High-throughput screening system of citrus bacterial cankerassociated transcription factors and its application to the regulation of citrus canker resistance

One of the main diseases that adversely impacts the global citrus industry is citrus bacterial canker(CBC),caused by the bacteria Xanthomonas citri subsp.citri(Xcc).Response to CBC is a complex process,with both proteinDNA as well as protein–protein interactions for the regulatory network.To detect such interactions in CBC resistant regulation,a citrus high-throughput screening system with 203 CBC-inducible transcription factors(TFs),were developed.Screening the upstream regulators of target by yeast-one hybrid(Y1H)methods was also performed.A regulatory module of CBC resistance was identified based on this system.One TF(CsDOF5.8)was explored due to its interactions with the 1-kb promoter fragment of CsPrx25,a resistant gene of CBC involved in reactive oxygen species(ROS)homeostasis regulation.Electrophoretic mobility shift assay(EMSA),dual-LUC assays,as well as transient overexpression of CsDOF5.8,further validated the interactions and transcriptional regulation.The CsDOF5.8–CsPrx25 promoter interaction revealed a complex pathway that governs the regulation of CBC resistance via H2O2homeostasis.The high-throughput Y1H/Y2H screening system could be an efficient tool for studying regulatory pathways or network of CBC resistance regulation.In addition,it could highlight the potential of these candidate genes as targets for efforts to breed CBC-resistant citrus varieties.

Roles of NAC transcription factors in cotton

Climate deterioration,water shortages,and abiotic stress are the main threats worldwide that seriously affect cotton growth,yield,and fiber quality.Therefore,research on improving cotton yield and tolerance to biotic and abiotic stresses is of great importance.The NAC proteins are crucial and plant-specific transcription factors(TFs)that are involved in cotton growth,development,and stress responses.The comprehensive utilization of cotton NAC TFs in the improvement of cotton varieties through novel biotechnological methods is feasible.Based on cotton genomic data,genome-wide identification and analyses have revealed potential functions of cotton NAC genes.Here,we comprehensively summarize the recent progress in understanding cotton NAC TFs roles in regulating responses to drought,salt,and Verticillium wilt-related stresses,as well as leaf senescence and the development of fibers,xylem,and glands.The detailed regulatory network of NAC proteins in cotton is also elucidated.Cotton NAC TFs directly bind to the promoters of genes associated with ABA biosynthesis and secondary cell-wall formation,participate in several biological processes by interacting with related proteins,and regulate the expression of downstream genes.Studies have shown that the overexpression of NAC TF genes in cotton and other model plants improve their drought or salt tolerance.This review elucidates the latest findings on the functions and regulation of cotton NAC proteins,broadens our understanding of cotton NAC TFs,and lays a fundamental foundation for further molecular breeding research in cotton.

Characteristics and expression of the TCP transcription factors family in Allium senescens reveal its potential roles in drought stress responses

Allium senescens,is an important economic and ecological grassland plant with drought-resistant characteristics.A TCP protein transcription factor is important in the regulation of plant development and adverse responses.However,the mechanism by which TCP transcription functions in drought resistance in Allium senescens is still not clear.Here,we obtained a total of 190,305 transcripts with 115,562 single gene clusters based on RNA-Seq sequencing of Allium senescens under drought stress.The total number of bases was 97,195,096 bp,and the average length was 841.06 bp.Furthermore,we found that there were eight genes of the TCP family that showed an upregulated expression trend under drought stress in Allium senescens.We carried out an investigation to determine the evolution and function of the AsTCP family and how they produce an effect in drought resistance.The 14 AsTCP genes were confirmed and divided into class I and class II containing CIN and CYC/TBI subfamilies,respectively.We also found that the expression of AsTCP17 was remarkably upregulated with drought treatment.Besides,the transformation of AsTCP17 in Arabidopsis revealed that the protective enzymes,namely polyphenol oxidase(POD)and superoxide dismutase(SOD),were increased by 0.4 and 0.8 times,respectively.Chlorophyll content was also increased,while the H2O2 and malondialdehyde(MDA)contents were decreased.Staining assays with 3,3′-diaminobenzidine(DAB)also suggested that the AsTCP17 downregulates reactive oxygen species(ROS)accumulation.In addition,overexpression of the AsTCP17 affected the accumulation of drought-related hormones in plants,and the synthesis of ABA.The expression of AtSVP and AtNCED3,related ABA synthesis pathway genes,indicated that the level of expression of AtSVP and AtNCED3 was obviously enhanced,with the overexpression of line 6 showing a 20.6-fold and 7.0-fold increase,respectively.Taken together,our findings systematically analyze the AsTCPs family at the transcriptome expression level in Allium senescens,and we also demonstrated that AsTCP17 protein,as a positive regulator,was involved in drought resistance of Allium senescens.In addition,our research contributes to the comprehensive understanding of the drought stress defense mechanism in herbaceous plants.

