Rice is a poor source of folate,an essential micronutrient for the body.Biofortification offers an effective way to enhance the folate content of rice and alleviate folate deficiencies in humans.In this study,we confi...Rice is a poor source of folate,an essential micronutrient for the body.Biofortification offers an effective way to enhance the folate content of rice and alleviate folate deficiencies in humans.In this study,we confirmed that OsADCS and OsGTPCHI,encoding the initial enzymes necessary for folate synthesis,positively regulate folate accumulation in knockout mutants of both japonica and indica rice backgrounds.The folate content in the low-folate japonica variety was slightly increased by the expression of the indica alleles driven by the endosperm-specific promoter.We further obtained co-expression lines by stacking OsADCS and OsGTPCHI genes;the folate accumulation in brown rice and polished rice reached 5.65μg/g and 2.95μg/g,respectively,representing 37.9-fold and 26.5-fold increases compared with the wild type.Transcriptomic analysis of rice grains from six transgenic lines showed that folate changes affected biological pathways involved in the synthesis and metabolism of rice seed storage substances,while the expression of other folate synthesis genes was weakly regulated.In addition,we identified Aus rice as a high-folate germplasm carrying superior haplotypes of OsADCS and OsGTPCHI through natural variation.This study provides an alternative and effective complementary strategy for rice biofortification,promoting the rational combination of metabolic engineering and conventional breeding to breed high-folate varieties.展开更多
Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-...Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.展开更多
Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(H...Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(HCC)remain unclear.HCC is a highly lethal malignant tumor.Given the limitations of traditional treatments,this study explored the expression level,clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets.Methods In this study,we used public databases to analyze the expression of INF2 in pan-cancer and HCC,as well as the impact of INF2 expression levels on HCC prognosis.Quantitative real time polymerase chain reaction(RT-qPCR),Western blot,and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues.The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples.Subsequently,the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments.Finally,the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments.Results INF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival,liver cirrhosis and pathological differentiation of HCC patients.The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC.In vivo and in vitro HCC models,upregulated expression of INF2 triggers the proliferation and migration of the HCC cell,while knockdown of INF2 could counteract this effect.INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression,thus promoting tumor progression.Conclusion INF2 is highly expressed in HCC and is associated with poor prognosis.High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression,and targeting INF2 may be beneficial for HCC patients with high expression of INF2.展开更多
The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose⁃catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monit...The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose⁃catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16℃in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni⁃NTA affinity column.Size⁃exclusion chromatography and SDS⁃PAGE analysis demonstrated that the puri⁃fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD^(+)as a coenzyme to NADP^(+).The optimal temperature and pH of the TeXDH were 40℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26%of the initial enzyme activity,while the divalent metal ions Mg^(2+)or Ca^(2+)could recover the enzyme activity of TeXDH,reaching 103.32%and 110.69%of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn^(2+),Ni^(2+),Cu^(2+),Zn^(2+),Co^(2+),and Cd^(2+)significantly inhibited the activity of TeXDH.ICP⁃MS and molecular doc⁃king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn^(2+)ions and 1 mol/L Mg^(2+)ion.Further⁃more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.展开更多
Since its discovery in the 1980s,the insect cell-baculovirus expression vector system(IC-BEVS)has been widely used in biomedical applications,such as recombinant protein expression,drug screening,vaccine development,g...Since its discovery in the 1980s,the insect cell-baculovirus expression vector system(IC-BEVS)has been widely used in biomedical applications,such as recombinant protein expression,drug screening,vaccine development,gene therapy and so on[1].As a eukaryotic system,IC-BEVS has great development prospects due to its advantages such as high safety,simple operation,simultaneous expression of multi-subunit proteins,and suitability for large-scale cultivation[2].展开更多
Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic(ANT)application and affect gene expression.In this study,we analyzed the expression of 13 key pancreati...Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic(ANT)application and affect gene expression.In this study,we analyzed the expression of 13 key pancreatic genes and blood physiology parameters after administering one maximum residue limit of herbicide glyphosate(GLY),two ANTs,and one anticoccidial drug(AD).A total of 260 Ross 308 broilers aged 1-40 d were divided into the following four groups of 65 birds each:control group,which was fed the main diet(MD),and three experimental groups,which were fed MD supplemented with GLY,GLY+ANTs(enrofloxacin and colistin methanesulfonate),and GLY+AD(ammonium maduramicin),respectively.The results showed that the addition of GLY,GLY+ANTs,and GLY+AD caused significant changes in the expression of several genes of physiological and economic importance.In particular,genes related to inflammation and apoptosis(interleukin 6(IL6),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase 6(CASP6))were downregulated by up to 99.1%,and those related to antioxidant protection(catalase(CAT),superoxide dismutase 1(SOD1)and peroxiredoxin 6(PRDX6))by up to 98.6%,compared to controls.There was also a significant decline in the values of immunological characteristics in the blood serum observed in the experimental groups,and certain changes in gene expression were concordant with changes in the functioning of the pancreas and blood.The changes revealed in gene expression and blood indices in response to GLY,ANTs,and AD provide insights into the possible mechanisms of action of these agents at the molecular level.Specifically,these changes may be indicative of physiological mechanisms to overcome the negative effects of GLY,GLY+ANTs,and GLY+AD in broilers.展开更多
