Reader proteins that bind specific methyllysine are important to biological functions of lysine methylation,but readers of many methyllysine sites are still unknown.Therefore,development of covalent probes is importan...Reader proteins that bind specific methyllysine are important to biological functions of lysine methylation,but readers of many methyllysine sites are still unknown.Therefore,development of covalent probes is important to identify readers from cell samples so as to understand biological roles of lysine methylation.Generally,readers bind methyllysine via aromatic cages that contain tryptophan,tyrosine and phenylalanine,that offer a unique motif for selective crosslinking.We recently reported a site-selective tryptophan crosslinking strategy based on dimethylsulfonium that mimics dimethyllysine to crosslink tryptophan in aromatic cages of readers.Since tyrosine is a key residue for binding affinity to methyllysine,especially some readers that do not contain tryptophan residues in the binding pocket.Here we developed strategies of site-selective crosslinking to tyrosine.Ultraviolet(UV)source was applied to excite tyrosine at neutral pH or phenoxide at basic p H,and subsequent single-electron transfer(SET)from Tyr*to sulfonium inside the binding pocket enables selective crosslinking.In consequence,methyllysine readers with tyrosine-containing aromatic cages could be selectively crosslinked by site-specific sulfonium peptide probes.In addition,we expanded substrates from aromatic cages to tyrosine residues of proximate contact with sulfonium probes.The pair of LgBiT and SmBiT exhibited orthogonal crosslinking in complicated cell samples.As a result,we may expand sulfonium tools to target local tyrosine in future investigations.展开更多
Detecting lung cancer early is crucial for improving survival rates,yet it remains a significant challenge due to many cases being diagnosed at advanced stages.This review aims to provide advances in epigenetics which...Detecting lung cancer early is crucial for improving survival rates,yet it remains a significant challenge due to many cases being diagnosed at advanced stages.This review aims to provide advances in epigenetics which have highlighted DNA methylation patterns as promising biomarkers for early detection,prognosis,and treatment response in lung cancer.Techniques like bisulfite conversion followed by PCR,digital droplet polymerase chain reaction,and next-generation sequencing are commonly used for detecting these methylation patterns,which occur early in the cancer development process and can be detected in non-invasive samples like blood and sputum.Key genes such as SHOX2 and RASSF1A have demonstrated high sensitivity and specificity in clinical studies,making them crucial for diagnostic purposes.However,several challenges remain to be overcome before these biomarkers can be widely adopted for use in clinical practice.Standardizing the assays and validating their effectiveness are critical steps.Additionally,integrating methylation biomarkers with existing diagnostic tools could significantly enhance the accuracy of lung cancer detection,providing a more comprehensive diagnostic approach.Although progress has been made in understanding and utilizing DNA methylation patterns for lung cancer detection,more research and extensive clinical trials are necessary to fully harness their potential.These efforts will help establish the robustness of methylation patterns as biomarkers and therapeutic targets,ultimately leading to better prevention,diagnosis,and treatment strategies for lung cancer.In conclusion,DNA methylation states represent a promising avenue for advancing early detection,accurate diagnosis,and management of lung cancer.展开更多
The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function a...The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function and signal transduction.Ophthalmic diseases are a kind of complex diseases,and their pathogenesis involves many factors such as genetic,environmental and individual differences.In addition,inflammation,oxidative stress and lipid metabolism,which abnormal DNA methylation is closely related to,are also considered to be major factors in eye diseases.The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive.In addition to the simple suppression of gene expression by hypermethylation,factors such as hypomethylation or demethylation,DNA methylation in non-promoter regions,interactions with other epigenetic modifications,and dynamic changes in DNA methylation must also be considered.Interestingly,although some genes are at abnormal methylation levels,their expression is not significantly changed,which indirectly reflects the complexity of gene regulation.This review aims to summarize and compare some relevant studies,and provide with new ideas and methods for the prevention and treatment of different eye diseases,such as glaucoma,retinoblastoma,and diabetic retinopathy.展开更多
Illegal hunting and trafficking of wildlife and their derivatives extort unprecedented population decline of relatively many species pushing them towards extinction.Notwithstanding contemporary counteracting intervent...Illegal hunting and trafficking of wildlife and their derivatives extort unprecedented population decline of relatively many species pushing them towards extinction.Notwithstanding contemporary counteracting interventions at international,regional,national and local levels,wildlife farming is advocated as an alternative approach to minimize pressure on wild populations.For wildlife farming to be an effective conservation tool,the integration of wildlife forensics is inevitable to allow distinction between captive-bred and wild-caught species.To this end,we analyzed methylation rates of skeletal muscle samples(pectoralis major,triceps brachii,gastrocnemius,biceps femoris,and neck muscles)from 60 captive-bred and 30 wild-caught Common Pheasant.A total of 13,507 differentially methylated regions were identified between five wild-caught and five captive-bred individuals through whole-genome methylation sequencing(WGBS).Based on the selected five methylation sites,LOC116231076,LOC116242223,ATAD2B,EGFL6,and HS2ST,quantitative detection technique was developed using methylation-sensitive high-resolution melting curve(MS-HRM)to measure methylation rates.The results showed significant differences in methylation rates at all differential sites between wild-caught and captive-bred individuals(|t|=0.67–33.10,P=0.000–0.042).The discrimination accuracy rate of each locus was highest in the gastrocnemius muscle and lowest in the neck muscle.The discrimination accuracy rate on LOC116231076,LOC116242223,ATAD2B,EGFL6,and HS2ST methylation sites for gastrocnemius muscle was 64.98%,100.00%,68.54%,63.79%,and 63.70%,respectively;and for neck muscle it was 67.42%,68.06%,83.61%,65.04%,and68.85%,respectively.The united discrimination accuracy rate of the five loci were 100.00%for gastrocnemius muscle,99.78%for biceps femoris muscle,97.52%for pectoralis major muscle,93.96%for triceps brachii muscle,and 91.63%for neck muscle,respectively.The panel also revealed excellent repeatability,reproducibility,sensitivity and universality to mammals and avian species.This study establishes an effective,accurate and low-cost identification technology for the identification of wild and farmed Common Pheasant,and also provides a reference for the development of identification methods for other species.展开更多
BACKGROUND Gastric cancer(GC)is a malignant tumor originating from gastric mucosal epithelial cells that has high morbidity and mortality.microRNAs(miR)are important diagnostic markers and therapeutic targets in this ...BACKGROUND Gastric cancer(GC)is a malignant tumor originating from gastric mucosal epithelial cells that has high morbidity and mortality.microRNAs(miR)are important diagnostic markers and therapeutic targets in this disease.AIM To explore the mechanism of miR-125a-5p in the pathogenesis of GC.METHODS The expression levels of miR-125a-5p,SERPINE1 and DNMT1 in GC cells and tissues were detected by real-time polymerase chain reaction(PCR)and Western blotting.Methylation-specific PCR was used to detect the level of miR-125a-5p methylation.A cell counting kit 8 assay,scratch test,and a Transwell assay were performed to detect the proliferation,migration,and invasiveness of HGC27 cells,respectively.The expression of the epithelial mesenchymal transition(EMT)-related proteins E-cadherin,N-cadherin and vimentin in HGC27 cells was detected by Western blotting,while the expression of vimentin was detected by immunofluorescence.RESULTS This study revealed that miR-125a-5p was expressed at low levels in GC clinical samples and cells and that miR-125a-5p overexpression inhibited the proliferation,migration,invasiveness and EMT of GC cells.Mechanistically,miR-125a-5p can reduce GC cell proliferation,promote E-cadherin expression,inhibit N-cadherin and vimentin expression,and reduce the EMT of GC cells,thus constraining GC cells to a certain extent.Moreover,DNMT1 inhibited miR-125a-5p expression by increasing the methylation of the miR-125a-5p promoter,thereby promoting the expression of SERPINE1,which acts together with miR-125a-5p to exert antagonistic effects on GC.CONCLUSION Our study revealed that DNMT1 promoted SERPINE1 protein expression by inducing miR-125a-5p methylation,which led to the proliferation,migration and occurrence of EMT in GC cells.展开更多