Transcription factor OsSPL10 interacts with OsJAmyb to regulate blast resistance in rice

Transcription factors(TFs)play essential roles in transcriptional reprogramming during activation of plant immune responses to pathogens.OsSPL10(SQUAMOSA promoter binding protein-like10)is an important TF regulating trichome development and salt tolerance in rice.Here we report that knockout of OsSPL10 reduces whereas its overexpression enhances rice resistance to blast disease.OsSPL10 positively regulates chitin-induced immune responses including reactive oxygen species(ROS)burst and callose deposition.We show that OsSPL10 physically associates with OsJAmyb,an important TF involved in jasmonic acid(JA)signaling,and positively regulates its protein stability.We then prove that OsJAmyb positively regulates resistance to blast.Our results reveal a molecular module consisting of OsSPL10 and OsJAmyb that positively regulates blast resistance.

Comparative transcriptome analysis of the climacteric of apple fruit uncovers the involvement of transcription factors affecting ethylene biosynthesis

Apple(Malus domestica)fruit generally undergoes a climacteric.During its ripening process,there is a peak in ethylene release and its firmness simultaneously decreases.Although more in-depth research into the mechanism of climacteric-type fruit ripening is being carried out,some aspects remain unclear.In this study,we compared the transcriptomes of 0-Pre and 15-Post(pre-and post-climacteric fruit),and 15-Post and 15-MCP[fruit treated with 1-MCP(1-methylcyclopropene)].Various transcription factors,such as MADS-box,ERF,NAC,Dof and SHF were identified among the DEGs(differential gene expressions).Furthermore,these transcription factors were selected for further validation analysis by qRT-PCR.Moreover,yeast one hybrid(Y1H),β-glucuronidase(GUS)transactivation assay and dual-luciferase reporter assay showed that MdAGL30,MdAGL104,MdERF008,MdNAC71,MdDof1.2,MdHSFB2a and MdHSFB3 bound to MdACS1 promoter and directly regulated its transcription,thereby regulating ethylene biosynthesis in apple fruit.Our results provide useful information and new insights for research on apple fruit ripening.

Identification of the target genes of AhTWRKY24 and AhTWRKY106 transcription factors reveals their regulatory network in Arachis hypogaea cv.Tifrunner using DAP-seq