Commercial cultivars of garlic,a popular condiment,are sterile,making genetic variation and germplasm innovation of this plant challenging.Understanding mechanism of gamete sterility in garlic and their key regulatory...Commercial cultivars of garlic,a popular condiment,are sterile,making genetic variation and germplasm innovation of this plant challenging.Understanding mechanism of gamete sterility in garlic and their key regulatory networks is therefore important for fertility restoration.In this work,we conducted a detailed phenotypic analysis of fertile and sterile garlic genotypes and found that enlargement of topset in the inflorescence of sterile genotypes led to abnormal flowers.Additional cytological observations showed that aberrant meiotic cytokinesis in sterile garlic ultimately resulted in pollen degeneration.Transcriptomics analysis of sterile and fertile genotypes identified possible molecular mechanisms underlying gamete abortion.A total of 100710 differentially expressed genes(DEGs)between the fertile and sterile garlic flowers at three stages of gamete development were identified,many of which were involved in homologous chromosome synapsis during meiosis,MYB transcription factor regulation,ribosome biogenesis and plant hormone signal transduction.Taken together,these results provide insight into the molecular mechanisms and regulatory networks underlying gamete development in garlic and point to a set of candidate genes for further functional characterization.展开更多
The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14...The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14756282819385 URL:https://www.techscience.com/or/v25n4/56833 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
Background Cotton is an industrial crop renowned for its multifaceted applications in the textiles,pharmaceuticals,and biofuel industries.Plant regeneration through somatic embryogenesis(SE)plays a crucial role in the...Background Cotton is an industrial crop renowned for its multifaceted applications in the textiles,pharmaceuticals,and biofuel industries.Plant regeneration through somatic embryogenesis(SE)plays a crucial role in the genetic improvement of cotton.There is a strong correlation between SE and zygotic embryogenesis(ZE)in plants.Furthermore,the strategy of ectopic expression of cotton genes into the model plant Arabidopsis has been a widely accepted approach for functional study.Result Based on previous spatial transcriptomics of cotton somatic embryos,two genes,Gh HAT5 and Gh CRK29,were identified.They are highly expressed in cotyledon and epidermal cells of cotton cotyledonary embryos,respectively.In this study,Gh HAT5 and Gh CRK29 were ectopically expressed in Arabidopsis to investigate their functions.The result showed that in Arabidopsis zygotic embryos,the overexpression of Gh HAT5 promoted the development of apical embryonic upper-tier cells and embryonic cotyledon,while the overexpression of Gh CRK29 promoted the development of apical embryonic lower-tier cells and embryonic radicle.Given the similarities between somatic and zygotic embryogenesis,these findings suggest that Gh HAT5 and Gh CRK29 are involved in cotton SE.We also speculate that these genes may promote the expression of the Arabidopsis endogenous gene At SCR,which is crucial for embryonic development.Conclusion These results revealed that Gh HAT5 and Gh CRK29 regulate embryonic development and are essential in advancing our understanding of cotton SE and facilitating targeted genetic manipulation strategies to improve industrial crop traits and agricultural sustainability.展开更多
Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several ...Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases,but population-based studies on associations between HT and KLF4 or KLF5 have rarely been reported.Therefore,the current study investigated the associations of genetic variants and m RNA expression levels of KLF4 and KLF5 with HT,as well as the effects of antihypertensive drugs on the expression levels of these genes.The associations of one single-nucleotide polymorphism(SNP)in KLF4 and three SNPs in KLF5with HT were analyzed using a combination of case-control and cohort studies.The study populations were selected from a community-based cohort in four regions of Jiangsu province.The risks of HT were estimated through logistic and Cox regression analyses.In addition,m RNA expression levels of KLF4 and KLF5 were detected in 246 controls and 385 HT cases selected from the aforementioned cohort.Among the HT cases,263were not taking antihypertensive drugs[AHD(-)]and 122 were taking antihypertensive drugs[AHD(+)].In the case-control study,SNP rs9573096(C>T)in KLF5 was significantly associated with an increased risk of HT in the additive model(adjusted odds ratio[OR],1.106;95%confidence interval[CI],1.009 to 1.212).In the cohort study of the normotensive population,rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model(adjusted hazards ratio[HR],1.199;95%CI,1.070 to 1.344).KLF4 and KLF5m RNA expression levels were significantly higher in the AHD(-)group than in the control group(P<0.05),but lower in the AHD(+)group than in the AHD(-)group(P<0.05).The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension,as well as the association of the indicative variations in m RNA expression levels of KLF4 and KLF5 with the risk of hypertension and antihypertensive treatment.展开更多
Laminarin oligosaccharides(LOSs)with a specific degree of polymerization prepared through the laminarin degradation via laminarinase present more significant nutritional functions and application values.Human intestin...Laminarin oligosaccharides(LOSs)with a specific degree of polymerization prepared through the laminarin degradation via laminarinase present more significant nutritional functions and application values.Human intestinal bacteria are promising potential producers of novel carbohydrate-active enzymes with unique properties.Here,a novel glycoside hydrolase family 128(GH128)laminarinase OUC-BsLam26 from the intestinal bacterium Bacteroides sp.CBA7301 was heterologously expressed and characterized.The recombinant OUC-BsLam26 with a molecular mass of 49.86 kDa exhibits highest activity(6.60 U/mg)at 45℃ and pH 6.0,which shows noticeable temperature and pH stability.The purified OUC-BsLam26 could degrade laminarin via an endo-type mode with the generation of laminaripentaose,laminaritetraose,laminaritriose,and laminaribiose,among them,laminaritetraose is the principal product,which accounts for 45.25% of the total products,which is significantly different from the reported GH128 laminarinases.The minimum recognition substrate of OUC-BsLam26 is laminarihexaose.Furthermore,OUC-BsLam26 also could catalyze the transglycosylation process with the production of some novel glycosides.Altogether,the intestinal bacterium Bacteroides sp.CBA7301 contains laminarinase with unique product composition and OUC-BsLam26 is a hopeful bio-catalyst with the potential to produce laminaritetraose and some novel glycosides.展开更多
DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expres...DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expression data generated. To address this, this paper employs a mixed-effects model to analyze gene expression data. In terms of data selection, 1176 genes from the white mouse gene expression dataset under two experimental conditions were chosen, setting up two conditions: pneumococcal infection and no infection, and constructing a mixed-effects model. After preprocessing the gene chip information, the data were imported into the model, preliminary results were calculated, and permutation tests were performed to biologically validate the preliminary results using GSEA. The final dataset consists of 20 groups of gene expression data from pneumococcal infection, which categorizes functionally related genes based on the similarity of their expression profiles, facilitating the study of genes with unknown functions.展开更多
