Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular...Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.展开更多
The chalcone isomerase gene OsCHI,one of the key genes in the flavonoid biosynthesis pathway,plays an important role in rice(Oryza sativa)resistance to abiotic stresses.This study reveals how the chalcone isomerase ge...The chalcone isomerase gene OsCHI,one of the key genes in the flavonoid biosynthesis pathway,plays an important role in rice(Oryza sativa)resistance to abiotic stresses.This study reveals how the chalcone isomerase gene family member OsCHI3 participates in rice responses to drought stress through the regulation of flavonoid biosynthesis.Overexpression of OsCHI3 increased the tolerance of rice to drought stress.In contrast,CRISPR/Cas9-mediated deletion of OsCHI3 reduced the drought tolerance of rice,an effect that is reversed by exogenous ABA treatment.Transcriptomic and physiological biochemical analyses indicated that flavonoids regulated by OsCHI3 not only scavenge reactive oxygen species(ROS)but also increase drought tolerance in rice by stimulating ABA biosynthesis through the regulation of OsNCED1 and OsABA8ox3 expression.These findings demonstrate that OsCHI3 increases drought stress tolerance in rice by activating the antioxidant defense system and the ABA metabolic pathway,providing new clues for drought-resistant rice breeding research.展开更多
Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulat...Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.展开更多
Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating...Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.展开更多
Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological bi...Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.展开更多
Heat stress causes overgrowth,leaf dryness and fruit malformation,which negatively impacts cucumber quality and yield.Yet,in spite of the devastating consequences of this abiotic stress,few genes for heat tolerance in...Heat stress causes overgrowth,leaf dryness and fruit malformation,which negatively impacts cucumber quality and yield.Yet,in spite of the devastating consequences of this abiotic stress,few genes for heat tolerance in cucumber have been identified.Here,the heat injury indices of 88 cucumber accessions representing diverse ecotypes were collected in two open-field environments,with naturally occurring high temperatures over two years.Seventeen of the 88 accessions were identified as highly heat-tolerant.Using a genome-wide association study,five loci(gHII3.1,gHII3.2,gHII3.3,gHII4.1 and gHII6.1)on three chromosomes associated with heat tolerance were detected.Pairwise linkage disequilibrium correlation,sequence polymorphisms,and qRT-PCR analyses at these loci,identified five candidate genes predicted to be casual for heat stress response in cucumber.CsaV3_3G04883,CsaV3_4G029050 and CsaV3_6G005370 each had nonsynonymous SNPs,and were significantly up-regulated by heat stress in the heat-tolerant genotypes.CsaV3_3G031890 was also induced by heat stress,but in the heatsensitive genotypes,and sequence polymorphism was only found in the promoter region.Identifying these candidate genes lays a foundation for understanding cucumber thermotolerance mechanisms.Our study is one of the few to examine heat stress in adult cucumber plants and it therefore fills a critical gap in knowledge.It is also an important first-step towards accelerating the breeding of robust heat-tolerant varieties.展开更多
Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment proc...Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment processes used in wastewater treatment plants have a limited efficiencies of antibiotics resistant bacteria(ARB)disinfection and ARGs degradation and even promote the proliferation of ARGs.Problematically,ARB and ARGs in effluent pose potential risks if they are not further treated.Photocatalytic oxidation is considered a promising disinfection technology,where the photocatalytic process generates many free radicals that enhance the interaction between light and deoxyribonucleic acid(DNA)for ARB elimination and subsequent degradation of ARGs.This reviewaims to illustrate the progress of photocatalytic oxidation technology for removing antibiotics resistant(AR)from wastewater in recent years.We discuss the sources and transfer of ARGs in wastewater.The overall removal efficiencies of ultraviolet radiation(UV)/chlorination,UV/ozone,UV/H_(2)O_(2),and UV/sulfate-radical based system for ARB and ARGs,as well as the experimental parameters and removal mechanisms,are systematically discussed.The contribution of photocatalytic materials based on TiO_(2) and g-C_(3)N_(4) to the inactivation of ARB and degradation of ARGs is highlighted,producingmany free radicals to attack ARB and ARGs while effectively limiting the horizontal gene transfer(HGT)in wastewater.Finally,based on the reviewed studies,future research directions are proposed to realize specific photocatalytic oxidation technology applications and overcome current challenges.展开更多