WRKY transcription factors(TFs)have been identified as important core regulators in the responses of plants to biotic and abiotic stresses.Cultivated peanut(Arachis hypogaea)is an important oil and protein crop.Previous studies have identified hundreds of WRKY TFs in peanut.However,their functions and regulatory networks remain unclear.Simultaneously,the AdWRKY40 TF is involved in drought tolerance in Arachis duranensis and has an orthologous relationship with the AhTWRKY24 TF,which has a homoeologous relationship with AhTWRKY106 TF in A.hypogaea cv.Tifrunner.To reveal how the homoeologous AhTWRKY24 and AhTWRKY106 TFs regulate the downstream genes,DNA affinity purification sequencing(DAP-seq)was performed to detect the binding sites of TFs at the genome-wide level.A total of 3486 downstream genes were identified that were collectively regulated by the AhTWRKY24 and AhTWRKY106 TFs.The results revealed that W-box elements were the binding sites for regulation of the downstream genes by AhTWRKY24 and AhTWRKY106 TFs.A gene ontology enrichment analysis indicated that these downstream genes were enriched in protein modification and reproduction in the biological process.In addition,RNA-seq data showed that the AhTWRKY24 and AhTWRKY106 TFs regulate differentially expressed genes involved in the response to drought stress.The AhTWRKY24 and AhTWRKY106 TFs can specifically regulate downstream genes,and they nearly equal the numbers of downstream genes from the two A.hypogaea cv.Tifrunner subgenomes.These results provide a theoretical basis to study the functions and regulatory networks of AhTWRKY24 and AhTWRKY106 TFs.

Age-related driving mechanisms of retinal diseases and neuroprotection by transcription factor EB-targeted therapy

Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.

Oncogene goosecoid is transcriptionally regulated by E2F1 and correlates with disease progression in prostate cancer

Background:Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer(PCa),the long tail of cancer genes remains to be defined.Goosecoid(GSC)has been implicated in cancer development.However,the comprehensive biological role of GSC in pan-cancer,specifically in PCa,remains unexplored.The aim of this study was to investigate the role of GSC in PCa development.Methods:We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Omnibus,German Cancer Research Center,and our in-house cohorts.First,we evaluated the expression of GSC and its association with patient prognosis,and identified GSC-relevant genetic alterations in cancers.Further,we focused on the clinical characterization and prognostic analysis of GSC in PCa.To understand the transcriptional regulation of GSC by E2F transcription factor 1(E2F1),we performed chromatin immunoprecipitation quantitative polymerase chain reaction(qPCR).Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib.Results:GSC expression was elevated in various tumors and significantly correlated with patient prognosis.The alterations of GSC contribute to the progression of various tumors especially in PCa.Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes.Further,GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score,advanced tumor stage,lymph node metastasis,and elevated prostate-specific antigen(PSA)levels.Mechanistically,the transcription factor,E2F1,stimulates GSC by binding to its promoter region.Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment.Conclusions:GSC was highly overexpressed and strongly correlated with patient prognosis in PCa.We found that GSC,regulated by E2F1,acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Wild soybean(Glycine soja)transcription factor GsWRKY40 plays positive roles in plant salt tolerance

Wild soybean(Glycine soja),a relative of cultivated soybean,shows high adaptability to adverse environmental conditions.We identified and characterized a wild soybean transcription factor gene,GsWRKY40,that promotes plant salt stress.GsWRKY40 was highly expressed in wild soybean roots and was up-regulated by salt treatment.GsWRKY40 was localized in nucleus and demonstrated DNA-binding activities but without transcriptional activation.Mutation and overexpression of GsWRKY40 altered salt tolerance of Arabidopsis plants.To understand the molecular mechanism of GsWRKY40 in regulating plant salt resistance,we screened a cDNA library and identified a GsWRKY40 interacting protein GsbHLH92 by using yeast two-hybrid approach.The physical interaction of GsWRKY40 and GsbHLH92 was confirmed by co-immunoprecipitation(co-IP),GST pull-down,and bimolecular fluorescence complementation(BiFC)techniques.Intriguingly,co-overexpression of GsWRKY40 and GsbHLH92 resulted in higher salt tolerance and lower ROS levels than overexpression of GsWRKY40 or GsbHLH92 in composite soybean plants,suggesting that GsWRKY40 and GsbHLH92 may synergistically regulate plant salt resistance through inhibiting ROS production.qRT-PCR data indicated that the expression level of GmSPOD1 gene encoding peroxidase was cooperatively regulated by GsWRKY40 and GsbHLH92,which was confirmed by using a dual luciferase report system and yeast one-hybrid experiment.Our study reveals a pathway that GsWRKY40 and GsbHLH92 collaboratively up-regulate plant salt resistance through impeding GmSPOD1 expression and reducing ROS levels,providing a novel perspective on the regulatory mechanisms underlying plant tolerance to abiotic stresses.

