup can be used to analyze the injection pressure conditions that increase the hydro-shearing perme...In this study,a high-confining pressure and real-time large-displacement shearing-flow setup was developed.The test setup can be used to analyze the injection pressure conditions that increase the hydro-shearing permeability and injection-induced seismicity during hot dry rock geothermal extraction.For optimizing injection strategies and improving engineering safety,real-time permeability,deformation,and energy release characteristics of fractured granite samples driven by injected water pressure under different critical sliding conditions were evaluated.The results indicated that:(1)A low injection water pressure induced intermittent small-deformation stick-slip behavior in fractures,and a high injection pressure primarily caused continuous high-speed large-deformation sliding in fractures.The optimal injection water pressure range was defined for enhancing hydraulic shear permeability and preventing large injection-induced earthquakes.(2)Under the same experimental conditions,fracture sliding was deemed as the major factor that enhanced the hydraulic shear-permeability enhancement and the maximum permeability increased by 36.54 and 41.59 times,respectively,in above two slip modes.(3)Based on the real-time transient evolution of water pressure during fracture sliding,the variation coefficients of slip rate,permeability,and water pressure were fitted,and the results were different from those measured under quasi-static conditions.(4)The maximum and minimum shear strength criteria for injection-induced fracture sliding were also determined(μ=0.6665 andμ=0.1645,respectively,μis friction coefficient).Using the 3D(three-dimensional)fracture surface scanning technology,the weakening effect of injection pressure on fracture surface damage characteristics was determined,which provided evidence for the geological markers of fault sliding mode and sliding nature transitions under the fluid influence.展开更多
The exponential expansion of the Internet of Things(IoT),Industrial Internet of Things(IIoT),and Transportation Management of Things(TMoT)produces vast amounts of real-time streaming data.Ensuring system dependability...The exponential expansion of the Internet of Things(IoT),Industrial Internet of Things(IIoT),and Transportation Management of Things(TMoT)produces vast amounts of real-time streaming data.Ensuring system dependability,operational efficiency,and security depends on the identification of anomalies in these dynamic and resource-constrained systems.Due to their high computational requirements and inability to efficiently process continuous data streams,traditional anomaly detection techniques often fail in IoT systems.This work presents a resource-efficient adaptive anomaly detection model for real-time streaming data in IoT systems.Extensive experiments were carried out on multiple real-world datasets,achieving an average accuracy score of 96.06%with an execution time close to 7.5 milliseconds for each individual streaming data point,demonstrating its potential for real-time,resourceconstrained applications.The model uses Principal Component Analysis(PCA)for dimensionality reduction and a Z-score technique for anomaly detection.It maintains a low computational footprint with a sliding window mechanism,enabling incremental data processing and identification of both transient and sustained anomalies without storing historical data.The system uses a Multivariate Linear Regression(MLR)based imputation technique that estimates missing or corrupted sensor values,preserving data integrity prior to anomaly detection.The suggested solution is appropriate for many uses in smart cities,industrial automation,environmental monitoring,IoT security,and intelligent transportation systems,and is particularly well-suited for resource-constrained edge devices.展开更多
In the foundry industries,process design has traditionally relied on manuals and complex theoretical calculations.With the advent of 3D design in casting,computer-aided design(CAD)has been applied to integrate the fea...In the foundry industries,process design has traditionally relied on manuals and complex theoretical calculations.With the advent of 3D design in casting,computer-aided design(CAD)has been applied to integrate the features of casting process,thereby expanding the scope of design options.These technologies use parametric model design techniques for rapid component creation and use databases to access standard process parameters and design specifications.However,3D models are currently