Short tandem repeats(STRs)modulate gene expression and contribute to trait variation.However,a systematic evaluation of the genomic characteristics of STRs has not been conducted,and their influence on gene expression...Short tandem repeats(STRs)modulate gene expression and contribute to trait variation.However,a systematic evaluation of the genomic characteristics of STRs has not been conducted,and their influence on gene expression in rice remains unclear.Here,we construct a map of 137,629 polymorphic STRs in the rice(Oryza sativa L.)genome using a population-scale resequencing dataset.A genome-wide survey encompassing 4726 accessions shows that the occurrence frequency,mutational patterns,chromosomal distribution,and functional properties of STRs are correlated with the sequences and lengths of repeat motifs.Leveraging a transcriptome dataset from 127 rice accessions,we identify 44,672 expression STRs(eSTRs)by modeling gene expression in response to the length variation of STRs.These eSTRs are notably enriched in the regulatory regions of genes with active transcriptional signatures.Population analysis identifies numerous STRs that have undergone genetic divergence among different rice groups and 1726 tagged STRs that may be associated with agronomic traits.By editing the(ACT)_(7) STR in OsFD1 promoter,we further experimentally validate its role in regulating gene expression and phenotype.Our study highlights the contribution of STRs to transcriptional regulation in plants and establishes the foundation for their potential use as alternative targets for genetic improvement.展开更多
As a member of the Cancer-Testis Antigens,the Melanoma-associated antigen(MAGE)family is typically expressed in normal tissues such as the testis.However,in various types of tumor cells,their expression is abnormally ...As a member of the Cancer-Testis Antigens,the Melanoma-associated antigen(MAGE)family is typically expressed in normal tissues such as the testis.However,in various types of tumor cells,their expression is abnormally activated,which is associated with multiple critical processes of tumor cells,including proliferation,apoptosis,immune evasion,DNA damage repair,and metastasis.The abnormal expression of MAGE family genes in multiple cancers and their multifaceted roles in tumor biology have made them an important target in cancer research and treatment.This review comprehensively explores various aspects of the relationship between the MAGE family and cancer,including the molecular characteristics of its members,transcriptional regulation mechanisms,expression patterns in different cancers,phenotypes and oncogenic mechanisms,poor clinical prognosis and potential as targets for immunotherapy.The expression patterns of these genes are closely linked to the clinical features of tumors,providing molecular markers and potential therapeutic targets for the early diagnosis,treatment,and prognostic assessment of cancer.展开更多
Artificial intelligence,such as deep learning technology,has advanced the study of facial expression recognition since facial expression carries rich emotional information and is significant for many naturalistic situ...Artificial intelligence,such as deep learning technology,has advanced the study of facial expression recognition since facial expression carries rich emotional information and is significant for many naturalistic situations.To pursue a high facial expression recognition accuracy,the network model of deep learning is generally designed to be very deep while the model’s real-time performance is typically constrained and limited.With MobileNetV3,a lightweight model with a good accuracy,a further study is conducted by adding a basic ResNet module to each of its existing modules and an SSH(Single Stage Headless Face Detector)context module to expand the model’s perceptual field.In this article,the enhanced model named Res-MobileNetV3,could alleviate the subpar of real-time performance and compress the size of large network models,which can process information at a rate of up to 33 frames per second.Although the improved model has been verified to be slightly inferior to the current state-of-the-art method in aspect of accuracy rate on the publically available face expression datasets,it can bring a good balance on accuracy,real-time performance,model size and model complexity in practical applications.展开更多
BACKGROUND ANAPC1,a key regulator of the ubiquitination in tumour development,has not been thoroughly studied in hepatocellular carcinoma(HCC).AIM To elucidate the expression of ANAPC1 in HCC and its potential regulat...BACKGROUND ANAPC1,a key regulator of the ubiquitination in tumour development,has not been thoroughly studied in hepatocellular carcinoma(HCC).AIM To elucidate the expression of ANAPC1 in HCC and its potential regulatory mechanism related to ubiquitination.METHODS Bulk RNA(RNA sequencing and microarrays),immunohistochemistry(IHC)tissues,and single-cell RNA sequencing(scRNA-seq)data were integrated to comprehensively investigate ANAPC1 expression in HCC.Clustered regularly interspaced short palindromic repeats analysis was performed to assess growth in HCC cell lines following ANAPC1 knockout.Enrichment analyses were conducted to explore the functions of ANAPC1.ScRNA-seq data was used to examine the cell cycle and metabolic levels.CellChat analysis was applied to investigate the interactions between ANAPC1 and different cell types.The relationship between ANAPC1 expression and drug concentration was analyzed.RESULTS ANAPC1 messenger RNA was found to be upregulated in bulk RNA,IHC tissues samples and malignant hepatocytes.The proliferation of JHH2 cell lines was most significantly inhibited after ANAPC1 knockdown.In biological pathways,the development of HCC was found to be linked to the regulation of ubiquitin-mediated proteolysis.Additionally,scRNA-seq results indicated that highly expressed ANAPC1 was in the G2/M phase,with increased glycolysis/gluconeogenesis activity.A CellChat analysis showed that ANAPC1 was associated with the regulation of the migration inhibitory factor-(cluster of differentiation 74+C-X-C chemokine receptor type 4)pathway.Higher ANAPC1 expression correlated with stronger effects of sorafenib,dasatinib,ibrutinib,lapatinib,nilotinib and afatinib.CONCLUSION The high expression level of ANAPC1 may regulate the cell cycle and metabolic levels of HCC through the ubiquitination-related pathway,thereby promoting disease progression.展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most common malignant gastrointestinal tumors worldwide,with high incidence and mortality rates.AIM To investigate the expression significance of the chromatin-remodeling...BACKGROUND Colorectal cancer(CRC)is one of the most common malignant gastrointestinal tumors worldwide,with high incidence and mortality rates.AIM To investigate the expression significance of the chromatin-remodeling protein MORC family CW-type zinc finger 4(MORC4)as a biomarker in CRC patients,and to explore its relationship with pathological features and prognosis.METHODS A total of 143 CRC specimens and 57 adjacent tissue specimens,surgically removed from our hospital between January 2020 and January 2021,were collected.MORC4 protein expression was assessed using immunohistochemistry after paraffin embedding.The relationship between MORC4 protein expression and clinicopathological characteristics of patients was analyzed.Kaplan-Meier survival curves were plotted to analyze the relationship between MORC4 protein expression and prognosis in CRC patients.RESULTS Compared with adjacent tissues,the expression rate of MORC4 protein in CRC tissues was significantly higher(P<0.05).No significant difference was observed in the high expression rate of MORC4 protein in CRC tissues among patients of different gender,age,tumor location,tumor diameter,and primary tumor status(P>0.05).However,significant differences were found in the high expression rate of MORC4 protein in patients with different degrees of differentiation,lymph node metastasis,distant metastasis,tumor-lymph node-metastasis stage,and serum carcinoembryonic antigen levels(P<0.05).Compared with patients with low MORC4 expression,patients with high MORC4 expression had a worse prognosis(P<0.05).CONCLUSION The upregulation of MORC4 expression in CRC patients is closely related to disease severity and prognosis,suggesting its potential as an evaluation biomarker,which warrants further investigation.展开更多