Sugarcane transcription factor ScWRKY4 negatively regulates resistance to pathogen infection through the JA signaling pathway

WRKY transcription factors,transcriptional regulators unique to plants,play an important role in defense response to pathogen infection.However,the resistance mechanisms of WRKY genes in sugarcane remain unclear.In the present study,gene ontology(GO)enrichment analysis revealed that WRKY gene family in sugarcane was extensively involved in the response to biotic stress and in defense response.We identified gene ScWRKY4,a classⅡc member of the WRKY gene family,in sugarcane cultivar ROC22.This gene was induced by salicylic acid(SA)and methyl jasmonate(MeJA)stress.Interestingly,expression of ScWRKY4 was down-regulated in smut-resistant sugarcane cultivars but up-regulated in smutsusceptible sugarcane cultivars infected with Sporisorium scitamineum.Moreover,stable overexpression of the ScWRKY4 gene in Nicotiana benthamiana enhanced susceptibility to Fusarium solani var.coeruleum and caused down-regulated expression of immune marker-related genes.Transcriptome analysis indicated suppressed expression of most JAZ genes in the signal transduction pathway.ScWRKY4 interacted with ScJAZ13 to repress its expression.We thus hypothesized that the ScWRKY4 gene was involved in the regulatory network of plant disease resistance,most likely through the JA signaling pathway.The present study depicting the molecular involvement of ScWRKY4 in sugarcane disease resistance lays a foundation for future investigation.

The BEL1-like transcription factor GhBLH5-A05 participates in cotton response to drought stress

Drought stress impairs crop growth and development.BEL1-like family transcription factors may be involved in plant response to drought stress,but little is known of the molecular mechanism by which these proteins regulate plant response and defense to drought stress.Here we show that the BEL1-like transcription factor GhBLH5-A05 functions in cotton(Gossypium hirsutum)response and defense to drought stress.Expression of GhBLH5-A05 in cotton was induced by drought stress.Overexpression of GhBLH5-A05 in both Arabidopsis and cotton increased drought tolerance,whereas silencing GhBLH5-A05 in cotton resulted in elevated sensitivity to drought stress.GhBLH5-A05 binds to cis elements in the promoters of GhRD20-A09 and GhDREB2C-D05 to activate the expression of these genes.GhBLH5-A05 interacted with the KNOX transcription factor GhKNAT6-A03.Co-expression of GhBLH5-A05 and GhKNAT6-A03 increased the transcription of GhRD20-A09 and GhDREB2C-D05.We conclude that GhBLH5-A05 acts as a regulatory factor with GhKNAT6-A03 functioning in cotton response to drought stress by activating the expression of the drought-responsive genes GhRD20-A09 and GhDREB2C-D05.

Gene expression,transcription factor binding and histone modification predict leaf adaxial-abaxial polarity related genes

Leaf adaxial-abaxial(ad-abaxial)polarity is crucial for leaf morphology and function,but the genetic machinery governing this process remains unclear.To uncover critical genes involved in leaf ad-abaxial patterning,we applied a combination of in silico prediction using machine learning(ML)and experimental analysis.A Random Forest model was trained using genes known to influence ad-abaxial polarity as ground truth.Gene expression data from various tissues and conditions as well as promoter regulation data derived from transcription factor chromatin immunoprecipitation sequencing(ChIP-seq)was used as input,enabling the prediction of novel ad-abaxial polarity-related genes and additional transcription factors.Parallel to this,available and newly-obtained transcriptome data enabled us to identify genes differentially expressed across leaf ad-abaxial sides.Based on these analyses,we obtained a set of 111 novel genes which are involved in leaf ad-abaxial specialization.To explore implications for vegetable crop breeding,we examined the conservation of expression patterns between Arabidopsis and Brassica rapa using single-cell transcriptomics.The results demonstrated the utility of our computational approach for predicting candidate genes in crop species.Our findings expand the understanding of the genetic networks governing leaf ad-abaxial differentiation in agriculturally important vegetables,enhancing comprehension of natural variation impacting leaf morphology and development,with demonstrable breeding applications.