still created through inputting or calling parameters,which requires numerous verifications through calculations to ensure the design rationality.This process may be significantly slowed down due to repetitive modifications and extended design time.As a result,there are increasingly urgent demands for a real-time verification mechanism to address this issue.Therefore,this study proposed a novel closed-loop model and software development method that integrated contextual design with real-time verification,dynamically verifying relevant rules for designing 3D casting components.Additionally,the study analyzed three typical closed-loop scenarios of agile design in an independent developed intelligent casting process system.It is believed that foundry industries can potentially benefit from favorably reduced design cycles to yield an enhanced competitive product market.展开更多
基金supported by the Rural & Environment Science & Analytical Services (RESAS) Division of the Scottish Government through project JHI-B1-1the Biotechnology and Biological Sciences Research Council (BBSRC) through awards BB/ S015663/1+2 种基金BB/X009068/1Research Leaders 2025 fellowship funded by European Union’s Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 754380the Research/Scientific Computing teams at The James Hutton Institute and NIAB for providing computational resources and technical support for the “UK’s Crop Diversity Bioinformatics HPC” (BBSRC grant BB/ S019669/1)。
文摘An accurate assessment of host and pathogen gene expression during infection is critical for understanding the molecular aspects of host-pathogen interactions.Often,pathogen-derived transcripts are difficult to ascertain at early infection stages owing to the unfavourable transcript representation compared to the host genes.In this study,we compare two sequencing techniques,RNAseq and enrichment sequencing(RenSeq and PenSeq)of cDNA,to investigate gene expression patterns in the doubled monoploid potato(DM)infected with the late blight pathogen Phytophthora infestans.Our results reveal distinct advantages of cDNA RenSeq and PenSeq over traditional RNAseq in terms of target gene representation and transcriptional quantification at early infection stages.Throughout the infection time course,cDNA enrichment sequencing enables transcriptomic analyses for more targeted host and pathogen genes.For highly expressed genes that were sampled in parallel by both cDNA enrichment and RNAseq,a high level of concordance in expression profiles is observed,indicative of at least semi-quantitative gene expression representation following enrichment.
基金Supported by the National Oncology Care Support Program,No.25000.056766/2015-64.
文摘BACKGROUND Adenomatous polyposis confers an increased risk of developing colorectal cancer.APC and MUTYH are the major genes investigated in patients suspected of having polyposis.In addition to APC and MUTYH genes,other genes,such as POLE,POLD1,NTHL1,MBD4,MSH3 and MLH3,have recently been associated with polyposis phenotypes,conferring heterogeneity in terms of the clinical,etiological and heritable aspects of patients with polyposis.AIM To investigate the underlying variant landscape in patients with suspected polyposis who lack variants in the APC and MUTYH genes using whole-exome sequencing.METHODS Twenty-seven participants were included in the study and subjected to germline whole-exome sequencing.In addition,their clinical-pathological,personal,and family history data were collected.RESULTS The mean age at diagnosis was 51 years,and most participants had attenuated forms of polyposis(88.9%),with 63.0%diagnosed with a primary tumor,mostly colorectal cancer(76.5%).Among the variants identified,17 were classified as pathogenic or likely pathogenic(in 12 participants),including variants in genes involved in the Wnt/β-catenin signaling pathway,such as ST7 L,A1CF,and DKK4,and variants in DNA-repair genes,such as NTHL1,PNKP,and PMS2,as well as a variant found at the FRK gene identified in a patient with classic polyposis at age 19 and with a family history of polyps.CONCLUSION This study identified novel genes potentially associated with polyposis in patients lacking germline pathogenic variants in the APC and MUTYH genes.These findings support the use of next-generation sequencing for screening,expanding the scope of polyposis-related variants beyond these two genes.
基金funded by the ICT Division of theMinistry of Posts,Telecommunications,and Information Technology of Bangladesh under Grant Number 56.00.0000.052.33.005.21-7(Tracking No.22FS15306)support from the University of Rajshahi.