This study is based on wireless optogenetic technology,utilizing the CRY2/CIB1 photosensitive system to achieve spatiotemporal control of PD-L1 expression.In vitro experiments showed that the surface PD-L1 positivity ...This study is based on wireless optogenetic technology,utilizing the CRY2/CIB1 photosensitive system to achieve spatiotemporal control of PD-L1 expression.In vitro experiments showed that the surface PD-L1 positivity rate of cells increased from 28.6±3.1%to 67.3±5.4%(P<0.001).In animal experiments,the terminal tumor volume in the light exposure group was 450±90 mm3,with a tumor inhibition rate of approximately 49.4%(P<0.001),and the median survival was extended to 32 days(compared to 24 days in the control group,P=0.004).Immunological tests revealed a significant increase in CD8+T cell infiltration(112±18 vs 52±10 cells/HPF,P<0.01),a 30%decrease in the proportion of Tregs(P<0.05),and an increase in the M1/M2 macrophage ratio to 1.8.The results suggest that the wireless optogenetic system can not only precisely regulate PD-L1 but also remodel the tumor immune microenvironment,providing a new approach for precise immunotherapy of GBM.展开更多
Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive...Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive thyroid-related cell lines cultured under simulated microgravity.Methods:Five thyroid-related cell lines—normal thyrocytes(Nthy-ori 3-1),papillary thyroid cancer(PTC)cells(SNU-790,TPC-1),poorly differentiated thyroid cancer cell(BCPAP),and anaplastic thyroid cancer cell(SNU-80)—were cultured under simulated microgravity(10-3 g)using a clinostat.Differentially expressed genes(DEGs)were analyzed using cDNA microarray,followed by functional annotation and assessment of aggressiveness via Transwell migration and invasion assays.Results:DEG analysis under simulated microgravity revealed distinct gene expression profiles by gravity condition,with 2980 DEGs in SNU-790,1033 in BCPAP,562 in TPC-1,477 in Nthy-ori 3-1,and 246 in SNU-80,as confirmed by hierarchical clustering.In PTC cell lines(SNU-790,TPC-1),G2–M phase–related genes were upregulated.In non-PTC cell lines(BCPAP,SNU-80),genes associated with innate immune response,Toll-like receptor signaling,were upregulated,whereas Hypoxia-Inducible Factor 1-alpha(HIF-1α)signaling-related genes were downregulated.Additionally,under simulated microgravity,significant migration was observed in SNU-790(3×104 cells)and BCPAP(2×104 and 3×104),while significant invasion occurred in SNU-790,Nthy-ori 3-1,and BCPAP at a seeding density of 2×104.Other conditions showed no significant differences.Conclusion:This study comprehensively evaluates the effects of simulated microgravity using a diverse panel of thyroid-related cell lines.Thesefindings provide valuable insight into how microgravity could influence cancer biology,emphasizing the importance of further research on cancer behavior in space environments and its implications for human health during long-term space missions.展开更多
Objective:To investigate the expression level of interleukin-17D(IL-17D)in the serum of patients with severe pneumonia and its correlation with disease severity.Methods:This study included 50 patients with severe pneu...Objective:To investigate the expression level of interleukin-17D(IL-17D)in the serum of patients with severe pneumonia and its correlation with disease severity.Methods:This study included 50 patients with severe pneumonia who were diagnosed and treated in the hospital from May 2024 to May 2025.The expression level of IL-17D in the serum of all patients was recorded.Patients were divided into severe and mild groups based on their disease severity.Gender,age,disease duration,presence of fever,atelectasis,pneumothorax,interleukin-2(IL-2),interleukin-4(IL-4),interleukin-6(IL-6),and interleukin-17D were selected as independent variables.Statistical software SPSS 22.00 was used for univariate analysis,and variables with statistical significance in the univariate analysis were included in a multivariate logistic regression analysis to determine the correlation between IL-17D and the severity of severe pneumonia.Results:The results of this study showed that the level of IL-17D in patients with severe pneumonia was significantly higher than the normal threshold.Univariate analysis indicated that atelectasis,IL-2,IL-6,and IL-17D were statistically significant(P<0.05)and could be considered as influencing factors for the severity of severe pneumonia.Multivariate logistic regression analysis revealed that atelectasis(OR=2.141,95%CI:1.684–2.391),IL-2(OR=2.884,95%CI:2.240–3.614),IL-6(OR=2.571,95%CI:2.190–2.943),and IL-17D(OR=2.416,95%CI:2.093–2.735)were positively correlated with the severity of severe pneumonia.Conclusion:The expression level of IL-17D in the serum of patients with severe pneumonia is higher than the normal threshold and is positively correlated with disease severity.展开更多
基金supported by the Central Public-Interest Scientific Institution Basal Research Fund,China(Grant No.CPSIBRF-CNRRI-202403)。
文摘Rice is a poor source of folate,an essential micronutrient for the body.Biofortification offers an effective way to enhance the folate content of rice and alleviate folate deficiencies in humans.In this study,we confirmed that OsADCS and OsGTPCHI,encoding the initial enzymes necessary for folate synthesis,positively regulate folate accumulation in knockout mutants of both japonica and indica rice backgrounds.The folate content in the low-folate japonica variety was slightly increased by the expression of the indica alleles driven by the endosperm-specific promoter.We further obtained co-expression lines by stacking OsADCS and OsGTPCHI genes;the folate accumulation in brown rice and polished rice reached 5.65μg/g and 2.95μg/g,respectively,representing 37.9-fold and 26.5-fold increases compared with the wild type.Transcriptomic analysis of rice grains from six transgenic lines showed that folate changes affected biological pathways involved in the synthesis and metabolism of rice seed storage substances,while the expression of other folate synthesis genes was weakly regulated.In addition,we identified Aus rice as a high-folate germplasm carrying superior haplotypes of OsADCS and OsGTPCHI through natural variation.This study provides an alternative and effective complementary strategy for rice biofortification,promoting the rational combination of metabolic engineering and conventional breeding to breed high-folate varieties.