In the mammalian genome,most CpGs are methylated.However,CpGs within the CpG islands(CGIs)are largely unmethylated,which are important for gene expression regulation.The mechanism underlying the low methylation levels...In the mammalian genome,most CpGs are methylated.However,CpGs within the CpG islands(CGIs)are largely unmethylated,which are important for gene expression regulation.The mechanism underlying the low methylation levels at CGIs remains largely elusive.KDM2 proteins(KDM2A and KDM2B)are H3K36me2 demethylases known to bind specifically at CGIs.Here,we report that depletion of each or both KDM2 proteins,or mutation of all their JmjC domains that harbor the H3K36me2 demethylation activity,leads to an increase in DNA methylation at selective CGIs.The Kdm2a/2b double knockout shows a stronger increase in DNA methylation compared with the single mutant of Kdm2a or Kdm2b,indicating that KDM2A and KDM2B redundantly regulate DNA methylation at CGIs.In addition,the increase of CGI DNA methylation upon mutations of KDM2 proteins is associated with the chromatin environment.Our findings reveal that KDM2A and KDM2B function redundantly in regulating DNA methylation at a subset of CGIs in an H3K36me2 demethylation-dependent manner.展开更多
Colitis-associated colorectal cancer(CAC),a serious complication of ulcerative colitis(UC),is associated with a poor prognosis.The vitamin D receptor(VDR)is recognized for its protective role in UC and CAC through the...Colitis-associated colorectal cancer(CAC),a serious complication of ulcerative colitis(UC),is associated with a poor prognosis.The vitamin D receptor(VDR)is recognized for its protective role in UC and CAC through the maintenance of intestinal barrier integrity and the regulation of inflammation.This study demonstrates a significant reduction in m^(6)A-related genes,particularly methyltransferase like 14(METTL14),in UC and CAC patients and identifies an association between METTL14 and VDR.In the azoxymethane(AOM)/dextran sodium sulfate(DSS)-induced mousemodel,vitamin D treatment increases METTL14 expression and reduces tumorburden,while Vdr-knockout mice exhibit lower METTL14 levels and increased tumorigenesis.In vitro,the VDR agonist calcipotriol upregulates METTL14 in NCM460 cells,with this effect attenuated by VDR knockdown.VDRknockdown inDLD-1colon cancer cellsdecreases METTL14 expressionand promotes proliferation,which is reversed by METTL14 overexpression.Mechanistic studies reveal that VDR regulates METTL14 expression via promoter binding,modulating key target genes such as SOX4,DROSH,and PHLPP2.This study highlights the role of the VDR-METTL14 axis as a protective mechanism in CAC and suggests its potential as a therapeutic target for preventing and treating CAC.展开更多
Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environme...Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's disease.However,the mechanism by which Sal mediates dopaminergic neuronal death remains unclear.In this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling pathway.The m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling pathway.Additionally,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to neurotoxicity.These findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and autophagy.Our results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.展开更多
BACKGROUND Cholangiocarcinoma(CCA),also known as bile duct cancer,is a devastating malignancy primarily affecting the biliary tract.AIM To assess their performance in clinical diagnosis and monitoring of CCA,plasma me...BACKGROUND Cholangiocarcinoma(CCA),also known as bile duct cancer,is a devastating malignancy primarily affecting the biliary tract.AIM To assess their performance in clinical diagnosis and monitoring of CCA,plasma methylation and circulating tumor cells were detected.METHODS Plasma samples were collected from Hubei Cancer Hospital(n=156).Plasma DNA was tested to detect SHOX2,HOXA9,SEPTIN9,and RASSF1A methylation using TaqMan PCR.Circulating tumor cells(CTCs)were detected in the peripheral blood of patients using the United States Food and Drug Administration-approved cell search system before and after clinical therapy.The CCA diagnostic value was estimated using the area under the curve.The independent prognosis risk factors for patients with CCA were estimated using Cox and logistic regression analyses.RESULTS The sensitivity and specificity of the four DNA plasma methylations exhibited 64.74%sensitivity and 93.88%specificity for detecting CCA.The receiver operating characteristic curve of the combined value for CCA diagnosis in plasma was 0.828±0.032.RASSF1A plasma methylation was related to the prognosis of patients with CCA.We determined the prognostic hazard ratio for CCA using CTC count,tumor stage,methylation,and carbohydrate antigen 19-9 levels as key factors.Our overall survival nomogram achieved a C-index of 0.705(0.605-0.805).CONCLUSION SHOX2,HOXA9,SEPTIN9,and RASSF1A plasma methylation demonstrated increased sensitivity for diagnosing CCA.RASSF1A plasma methylation and CTCs were valuable predictors to assess CCA prognosis and recurrence.展开更多
Arsenic(As)methylation in soils affects the environmental behavior of As,excessive accumulation of dimethylarsenate(DMA)in rice plants leads to straighthead disease and a serious drop in crop yield.Understanding the m...Arsenic(As)methylation in soils affects the environmental behavior of As,excessive accumulation of dimethylarsenate(DMA)in rice plants leads to straighthead disease and a serious drop in crop yield.Understanding the mobility and transformation of methylated arsenic in redox-changing paddy fields is crucial for food security.Here,soils including unarsenic contaminated(N-As),low-arsenic(L-As),medium-arsenic(M-As),and high-arsenic(H-As)soils were incubated under continuous anoxic,continuous oxic,and consecutive anoxic/oxic treatments respectively,to profile arsenic methylating process and microbial species involved in the As cycle.Under anoxic-oxic(A-O)treatment,methylated arsenic was significantly increased once oxygen was introduced into the incubation system.The methylated arsenic concentrations were up to 2-24 times higher than those in anoxic(A),oxic(O),and oxic-anoxic(O-A)treatments,under which arsenic was methylated slightly and then decreased in all four As concentration soils.In fact,the most plentiful arsenite S-adenosylmethionine methyltransferase genes(arsM)contributed to the increase in As methylation.Proteobacteria(40.8%-62.4%),Firmicutes(3.5%-15.7%),and Desulfobacterota(5.3%-13.3%)were the major microorganisms related to this process.These microbial increasedmarkedly and played more important roles after oxygen was introduced,indicating that they were potential keystone microbial groups for As methylation in the alternating anoxic(flooding)and oxic(drainage)environment.The novel findings provided newinsights into the reoxidation-driven arsenic methylation processes and the model could be used for further risk estimation in periodically flooded paddy fields.展开更多
Background N^(6)-methyladenosine(m^(6)A)methylation is a key epigenetic modification that can modulate gene expression and strongly affect mammalian developmental processes.However,the genome-wide methylation of long ...Background N^(6)-methyladenosine(m^(6)A)methylation is a key epigenetic modification that can modulate gene expression and strongly affect mammalian developmental processes.However,the genome-wide methylation of long non-coding RNAs(lncRNAs)and its implications for the development of skeletal muscle remain poorly understood.Bovine skeletal muscle samples from five developmental stages were analyzed in this study to establish lncRNA methylome and transcriptomic maps.Results Globally,59.67%of lncRNAs in skeletal muscle with m^(6)A modifications,and this percentage decreased progressively during development.lncRNA expression levels were positively associated with the number of m^(6)A peaks,with lncRNAs possessing 3 or more peaks showing significantly higher expression levels than those with 1 or 2 peaks.Specific lncRNAs involved in skeletal muscle development were identified through two analytical approaches.The first approach employed weighted gene co-expression network analysis(WGCNA)of transcriptomic data to identify correlations between annotated lncRNAs and growth-related traits,resulting in 21 candidate hub lncRNAs.The intersection of these 21 hub lncRNAs with 151 differentially methylated lncRNAs(DM-lncRNAs)identified 10 shared candidate lncRNAs.The second approach integrated MeRIP-seq and RNA-seq data to identify 36 lncRNAs that were both differentially m^(6)A modified and differentially expressed(dme-lncRNAs).GO and KEGG enrichment analyses of cis-target genes associated with these dme-lncRNAs identified eight candidate lncRNAs.Combining the results from the two approaches identified 16 key m^(6)A-modified lncRNAs likely involved in skeletal muscle development.Conclusions These findings highlight the regulatory and functional significance of dynamic lncRNA methylation in skeletal muscle development.展开更多