文摘The Internet of Things(IoT)and mobile technology have significantly transformed healthcare by enabling real-time monitoring and diagnosis of patients.Recognizing Medical-Related Human Activities(MRHA)is pivotal for healthcare systems,particularly for identifying actions critical to patient well-being.However,challenges such as high computational demands,low accuracy,and limited adaptability persist in Human Motion Recognition(HMR).While some studies have integrated HMR with IoT for real-time healthcare applications,limited research has focused on recognizing MRHA as essential for effective patient monitoring.This study proposes a novel HMR method tailored for MRHA detection,leveraging multi-stage deep learning techniques integrated with IoT.The approach employs EfficientNet to extract optimized spatial features from skeleton frame sequences using seven Mobile Inverted Bottleneck Convolutions(MBConv)blocks,followed by Convolutional Long Short Term Memory(ConvLSTM)to capture spatio-temporal patterns.A classification module with global average pooling,a fully connected layer,and a dropout layer generates the final predictions.The model is evaluated on the NTU RGB+D 120 and HMDB51 datasets,focusing on MRHA such as sneezing,falling,walking,sitting,etc.It achieves 94.85%accuracy for cross-subject evaluations and 96.45%for cross-view evaluations on NTU RGB+D 120,along with 89.22%accuracy on HMDB51.Additionally,the system integrates IoT capabilities using a Raspberry Pi and GSM module,delivering real-time alerts via Twilios SMS service to caregivers and patients.This scalable and efficient solution bridges the gap between HMR and IoT,advancing patient monitoring,improving healthcare outcomes,and reducing costs.
基金financially supported by National Key R&D Program(2021YFF0701905)。
文摘In order to save manpower and time costs,and to achieve simultaneous detection of multiple animal-derived components in meat and meat products,this study used multiple nucleotide polymorphism(MNP)marker technology based on the principle of high-throughput sequencing,and established a multi-locus 10 animalderived components identification method of cattle,goat,sheep,donkey,horse,chicken,duck,goose,pigeon,quail in meat and meat products.The specific loci of each species could be detected and the species could be accurately identified,including 5 loci for cattle and duck,3 loci for sheep,9 loci for chicken and horse,10 loci for goose and pigeon,6 loci for quail and 1 locus for donkey and goat,and an adulteration model was established to simulate commercially available samples.The results showed that the method established in this study had high throughput,good repeatability and accuracy,and was able to identify 10 animalderived components simultaneously with 100%repeatability accuracy.The detection limit was 0.1%(m/m)in simulated samples of chicken,duck and horse.Using the method established in this study to test commercially available samples,4 samples from 14 commercially available samples were detected to be inconsistent with the labels,of which 2 did not contain the target ingredient and 2 were adulterated with small amounts of other ingredients.
基金Supported by School-Level Key Projects at Bengbu Medical College,No.2021byzd109.
文摘BACKGROUND Gallbladder neuroendocrine carcinoma(NEC)represents a subtype of gallbladder malignancies characterized by a low incidence,aggressive nature,and poor prognosis.Despite its clinical severity,the genetic alterations,mechanisms,and signaling pathways underlying gallbladder NEC remain unclear.CASE SUMMARY This case study presents a rare instance of primary gallbladder NEC in a 73-year-old female patient,who underwent a radical cholecystectomy with hepatic hilar lymphadenectomy and resection of liver segments IV-B and V.Targeted gene sequencing and bioinformatics analysis tools,including STRING,GeneMANIA,Metascape,TRRUST,Sangerbox,cBioPortal and GSCA,were used to analyze the biological functions and features of mutated genes in gallbladder NEC.Twelve mutations(APC,ARID2,IFNA6,KEAP1,RB1,SMAD4,TP53,BTK,GATA1,GNAS,and PRDM3)were identified,and the tumor mutation burden was determined to be 9.52 muts/Mb via targeted gene sequencing.A protein-protein interaction network showed significant interactions among the twelve mutated genes.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to assess mutation functions and pathways.The results revealed 40 tumor-related pathways.A key regulatory factor for gallbladder NEC-related genes was identified,and its biological functions and features were compared with those of gallbladder carcinoma.CONCLUSION Gallbladder NEC requires standardized treatment.Comparisons with other gallbladder carcinomas revealed clinical phenotypes,molecular alterations,functional characteristics,and enriched pathways.
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,No.82301403(to DZ)。
文摘Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative disorders.Glial cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous system.Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord.Here,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal cord.To explore the conservation and divergence across species,we compared these findings with those from mice.In the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic subclusters.In the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice.Additionally,we detected sex differences in gene expression in human spinal cord glial cells.Specifically,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in females.In all microglial subtypes,all differentially expressed genes were located on the sex chromosomes.In addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in males.Collectively,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cordrelated illnesses,including chronic pain,amyotrophic lateral sclerosis,and multiple sclerosis.