基金supported by the National Natural Science Foundation of China,Nos.32371065(to CL)and 32170950(to LY)the Natural Science Foundation of the Guangdong Province,No.2023A1515010899(to CL)the Science and Technology Projects in Guangzhou,Nos.2023A4J0578 and 2024A03J0180(to CW)。
文摘Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear memory.Cylindromatosis(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B pathway.CYLD is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly expressed.Emerging studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like behaviors.However,the precise role of CYLD in glutamatergic neurons is largely unknown.Here,we first proposed involvement of CYLD in cued fear expression.We next constructed transgenic model mice with specific deletion of Cyld from glutamatergic neurons.Our results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male mice.Further,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male mice.Altogether,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial activation.This may contribute,at least in part,to cued fear expression.
文摘Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(HCC)remain unclear.HCC is a highly lethal malignant tumor.Given the limitations of traditional treatments,this study explored the expression level,clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets.Methods In this study,we used public databases to analyze the expression of INF2 in pan-cancer and HCC,as well as the impact of INF2 expression levels on HCC prognosis.Quantitative real time polymerase chain reaction(RT-qPCR),Western blot,and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues.The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples.Subsequently,the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments.Finally,the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments.Results INF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival,liver cirrhosis and pathological differentiation of HCC patients.The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC.In vivo and in vitro HCC models,upregulated expression of INF2 triggers the proliferation and migration of the HCC cell,while knockdown of INF2 could counteract this effect.INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression,thus promoting tumor progression.Conclusion INF2 is highly expressed in HCC and is associated with poor prognosis.High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression,and targeting INF2 may be beneficial for HCC patients with high expression of INF2.
基金湖南省教育厅基金优秀青年项目(No.22B0482)湖南科技大学博士启动基金(No.E51992 and E51993)资助。
文摘The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose⁃catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16℃in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni⁃NTA affinity column.Size⁃exclusion chromatography and SDS⁃PAGE analysis demonstrated that the puri⁃fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD^(+)as a coenzyme to NADP^(+).The optimal temperature and pH of the TeXDH were 40℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26%of the initial enzyme activity,while the divalent metal ions Mg^(2+)or Ca^(2+)could recover the enzyme activity of TeXDH,reaching 103.32%and 110.69%of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn^(2+),Ni^(2+),Cu^(2+),Zn^(2+),Co^(2+),and Cd^(2+)significantly inhibited the activity of TeXDH.ICP⁃MS and molecular doc⁃king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn^(2+)ions and 1 mol/L Mg^(2+)ion.Further⁃more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.
文摘Since its discovery in the 1980s,the insect cell-baculovirus expression vector system(IC-BEVS)has been widely used in biomedical applications,such as recombinant protein expression,drug screening,vaccine development,gene therapy and so on[1].As a eukaryotic system,IC-BEVS has great development prospects due to its advantages such as high safety,simple operation,simultaneous expression of multi-subunit proteins,and suitability for large-scale cultivation[2].
基金supported by the Russian Science Foundation(No.22-16-00128),“Investigation of the Toxic Effect of Glyphosates on the Functional State of the Bird Intestinal Microbial Community,Their Growth and Development,and the Development of a Biological Product Based on the Glyphosate Degrading Strain”.
文摘Drugs and pesticide residues in broiler feed can compromise the therapeutic and production benefits of antibiotic(ANT)application and affect gene expression.In this study,we analyzed the expression of 13 key pancreatic genes and blood physiology parameters after administering one maximum residue limit of herbicide glyphosate(GLY),two ANTs,and one anticoccidial drug(AD).A total of 260 Ross 308 broilers aged 1-40 d were divided into the following four groups of 65 birds each:control group,which was fed the main diet(MD),and three experimental groups,which were fed MD supplemented with GLY,GLY+ANTs(enrofloxacin and colistin methanesulfonate),and GLY+AD(ammonium maduramicin),respectively.The results showed that the addition of GLY,GLY+ANTs,and GLY+AD caused significant changes in the expression of several genes of physiological and economic importance.In particular,genes related to inflammation and apoptosis(interleukin 6(IL6),prostaglandin-endoperoxide synthase 2(PTGS2),and caspase 6(CASP6))were downregulated by up to 99.1%,and those related to antioxidant protection(catalase(CAT),superoxide dismutase 1(SOD1)and peroxiredoxin 6(PRDX6))by up to 98.6%,compared to controls.There was also a significant decline in the values of immunological characteristics in the blood serum observed in the experimental groups,and certain changes in gene expression were concordant with changes in the functioning of the pancreas and blood.The changes revealed in gene expression and blood indices in response to GLY,ANTs,and AD provide insights into the possible mechanisms of action of these agents at the molecular level.Specifically,these changes may be indicative of physiological mechanisms to overcome the negative effects of GLY,GLY+ANTs,and GLY+AD in broilers.
基金supported by the National Characteristic Vegetable Industry Technology System of China(Grant No.CARS24-A-07)the Jiangsu Modern Agricultural Industry Technology System Construction Special Fund(Grant No.JATS[2023]050)Xuzhou Academy of Agricultural Sciences Research Fund Project(Grant No.XM2021003)。
文摘Commercial cultivars of garlic,a popular condiment,are sterile,making genetic variation and germplasm innovation of this plant challenging.Understanding mechanism of gamete sterility in garlic and their key regulatory networks is therefore important for fertility restoration.In this work,we conducted a detailed phenotypic analysis of fertile and sterile garlic genotypes and found that enlargement of topset in the inflorescence of sterile genotypes led to abnormal flowers.Additional cytological observations showed that aberrant meiotic cytokinesis in sterile garlic ultimately resulted in pollen degeneration.Transcriptomics analysis of sterile and fertile genotypes identified possible molecular mechanisms underlying gamete abortion.A total of 100710 differentially expressed genes(DEGs)between the fertile and sterile garlic flowers at three stages of gamete development were identified,many of which were involved in homologous chromosome synapsis during meiosis,MYB transcription factor regulation,ribosome biogenesis and plant hormone signal transduction.Taken together,these results provide insight into the molecular mechanisms and regulatory networks underlying gamete development in garlic and point to a set of candidate genes for further functional characterization.