The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers...The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers are the predominant choices and have been extensively investigated and reviewed.Beyond these vectors,polymeric nanocarriers also hold the promise in therapeutic gene delivery owing to their versatile functionalities,such as improving the stability,cellar uptake and endosomal escape of nucleic acid drugs,along with precise delivery to targeted tissues.This review presents a brief overview of the status quo of the emerging polymeric nanocarriers for therapeutic gene delivery,focusing on key cationic polymers,nanocarrier types,and preparation methods.It also highlights targeted diseases,strategies to improve delivery efficiency,and potential future directions in this research area.The review is hoped to inspire the development,optimization,and clinical translation of highly efficient polymeric nanocarriers for therapeutic gene delivery.展开更多
Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,w...Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,whereas the MYB gene family has not been systematically studied in wax gourd.In this study,we performed genome-wide identification of the MYB gene family in wax gourd and analyzed their phylogenetic relationship,MYB DNA-binding domain(MYB DBD),gene structure,protein motif,synteny,duplication mode and expression pattern.As a result,a total of 215 BhMYB genes(BhMYBs)were identified,belonging to four subfamilies:1R-,2R-,3R-and 4R-MYB subfamilies.Genes of 1R-MYB subfamily and 2R-MYB subfamily were subdivided into different subgroups respectively.The analysis of MYB DBD,gene structure and protein motif showed that the most genes in the same subgroup had similar characteristics and the 2R-MYB genes were more conserved than the 1R-MYB genes.Interestingly,the long terminal retrotransposons(LTR-RTs)were found in the long introns of several BhMYBs.The results of synteny analysis showed that there were more syntenic gene pairs between wax gourd and other cucurbit crops,while the least number of syntenic gene pairs existed between wax gourd and rice.Gene duplication was the main reason for the expansion of the MYB gene family in wax gourd,with the transposed duplication(TRD)mode contributing more.All duplication BhMYB genes were under purifying selection pressure.Further expression analysis showed that many BhMYBs exhibited obvious tissue-specific expression and several BhMYBs were significantly induced by one or more abiotic stresses.BhMYB79 was particularly expressed in roots and significantly induced by salt,drought,cold and heat stresses,overexpression of which led to reduced tolerance to salt stress in Arabidopsis.In conclusion,our results provide a systematic analysis of wax gourd MYB gene family and facilitate the biological role study of BhMYB79 during wax gourd salt stress response process.展开更多
Polyembryony has posed a significant impediment to the advancement of citrus hybrid breeding.FhRWP is widely regarded as a pivotal factor governing asexual reproduction in citrus,and prior research has demonstrated th...Polyembryony has posed a significant impediment to the advancement of citrus hybrid breeding.FhRWP is widely regarded as a pivotal factor governing asexual reproduction in citrus,and prior research has demonstrated that FhARID1,acting as an upstream regulator,modulates FhRWP expression.In this study,we performed a genome-wide characterization of the ARID-HMG-related genes using the short juvenile minicitrus Fortunella hindsii.A total of 20 ARID-HMG-related genes were identified.Protein interaction network and enrichment analysis suggested that ARID-HMG-related proteins might might be involved in chromatin remodeling complexes.Knockout of FhARID1 in F.hindsii did not induce the conversion from polyembryony to monoembryony.However,fharid1 plants in T1 generation exhibited abnormal proliferation at axillary buds,which is similar to phenotype of fhrwp plants.Expression analysis of fharid1 ovary tissues revealed the downregulation of FhRWP.The results indicated that FhARID1,as an upstream regulator of FhRWP,has an effect on the development of citrus axillary buds.Expression analysis of overexpressed leaves of FhARID1 lines showed that no significant up-regulation of FhRWP,indicating that FhARID1 is not the sole upstream regulatory factor of FhRWP.Only FhARID2 showed a correlation in expression with FhARID1 among the ARID-related genes,further supporting the notion that this gene may be involved in complex formation rather than acting alone.Yeast two-hybrid and MS/MS spectra further indicated that FhARID1 function requires casein kinase II-mediated post-transcriptional phosphorylation.This study elucidated the function of FhARID1 in citrus apomixis and axillary bud development,providing a fundamental basis for understanding the role of ARID-HMG-related genes.展开更多
Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dyn...Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dynamic changes in soil communities,potential bacterial pathogens,and ARG profiles under various organicmaterial treatments during RSD,including distillers’grains,potato peel,peanut vine,and peanut vine combined with charcoal.Results revealed that applying diverse organic materials in RSD significantly altered bacterial community composition and diminished the relative abundance of potential bacterial pathogens(P<0.05).The relative abundance of high-risk ARGs decreased by 10.7%-30.6%after RSD treatments,the main decreased ARG subtypeswere AAC(3)_Via,dfrA1,ErmB,lnuB,aadA.Actinobacteria was the primary host of ARGs and was suppressed by RSD.Soil physicochemical properties,such as total nitrogen,soil pH,total carbon,were crucial factors affecting ARG profiles.Our findings demonstrated that RSD treatment inhibited pathogenic bacteria and could be an option for reducing high-risk ARG proliferation in soil.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorec...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into cell.METHODS A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection.The genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥2.RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.CONCLUSION Despite the low number of patients analyzed,these preliminary results seem to be promising.Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy.Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.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
A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to ...A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to address the underlying neuronal loss.This highlights that the elusive goals of halting progression and restoring damaged neurons limit the long-term impact of current approaches.Recent clinical trials using gene therapy have demonstrated the safety of various vector delivery systems,dosages,and transgenes expressed in the central nervous system,signifying tangible and substantial progress in applying gene therapy as a promising Parkinson’s disease treatment.Intriguingly,at diagnosis,many dopamine neurons remain in the substantia nigra,offering a potential window for recovery and survival.We propose that modulating these surviving dopamine neurons and axons in the substantia nigra and striatum using gene therapy offers a potentially more impactful therapeutic approach for future research.Moreover,innovative gene therapies that focus on preserving the remaining elements may have significant potential for enhancing long-term outcomes and the quality of life for patients with Parkinson’s disease.In this review,we provide a perspective on how gene therapy can protect vulnerable elements in the substantia nigra and striatum,offering a novel approach to addressing Parkinson’s disease at its core.展开更多
The effects of disinfectants and plasmid-based antibiotic resistance genes(ARGs)on the growth of microorganisms and the plasmid-mediated transfer of ARGs in the water and biofilm of the drinkingwater distribution syst...The effects of disinfectants and plasmid-based antibiotic resistance genes(ARGs)on the growth of microorganisms and the plasmid-mediated transfer of ARGs in the water and biofilm of the drinkingwater distribution system under simulated conditionswere explored.The heterotrophic plate count of the water in reactors with 0.1 mg/L NaClO and NH_(2)Cl was higher than in the control groups.Therewas no similar phenomenon in biofilm.In thewater of reactors containing NaClO,the aphA and bla geneswere lower than in the antibiotic resistant bacteria group,while both genes were higher in the water of reactors with NH_(2)Cl than in the control group.Chloramine may promote the transfer of ARGs in the water phase.Both genes in the biofilm of the reactors containing chlorine were lower than the control group.Correlation analysis between ARGs and water quality parameters revealed that the copy numbers of the aphA gene were significantly positively correlated with the copy numbers of the bla gene in water and significantly negatively correlated in biofilm(p<0.05).The results of the sequencing assay showed that bacteria in the biofilm,in the presence of disinfectant,were primarily Gram-negative.1.0 mg/L chlorine decreased the diversity of the community in the biofilm.The relative abundance of some bacteria that may undergo transfer increased in the biofilm of the reactor containing 0.1 mg/L chlorine.展开更多