文摘Along with process control,perception represents the main function performed by the Edge Layer of an Internet of Things(IoT)network.Many of these networks implement various applications where the response time does not represent an important parameter.However,in critical applications,this parameter represents a crucial aspect.One important sensing device used in IoT designs is the accelerometer.In most applications,the response time of the embedded driver software handling this device is generally not analysed and not taken into account.In this paper,we present the design and implementation of a predictable real-time driver stack for a popular accelerometer and gyroscope device family.We provide clear justifications for why this response time is extremely important for critical applications in the acquisition process of such data.We present extensive measurements and experimental results that demonstrate the predictability of our solution,making it suitable for critical real-time systems.
基金Supported by Open Project of Key Laboratory of Hubei Province(No.2023KFZZ026).
文摘AIM:To estimate if nanopore targeted sequencing(NTS)could identify pathogens causing postoperative endophthalmitis and further determine the feasibility of clinical application of NTS.METHODS:A total of 55 patients(55 eyes)with postoperative endophthalmitis were retrospectively included in this study with their medical records.Intraocular fluid samples were examined by NTS and microbial culture.All included patients had undergone examinations including measurement of best corrected visual acuity(BCVA)and intraocular pressure(IOP),slit-lamp biomicroscopy,and indirect ophthalmoscopy;additionally,they underwent B-ultrasound,anterior segment photography,and fundus photography if necessary.RESULTS:Among 55 patients with postoperative endophthalmitis,the age was 65.25±15.04y and there were 30 female(54.54%)patients.Forty-one(74.54%)vitreous humor samples and fourteen(25.45%)aqueous humor samples were sent for both NTS and microbial culture.NTS had a notable higher detection rate than microbial culture in detecting pathogens(90.91%vs 38.18%,χ^(2)=33.409,P<0.001).NTS exhibited high sensitivity of pathogen detection in both microbial culture positive and negative samples(100%and 85.29%,respectively).In 16 of 21(76.19%)patients who showed culture-positivity,their results corresponded with those of NTS.Moreover,in two patients(9.52%),NTS showed a better species resolution than microbial culture;in three patients(14.28%),NTS identified additional pathogens.As for fungus,the positive detection rate of NTS was significantly higher than that of microbial culture(20%vs 3.64%,χ^(2)=7.066,P=0.008).Also,NTS could detect multi-infection by bacteria and fungi than microbial culture(32.73%vs 0,χ^(2)=21.522,P<0.001).NTS could detect bacteria as well as fungi simultaneously within 48h in all patients.Meanwhile,NTS had a shorter detection time than microbial culture(1.13±0.34 vs 2.67±0.55d,Z=-9.218,P<0.001).After the NTS results were obtained,15 patients received additional intravitreal/intracameral anti-infection treatment.At follow-up,there was a statistically significant improvement in the visual acuity relative to the baseline(Z=−5.222,P<0.001).CONCLUSION:NTS can provide rapid identification and highly sensitive detection of pathogens among patients with postoperative endophthalmitis,which can guide anti-infection treatment and improve visual prognosis.
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.
基金supported by the National Natural Science Foundation of China(No.22277093)the Key Research and Development Project of Hubei Province(No.2023BCB094)。
文摘N^(6)-methyladenine(6mA)is a prevalent DNA modification and is involved in a wide range of human diseases.Previous studies have indicated that 6mA is enriched in mitochondrial DNA(mtDNA)of mammals.By employing an evolved adenine deaminase,we developed a deaminase-mediated sequencing(DM-seq)method that could achieve genome-wide mapping of 6mA in mammalian mtDNA at single-base resolution.In this study,we used an engineered adenine deaminase,known as TadA8e protein,to map 6mA in mtDNA of hepatocellular carcinoma(HCC)by DM-seq.Through high-throughput sequencing,we identified sixteen 6mA sites in both HCC and adjacent normal tissue mtDNA.The results revealed an increased overall 6mA level in mtDNA associated with HCC.Furthermore,an elevation in 6mA level was observed alongside a decrease in the m RNA levels of the corresponding genes,indicating that increased6mA level hindered transcription processes related to these genes.These findings demonstrate that 6mA in mtDNA is correlated with HCC and provide evidence supporting the inhibitory effect of elevated 6mA level on subsequent transcriptional activity.This research illuminates the intricate relationship between 6mA modification and transcriptional regulation in the context of HCC,offering valuable insights into the role of 6mA modification in HCC pathogenesis.