Cone-rod homeobox transcriptionally activates TCF7 to promote the proliferation of retinal pigment epithelial and retinoblastoma cells in vitro

AIM:To investigate the proliferation regulatory effect of cone-rod homeobox(CRX)in retinal pigment epithelium(RPE)and retinoblastoma(RB)cells to explore the potential application and side effect(oncogenic potential)of CRXbased gene therapy in RPE-based retinopathies.METHODS:Adult human retinal pigment epithelial(ARPE)-19 and human retinal pigment epithelial(RPE)-1 cells and Y79 RB cell were used in the study.Genetic manipulation was performed by lentivirus-based technology.The cell proliferation was determined by a CellTiter-Glo Reagent.The mRNA and protein levels were determined by quantitative real-time polymerase chain reaction(qPCR)and Western blot assay.The transcriptional activity of the promoter was determined by luciferase reporter gene assay.The bindings between CRX and transcription factor 7(TCF7)promoter as well as TCF7 and the promoters of TCF7 target genes were examined by chromatin immunoprecipitation(ChIP)assay.The transcription of the TCF7 was determined by a modified nuclear run-on assay.RESULTS:CRX overexpression and knockdown significantly increased(n=3,P<0.05 in all the cells)and decreased(n=3,P<0.01 in all the cells)the proliferation of RPE and RB cells.CRX overexpression and knockdown significantly increased and deceased the mRNA levels of Wnt signaling target genes[including MYC proto-oncogene(MYC),JUN,FOS like 1(FOSL1),CCND1,cyclin D2(CCND2),cyclin D3(CCND3),cellular communication network factor 4(CCN4),peroxisome proliferator activated receptor delta(PPARD),and matrix metallopeptidase 7(MMP7)]and the luciferase activity driven by the Wnt signaling transcription factor(TCF7).TCF7 overexpression and knockdown significantly increased and decreased the proliferation of RPE and RB cells and depletion of TCF7 significantly abolished the stimulatory effect of CRX on the proliferation of RPE and RB cells.CRX overexpression and knockdown significantly increased and decreased the mRNA level of TCF7 and the promoter of TCF7 was significantly immunoprecipitated by CRX antibody.CONCLUSION:CRX transcriptionally activates TCF7 to promote the proliferation of RPE and RB cells in vitro.CRX is a potential target for RPE-based regenerative medicine.The potential risk of this strategy,tumorigenic potential,should be considered.

Cu Stress-Induced Transcriptome Alterations in Sorghum and Expression Analysis of the Transcription Factor-Encoding Gene SbWRKY24

Sorghum is not only an important bio-energy crop but also a vital raw material for brewing.Exogenous copper affects the growth and metabolism of crops in specific ways.This study identified 8475 differentially expressed genes(DEGs)by high-throughput transcriptome sequencing in the sorghum cultivar‘Jinnuoliang 2’after 24 h of treatment with 10 mM CuSO4.Using GO analysis,476 genes were functionally annotated,which were mainly related to catabolism and biosynthetic processes.Additionally,90 pathways were annotated by employing the KEGG analysis.Among them,glutathione metabolism and peroxisome were induced,while photosynthesis,photosynthesis-antenna protein,and carbon sequestration of photosynthetic organisms were inhibited.Of the DEGs,399 were identified to encode transcription factors belonging to 49 families.This study also identified a WRKY transcription factor-encoding gene SbWRKY24 from the transcriptome data.For studying its function,the relative expression levels of SbWRKY24 in roots and leaves post-treatment with different growth hormones and exposure to a variety of abiotic stresses were detected by RT-qPCR.SbWRKY24 showed treatment-and tis-sue-specific expression patterns,indicating its unique role in stress tolerance.This study lays a theoretical basis for the functional exploration of SbWRKY24,elucidating the mechanism of copper resistance,and elaborating on the stress responses in sorghum.It also guides the exploration of the molecular mechanism of copper ions inducing intracellular signal transduction pathways.