Gas-phase synthesis of glycolide(GL)from methyl glycolate(MG)is of great significance for producing biodegradable polyglycolic acid.Here,we report a detailed thermodynamics study for the gas-phase synthesis of GL from...Gas-phase synthesis of glycolide(GL)from methyl glycolate(MG)is of great significance for producing biodegradable polyglycolic acid.Here,we report a detailed thermodynamics study for the gas-phase synthesis of GL from MG,which involves complex reaction pathways,by utilizing the Gibbs free energy minimization method.The results indicate that the decompositions of MG and GL and the polymerization of MG are thermodynamically favorable as compared with the target pathway,i.e.,the cyclization of MG.Effects of the reaction conditions including temperature,pressure and feed composition on the formation of GL and linear polymers have also been addressed,which demonstrate that the higher temperature and lower pressure can effectively inhibit the formation of linear methyl ester dimer and improve the selectivity to GL.In addition,the higher N_(2)/MG ratio is beneficial for the formation of GL in the process promoted by catalysts.These thermodynamics results indicate that the process promoted by catalysts would benefit from the kinetics control by high-performance catalysts and the operation at high temperature,low pressure and high N_(2)/MG ratio to enhance the yield of targeted GL.The insights demonstrated here from thermodynamics are valuable for guiding the design of catalysts and/or optimization of reaction conditions for the gas-phase synthesis of GL from MG.展开更多
Background Thidiazuron(TDZ)is a widely used chemical defoliant in commercial cotton production and is often combined with the herbicide Diuron to form the commercial defoliant mixture known as TDZ·Diuron(T·D...Background Thidiazuron(TDZ)is a widely used chemical defoliant in commercial cotton production and is often combined with the herbicide Diuron to form the commercial defoliant mixture known as TDZ·Diuron(T·D,540 g·L^(-1)suspension).However,due to increasing concerns about the environmental and biological risks posed by Diuron,there is an urgent need to develop safer and more effective alternatives.Jasmonic acid(JA)and its derivatives are key phytohormones in organ senescence and abscission.Results Greenhouse experiments at the seedling stage revealed that Me-JA(0.8 mmol·L^(-1))alone did not induce defoliation.However,its co-application with TDZ(0.45 mmol·L^(-1))at concentrations of 0.6,0.8,and 1.0 mmol·L^(-1)significantly enhanced defoliation efficacy.The most effective combination—TDZ with 0.8 mmol·L^(-1)Me-JA—achieved a 100%defoliation rate at 5 days after treatment(DAT),23.7 percentage points higher than TDZ alone,and comparable to the commercial TDZ·Diuron formulation with equivalent TDZ content.Field trials conducted in Beijing(Shangzhuang),Hebei(Hejian),and Xinjiang(Shihezi)confirmed that the combination of 0.6 mmol·L^(-1)Me-JA with 1.70 mmol·L^(-1)TDZ provided optimal defoliation performance.At 21 DAT,the defoliation rate increased by 13.5–16.3 percentage points compared with TDZ alone.Furthermore,boll opening rates improved by 5.7–12.7 percentage points relative to TDZ-only treatments.Phytohormonal analyses from the Shangzhuang site showed that the combined treatment significantly altered hormone levels in both leaves and petioles.Compared with TDZ alone,the mixture reduced concentrations of auxin(IAA),cytokinins(Z+ZR,iP+iPA,DHZ+DHZR),and gibberellic acid(GA3),while increasing levels of JA,abscisic acid(ABA),and brassinosteroids(BR).These hormonal shifts may underlie the enhanced defoliation observed with the combined treatment.Importantly,the TDZ-Me-JA combination did not adversely affect cotton yield,yield components,or fiber quality.Conclusion The combination of Me-JA and TDZ has a good defoliation effect without affecting crop yield or fiber quality.And it provides a promising foundation for the development of novel,environmentally friendly cotton defoliants.展开更多
AIM:To explore the methylation status of MSH6 in retinoblastoma(RB)and its impact on clinicopathological features and diagnosis.METHODS:Differentially expressed genes were identified through bioinformatics screening o...AIM:To explore the methylation status of MSH6 in retinoblastoma(RB)and its impact on clinicopathological features and diagnosis.METHODS:Differentially expressed genes were identified through bioinformatics screening of the GSE24673 and GSE125903 datasets,combined with GeneCards database analysis.A total of 102 RB patients and 62 traumaenucleated controls between January 2018 and December 2023 were enrolled,with their clinicopathological data and retinal tissues collected.The mRNA and methylation levels of MSH6 in retinal tissues were detected using real-time quantitative polymerase chain reaction(PCR)and methylation-specific PCR.Western blot analysis was conducted in one pair of RB and control tissues for preliminary protein-level validation of MSH6 expression.Based on the methylation status of MSH6,RB patients were categorized into two groups:low-methylation and highmethylation.Both univariate and multivariate analyses were conducted to identify independent factors influencing the methylation levels using clinicopathological data.Receiver operating characteristic(ROC)curves were applied to evaluate the diagnostic potential of MSH6 methylation in RB.RESULTS:Bioinformatics analysis of public datasets revealed that MSH6 expression was downregulated across multiple cancers,RB.Consistently,in clinical RB tissues,MSH6 mRNA expression was significantly lower than that in control retinal tissues,whereas the promoter methylation level of MSH6 was markedly higher(both P<0.001),indicating that promoter hypermethylation may contribute to transcriptional silencing of MSH6 in RB.Patients with higher MSH6 methylation levels showed more advanced pathological classification and a higher frequency of metastasis.Multivariate logistic regression confirmed that metastatic status(P=0.008,OR=3.51)and pathological classification(P=0.005,OR=3.7)were independent factors associated with MSH6 methylation.Receiver operating characteristic(ROC)analysis demonstrated that MSH6 methylation could effectively distinguish RB tissues from non-tumorous controls(AUC=0.847,sensitivity=78.43%,specificity=80.65%),suggesting that MSH6 hypermethylation may serve as a potential diagnostic biomarker for RB.CONCLUSION:The methylation level of the MSH6 gene may be a key factor in RB pathogenesis.The methylation status of the MSH6 gene is closely associated with clinicopathological features and shows diagnostic potential.展开更多
Lymphomas represent one of the most common malignant diseases in young men and an important issue is how treatments will affect their reproductive health.It has been hypothesized that chemotherapies,similarly to envir...Lymphomas represent one of the most common malignant diseases in young men and an important issue is how treatments will affect their reproductive health.It has been hypothesized that chemotherapies,similarly to environmental chemicals,may alter the spermatogenic epigenome.Here,we report the genomic and epigenomic profiling of the sperm DNA from a 31-year-old Hodgkin lymphoma patient who faced recurrent spontaneous miscarriages in his couple 11-26 months after receiving chemotherapy with adriamycin,bleomycin,vinblastine,and dacarbazine(ABVD).In order to capture the potential deleterious impact of the ABVD treatment on mutational and methylation changes,we compared sperm DNA before and 26 months after chemotherapy with whole-genome sequencing(WGS)and reduced representation bisulfite sequencing(RRBS).The WGS analysis identified 403 variants following ABVD treatment,including 28 linked to genes crucial for embryogenesis.However,none were found in coding regions,indicating no impact of chemotherapy on protein function.The RRBS analysis identified 99high-quality differentially methylated regions(hqDMRs)for which methylation status changed upon chemotherapy.Those hqDRMs were associated with 87 differentially methylated genes,among which 14 are known to be important or expressed during embryo development.While no variants were detected in coding regions,promoter regions of several genes potentially important for embryo development contained variants or displayed an altered methylated status.These might in turn modify the corresponding gene expression and thus affect their function during key stages of embryogenesis,leading to potential developmental disorders or miscarriages.展开更多