Objective:Keratoconus(KC)is a progressive corneal ectasia disorder,arising from a myriad of causes including genetic predispositions,environmental factors,biomechanical influences,and inflammatory reactions.This study...Objective:Keratoconus(KC)is a progressive corneal ectasia disorder,arising from a myriad of causes including genetic predispositions,environmental factors,biomechanical influences,and inflammatory reactions.This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population.Methods:Twenty-five patients with primary KC as well as 50 unrelated population matched healthy controls,were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population.Sanger sequencing and whole-exome sequencing(WES)were used to analyze mutations in the zinc finger protein 469(ZNF469)gene.Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis.Results:Five novel heterozygous missense variants were identified in KC patients.Among them,2 compound heterozygous variants,c.8986G>C(p.E2996Q)with c.11765A>C(p.D3922A),and c.4423C>G(p.L1475V)with c.10633G>A(p.G3545R),were determined to be possible pathogenic factors for KC.Conclusion:Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population.These mutation sites may provide valuable information for future genetic screening of KC patients and their families.展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
Helicobacter pylori infection represents a widespread chronic condition with varying prevalence influenced by race, ethnicity, and geography. The severity of H. pylori-associated diseases is determined by an array of ...Helicobacter pylori infection represents a widespread chronic condition with varying prevalence influenced by race, ethnicity, and geography. The severity of H. pylori-associated diseases is determined by an array of virulence factors. Although extensive studies have been conducted globally, data on the distribution of Helicobacter pylori virulence genes in Libya remain limited, constraining insights into the pathogenicity of local strains and hindering the development of targeted interventions. This study aimed to evaluate the prevalence of H. pylori infection, characterize essential virulence genes [vacA variants (s1/s2, m1/m2), cagA, and iceA1], and examine their association with gastroduodenal diseases among Libyan patients. Gastric biopsies from 144 participants were analyzed using polymerase chain reaction (PCR) assays, and risk factor data were collected via questionnaires. H. pylori was detected in 63.2% of samples by PCR. The vacA gene was present in 84.6% of cases, cagA in 58.2%, and iceA1 in 29.7%. Among vacA variants, s1 allele was most common (53.2%), followed by m1 (42.9%), m2 (37.7%), and s2 (13%) alleles. Significant associations were identified between specific virulence genes and the development of gastroduodenal diseases, highlighting their role in pathogenicity. This investigation is one of Libya’s first comprehensive assessments of H. pylori virulence factors, addressing a critical epidemiological gap. The high prevalence of virulence genes suggests their potential as disease biomarkers. These findings contribute to a deeper understanding of H. pylori pathogenicity within the Libyan population and establish a basis for future clinical interventions and public health strategies to manage and prevent H. pylori-associated diseases in Libya and comparable regions.展开更多
Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functio...Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.展开更多
BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine recept...BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.展开更多
基金supported by the National Natural Science Foundation of China,No.82101340(to FJ).
文摘Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.
基金supported by Science and Technology Innovation Program of Hunan province(2024NK1010,2023NK1010,2023ZJ1080)the National Natural Science Foundation of China(U21A20208).
文摘The chalcone isomerase gene OsCHI,one of the key genes in the flavonoid biosynthesis pathway,plays an important role in rice(Oryza sativa)resistance to abiotic stresses.This study reveals how the chalcone isomerase gene family member OsCHI3 participates in rice responses to drought stress through the regulation of flavonoid biosynthesis.Overexpression of OsCHI3 increased the tolerance of rice to drought stress.In contrast,CRISPR/Cas9-mediated deletion of OsCHI3 reduced the drought tolerance of rice,an effect that is reversed by exogenous ABA treatment.Transcriptomic and physiological biochemical analyses indicated that flavonoids regulated by OsCHI3 not only scavenge reactive oxygen species(ROS)but also increase drought tolerance in rice by stimulating ABA biosynthesis through the regulation of OsNCED1 and OsABA8ox3 expression.These findings demonstrate that OsCHI3 increases drought stress tolerance in rice by activating the antioxidant defense system and the ABA metabolic pathway,providing new clues for drought-resistant rice breeding research.
基金supported by the National Natural Science Foundation of China,Nos.82271411(to RG),51803072(to WLiu)grants from the Department of Finance of Jilin Province,Nos.2022SCZ25(to RG),2022SCZ10(to WLiu),2021SCZ07(to RG)+2 种基金Jilin Provincial Science and Technology Program,No.YDZJ202201ZYTS038(to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University,No.2022qnpy11(to WLuo)The Project of China-Japan Union Hospital of Jilin University,No.XHQMX20233(to RG)。
文摘Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.