文摘The published article titled“MicroRNA-221-3p Plays an Oncogenic Role in Gastric Carcinoma by Inhibiting PTEN Expression”has been retracted from Oncology Research,Vol.25,No.4,2017,pp.523–536.DOI:10.3727/096504016X14756282819385 URL:https://www.techscience.com/or/v25n4/56833 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
基金supported by the National Key Research and Development Program of China(No.2022YFD1200300)。
文摘Background Cotton is an industrial crop renowned for its multifaceted applications in the textiles,pharmaceuticals,and biofuel industries.Plant regeneration through somatic embryogenesis(SE)plays a crucial role in the genetic improvement of cotton.There is a strong correlation between SE and zygotic embryogenesis(ZE)in plants.Furthermore,the strategy of ectopic expression of cotton genes into the model plant Arabidopsis has been a widely accepted approach for functional study.Result Based on previous spatial transcriptomics of cotton somatic embryos,two genes,Gh HAT5 and Gh CRK29,were identified.They are highly expressed in cotyledon and epidermal cells of cotton cotyledonary embryos,respectively.In this study,Gh HAT5 and Gh CRK29 were ectopically expressed in Arabidopsis to investigate their functions.The result showed that in Arabidopsis zygotic embryos,the overexpression of Gh HAT5 promoted the development of apical embryonic upper-tier cells and embryonic cotyledon,while the overexpression of Gh CRK29 promoted the development of apical embryonic lower-tier cells and embryonic radicle.Given the similarities between somatic and zygotic embryogenesis,these findings suggest that Gh HAT5 and Gh CRK29 are involved in cotton SE.We also speculate that these genes may promote the expression of the Arabidopsis endogenous gene At SCR,which is crucial for embryonic development.Conclusion These results revealed that Gh HAT5 and Gh CRK29 regulate embryonic development and are essential in advancing our understanding of cotton SE and facilitating targeted genetic manipulation strategies to improve industrial crop traits and agricultural sustainability.
基金supported by the National Natural Science Foundation of China(Grant Nos.81872686 and 82173611)the National Key Research and Development Program of China(Grant No.2018YFC2000703)the Priority Academic Program for the Development of Jiangsu Higher Education Institutions(Public Health and Preventive Medicine)。
文摘Hypertension(HT)is a major risk factor for cardiovascular diseases.Krüppel-like factors(KLFs)are important transcription factors in eukaryotes.Studies have reported that KLF4 and KLF5 are correlated with several cardiovascular diseases,but population-based studies on associations between HT and KLF4 or KLF5 have rarely been reported.Therefore,the current study investigated the associations of genetic variants and m RNA expression levels of KLF4 and KLF5 with HT,as well as the effects of antihypertensive drugs on the expression levels of these genes.The associations of one single-nucleotide polymorphism(SNP)in KLF4 and three SNPs in KLF5with HT were analyzed using a combination of case-control and cohort studies.The study populations were selected from a community-based cohort in four regions of Jiangsu province.The risks of HT were estimated through logistic and Cox regression analyses.In addition,m RNA expression levels of KLF4 and KLF5 were detected in 246 controls and 385 HT cases selected from the aforementioned cohort.Among the HT cases,263were not taking antihypertensive drugs[AHD(-)]and 122 were taking antihypertensive drugs[AHD(+)].In the case-control study,SNP rs9573096(C>T)in KLF5 was significantly associated with an increased risk of HT in the additive model(adjusted odds ratio[OR],1.106;95%confidence interval[CI],1.009 to 1.212).In the cohort study of the normotensive population,rs9573096 in KLF5 was also significantly associated with an increased risk of HT in the additive model(adjusted hazards ratio[HR],1.199;95%CI,1.070 to 1.344).KLF4 and KLF5m RNA expression levels were significantly higher in the AHD(-)group than in the control group(P<0.05),but lower in the AHD(+)group than in the AHD(-)group(P<0.05).The current study demonstrated the associations of KLF4 and KLF5 genetic variants with hypertension,as well as the association of the indicative variations in m RNA expression levels of KLF4 and KLF5 with the risk of hypertension and antihypertensive treatment.
基金supported by the National Natural Science Foundation of China(32072159)Natural Science Foundation of Hainan Province(322QN338)+4 种基金Young Talent of Lifting Engineering for Science and Technology in Shandong,China(SDAST2021qt18)Qingdao Science and Technology Plan Key Research and Development Project(22-3-3-hygg-28-hy)Fundamental Research Funds for the Central Universities(202262003)Taishan Scholar Project of Shandong Province(tsqn202312099)Support Program for Youth Innovation Technology in Colleges and Universities of Shandong Province(2023KJ041)。
文摘Laminarin oligosaccharides(LOSs)with a specific degree of polymerization prepared through the laminarin degradation via laminarinase present more significant nutritional functions and application values.Human intestinal bacteria are promising potential producers of novel carbohydrate-active enzymes with unique properties.Here,a novel glycoside hydrolase family 128(GH128)laminarinase OUC-BsLam26 from the intestinal bacterium Bacteroides sp.CBA7301 was heterologously expressed and characterized.The recombinant OUC-BsLam26 with a molecular mass of 49.86 kDa exhibits highest activity(6.60 U/mg)at 45℃ and pH 6.0,which shows noticeable temperature and pH stability.The purified OUC-BsLam26 could degrade laminarin via an endo-type mode with the generation of laminaripentaose,laminaritetraose,laminaritriose,and laminaribiose,among them,laminaritetraose is the principal product,which accounts for 45.25% of the total products,which is significantly different from the reported GH128 laminarinases.The minimum recognition substrate of OUC-BsLam26 is laminarihexaose.Furthermore,OUC-BsLam26 also could catalyze the transglycosylation process with the production of some novel glycosides.Altogether,the intestinal bacterium Bacteroides sp.CBA7301 contains laminarinase with unique product composition and OUC-BsLam26 is a hopeful bio-catalyst with the potential to produce laminaritetraose and some novel glycosides.