Significant risk factors for intensive care unit-acquired weakness:A processing strategy based on repeated machine learning

BACKGROUND Intensive care unit-acquired weakness(ICU-AW)is a common complication that significantly impacts the patient's recovery process,even leading to adverse outcomes.Currently,there is a lack of effective preventive measures.AIM To identify significant risk factors for ICU-AW through iterative machine learning techniques and offer recommendations for its prevention and treatment.METHODS Patients were categorized into ICU-AW and non-ICU-AW groups on the 14th day post-ICU admission.Relevant data from the initial 14 d of ICU stay,such as age,comorbidities,sedative dosage,vasopressor dosage,duration of mechanical ventilation,length of ICU stay,and rehabilitation therapy,were gathered.The relationships between these variables and ICU-AW were examined.Utilizing iterative machine learning techniques,a multilayer perceptron neural network model was developed,and its predictive performance for ICU-AW was assessed using the receiver operating characteristic curve.RESULTS Within the ICU-AW group,age,duration of mechanical ventilation,lorazepam dosage,adrenaline dosage,and length of ICU stay were significantly higher than in the non-ICU-AW group.Additionally,sepsis,multiple organ dysfunction syndrome,hypoalbuminemia,acute heart failure,respiratory failure,acute kidney injury,anemia,stress-related gastrointestinal bleeding,shock,hypertension,coronary artery disease,malignant tumors,and rehabilitation therapy ratios were significantly higher in the ICU-AW group,demonstrating statistical significance.The most influential factors contributing to ICU-AW were identified as the length of ICU stay(100.0%)and the duration of mechanical ventilation(54.9%).The neural network model predicted ICU-AW with an area under the curve of 0.941,sensitivity of 92.2%,and specificity of 82.7%.CONCLUSION The main factors influencing ICU-AW are the length of ICU stay and the duration of mechanical ventilation.A primary preventive strategy,when feasible,involves minimizing both ICU stay and mechanical ventilation duration.

Phase separation and transcriptional regulation in cancer development

Liquid-liquid phase separation,a novel biochemical phenomenon,has been increasingly studied for its medical applications.It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes.During transcriptional regulation,dynamic condensates are formed through interactions between transcriptional elements,such as transcription factors,coactivators,and mediators.Cancer is a disease characterized by uncontrolled cell proliferation,but the precise mechanisms underlying tumorigenesis often remain to be elucidated.Emerging evidence has linked abnormal transcriptional condensates to several diseases,especially cancer,implying that phase separation plays an important role in tumorigenesis.Condensates formed by phase separation may have an effect on gene transcription in tumors.In the present review,we focus on the correlation between phase separation and transcriptional regulation,as well as how this phenomenon contributes to cancer development.

Prognostic significance of oligodendrocyte transcription factor 2 expression in glioma patients:A systematic review and metaanalys

BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify novel diagnostic biomarkers and therapeutic targets of glioma to effectively improve treatment outcomes.AIM To investigate the association between oligodendrocyte transcription factor 2(Olig2)expression and the outcomes of glioma patients.METHODS The PubMed,Embase,Cochrane Library,and China National Knowledge Infrastructure databases were searched for studies(published up to October 2023)that investigated the relationship between Olig2 expression and prognosis of glioma patients.The quality of the studies was assessed using the Newcastle Ottawa Scale.Data analyses were performed using Stata Version 12.0 software.RESULTS A total of 1205 glioma patients from six studies were included in the metaanalysis.High Olig2 expression was associated with better outcomes in glioma patients[hazard ratio(HR):0.81;95%(confidence interval)CI:0.51-1.27;P=0.000].Furthermore,the results of subgroup meta-analysis showed that high expression of Olig2 was associated with poor overall survival in European patients(HR:1.34;95%CI:0.79-2.27)and better prognosis in Asian patients(HR:0.43;95%CI:0.22-0.84).The sensitivity analysis showed that no single study had a significant effect on pooled HR,and there was also no indication of publication bias according to the Egger’s and Begger’s P value test or funnel plot test.CONCLUSION High Olig2 expression may have a positive impact on the prognosis of glioma patients,and should be investigated further as a prognostic biomarker and therapeutic target for glioma.