The prevalence of stunting in Indonesian children under five years of age is approximately 20%.Chronic maternal malnutrition contributes to the risk of stunting by affecting global DNA methylation.In the present study...The prevalence of stunting in Indonesian children under five years of age is approximately 20%.Chronic maternal malnutrition contributes to the risk of stunting by affecting global DNA methylation.In the present study,we aimed to evaluate the levels of 5-methyl-cytosine(5mC)as a surrogate marker of global DNA methylation in buccal swabs and its potential association with the risk of stunting and cognitive performance.The levels of 5mC were measured using an enzyme-linked immunosorbent assay.The Wechsler Preschool and Primary Scale of Intelligence(WPPSI)was used to measure cognitive function.Buccal swab DNA samples and anthropometric data were collected from a total of 231 children aged zero to five years.In this cross-sectional cohort,the prevalence of stunting was 37%in 138 children aged zero to two years and 30%in 93 children aged over two years.The univariable analysis revealed that the levels of 5mC in buccal swab DNA were significantly lower in severely stunted children(median,2.84;interquartile range[IQR],2.39–4.62)and children aged less than two years(median,2.81;IQR,2.53–4.62)than those in normal children(median,3.75;IQR,2.80–4.74;P-value,0.028)and children aged over four years(median,4.01;IQR,3.39–4.87;P-value<0.001),respectively.We also found that the average cognitive scores tended to be low in boys and stunted children,although the differences were not statistically significant.Furthermore,the levels of 5mC found in buccal swab and mouthwash DNA were not associated with cognitive scores.展开更多
Moso bamboo holds significant economic importance in China,serving various purposes,such as food,material,ornamentation,and greenery.Despite its versatility,the occurrence of flowering in Moso bamboo poses a threat to...Moso bamboo holds significant economic importance in China,serving various purposes,such as food,material,ornamentation,and greenery.Despite its versatility,the occurrence of flowering in Moso bamboo poses a threat to bamboo forests,resulting in substantial losses.The underlying cause of bamboo flowering remains elusive.Dynamic fluctuations in DNA methylation govern the transcriptional levels of crucial genes pivotal for plant growth and development.In this study,we conducted comprehensive DNA methylation(by whole-genome bisulfite sequencing)and transcriptome(by RNA-seq)analyses on non-flowering leaves,flowering leaves,and spikelets of Moso bamboo.Our findings revealed a notable reduction in the overall DNA methylation level,particularly CHH methylation,from leaves to spikelets,influencing the expression of differentially regulated genes.Notably,we identified DNA methylation as a regulatory mechanism for numerous flowering-related genes,including SPLs,FT,and SOC1.Specifically,the SPL3f gene,a key regulator of the aging pathway,exhibited hypomethylation and a high expression level in spikelets.Conversely,SOC1c displayed transcriptional silencing attributed to hypermethylation in the CHH context in the leaves of non-flowering plants.DNA methylation may affect the flowering mechanism of Moso bamboo by regulating the expression of key genes.In summary,our results shed light on the dynamic changes in DNA methylation between leaves and spikelets,unraveling an important epigenetic modification mechanism for flowering in Moso bamboo.展开更多
The problems of tailings storage and high-stress conditions in deep mining have emerged as critical factors that limit the security,efficiency,and sustainability of such mines.This study explores the potential to util...The problems of tailings storage and high-stress conditions in deep mining have emerged as critical factors that limit the security,efficiency,and sustainability of such mines.This study explores the potential to utilize tungsten tailings to create cementitious backfill(CTB)materials and investigates the macroscopic strength features and microscopic damage evolution mechanisms of different-sized CTBs with varying dosages of hydroxypropyl methyl cellulose(HPMC).Specimens with bottom diameters of 50,75,and 100 mm are combined with HPMC dosages of 0,0.15wt%,0.25wt%,and 0.35wt%.A diameter/height ratio of 1:2 is maintained for all CTB specimens.The experimental results show that as the HPMC dosage is increased from 0 to 0.35wt%,the uniaxial compressive strength(UCS)of the CTBs decreases significantly in a linear manner.The 75 mm×150 mm CTB specimen exhibits relatively high plasticity and toughness,with good plastic deformation and energy absorption capabilities,indicating significant size effects.HPMC introduces connected bubbles during the CTB pouring process,but it exhibits anti-segregation and anti-bleeding characteristics,thus reducing tailing settling.The hydration reaction of the CTB doped with HPMC is more uniform,and the Ca/Si atomic ratio dispersion at different sites is smaller.The three CTB sizes all exhibit combined tensile and shear failure,with the 75 mm×150 mm specimen exhibiting macroscopic tensile cracks and relatively few shear cracks.At the micro-scale,excessive ettringite and hydrated calcium silicate are interwoven and fuse,and the tungsten tailings are tightly wrapped.These results provide valuable data and notional insights for optimizing the fluidity of the backfill,and elucidate the strength and damage evolution of solidified materials during filling and extraction.This study contributes to the advancement of green,economical,safe,and sustainable mining practices.展开更多
DNA methylation plays important roles in regulating gene expression during development.However,little is known about the influence of DNA methylation on secondary metabolism during leaf development in the tea plant(Ca...DNA methylation plays important roles in regulating gene expression during development.However,little is known about the influence of DNA methylation on secondary metabolism during leaf development in the tea plant(Camellia sinensis).In this study,we combined the methylome,transcriptome,and metabolome to investigate the dynamic changes in DNA methylation and its potential regulatory roles in secondary metabolite biosynthesis.In this study,the level of genomic DNA methylation increased as leaf development progressed from tender to old leaf.It additionally exhibited a similar distribution across the genomic background at the two distinct developmental stages studied.Notably,integrated analysis of transcriptomic and methylomic data showed that DNA hypermethylation primarily occurred in genes of the phenylpropanoid,flavonoid,and terpenoid biosynthesis pathways.The effect of methylation on transcription of these secondary metabolite biosynthesis genes was dependent on the location of methylation(i.e.,in the promoter,gene or intergenic regions)and the sequence context(i.e.,CpG,CHG,or CHH).Changes in the content of catechins and terpenoids were consistent with the changes in gene transcription and the methylation state of structural genes,such as serine carboxypeptidase-like acyltransferases 1A(SCPL1A),leucoanthocyanidin reductase(LAR),and nerolidol synthase(NES).Our study provides valuable information for dissecting the effects of DNA methylation on regulation of genes involved in secondary metabolism during tea leaf development.展开更多
BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role ...BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role in this process.AIM To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.METHODS We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation,and studies on DNA methylation and T2D through January 15,2024.RESULTS We identified six genes(Alu,CABLES1,CDH1,PDX1,PTEN,PTPRN2)related to pesticide exposure and T2D.We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.CONCLUSION DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.展开更多
基金the support from National Natural Science Foundation of China(No.22161132006)Key R&D Program of Zhejiang(No.2024SSYS0036)Westlake University Startup。
文摘Reader proteins that bind specific methyllysine are important to biological functions of lysine methylation,but readers of many methyllysine sites are still unknown.Therefore,development of covalent probes is important to identify readers from cell samples so as to understand biological roles of lysine methylation.Generally,readers bind methyllysine via aromatic cages that contain tryptophan,tyrosine and phenylalanine,that offer a unique motif for selective crosslinking.We recently reported a site-selective tryptophan crosslinking strategy based on dimethylsulfonium that mimics dimethyllysine to crosslink tryptophan in aromatic cages of readers.Since tyrosine is a key residue for binding affinity to methyllysine,especially some readers that do not contain tryptophan residues in the binding pocket.Here we developed strategies of site-selective crosslinking to tyrosine.Ultraviolet(UV)source was applied to excite tyrosine at neutral pH or phenoxide at basic p H,and subsequent single-electron transfer(SET)from Tyr*to sulfonium inside the binding pocket enables selective crosslinking.In consequence,methyllysine readers with tyrosine-containing aromatic cages could be selectively crosslinked by site-specific sulfonium peptide probes.In addition,we expanded substrates from aromatic cages to tyrosine residues of proximate contact with sulfonium probes.The pair of LgBiT and SmBiT exhibited orthogonal crosslinking in complicated cell samples.As a result,we may expand sulfonium tools to target local tyrosine in future investigations.