基金Dean's Office Howard University College of Medicine,Grant/Award Number:Bridge Fund/Pilot Study AwardNational Center on Minority Health and Health Disparities,Grant/Award Number:RCMI/IDC Award U54MD007597National Institute of Child Health and Human Development,Grant/Award Number:R03HD095417 and R16HD116702。
文摘Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.
基金supported by Hunan Provincial Key Research and Development Program,No.2021SK2002(to BW)the Natural Science Foundation of Hunan Province of China(General Program),No.2021JJ30938(to YL)。
文摘Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.
基金supported by Beijing Joint Research Program for Germplasm Innovation and New Variety Breeding(Grant No.G20220628003-03)Chongqing Municipal People's Government and Chinese Academy of Agricultural Sciences strategic cooperation project,Key-Area Research and Development Program of Guangdong Province(Grant No.2020B020220001)+3 种基金the Earmarked Fund for Modern Agro-industry Technology Research System(Grant No.CARS-23)Science and Technology Innovation Program of the Chinese Academy of Agricultural Science(Grant No.CAAS-ASTIP-IVFCAAS)Central public-interest Scientific Institution Basal Research Fund(Grant No.Y2017PT52)the Key Laboratory of Biology and Genetic Improvement of Horticultural Crops,Ministry of Agriculture,P.R.China。
文摘Heat stress causes overgrowth,leaf dryness and fruit malformation,which negatively impacts cucumber quality and yield.Yet,in spite of the devastating consequences of this abiotic stress,few genes for heat tolerance in cucumber have been identified.Here,the heat injury indices of 88 cucumber accessions representing diverse ecotypes were collected in two open-field environments,with naturally occurring high temperatures over two years.Seventeen of the 88 accessions were identified as highly heat-tolerant.Using a genome-wide association study,five loci(gHII3.1,gHII3.2,gHII3.3,gHII4.1 and gHII6.1)on three chromosomes associated with heat tolerance were detected.Pairwise linkage disequilibrium correlation,sequence polymorphisms,and qRT-PCR analyses at these loci,identified five candidate genes predicted to be casual for heat stress response in cucumber.CsaV3_3G04883,CsaV3_4G029050 and CsaV3_6G005370 each had nonsynonymous SNPs,and were significantly up-regulated by heat stress in the heat-tolerant genotypes.CsaV3_3G031890 was also induced by heat stress,but in the heatsensitive genotypes,and sequence polymorphism was only found in the promoter region.Identifying these candidate genes lays a foundation for understanding cucumber thermotolerance mechanisms.Our study is one of the few to examine heat stress in adult cucumber plants and it therefore fills a critical gap in knowledge.It is also an important first-step towards accelerating the breeding of robust heat-tolerant varieties.
基金supported by the National Natural Science Foundation of China (Nos.52100182 and 52300204)the the Science and Technology Innovation Program of Hunan Province (No.2023RC3122).
文摘Because of the recent widespread usage of antibiotics,the acquisition and dissemination of antibiotic-resistance genes(ARGs)were prevalent in the majority of habitats.Generally,the biological wastewater treatment processes used in wastewater treatment plants have a limited efficiencies of antibiotics resistant bacteria(ARB)disinfection and ARGs degradation and even promote the proliferation of ARGs.Problematically,ARB and ARGs in effluent pose potential risks if they are not further treated.Photocatalytic oxidation is considered a promising disinfection technology,where the photocatalytic process generates many free radicals that enhance the interaction between light and deoxyribonucleic acid(DNA)for ARB elimination and subsequent degradation of ARGs.This reviewaims to illustrate the progress of photocatalytic oxidation technology for removing antibiotics resistant(AR)from wastewater in recent years.We discuss the sources and transfer of ARGs in wastewater.The overall removal efficiencies of ultraviolet radiation(UV)/chlorination,UV/ozone,UV/H_(2)O_(2),and UV/sulfate-radical based system for ARB and ARGs,as well as the experimental parameters and removal mechanisms,are systematically discussed.The contribution of photocatalytic materials based on TiO_(2) and g-C_(3)N_(4) to the inactivation of ARB and degradation of ARGs is highlighted,producingmany free radicals to attack ARB and ARGs while effectively limiting the horizontal gene transfer(HGT)in wastewater.Finally,based on the reviewed studies,future research directions are proposed to realize specific photocatalytic oxidation technology applications and overcome current challenges.
