The development of methylation protocol has attracted intense attention owing to"magic methyl effect"in drug discovery.Meanwhile,the indole scaffold is prevalence in the natural products and pharmacophores.D...The development of methylation protocol has attracted intense attention owing to"magic methyl effect"in drug discovery.Meanwhile,the indole scaffold is prevalence in the natural products and pharmacophores.Despite the advances in other site selective methylation,there is scarce reports for C4 methylation of indoles and combination of a carbonyl group rearrangement with C—H methylation on indole ring.Herein,the C4 methylation of indoles and the steric controlled C4-methylation/carbonyl group migration are reported.The large steric hindrance at carbonyl group facilitates the carbonyl group migration,which provides a straightforward protocol for the synthesis of C2/C4 disubstituted indoles.展开更多
In vitro maturation(IvM)of human oocytes offers cost efficiency and minimal invasiveness,serving as a valuable supplementary tool in assisted reproduction for fertility preservation,ovarian hyperstimulation syndrome p...In vitro maturation(IvM)of human oocytes offers cost efficiency and minimal invasiveness,serving as a valuable supplementary tool in assisted reproduction for fertility preservation,ovarian hyperstimulation syndrome prevention,and other reproductive strategies.Despite its availability for three decades,the clinical use of IVM remains limited due to efficacy and safety concerns.This study examines the DNA methylation profile of IVM oocytes collected during laparoscopic/hysteroscopic surgeries compared to in vivo matured oocytes via reduced representation bisulfite sequencing.Results indicate IVM oocytes exhibit a higher global methylation level.Differentially methylated regions(DMRs)analysis reveals that the in vitro group displays more hypermethylated and fewer hypomethylated DMRs compared to the in vivo group.Additionally,the in vitro group exhibits a higher level of non-CpG methylation than the in vivo group.However,no significant correlation between methylation levels and transcriptional activity in these oocytes is found,especially for those specific imprinted genes or genes related to embryonic development.These findings shed light on the epigenetic landscape of IvM oocytes,contributing to the ongoing assessment of their clinical feasibility and safety in assisted reproduction.展开更多
DNA methylation is an important promising biomarker for cancer diagnosis and monitoring.Therefore,the assessment of DNA methylation levels is helpful for the prognosis and diagnosis of cancer.However,it is still a hug...DNA methylation is an important promising biomarker for cancer diagnosis and monitoring.Therefore,the assessment of DNA methylation levels is helpful for the prognosis and diagnosis of cancer.However,it is still a huge challenge to sensitively and accurately quantify the levels of DNA methylation in clinical sample.In this work,we proposed a protospacer adjacent motif(PAM)-free mediated CRISPR-Cas12a ultra-sensitive and quantitative DNA methylation detection method.Through recognizing the ds DNA with toehold region,CRISPR-Cas12a not only got rid of the limitation of PAM,but also improved its distinction ability for single Cp G site methylation,nearly 5-fold that of conventional PAM-containing ds DNA.We further introduced assist-strand and design an artificial mismatch to greatly improve the ability to distinguish single Cp G methylation site.Our results showed that the discrimination factor was >200.Then,we constructed toe-ds DNA by using “heating and freezing”,which made our method universally applicable and feasible.In addition,we greatly simplified the difficulty of primer design.Our method detected four highly methylated genes acyl carrier protein(ACP),CLV3/ESR-related(CLE),Disabled(DAB) and Homeobox(HOX) with a detection limit of 0.01 % and excellent linearity in DNA methylation standards.Then,we verified the clinical utility of this method in 29 hepatocellular carcinomas,11 ovarian cancers and4 health people.In conclusion,we have successfully constructed a PAM-free CRISPR-Cas12a DNA methylation quantification method,which achieves high congruence in sensitivity,specificity and universality,fully demonstrating its significant clinical application value.展开更多
Major chemical ionic components in water serve as indicators of natural factors in the areas traversed by water bodies,and are thus widely used to elucidate key hydrogeochemical processes,including rock weathering,aqu...Major chemical ionic components in water serve as indicators of natural factors in the areas traversed by water bodies,and are thus widely used to elucidate key hydrogeochemical processes,including rock weathering,aquatic evaporation-crystallization,and the input of precipitation-derived materials into river basins.A total of 208 water samples were collected between August 2021 and August 2022 to investigate the hydrochemical characteristics and their influencing factors of the surface water and the groundwater in the Mingyong River Basin.To systematically analyze the data,we combined hydrogeochemical and statistical methods:descriptive statistics characterized ion concentration and physicochemical parameter distributions;Piper trilinear diagrams classified hydrochemical types;Pearson correlation analysis assessed ion-ion and ionTDS dependencies;Gibbs diagrams and ion ratio analysis identified solute sources;and the absolute principal component score-multiple linear regression(APCS-MLR)model quantified the contribution rates of different influencing factors.The results revealed that the dominant cations in the surface water and groundwater are Ca^(2+)and Mg^(2+),while the dominant anions are HCO_(3)^(-)and SO_(4)^(2-).The groundwater exhibits an extended residence time within rock strata,facilitating prolonged interaction with soluble minerals and intensifying the water-rock reaction process,thereby resulting in higher levels of electrical conductivity(EC),pH,and total dissolved solids(TDS)than those in the surface water.Secondly,the parameters of the surface water and groundwater indicate positive correlation.The weathering of rocks constitutes the primary solute source in the water of the basin.The hydrochemical composition of the basin water is primarily influenced by both carbonate and silicate rocks,with a minor contribution from evaporite rocks.The water bodies in the basin are affected by anthropogenic activities.The surface water is influenced by four sources,namely lixiviation-enrich,human activities,geological environmental,and unknown sources.The groundwater is influenced by five sources,namely lixiviation-enrich,primary geological,human activities,geological environmental,and unknown sources.展开更多