文摘Detecting lung cancer early is crucial for improving survival rates,yet it remains a significant challenge due to many cases being diagnosed at advanced stages.This review aims to provide advances in epigenetics which have highlighted DNA methylation patterns as promising biomarkers for early detection,prognosis,and treatment response in lung cancer.Techniques like bisulfite conversion followed by PCR,digital droplet polymerase chain reaction,and next-generation sequencing are commonly used for detecting these methylation patterns,which occur early in the cancer development process and can be detected in non-invasive samples like blood and sputum.Key genes such as SHOX2 and RASSF1A have demonstrated high sensitivity and specificity in clinical studies,making them crucial for diagnostic purposes.However,several challenges remain to be overcome before these biomarkers can be widely adopted for use in clinical practice.Standardizing the assays and validating their effectiveness are critical steps.Additionally,integrating methylation biomarkers with existing diagnostic tools could significantly enhance the accuracy of lung cancer detection,providing a more comprehensive diagnostic approach.Although progress has been made in understanding and utilizing DNA methylation patterns for lung cancer detection,more research and extensive clinical trials are necessary to fully harness their potential.These efforts will help establish the robustness of methylation patterns as biomarkers and therapeutic targets,ultimately leading to better prevention,diagnosis,and treatment strategies for lung cancer.In conclusion,DNA methylation states represent a promising avenue for advancing early detection,accurate diagnosis,and management of lung cancer.
文摘The methylation of DNA is a prevalent epigenetic modification that plays a crucial role in the pathological progression of ocular diseases.DNA methylation can regulate gene expression,thereby affecting cell function and signal transduction.Ophthalmic diseases are a kind of complex diseases,and their pathogenesis involves many factors such as genetic,environmental and individual differences.In addition,inflammation,oxidative stress and lipid metabolism,which abnormal DNA methylation is closely related to,are also considered to be major factors in eye diseases.The current understanding of DNA methylation in eye diseases is becoming more complex and comprehensive.In addition to the simple suppression of gene expression by hypermethylation,factors such as hypomethylation or demethylation,DNA methylation in non-promoter regions,interactions with other epigenetic modifications,and dynamic changes in DNA methylation must also be considered.Interestingly,although some genes are at abnormal methylation levels,their expression is not significantly changed,which indirectly reflects the complexity of gene regulation.This review aims to summarize and compare some relevant studies,and provide with new ideas and methods for the prevention and treatment of different eye diseases,such as glaucoma,retinoblastoma,and diabetic retinopathy.
基金supported by the Fundamental Research Funds for the Central Universities(2572020DR10)Project on the Investigation,Supervision and Industry Regulation of Rare and Endangered Species(2024)。
文摘Illegal hunting and trafficking of wildlife and their derivatives extort unprecedented population decline of relatively many species pushing them towards extinction.Notwithstanding contemporary counteracting interventions at international,regional,national and local levels,wildlife farming is advocated as an alternative approach to minimize pressure on wild populations.For wildlife farming to be an effective conservation tool,the integration of wildlife forensics is inevitable to allow distinction between captive-bred and wild-caught species.To this end,we analyzed methylation rates of skeletal muscle samples(pectoralis major,triceps brachii,gastrocnemius,biceps femoris,and neck muscles)from 60 captive-bred and 30 wild-caught Common Pheasant.A total of 13,507 differentially methylated regions were identified between five wild-caught and five captive-bred individuals through whole-genome methylation sequencing(WGBS).Based on the selected five methylation sites,LOC116231076,LOC116242223,ATAD2B,EGFL6,and HS2ST,quantitative detection technique was developed using methylation-sensitive high-resolution melting curve(MS-HRM)to measure methylation rates.The results showed significant differences in methylation rates at all differential sites between wild-caught and captive-bred individuals(|t|=0.67–33.10,P=0.000–0.042).The discrimination accuracy rate of each locus was highest in the gastrocnemius muscle and lowest in the neck muscle.The discrimination accuracy rate on LOC116231076,LOC116242223,ATAD2B,EGFL6,and HS2ST methylation sites for gastrocnemius muscle was 64.98%,100.00%,68.54%,63.79%,and 63.70%,respectively;and for neck muscle it was 67.42%,68.06%,83.61%,65.04%,and68.85%,respectively.The united discrimination accuracy rate of the five loci were 100.00%for gastrocnemius muscle,99.78%for biceps femoris muscle,97.52%for pectoralis major muscle,93.96%for triceps brachii muscle,and 91.63%for neck muscle,respectively.The panel also revealed excellent repeatability,reproducibility,sensitivity and universality to mammals and avian species.This study establishes an effective,accurate and low-cost identification technology for the identification of wild and farmed Common Pheasant,and also provides a reference for the development of identification methods for other species.
基金the Research Program of the Science and Technology Department of Yunnan Province,No.202101AY070001-204.
文摘BACKGROUND Gastric cancer(GC)is a malignant tumor originating from gastric mucosal epithelial cells that has high morbidity and mortality.microRNAs(miR)are important diagnostic markers and therapeutic targets in this disease.AIM To explore the mechanism of miR-125a-5p in the pathogenesis of GC.METHODS The expression levels of miR-125a-5p,SERPINE1 and DNMT1 in GC cells and tissues were detected by real-time polymerase chain reaction(PCR)and Western blotting.Methylation-specific PCR was used to detect the level of miR-125a-5p methylation.A cell counting kit 8 assay,scratch test,and a Transwell assay were performed to detect the proliferation,migration,and invasiveness of HGC27 cells,respectively.The expression of the epithelial mesenchymal transition(EMT)-related proteins E-cadherin,N-cadherin and vimentin in HGC27 cells was detected by Western blotting,while the expression of vimentin was detected by immunofluorescence.RESULTS This study revealed that miR-125a-5p was expressed at low levels in GC clinical samples and cells and that miR-125a-5p overexpression inhibited the proliferation,migration,invasiveness and EMT of GC cells.Mechanistically,miR-125a-5p can reduce GC cell proliferation,promote E-cadherin expression,inhibit N-cadherin and vimentin expression,and reduce the EMT of GC cells,thus constraining GC cells to a certain extent.Moreover,DNMT1 inhibited miR-125a-5p expression by increasing the methylation of the miR-125a-5p promoter,thereby promoting the expression of SERPINE1,which acts together with miR-125a-5p to exert antagonistic effects on GC.CONCLUSION Our study revealed that DNMT1 promoted SERPINE1 protein expression by inducing miR-125a-5p methylation,which led to the proliferation,migration and occurrence of EMT in GC cells.
基金supported by the National Natural Science Foundation of China(32070607)the National Key Research and Development Program of China(2020YFA0804000)the CAS Project for Young Scientists in Basic Research(YSBR-012).