文摘DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expression data generated. To address this, this paper employs a mixed-effects model to analyze gene expression data. In terms of data selection, 1176 genes from the white mouse gene expression dataset under two experimental conditions were chosen, setting up two conditions: pneumococcal infection and no infection, and constructing a mixed-effects model. After preprocessing the gene chip information, the data were imported into the model, preliminary results were calculated, and permutation tests were performed to biologically validate the preliminary results using GSEA. The final dataset consists of 20 groups of gene expression data from pneumococcal infection, which categorizes functionally related genes based on the similarity of their expression profiles, facilitating the study of genes with unknown functions.
基金supported by the National Natural Science Foundation of China(32172010)the Major Program of Guangdong Basic and Applied Basic Research(2019B030302006).
文摘Short tandem repeats(STRs)modulate gene expression and contribute to trait variation.However,a systematic evaluation of the genomic characteristics of STRs has not been conducted,and their influence on gene expression in rice remains unclear.Here,we construct a map of 137,629 polymorphic STRs in the rice(Oryza sativa L.)genome using a population-scale resequencing dataset.A genome-wide survey encompassing 4726 accessions shows that the occurrence frequency,mutational patterns,chromosomal distribution,and functional properties of STRs are correlated with the sequences and lengths of repeat motifs.Leveraging a transcriptome dataset from 127 rice accessions,we identify 44,672 expression STRs(eSTRs)by modeling gene expression in response to the length variation of STRs.These eSTRs are notably enriched in the regulatory regions of genes with active transcriptional signatures.Population analysis identifies numerous STRs that have undergone genetic divergence among different rice groups and 1726 tagged STRs that may be associated with agronomic traits.By editing the(ACT)_(7) STR in OsFD1 promoter,we further experimentally validate its role in regulating gene expression and phenotype.Our study highlights the contribution of STRs to transcriptional regulation in plants and establishes the foundation for their potential use as alternative targets for genetic improvement.
基金supported by Startup Fund for Young Faculty at SJTU(SFYF at SJTU)(No.24X010500176).
文摘As a member of the Cancer-Testis Antigens,the Melanoma-associated antigen(MAGE)family is typically expressed in normal tissues such as the testis.However,in various types of tumor cells,their expression is abnormally activated,which is associated with multiple critical processes of tumor cells,including proliferation,apoptosis,immune evasion,DNA damage repair,and metastasis.The abnormal expression of MAGE family genes in multiple cancers and their multifaceted roles in tumor biology have made them an important target in cancer research and treatment.This review comprehensively explores various aspects of the relationship between the MAGE family and cancer,including the molecular characteristics of its members,transcriptional regulation mechanisms,expression patterns in different cancers,phenotypes and oncogenic mechanisms,poor clinical prognosis and potential as targets for immunotherapy.The expression patterns of these genes are closely linked to the clinical features of tumors,providing molecular markers and potential therapeutic targets for the early diagnosis,treatment,and prognostic assessment of cancer.
基金supported by China Academy of Railway Sciences Corporation Limited(No.2021YJ127).
文摘Artificial intelligence,such as deep learning technology,has advanced the study of facial expression recognition since facial expression carries rich emotional information and is significant for many naturalistic situations.To pursue a high facial expression recognition accuracy,the network model of deep learning is generally designed to be very deep while the model’s real-time performance is typically constrained and limited.With MobileNetV3,a lightweight model with a good accuracy,a further study is conducted by adding a basic ResNet module to each of its existing modules and an SSH(Single Stage Headless Face Detector)context module to expand the model’s perceptual field.In this article,the enhanced model named Res-MobileNetV3,could alleviate the subpar of real-time performance and compress the size of large network models,which can process information at a rate of up to 33 frames per second.Although the improved model has been verified to be slightly inferior to the current state-of-the-art method in aspect of accuracy rate on the publically available face expression datasets,it can bring a good balance on accuracy,real-time performance,model size and model complexity in practical applications.
基金Co-first authors:Yu-Xing Tang 0000-0003-4382-4942Co-first authors:Wei-Zi Wu+8 种基金Corresponding author:Gang Chen,MD,Professor,Department of Pathology,The First Affiliated Hospital of Guangxi Medical University,No.6 Shuangyong Road,Nanning 530021,Guangxi Zhuang Autonomous Region,China.chengang@gxmu.edu.cn,0000-0003-2402-2987Co-corresponding authors:Yan-Ting ZhanSheng-Sheng Zhou,0000-0003-2414-460XDa-Tong Zeng,0000-0002-3338-4122Guang-Cai Zheng,0009-0001-5921-6688Rong-Quan He,0000-0002-7752-2080Di-Yuan Qin,0009-0003-3214-4762Wan-Ying Huang,0000-0002-8314-5963Yu-Lu Tang,0009-0004-0462-618X。
文摘BACKGROUND ANAPC1,a key regulator of the ubiquitination in tumour development,has not been thoroughly studied in hepatocellular carcinoma(HCC).AIM To elucidate the expression of ANAPC1 in HCC and its potential regulatory mechanism related to ubiquitination.METHODS Bulk RNA(RNA sequencing and microarrays),immunohistochemistry(IHC)tissues,and single-cell RNA sequencing(scRNA-seq)data were integrated to comprehensively investigate ANAPC1 expression in HCC.Clustered regularly interspaced short palindromic repeats analysis was performed to assess growth in HCC cell lines following ANAPC1 knockout.Enrichment analyses were conducted to explore the functions of ANAPC1.ScRNA-seq data was used to examine the cell cycle and metabolic levels.CellChat analysis was applied to investigate the interactions between ANAPC1 and different cell types.The relationship between ANAPC1 expression and drug concentration was analyzed.RESULTS ANAPC1 messenger RNA was found to be upregulated in bulk RNA,IHC tissues samples and malignant hepatocytes.The proliferation of JHH2 cell lines was most significantly inhibited after ANAPC1 knockdown.In biological pathways,the development of HCC was found to be linked to the regulation of ubiquitin-mediated proteolysis.Additionally,scRNA-seq results indicated that highly expressed ANAPC1 was in the G2/M phase,with increased glycolysis/gluconeogenesis activity.A CellChat analysis showed that ANAPC1 was associated with the regulation of the migration inhibitory factor-(cluster of differentiation 74+C-X-C chemokine receptor type 4)pathway.Higher ANAPC1 expression correlated with stronger effects of sorafenib,dasatinib,ibrutinib,lapatinib,nilotinib and afatinib.CONCLUSION The high expression level of ANAPC1 may regulate the cell cycle and metabolic levels of HCC through the ubiquitination-related pathway,thereby promoting disease progression.