基金Supported by the National Natural Science Foundation of China(No.82071312).
文摘AIM:To explore the immune cell infiltration and molecular mechanisms of retinal ischemia-reperfusion injury(RIRI)to identify potential therapeutic targets.METHODS:In the bulk RNA-seq analysis,This study performed differential gene expression analysis,weighted gene co-expression network analysis,and protein-protein interaction network analysis to identify hub genes.QuanTIseq was used to determine the composition of infiltrating immune cells.Following the identification of hub genes,single-cell RNA-seq analysis was employed to pinpoint the specific immune cell types expressing these hub genes.Cell-cell communication analysis to explore signaling pathways and interactions between immune cells was further performed.Finally,the expression of these key immune regulators in vivo using quantitative real-time polymerase chain reaction(qRT-PCR)was validated.RESULTS:Bulk RNA-seq analysis identified Stat2,Irf7,Irgm1,Igtp,Parp9,Irgm2,Nlrc5,and Tap1 as hub genes,with strong correlations to immune cell infiltration.Single-cell RNA-seq analysis further revealed six immune cell clusters,showing Irf7 predominantly in microglia and Tap1 in dendritic cells(DCs).And cell-cell communication analysis showed that microglia and DCs play central roles in coordinating immune activity.qRT-PCR validated the upregulation of these genes.CONCLUSION:In the acute phase of RIRI,Irf7 and Tap1 may be the potential therapeutic targets to reduce inflammation and promote neurological function recovery.
文摘Real-time semantic segmentation tasks place stringent demands on network inference speed,often requiring a reduction in network depth to decrease computational load.However,shallow networks tend to exhibit degradation in feature extraction completeness and inference accuracy.Therefore,balancing high performance with real-time requirements has become a critical issue in the study of real-time semantic segmentation.To address these challenges,this paper proposes a lightweight bilateral dual-residual network.By introducing a novel residual structure combined with feature extraction and fusion modules,the proposed network significantly enhances representational capacity while reducing computational costs.Specifically,an improved compound residual structure is designed to optimize the efficiency of information propagation and feature extraction.Furthermore,the proposed feature extraction and fusion module enables the network to better capture multi-scale information in images,improving the ability to detect both detailed and global semantic features.Experimental results on the publicly available Cityscapes dataset demonstrate that the proposed lightweight dual-branch network achieves outstanding performance while maintaining low computational complexity.In particular,the network achieved a mean Intersection over Union(mIoU)of 78.4%on the Cityscapes validation set,surpassing many existing semantic segmentation models.Additionally,in terms of inference speed,the network reached 74.5 frames per second when tested on an NVIDIA GeForce RTX 3090 GPU,significantly improving real-time performance.
基金supported by the National Natural Science Foundation of China(No.22306076)the Natural Science Foundation of Jiangsu Province(No.BK20230676)the Natural Science Foundation of Jiangsu Higher Education Institutions of China(No.22KJB610011).
文摘Here,a novel real-time monitoring sensor that integrates the oxidation of peroxymonosulfate(PMS)and the in situ monitoring of the pollutant degradation process is proposed.Briefly,FeCo@carbon fiber(FeCo@CF)was utilized as the anode electrode,while graphite rods served as the cathode electrode in assembling the galvanic cell.The FeCo@CF electrode exhibited rapid reactivity with PMS,generating reactive oxygen species that efficiently degrade organic pollutants.The degradation experiments indicate that complete bisphenol A(BPA)degradation was achieved within 10 min under optimal conditions.The real-time electrochemical signal was measured in time during the catalytic reaction,and a linear relationship between BPA concentration and the real-time charge(Q)was confirmed by the equation ln(C0/C)=4.393Q(correlation coefficients,R^(2)=0.998).Furthermore,experiments conducted with aureomycin and tetracycline further validated the effectiveness of the monitoring sensor.First-principles investigation confirmed the superior adsorption energy and improved electron transfer in FeCo@CF.The integration of pollutant degradation with in situ monitoring of catalytic reactions offers promising prospects for expanding the scope of the monitoring of catalytic processes and making significant contributions to environmental purification.