文摘In the mammalian genome,most CpGs are methylated.However,CpGs within the CpG islands(CGIs)are largely unmethylated,which are important for gene expression regulation.The mechanism underlying the low methylation levels at CGIs remains largely elusive.KDM2 proteins(KDM2A and KDM2B)are H3K36me2 demethylases known to bind specifically at CGIs.Here,we report that depletion of each or both KDM2 proteins,or mutation of all their JmjC domains that harbor the H3K36me2 demethylation activity,leads to an increase in DNA methylation at selective CGIs.The Kdm2a/2b double knockout shows a stronger increase in DNA methylation compared with the single mutant of Kdm2a or Kdm2b,indicating that KDM2A and KDM2B redundantly regulate DNA methylation at CGIs.In addition,the increase of CGI DNA methylation upon mutations of KDM2 proteins is associated with the chromatin environment.Our findings reveal that KDM2A and KDM2B function redundantly in regulating DNA methylation at a subset of CGIs in an H3K36me2 demethylation-dependent manner.
基金funded by National High-Level Hospital Clinical Research Funding (2022-PUMCH-A-203)CAMS Innovation Fund for Medical Sciences (2021-I2M-1-001)+4 种基金Health Research & Special Projects Grant of China (201002020 and 201502005)The Integrated Entrusted Project of Research Funding at Peking Union Medical College Hospital (ZC201903347)the National Natural Science Foundation of China (81970495)Capital Health Development Scientific Research Fund (2022-2-4014)Peking Union Medical College Hospital Research Funding for Postdoc (kyfyjj202315)
文摘Colitis-associated colorectal cancer(CAC),a serious complication of ulcerative colitis(UC),is associated with a poor prognosis.The vitamin D receptor(VDR)is recognized for its protective role in UC and CAC through the maintenance of intestinal barrier integrity and the regulation of inflammation.This study demonstrates a significant reduction in m^(6)A-related genes,particularly methyltransferase like 14(METTL14),in UC and CAC patients and identifies an association between METTL14 and VDR.In the azoxymethane(AOM)/dextran sodium sulfate(DSS)-induced mousemodel,vitamin D treatment increases METTL14 expression and reduces tumorburden,while Vdr-knockout mice exhibit lower METTL14 levels and increased tumorigenesis.In vitro,the VDR agonist calcipotriol upregulates METTL14 in NCM460 cells,with this effect attenuated by VDR knockdown.VDRknockdown inDLD-1colon cancer cellsdecreases METTL14 expressionand promotes proliferation,which is reversed by METTL14 overexpression.Mechanistic studies reveal that VDR regulates METTL14 expression via promoter binding,modulating key target genes such as SOX4,DROSH,and PHLPP2.This study highlights the role of the VDR-METTL14 axis as a protective mechanism in CAC and suggests its potential as a therapeutic target for preventing and treating CAC.
基金supported by the National Natural Science Foundation of China,Nos.82271283(to XC),91854115(to JW),31970044(to JW)the Natural Science Foundation of Beijing,No.7202001(to XC)the Scientific Research Project of Beijing Educational Committee,No.KM202010005022(to XC)。
文摘Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's disease.However,the mechanism by which Sal mediates dopaminergic neuronal death remains unclear.In this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling pathway.The m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling pathway.Additionally,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to neurotoxicity.These findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and autophagy.Our results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.
基金Supported by the Medical Talents of Wuhan Health and Family Planning Commission,No.2017[51](to Yu J)the Medical Talents of Wuhan Hospital of Traditional Chinese and Western Medicine(to Yu J)+1 种基金the Hubei Natural Science Foundation,No.2023AFB1091Wuhan Medical Research Project,No.WX23A36(to Yu J).
文摘BACKGROUND Cholangiocarcinoma(CCA),also known as bile duct cancer,is a devastating malignancy primarily affecting the biliary tract.AIM To assess their performance in clinical diagnosis and monitoring of CCA,plasma methylation and circulating tumor cells were detected.METHODS Plasma samples were collected from Hubei Cancer Hospital(n=156).Plasma DNA was tested to detect SHOX2,HOXA9,SEPTIN9,and RASSF1A methylation using TaqMan PCR.Circulating tumor cells(CTCs)were detected in the peripheral blood of patients using the United States Food and Drug Administration-approved cell search system before and after clinical therapy.The CCA diagnostic value was estimated using the area under the curve.The independent prognosis risk factors for patients with CCA were estimated using Cox and logistic regression analyses.RESULTS The sensitivity and specificity of the four DNA plasma methylations exhibited 64.74%sensitivity and 93.88%specificity for detecting CCA.The receiver operating characteristic curve of the combined value for CCA diagnosis in plasma was 0.828±0.032.RASSF1A plasma methylation was related to the prognosis of patients with CCA.We determined the prognostic hazard ratio for CCA using CTC count,tumor stage,methylation,and carbohydrate antigen 19-9 levels as key factors.Our overall survival nomogram achieved a C-index of 0.705(0.605-0.805).CONCLUSION SHOX2,HOXA9,SEPTIN9,and RASSF1A plasma methylation demonstrated increased sensitivity for diagnosing CCA.RASSF1A plasma methylation and CTCs were valuable predictors to assess CCA prognosis and recurrence.
基金supported by the Shandong Province Natural Science Foundation of Major Basic Research Program (No.ZR2020ZD34)the Key Projects of the National Natural Science Foundation of China (No.42230706)+3 种基金the National Natural Science Foundation of China (No.42307164)the China Postdoctoral Science Foundation (Nos.2023TQ0191 and 2023M732060)the Shandong Postdoctoral Science Foundation (No.SDBX2023041)and the Qingdao Postdoctoral Science Foundation (No.QDBSH20230202052).
文摘Arsenic(As)methylation in soils affects the environmental behavior of As,excessive accumulation of dimethylarsenate(DMA)in rice plants leads to straighthead disease and a serious drop in crop yield.Understanding the mobility and transformation of methylated arsenic in redox-changing paddy fields is crucial for food security.Here,soils including unarsenic contaminated(N-As),low-arsenic(L-As),medium-arsenic(M-As),and high-arsenic(H-As)soils were incubated under continuous anoxic,continuous oxic,and consecutive anoxic/oxic treatments respectively,to profile arsenic methylating process and microbial species involved in the As cycle.Under anoxic-oxic(A-O)treatment,methylated arsenic was significantly increased once oxygen was introduced into the incubation system.The methylated arsenic concentrations were up to 2-24 times higher than those in anoxic(A),oxic(O),and oxic-anoxic(O-A)treatments,under which arsenic was methylated slightly and then decreased in all four As concentration soils.In fact,the most plentiful arsenite S-adenosylmethionine methyltransferase genes(arsM)contributed to the increase in As methylation.Proteobacteria(40.8%-62.4%),Firmicutes(3.5%-15.7%),and Desulfobacterota(5.3%-13.3%)were the major microorganisms related to this process.These microbial increasedmarkedly and played more important roles after oxygen was introduced,indicating that they were potential keystone microbial groups for As methylation in the alternating anoxic(flooding)and oxic(drainage)environment.The novel findings provided newinsights into the reoxidation-driven arsenic methylation processes and the model could be used for further risk estimation in periodically flooded paddy fields.
基金supported by the National Key R&D Program of China(2023YFD1300103)the Science and Technology Plan Project of Yantai City(2023ZDCX024)+5 种基金the National Natural Science Foundation of China(32372852)the Science Fund for Distinguished Young Scholars of Shaanxi Province(2024JC-JCQN-30)Shaanxi Provincial Innovation Leadership Program in Sciences and Technologies for Young and Middle-aged Scientists(2023SR205)the China Agriculture Research System-beef(CARS-37)the Innovation Team of Cattle Industry in Technological System of Shandong Modern Agriculture Industry(SDAIT-09-03)the Key Research and Development Project in Shandong Province(Competitive Innovation Platform)(2022CXPT010).