基金supported by National Natural Science Foundation of China(82104082)Natural Science Foundation of Qinghai Province(2024-ZJ-911).
文摘The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers are the predominant choices and have been extensively investigated and reviewed.Beyond these vectors,polymeric nanocarriers also hold the promise in therapeutic gene delivery owing to their versatile functionalities,such as improving the stability,cellar uptake and endosomal escape of nucleic acid drugs,along with precise delivery to targeted tissues.This review presents a brief overview of the status quo of the emerging polymeric nanocarriers for therapeutic gene delivery,focusing on key cationic polymers,nanocarrier types,and preparation methods.It also highlights targeted diseases,strategies to improve delivery efficiency,and potential future directions in this research area.The review is hoped to inspire the development,optimization,and clinical translation of highly efficient polymeric nanocarriers for therapeutic gene delivery.
基金supported by the Key-Area Research and Development Program of Guangdong Province(Grant No.2020B020220003)National Natural Science Foundation of China(32202504)+2 种基金Guangdong Basic and Applied Basic Research Foundation(Grant No.2023A1515030049)Guangdong Rural Revitalization Strategy Special Project(Grant No.2023-NJS-00-003)Special fund for scientific and technological talents introduction of Guangdong Academy of Agricultural Sciences(Grant No.R2021YJ-YB2004)。
文摘Wax gourd(Benincasa hispida)is an important cucurbit crop with economic and medicinal value.The myeloblastosis(MYB)gene family is one of the largest gene families in plants and regulates various biological processes,whereas the MYB gene family has not been systematically studied in wax gourd.In this study,we performed genome-wide identification of the MYB gene family in wax gourd and analyzed their phylogenetic relationship,MYB DNA-binding domain(MYB DBD),gene structure,protein motif,synteny,duplication mode and expression pattern.As a result,a total of 215 BhMYB genes(BhMYBs)were identified,belonging to four subfamilies:1R-,2R-,3R-and 4R-MYB subfamilies.Genes of 1R-MYB subfamily and 2R-MYB subfamily were subdivided into different subgroups respectively.The analysis of MYB DBD,gene structure and protein motif showed that the most genes in the same subgroup had similar characteristics and the 2R-MYB genes were more conserved than the 1R-MYB genes.Interestingly,the long terminal retrotransposons(LTR-RTs)were found in the long introns of several BhMYBs.The results of synteny analysis showed that there were more syntenic gene pairs between wax gourd and other cucurbit crops,while the least number of syntenic gene pairs existed between wax gourd and rice.Gene duplication was the main reason for the expansion of the MYB gene family in wax gourd,with the transposed duplication(TRD)mode contributing more.All duplication BhMYB genes were under purifying selection pressure.Further expression analysis showed that many BhMYBs exhibited obvious tissue-specific expression and several BhMYBs were significantly induced by one or more abiotic stresses.BhMYB79 was particularly expressed in roots and significantly induced by salt,drought,cold and heat stresses,overexpression of which led to reduced tolerance to salt stress in Arabidopsis.In conclusion,our results provide a systematic analysis of wax gourd MYB gene family and facilitate the biological role study of BhMYB79 during wax gourd salt stress response process.
基金funded by the National Key Research and Development Program of China(Grant No.2022YFF1003100)Modern Citrus Industry Technology System of China(Grant No.CARS-26).