Biological factors driving colorectal cancer metastasis

Approximately 20%of colorectal cancer(CRC)patients present with metastasis at diagnosis.Among Stage I-III CRC patients who undergo surgical resection,18%typically suffer from distal metastasis within the first three years following initial treatment.The median survival duration after the diagnosis of metastatic CRC(mCRC)is only 9 mo.mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue,allowing cancer cells to spread from primary to distant organs;however,increa-sing evidence suggests that the mCRC process can begin early in tumor development.CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations.Different genomic and nongenomic events can induce subclone diversity,which leads to cancer and metastasis.Throughout the course of mCRC,metastatic cascades are associated with invasive cancer cell migration through the circulatory system,extravasation,distal seeding,dormancy,and reactivation,with each step requiring specific molecular functions.However,cancer cells presenting neoantigens can be recognized and eliminated by the immune system.In this review,we explain the biological factors that drive CRC metastasis,namely,genomic instability,epigenetic instability,the metastatic cascade,the cancer-immunity cycle,and external lifestyle factors.Despite remarkable progress in CRC research,the role of molecular classification in therapeutic intervention remains unclear.This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

Prevalence and risk factors of diabetes mellitus among elderly patients in the Lugu community

BACKGROUND Age is a significant risk factor of diabetes mellitus(DM).With the develop of population aging,the incidence of DM remains increasing.Understanding the epidemiology of DM among elderly individuals in a certain area contributes to the DM interventions for the local elderly individuals with high risk of DM.AIM To explore the prevalence of DM among elderly individuals in the Lugu community and analyze the related risk factors to provide a valid scientific basis for the health management of elderly individuals.METHODS A total of 4816 elderly people who came to the community for physical examination were retrospectively analyzed.The prevalence of DM among the elderly was calculated.The individuals were divided into a DM group and a non-DM group according to the diagnosis of DM to compare the differences in diastolic blood pressure(DBP)and systolic blood pressure(SBP),fasting blood glucose,body mass index(BMI),waist-to-hip ratio(WHR)and incidence of hypertension(HT),coronary heart disease(CHD),and chronic kidney disease(CKD).RESULTS DM was diagnosed in 32.70%of the 4816 elderly people.The BMI of the DM group(25.16±3.35)was greater than that of the non-DM group(24.61±3.78).The WHR was 0.90±0.04 in the non-DM group and 0.90±0.03 in the DM group,with no significant difference.The left SBP and SBP in the DM group were 137.9 mmHg±11.92 mmHg and 69.95 mmHg±7.75 mmHg,respectively,while they were 126.6 mmHg±12.44 mmHg and 71.15 mmHg±12.55 mmHg,respectively,in the non-DM group.These findings indicate higher SBP and lower DBP in DM patients than in those without DM.In the DM group,1274 patients were diagnosed with HT,accounting for 80.89%.Among the 3241 non-DM patients,1743(53.78%)were hypertensive and 1498(46.22%)were nonhypertensive.The DM group had more cases of HT than did the non-DM group.There were more patients with CHD or CKD in the DM group than in the non-DM group.There were more patients who drank alcohol more frequently(≥3 times)in the DM group than in the non-DM group.CONCLUSION Older adults in the Lugu community are at a greater risk of DM.In elderly individuals,DM is closely related to high BMI and HT,CHD,and CKD.Physical examinations should be actively carried out for elderly people to determine their BMI,SBP,DBP,and other signs,and sufficient attention should be given to abnormalities in the above signs before further diagnosis.