文摘Background N^(6)-methyladenosine(m^(6)A)methylation is a key epigenetic modification that can modulate gene expression and strongly affect mammalian developmental processes.However,the genome-wide methylation of long non-coding RNAs(lncRNAs)and its implications for the development of skeletal muscle remain poorly understood.Bovine skeletal muscle samples from five developmental stages were analyzed in this study to establish lncRNA methylome and transcriptomic maps.Results Globally,59.67%of lncRNAs in skeletal muscle with m^(6)A modifications,and this percentage decreased progressively during development.lncRNA expression levels were positively associated with the number of m^(6)A peaks,with lncRNAs possessing 3 or more peaks showing significantly higher expression levels than those with 1 or 2 peaks.Specific lncRNAs involved in skeletal muscle development were identified through two analytical approaches.The first approach employed weighted gene co-expression network analysis(WGCNA)of transcriptomic data to identify correlations between annotated lncRNAs and growth-related traits,resulting in 21 candidate hub lncRNAs.The intersection of these 21 hub lncRNAs with 151 differentially methylated lncRNAs(DM-lncRNAs)identified 10 shared candidate lncRNAs.The second approach integrated MeRIP-seq and RNA-seq data to identify 36 lncRNAs that were both differentially m^(6)A modified and differentially expressed(dme-lncRNAs).GO and KEGG enrichment analyses of cis-target genes associated with these dme-lncRNAs identified eight candidate lncRNAs.Combining the results from the two approaches identified 16 key m^(6)A-modified lncRNAs likely involved in skeletal muscle development.Conclusions These findings highlight the regulatory and functional significance of dynamic lncRNA methylation in skeletal muscle development.
基金supported by the National Natural Science Foundation of China(22478106,22178102,and 22332003)Shanghai Rising-Star Program(23QA1401900)+1 种基金Young Elite Scientists Sponsorship Programby CAST(2023QNRC001)the Open Project of Yunnan Precious Metals Laboratory Co.,Ltd(YPML-2023050272).
文摘Gas-phase synthesis of glycolide(GL)from methyl glycolate(MG)is of great significance for producing biodegradable polyglycolic acid.Here,we report a detailed thermodynamics study for the gas-phase synthesis of GL from MG,which involves complex reaction pathways,by utilizing the Gibbs free energy minimization method.The results indicate that the decompositions of MG and GL and the polymerization of MG are thermodynamically favorable as compared with the target pathway,i.e.,the cyclization of MG.Effects of the reaction conditions including temperature,pressure and feed composition on the formation of GL and linear polymers have also been addressed,which demonstrate that the higher temperature and lower pressure can effectively inhibit the formation of linear methyl ester dimer and improve the selectivity to GL.In addition,the higher N_(2)/MG ratio is beneficial for the formation of GL in the process promoted by catalysts.These thermodynamics results indicate that the process promoted by catalysts would benefit from the kinetics control by high-performance catalysts and the operation at high temperature,low pressure and high N_(2)/MG ratio to enhance the yield of targeted GL.The insights demonstrated here from thermodynamics are valuable for guiding the design of catalysts and/or optimization of reaction conditions for the gas-phase synthesis of GL from MG.
基金funded by the China Agriculture Research System(CARS–15–16)。
文摘Background Thidiazuron(TDZ)is a widely used chemical defoliant in commercial cotton production and is often combined with the herbicide Diuron to form the commercial defoliant mixture known as TDZ·Diuron(T·D,540 g·L^(-1)suspension).However,due to increasing concerns about the environmental and biological risks posed by Diuron,there is an urgent need to develop safer and more effective alternatives.Jasmonic acid(JA)and its derivatives are key phytohormones in organ senescence and abscission.Results Greenhouse experiments at the seedling stage revealed that Me-JA(0.8 mmol·L^(-1))alone did not induce defoliation.However,its co-application with TDZ(0.45 mmol·L^(-1))at concentrations of 0.6,0.8,and 1.0 mmol·L^(-1)significantly enhanced defoliation efficacy.The most effective combination—TDZ with 0.8 mmol·L^(-1)Me-JA—achieved a 100%defoliation rate at 5 days after treatment(DAT),23.7 percentage points higher than TDZ alone,and comparable to the commercial TDZ·Diuron formulation with equivalent TDZ content.Field trials conducted in Beijing(Shangzhuang),Hebei(Hejian),and Xinjiang(Shihezi)confirmed that the combination of 0.6 mmol·L^(-1)Me-JA with 1.70 mmol·L^(-1)TDZ provided optimal defoliation performance.At 21 DAT,the defoliation rate increased by 13.5–16.3 percentage points compared with TDZ alone.Furthermore,boll opening rates improved by 5.7–12.7 percentage points relative to TDZ-only treatments.Phytohormonal analyses from the Shangzhuang site showed that the combined treatment significantly altered hormone levels in both leaves and petioles.Compared with TDZ alone,the mixture reduced concentrations of auxin(IAA),cytokinins(Z+ZR,iP+iPA,DHZ+DHZR),and gibberellic acid(GA3),while increasing levels of JA,abscisic acid(ABA),and brassinosteroids(BR).These hormonal shifts may underlie the enhanced defoliation observed with the combined treatment.Importantly,the TDZ-Me-JA combination did not adversely affect cotton yield,yield components,or fiber quality.Conclusion The combination of Me-JA and TDZ has a good defoliation effect without affecting crop yield or fiber quality.And it provides a promising foundation for the development of novel,environmentally friendly cotton defoliants.
文摘AIM:To explore the methylation status of MSH6 in retinoblastoma(RB)and its impact on clinicopathological features and diagnosis.METHODS:Differentially expressed genes were identified through bioinformatics screening of the GSE24673 and GSE125903 datasets,combined with GeneCards database analysis.A total of 102 RB patients and 62 traumaenucleated controls between January 2018 and December 2023 were enrolled,with their clinicopathological data and retinal tissues collected.The mRNA and methylation levels of MSH6 in retinal tissues were detected using real-time quantitative polymerase chain reaction(PCR)and methylation-specific PCR.Western blot analysis was conducted in one pair of RB and control tissues for preliminary protein-level validation of MSH6 expression.Based on the methylation status of MSH6,RB patients were categorized into two groups:low-methylation and highmethylation.Both univariate and multivariate analyses were conducted to identify independent factors influencing the methylation levels using clinicopathological data.Receiver operating characteristic(ROC)curves were applied to evaluate the diagnostic potential of MSH6 methylation in RB.RESULTS:Bioinformatics analysis of public datasets revealed that MSH6 expression was downregulated across multiple cancers,RB.Consistently,in clinical RB tissues,MSH6 mRNA expression was significantly lower than that in control retinal tissues,whereas the promoter methylation level of MSH6 was markedly higher(both P<0.001),indicating that promoter hypermethylation may contribute to transcriptional silencing of MSH6 in RB.Patients with higher MSH6 methylation levels showed more advanced pathological classification and a higher frequency of metastasis.Multivariate logistic regression confirmed that metastatic status(P=0.008,OR=3.51)and pathological classification(P=0.005,OR=3.7)were independent factors associated with MSH6 methylation.Receiver operating characteristic(ROC)analysis demonstrated that MSH6 methylation could effectively distinguish RB tissues from non-tumorous controls(AUC=0.847,sensitivity=78.43%,specificity=80.65%),suggesting that MSH6 hypermethylation may serve as a potential diagnostic biomarker for RB.CONCLUSION:The methylation level of the MSH6 gene may be a key factor in RB pathogenesis.The methylation status of the MSH6 gene is closely associated with clinicopathological features and shows diagnostic potential.