文摘Polyembryony has posed a significant impediment to the advancement of citrus hybrid breeding.FhRWP is widely regarded as a pivotal factor governing asexual reproduction in citrus,and prior research has demonstrated that FhARID1,acting as an upstream regulator,modulates FhRWP expression.In this study,we performed a genome-wide characterization of the ARID-HMG-related genes using the short juvenile minicitrus Fortunella hindsii.A total of 20 ARID-HMG-related genes were identified.Protein interaction network and enrichment analysis suggested that ARID-HMG-related proteins might might be involved in chromatin remodeling complexes.Knockout of FhARID1 in F.hindsii did not induce the conversion from polyembryony to monoembryony.However,fharid1 plants in T1 generation exhibited abnormal proliferation at axillary buds,which is similar to phenotype of fhrwp plants.Expression analysis of fharid1 ovary tissues revealed the downregulation of FhRWP.The results indicated that FhARID1,as an upstream regulator of FhRWP,has an effect on the development of citrus axillary buds.Expression analysis of overexpressed leaves of FhARID1 lines showed that no significant up-regulation of FhRWP,indicating that FhARID1 is not the sole upstream regulatory factor of FhRWP.Only FhARID2 showed a correlation in expression with FhARID1 among the ARID-related genes,further supporting the notion that this gene may be involved in complex formation rather than acting alone.Yeast two-hybrid and MS/MS spectra further indicated that FhARID1 function requires casein kinase II-mediated post-transcriptional phosphorylation.This study elucidated the function of FhARID1 in citrus apomixis and axillary bud development,providing a fundamental basis for understanding the role of ARID-HMG-related genes.
基金supported by the Key Research and Development Program of Shandong Province,China(No 2021CXGC010803)Pan’an County Chinese Medicine Industry Project(No.PZYF202103).
文摘Reductive soil disinfestation(RSD)is commonly employed for soil remediation in greenhouse cultivation.However,its influence on antibiotic resistance genes(ARGs)in soil remains uncertain.This study investigated the dynamic changes in soil communities,potential bacterial pathogens,and ARG profiles under various organicmaterial treatments during RSD,including distillers’grains,potato peel,peanut vine,and peanut vine combined with charcoal.Results revealed that applying diverse organic materials in RSD significantly altered bacterial community composition and diminished the relative abundance of potential bacterial pathogens(P<0.05).The relative abundance of high-risk ARGs decreased by 10.7%-30.6%after RSD treatments,the main decreased ARG subtypeswere AAC(3)_Via,dfrA1,ErmB,lnuB,aadA.Actinobacteria was the primary host of ARGs and was suppressed by RSD.Soil physicochemical properties,such as total nitrogen,soil pH,total carbon,were crucial factors affecting ARG profiles.Our findings demonstrated that RSD treatment inhibited pathogenic bacteria and could be an option for reducing high-risk ARG proliferation in soil.
基金Supported by Romanian Ministry of Research,Innovation and Digitization,No.PN23.16.02.04 and No.31PFE/30.12.2021.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United States.As for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and progression.AIM To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into cell.METHODS A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical resection.The genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥2.RESULTS We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph nodes.CONCLUSION Despite the low number of patients analyzed,these preliminary results seem to be promising.Addressing lipid metabolism through a broad strategy could be a beneficial way to treat this malignancy.Future in vitro and in vivo studies on these genes may offer important insights into the mechanisms linking PDAC with the long-chain FA import pathway.
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 Research Foundation of Korea(RS-2023-00245298)the Korea Healthcare Technology R&D(HI21C1795)grants,funded by the Korean government(to SRK).
文摘A critical unaddressed problem in Parkinson’s disease is the lack of therapy that slows or hampers neurodegeneration.While medications effectively manage symptoms,they offer no long-term benefit because they fail to address the underlying neuronal loss.This highlights that the elusive goals of halting progression and restoring damaged neurons limit the long-term impact of current approaches.Recent clinical trials using gene therapy have demonstrated the safety of various vector delivery systems,dosages,and transgenes expressed in the central nervous system,signifying tangible and substantial progress in applying gene therapy as a promising Parkinson’s disease treatment.Intriguingly,at diagnosis,many dopamine neurons remain in the substantia nigra,offering a potential window for recovery and survival.We propose that modulating these surviving dopamine neurons and axons in the substantia nigra and striatum using gene therapy offers a potentially more impactful therapeutic approach for future research.Moreover,innovative gene therapies that focus on preserving the remaining elements may have significant potential for enhancing long-term outcomes and the quality of life for patients with Parkinson’s disease.In this review,we provide a perspective on how gene therapy can protect vulnerable elements in the substantia nigra and striatum,offering a novel approach to addressing Parkinson’s disease at its core.
基金supported by the Natural Science Foundation of China(No.52070145,51778453).