基金Supported by the Scientific Research Topic of Jiangsu Provincial Health Care Commission,No.M2021017the High-level Talent Research Project of the Second Hospital of Nanjing,No.0313504the Nanjing Second Hospital Academic Leader Program,No.0313506.
文摘BACKGROUND Understanding the status and function of tumor-infiltrating immune cells is essential for improving immunotherapeutic effects and predicting the clinical response in human patients with carcinoma.However,little is known about tumor-infiltrating immune cells,and the corresponding research results in hepatocellular carcinoma(HCC)are limited.AIM To investigate potential biomarker genes that are important for the development of HCC and to understand how immune cell subsets react throughout this process.METHODS Using single-cell RNA sequencing and T-cell receptor sequencing,the heterogeneity and potential functions of immune cell subpopulations from HCC tissue and normal tissue adjacent to carcinoma,as well as their possible interactions,were analyzed.RESULTS Eight T-cell clusters from patients were analyzed and identified using bioinformatics,including six typical major Tcell clusters and two newly identified T-cell clusters,among which Fc epsilon receptor 1G+T cells were characterized by the upregulation of Fc epsilon receptor 1G,tyrosine kinase binding protein,and T cell receptor delta constant,whereas metallothionein 1E+T cells proliferated significantly in tumors.Differentially expressed genes,such as regulator of cell cycle,cysteine and serine rich nuclear protein 1,SMAD7 and metallothionein 1E,were identified as significantly upregulated in tumors and have potential as biomarkers.In association with T-cell receptor analysis,we inferred the clonal expansion characteristics of each T-cell cluster in HCC patients.CONCLUSION We identified lymphocyte subpopulations and potential biomarker genes critical for HCC development and revealed the clonal amplification of infiltrating T cells.These data provide valuable resources for understanding the response of immune cell subsets in HCC.
基金National Key Research and Development Program of China,Grant/Award Number:2022ZD0210100Beijing Nova Star Program,Grant/Award Number:2022002+2 种基金Natural Science Foundation of Beijing and Haidian Collaboration Foundation,Grant/Award Number:L232079National Natural Science Foundation of China,Grant/Award Number:82172608,82273343,81902975 and 82101356Capital Medical University Fund for Excellent Young Scholars,Grant/Award Number:KCB2304。
文摘Background:Medulloblastoma(MB)is one of the most common malignant brain tumors that mainly affect children.Various approaches have been used to model MB to facilitate investigating tumorigenesis.This study aims to compare the recapitulation of MB between subcutaneous patient-derived xenograft(sPDX),intracranial patient-derived xenograft(iPDX),and genetically engineered mouse models(GEMM)at the single-cell level.Methods:We obtained primary human sonic hedgehog(SHH)and group 3(G3)MB samples from six patients.For each patient specimen,we developed two sPDX and iPDX models,respectively.Three Patch+/-GEMM models were also included for sequencing.Single-cell RNA sequencing was performed to compare gene expression profiles,cellular composition,and functional pathway enrichment.Bulk RNA-seq deconvolution was performed to compare cellular composition across models and human samples.Results:Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single-cell level within the SHH and G3 subgroups,followed by the GEMM model and iPDX.The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment(TME)cells that can be clustered in human SHH tumors,including a higher proportion of tumor-associated astrocytes and immune cells,and an additional cluster of vascular endothelia when compared to human SHH tumors.Conclusions:This study was the first to compare experimental models for MB at the single-cell level,providing value insights into model selection for different research purposes.sPDX and iPDX are suitable for drug testing and personalized therapy screenings,whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.
基金supported by the National Natural Science Foundation of China (Grant No.52122405)Science and Technology Major Project of Shanxi Province,China (Grant No.202101060301024)Science and Technology Major Project of Xizang Autonomous Region,China (Grant No.XZ202201ZD0004G0204).