文摘Lymphomas represent one of the most common malignant diseases in young men and an important issue is how treatments will affect their reproductive health.It has been hypothesized that chemotherapies,similarly to environmental chemicals,may alter the spermatogenic epigenome.Here,we report the genomic and epigenomic profiling of the sperm DNA from a 31-year-old Hodgkin lymphoma patient who faced recurrent spontaneous miscarriages in his couple 11-26 months after receiving chemotherapy with adriamycin,bleomycin,vinblastine,and dacarbazine(ABVD).In order to capture the potential deleterious impact of the ABVD treatment on mutational and methylation changes,we compared sperm DNA before and 26 months after chemotherapy with whole-genome sequencing(WGS)and reduced representation bisulfite sequencing(RRBS).The WGS analysis identified 403 variants following ABVD treatment,including 28 linked to genes crucial for embryogenesis.However,none were found in coding regions,indicating no impact of chemotherapy on protein function.The RRBS analysis identified 99high-quality differentially methylated regions(hqDMRs)for which methylation status changed upon chemotherapy.Those hqDRMs were associated with 87 differentially methylated genes,among which 14 are known to be important or expressed during embryo development.While no variants were detected in coding regions,promoter regions of several genes potentially important for embryo development contained variants or displayed an altered methylated status.These might in turn modify the corresponding gene expression and thus affect their function during key stages of embryogenesis,leading to potential developmental disorders or miscarriages.
基金Ministry of Education,Culture,Research,and Technology of the Republic of Indonesia through the Kedaireka 2022 Matching Fund Programme(Grant No.282/E1/KS.060.02/2022)。
文摘The prevalence of stunting in Indonesian children under five years of age is approximately 20%.Chronic maternal malnutrition contributes to the risk of stunting by affecting global DNA methylation.In the present study,we aimed to evaluate the levels of 5-methyl-cytosine(5mC)as a surrogate marker of global DNA methylation in buccal swabs and its potential association with the risk of stunting and cognitive performance.The levels of 5mC were measured using an enzyme-linked immunosorbent assay.The Wechsler Preschool and Primary Scale of Intelligence(WPPSI)was used to measure cognitive function.Buccal swab DNA samples and anthropometric data were collected from a total of 231 children aged zero to five years.In this cross-sectional cohort,the prevalence of stunting was 37%in 138 children aged zero to two years and 30%in 93 children aged over two years.The univariable analysis revealed that the levels of 5mC in buccal swab DNA were significantly lower in severely stunted children(median,2.84;interquartile range[IQR],2.39–4.62)and children aged less than two years(median,2.81;IQR,2.53–4.62)than those in normal children(median,3.75;IQR,2.80–4.74;P-value,0.028)and children aged over four years(median,4.01;IQR,3.39–4.87;P-value<0.001),respectively.We also found that the average cognitive scores tended to be low in boys and stunted children,although the differences were not statistically significant.Furthermore,the levels of 5mC found in buccal swab and mouthwash DNA were not associated with cognitive scores.
基金supported by the National Natural Science Foundation of China(Grant No.32160142)the Guangxi Natural Science Foundation(Grant No.2023GXNSFDA026034)+3 种基金the Sugarcane Research Foundation of Guangxi University(Grant No.2022GZA002)the State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources(Grant No.SKLCUSAb202302)the National Natural Science Foundation of China(Grant No.31960051)the Natural Science Foundation for Young Scientists of Jiangxi Province(Grant No.20192ACB21005).
文摘Moso bamboo holds significant economic importance in China,serving various purposes,such as food,material,ornamentation,and greenery.Despite its versatility,the occurrence of flowering in Moso bamboo poses a threat to bamboo forests,resulting in substantial losses.The underlying cause of bamboo flowering remains elusive.Dynamic fluctuations in DNA methylation govern the transcriptional levels of crucial genes pivotal for plant growth and development.In this study,we conducted comprehensive DNA methylation(by whole-genome bisulfite sequencing)and transcriptome(by RNA-seq)analyses on non-flowering leaves,flowering leaves,and spikelets of Moso bamboo.Our findings revealed a notable reduction in the overall DNA methylation level,particularly CHH methylation,from leaves to spikelets,influencing the expression of differentially regulated genes.Notably,we identified DNA methylation as a regulatory mechanism for numerous flowering-related genes,including SPLs,FT,and SOC1.Specifically,the SPL3f gene,a key regulator of the aging pathway,exhibited hypomethylation and a high expression level in spikelets.Conversely,SOC1c displayed transcriptional silencing attributed to hypermethylation in the CHH context in the leaves of non-flowering plants.DNA methylation may affect the flowering mechanism of Moso bamboo by regulating the expression of key genes.In summary,our results shed light on the dynamic changes in DNA methylation between leaves and spikelets,unraveling an important epigenetic modification mechanism for flowering in Moso bamboo.
基金National Key Research and Development Program of China(No.2022YFC2905004).
文摘The problems of tailings storage and high-stress conditions in deep mining have emerged as critical factors that limit the security,efficiency,and sustainability of such mines.This study explores the potential to utilize tungsten tailings to create cementitious backfill(CTB)materials and investigates the macroscopic strength features and microscopic damage evolution mechanisms of different-sized CTBs with varying dosages of hydroxypropyl methyl cellulose(HPMC).Specimens with bottom diameters of 50,75,and 100 mm are combined with HPMC dosages of 0,0.15wt%,0.25wt%,and 0.35wt%.A diameter/height ratio of 1:2 is maintained for all CTB specimens.The experimental results show that as the HPMC dosage is increased from 0 to 0.35wt%,the uniaxial compressive strength(UCS)of the CTBs decreases significantly in a linear manner.The 75 mm×150 mm CTB specimen exhibits relatively high plasticity and toughness,with good plastic deformation and energy absorption capabilities,indicating significant size effects.HPMC introduces connected bubbles during the CTB pouring process,but it exhibits anti-segregation and anti-bleeding characteristics,thus reducing tailing settling.The hydration reaction of the CTB doped with HPMC is more uniform,and the Ca/Si atomic ratio dispersion at different sites is smaller.The three CTB sizes all exhibit combined tensile and shear failure,with the 75 mm×150 mm specimen exhibiting macroscopic tensile cracks and relatively few shear cracks.At the micro-scale,excessive ettringite and hydrated calcium silicate are interwoven and fuse,and the tungsten tailings are tightly wrapped.These results provide valuable data and notional insights for optimizing the fluidity of the backfill,and elucidate the strength and damage evolution of solidified materials during filling and extraction.This study contributes to the advancement of green,economical,safe,and sustainable mining practices.
基金supported by the Natural Science Foundation of Guangdong Province(Grant Nos.2022A1515111141 and 2023A1515010786)。
文摘DNA methylation plays important roles in regulating gene expression during development.However,little is known about the influence of DNA methylation on secondary metabolism during leaf development in the tea plant(Camellia sinensis).In this study,we combined the methylome,transcriptome,and metabolome to investigate the dynamic changes in DNA methylation and its potential regulatory roles in secondary metabolite biosynthesis.In this study,the level of genomic DNA methylation increased as leaf development progressed from tender to old leaf.It additionally exhibited a similar distribution across the genomic background at the two distinct developmental stages studied.Notably,integrated analysis of transcriptomic and methylomic data showed that DNA hypermethylation primarily occurred in genes of the phenylpropanoid,flavonoid,and terpenoid biosynthesis pathways.The effect of methylation on transcription of these secondary metabolite biosynthesis genes was dependent on the location of methylation(i.e.,in the promoter,gene or intergenic regions)and the sequence context(i.e.,CpG,CHG,or CHH).Changes in the content of catechins and terpenoids were consistent with the changes in gene transcription and the methylation state of structural genes,such as serine carboxypeptidase-like acyltransferases 1A(SCPL1A),leucoanthocyanidin reductase(LAR),and nerolidol synthase(NES).Our study provides valuable information for dissecting the effects of DNA methylation on regulation of genes involved in secondary metabolism during tea leaf development.
文摘BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role in this process.AIM To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.METHODS We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation,and studies on DNA methylation and T2D through January 15,2024.RESULTS We identified six genes(Alu,CABLES1,CDH1,PDX1,PTEN,PTPRN2)related to pesticide exposure and T2D.We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.CONCLUSION DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.