文摘The effects of disinfectants and plasmid-based antibiotic resistance genes(ARGs)on the growth of microorganisms and the plasmid-mediated transfer of ARGs in the water and biofilm of the drinkingwater distribution system under simulated conditionswere explored.The heterotrophic plate count of the water in reactors with 0.1 mg/L NaClO and NH_(2)Cl was higher than in the control groups.Therewas no similar phenomenon in biofilm.In thewater of reactors containing NaClO,the aphA and bla geneswere lower than in the antibiotic resistant bacteria group,while both genes were higher in the water of reactors with NH_(2)Cl than in the control group.Chloramine may promote the transfer of ARGs in the water phase.Both genes in the biofilm of the reactors containing chlorine were lower than the control group.Correlation analysis between ARGs and water quality parameters revealed that the copy numbers of the aphA gene were significantly positively correlated with the copy numbers of the bla gene in water and significantly negatively correlated in biofilm(p<0.05).The results of the sequencing assay showed that bacteria in the biofilm,in the presence of disinfectant,were primarily Gram-negative.1.0 mg/L chlorine decreased the diversity of the community in the biofilm.The relative abundance of some bacteria that may undergo transfer increased in the biofilm of the reactor containing 0.1 mg/L chlorine.
基金supported by the National Natural Science Foundation(82271057)the Natural Science Foundation of Hunan Province(2023JJ30818),China。
文摘Objective:Keratoconus(KC)is a progressive corneal ectasia disorder,arising from a myriad of causes including genetic predispositions,environmental factors,biomechanical influences,and inflammatory reactions.This study aims to identify potential pathogenetic gene mutations in patients with sporadic KC in the Han Chinese population.Methods:Twenty-five patients with primary KC as well as 50 unrelated population matched healthy controls,were included in this study to identify potential pathogenic gene mutations among sporadic KC patients in the Han Chinese population.Sanger sequencing and whole-exome sequencing(WES)were used to analyze mutations in the zinc finger protein 469(ZNF469)gene.Bioinformatics analysis was conducted to explore the potential role of ZNF469 in KC pathogenesis.Results:Five novel heterozygous missense variants were identified in KC patients.Among them,2 compound heterozygous variants,c.8986G>C(p.E2996Q)with c.11765A>C(p.D3922A),and c.4423C>G(p.L1475V)with c.10633G>A(p.G3545R),were determined to be possible pathogenic factors for KC.Conclusion:Mutations in the ZNF469 gene may contribute to the development of KC in the Han Chinese population.These mutation sites may provide valuable information for future genetic screening of KC patients and their families.
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
文摘Helicobacter pylori infection represents a widespread chronic condition with varying prevalence influenced by race, ethnicity, and geography. The severity of H. pylori-associated diseases is determined by an array of virulence factors. Although extensive studies have been conducted globally, data on the distribution of Helicobacter pylori virulence genes in Libya remain limited, constraining insights into the pathogenicity of local strains and hindering the development of targeted interventions. This study aimed to evaluate the prevalence of H. pylori infection, characterize essential virulence genes [vacA variants (s1/s2, m1/m2), cagA, and iceA1], and examine their association with gastroduodenal diseases among Libyan patients. Gastric biopsies from 144 participants were analyzed using polymerase chain reaction (PCR) assays, and risk factor data were collected via questionnaires. H. pylori was detected in 63.2% of samples by PCR. The vacA gene was present in 84.6% of cases, cagA in 58.2%, and iceA1 in 29.7%. Among vacA variants, s1 allele was most common (53.2%), followed by m1 (42.9%), m2 (37.7%), and s2 (13%) alleles. Significant associations were identified between specific virulence genes and the development of gastroduodenal diseases, highlighting their role in pathogenicity. This investigation is one of Libya’s first comprehensive assessments of H. pylori virulence factors, addressing a critical epidemiological gap. The high prevalence of virulence genes suggests their potential as disease biomarkers. These findings contribute to a deeper understanding of H. pylori pathogenicity within the Libyan population and establish a basis for future clinical interventions and public health strategies to manage and prevent H. pylori-associated diseases in Libya and comparable regions.
基金supported by a grant from the Progressive MS Alliance(BRAVE in MS)Le Grand Portage Fund。
文摘Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
基金Supported by Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,funded by the Ministry of Health&Welfare,Republic of Korea,No.RS-2022-KH129889.
文摘BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.