文摘In this study,a high-confining pressure and real-time large-displacement shearing-flow setup was developed.The test setup can be used to analyze the injection pressure conditions that increase the hydro-shearing permeability and injection-induced seismicity during hot dry rock geothermal extraction.For optimizing injection strategies and improving engineering safety,real-time permeability,deformation,and energy release characteristics of fractured granite samples driven by injected water pressure under different critical sliding conditions were evaluated.The results indicated that:(1)A low injection water pressure induced intermittent small-deformation stick-slip behavior in fractures,and a high injection pressure primarily caused continuous high-speed large-deformation sliding in fractures.The optimal injection water pressure range was defined for enhancing hydraulic shear permeability and preventing large injection-induced earthquakes.(2)Under the same experimental conditions,fracture sliding was deemed as the major factor that enhanced the hydraulic shear-permeability enhancement and the maximum permeability increased by 36.54 and 41.59 times,respectively,in above two slip modes.(3)Based on the real-time transient evolution of water pressure during fracture sliding,the variation coefficients of slip rate,permeability,and water pressure were fitted,and the results were different from those measured under quasi-static conditions.(4)The maximum and minimum shear strength criteria for injection-induced fracture sliding were also determined(μ=0.6665 andμ=0.1645,respectively,μis friction coefficient).Using the 3D(three-dimensional)fracture surface scanning technology,the weakening effect of injection pressure on fracture surface damage characteristics was determined,which provided evidence for the geological markers of fault sliding mode and sliding nature transitions under the fluid influence.
基金funded by the Ongoing Research Funding Program(ORF-2025-890)King Saud University,Riyadh,Saudi Arabia and was supported by the Competitive Research Fund of theUniversity of Aizu,Japan.
文摘The exponential expansion of the Internet of Things(IoT),Industrial Internet of Things(IIoT),and Transportation Management of Things(TMoT)produces vast amounts of real-time streaming data.Ensuring system dependability,operational efficiency,and security depends on the identification of anomalies in these dynamic and resource-constrained systems.Due to their high computational requirements and inability to efficiently process continuous data streams,traditional anomaly detection techniques often fail in IoT systems.This work presents a resource-efficient adaptive anomaly detection model for real-time streaming data in IoT systems.Extensive experiments were carried out on multiple real-world datasets,achieving an average accuracy score of 96.06%with an execution time close to 7.5 milliseconds for each individual streaming data point,demonstrating its potential for real-time,resourceconstrained applications.The model uses Principal Component Analysis(PCA)for dimensionality reduction and a Z-score technique for anomaly detection.It maintains a low computational footprint with a sliding window mechanism,enabling incremental data processing and identification of both transient and sustained anomalies without storing historical data.The system uses a Multivariate Linear Regression(MLR)based imputation technique that estimates missing or corrupted sensor values,preserving data integrity prior to anomaly detection.The suggested solution is appropriate for many uses in smart cities,industrial automation,environmental monitoring,IoT security,and intelligent transportation systems,and is particularly well-suited for resource-constrained edge devices.
基金the financial support of the Natural Science Foundation of Hubei Province,China (Grant No.2022CFB770)。
文摘In the foundry industries,process design has traditionally relied on manuals and complex theoretical calculations.With the advent of 3D design in casting,computer-aided design(CAD)has been applied to integrate the features of casting process,thereby expanding the scope of design options.These technologies use parametric model design techniques for rapid component creation and use databases to access standard process parameters and design specifications.However,3D models are currently still created through inputting or calling parameters,which requires numerous verifications through calculations to ensure the design rationality.This process may be significantly slowed down due to repetitive modifications and extended design time.As a result,there are increasingly urgent demands for a real-time verification mechanism to address this issue.Therefore,this study proposed a novel closed-loop model and software development method that integrated contextual design with real-time verification,dynamically verifying relevant rules for designing 3D casting components.Additionally,the study analyzed three typical closed-loop scenarios of agile design in an independent developed intelligent casting process system.It is believed that foundry industries can potentially benefit from favorably reduced design cycles to yield an enhanced competitive product market.