基金was approved by the Ethics Committee of Cangzhou Central Hospital,No.29795793.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most common malignant gastrointestinal tumors worldwide,with high incidence and mortality rates.AIM To investigate the expression significance of the chromatin-remodeling protein MORC family CW-type zinc finger 4(MORC4)as a biomarker in CRC patients,and to explore its relationship with pathological features and prognosis.METHODS A total of 143 CRC specimens and 57 adjacent tissue specimens,surgically removed from our hospital between January 2020 and January 2021,were collected.MORC4 protein expression was assessed using immunohistochemistry after paraffin embedding.The relationship between MORC4 protein expression and clinicopathological characteristics of patients was analyzed.Kaplan-Meier survival curves were plotted to analyze the relationship between MORC4 protein expression and prognosis in CRC patients.RESULTS Compared with adjacent tissues,the expression rate of MORC4 protein in CRC tissues was significantly higher(P<0.05).No significant difference was observed in the high expression rate of MORC4 protein in CRC tissues among patients of different gender,age,tumor location,tumor diameter,and primary tumor status(P>0.05).However,significant differences were found in the high expression rate of MORC4 protein in patients with different degrees of differentiation,lymph node metastasis,distant metastasis,tumor-lymph node-metastasis stage,and serum carcinoembryonic antigen levels(P<0.05).Compared with patients with low MORC4 expression,patients with high MORC4 expression had a worse prognosis(P<0.05).CONCLUSION The upregulation of MORC4 expression in CRC patients is closely related to disease severity and prognosis,suggesting its potential as an evaluation biomarker,which warrants further investigation.
文摘This study is based on wireless optogenetic technology,utilizing the CRY2/CIB1 photosensitive system to achieve spatiotemporal control of PD-L1 expression.In vitro experiments showed that the surface PD-L1 positivity rate of cells increased from 28.6±3.1%to 67.3±5.4%(P<0.001).In animal experiments,the terminal tumor volume in the light exposure group was 450±90 mm3,with a tumor inhibition rate of approximately 49.4%(P<0.001),and the median survival was extended to 32 days(compared to 24 days in the control group,P=0.004).Immunological tests revealed a significant increase in CD8+T cell infiltration(112±18 vs 52±10 cells/HPF,P<0.01),a 30%decrease in the proportion of Tregs(P<0.05),and an increase in the M1/M2 macrophage ratio to 1.8.The results suggest that the wireless optogenetic system can not only precisely regulate PD-L1 but also remodel the tumor immune microenvironment,providing a new approach for precise immunotherapy of GBM.
文摘Background:With growing interest in space exploration,understanding microgravity’s impact on human health is essential.This study aims to investigate gene expression changes and migration and invasion potential infive thyroid-related cell lines cultured under simulated microgravity.Methods:Five thyroid-related cell lines—normal thyrocytes(Nthy-ori 3-1),papillary thyroid cancer(PTC)cells(SNU-790,TPC-1),poorly differentiated thyroid cancer cell(BCPAP),and anaplastic thyroid cancer cell(SNU-80)—were cultured under simulated microgravity(10-3 g)using a clinostat.Differentially expressed genes(DEGs)were analyzed using cDNA microarray,followed by functional annotation and assessment of aggressiveness via Transwell migration and invasion assays.Results:DEG analysis under simulated microgravity revealed distinct gene expression profiles by gravity condition,with 2980 DEGs in SNU-790,1033 in BCPAP,562 in TPC-1,477 in Nthy-ori 3-1,and 246 in SNU-80,as confirmed by hierarchical clustering.In PTC cell lines(SNU-790,TPC-1),G2–M phase–related genes were upregulated.In non-PTC cell lines(BCPAP,SNU-80),genes associated with innate immune response,Toll-like receptor signaling,were upregulated,whereas Hypoxia-Inducible Factor 1-alpha(HIF-1α)signaling-related genes were downregulated.Additionally,under simulated microgravity,significant migration was observed in SNU-790(3×104 cells)and BCPAP(2×104 and 3×104),while significant invasion occurred in SNU-790,Nthy-ori 3-1,and BCPAP at a seeding density of 2×104.Other conditions showed no significant differences.Conclusion:This study comprehensively evaluates the effects of simulated microgravity using a diverse panel of thyroid-related cell lines.Thesefindings provide valuable insight into how microgravity could influence cancer biology,emphasizing the importance of further research on cancer behavior in space environments and its implications for human health during long-term space missions.
基金Chongqing Shapingba District Technology Innovation Project(Project No.:2024046)。
文摘Objective:To investigate the expression level of interleukin-17D(IL-17D)in the serum of patients with severe pneumonia and its correlation with disease severity.Methods:This study included 50 patients with severe pneumonia who were diagnosed and treated in the hospital from May 2024 to May 2025.The expression level of IL-17D in the serum of all patients was recorded.Patients were divided into severe and mild groups based on their disease severity.Gender,age,disease duration,presence of fever,atelectasis,pneumothorax,interleukin-2(IL-2),interleukin-4(IL-4),interleukin-6(IL-6),and interleukin-17D were selected as independent variables.Statistical software SPSS 22.00 was used for univariate analysis,and variables with statistical significance in the univariate analysis were included in a multivariate logistic regression analysis to determine the correlation between IL-17D and the severity of severe pneumonia.Results:The results of this study showed that the level of IL-17D in patients with severe pneumonia was significantly higher than the normal threshold.Univariate analysis indicated that atelectasis,IL-2,IL-6,and IL-17D were statistically significant(P<0.05)and could be considered as influencing factors for the severity of severe pneumonia.Multivariate logistic regression analysis revealed that atelectasis(OR=2.141,95%CI:1.684–2.391),IL-2(OR=2.884,95%CI:2.240–3.614),IL-6(OR=2.571,95%CI:2.190–2.943),and IL-17D(OR=2.416,95%CI:2.093–2.735)were positively correlated with the severity of severe pneumonia.Conclusion:The expression level of IL-17D in the serum of patients with severe pneumonia is higher than the normal threshold and is positively correlated with disease severity.