Background:The trajectory of intrinsic capacity(IC)among the older population is characterized by its diversity and is predictive of adverse health outcomes such as disability,nursing home admission,decline in quality...Background:The trajectory of intrinsic capacity(IC)among the older population is characterized by its diversity and is predictive of adverse health outcomes such as disability,nursing home admission,decline in quality of life,and mortality.Gaining an understanding of the trajectory of IC and the factors that influence it is of paramount importance for fostering healthy aging.This research is focused on exploring the trajectory of IC among older adults in China and examining the factors that influence it.Methods:This observational longitudinal cohort study leveraged data from the China Health and Retirement Longitudinal Study(CHARLS),which was conducted in the years 2011,2013,and 2015.For the purpose of this analysis,a total of 2,233 participants who were aged 60 and over were included.A Growth Mixture Model(GMM)was utilized to define trajectory categories for IC.Influential factors were ascertained based on the health ecology model,and binary logistic regression analysis was utilized to investigate the factors linked with the different trajectory categories.Results:Two distinct trajectory classes of IC were identified:Class 1,the normal-stable group,encompassed 90.4%of the elderly population,while Class 2,the declining group,made up 9.6%.Advanced age and a history of stroke were found to be significantly associated with Class 2.High scores in activities of daily living(ADL),employment status,receiving primary or junior high school education,and residence in the East or Central regions of China were significantly linked with Class 1.Conclusion:The trajectory of IC among older Chinese adults is marked by its heterogeneity.Advanced age and a history of stroke are significant risk factors for a declining IC trajectory,while higher ADL scores,being employed,receiving primary or junior high school education,and residing in the East or Central regions of China are protective factors associated with a stable IC trajectory.Healthcare institutions must closely monitor IC levels and understand these trajectory patterns to implement personalized and targeted interventions promptly to maintain IC at a healthy level and advocate for healthy aging.展开更多
Fig(Ficus carica L.)with purple-red peel cultivars are popular among consumers and exhibit better storability.While DNA methylation influences fruit ripening and color development,its specific role in fig fruit remain...Fig(Ficus carica L.)with purple-red peel cultivars are popular among consumers and exhibit better storability.While DNA methylation influences fruit ripening and color development,its specific role in fig fruit remains unclear.This study explores the impact of DNA methylation on the fig peel coloration.Enzymatic colorimetric detection revealed that the level of‘Purple Peel’fig DNA methylation decreases with fig fruit ripening and coloring.Treatment of young fruit with the DNA-methylation inhibitor azacytidine induced peel coloration,suggesting that a decrease in DNA-methylation level promotes fig peel coloration.Seven members of DNA methyltransferases and three members of DNA demethylases were identified from a high-level fig genome,highlighting FcMET1 and FcDRM2 as stable proteins,ensuring functional expression.Reference to the Arabidopsis protein interaction network map predicted that FcMET1 is in a central position,suggesting a crucial regulatory role in multiple biological processes.Correlation analysis revealed a positive correlation between FcMET1 expression during peel development and the level of total DNA methylation.Weighted gene co-expression network analysis identified co-expression of FcMET1 with the color-related transcription factors MYB,bHLH and WD40,as well as with eight structural genes in the flavonoid-biosynthesis pathway.The expression of FcUFGT3 was negatively correlated with that of FcMET1.McrBC-PCR and Bisulfite Sequencing detection showed that a low methylation level of the FcUFGT3 promoter corresponds with its high expression in colored fig.This investigation of the mechanism of DNA methylation provides a theoretical basis for understanding the role of DNA-methylation modifications in fig ripening and coloring.展开更多
This paper provides a systematic review of the histochemical localization,content characteristics,and influencing factors of saponins in Pseudostellaria heterophylla based on an extensive literature survey.It provides...This paper provides a systematic review of the histochemical localization,content characteristics,and influencing factors of saponins in Pseudostellaria heterophylla based on an extensive literature survey.It provides an in-depth analysis and summary of the effects of biological factors,environmental conditions,agronomic practices,processing methods,and continuous cropping obstacles on the synthesis of P.heterophylla saponins,as well as their underlying mechanisms.Based on identified gaps in the current literature,future research directions and prospects are proposed.The findings of this review offer valuable insights for advancing the understanding of the saponin biosynthesis mechanisms in P.heterophylla and for enhancing its quality.展开更多
The discharge of micro-polluted water from sources such as agricultural runoff,urban stormwater,and treated effluents presents significant challenges to aquatic ecosystems.Constructed wetlands(CWs)have gained recog-ni...The discharge of micro-polluted water from sources such as agricultural runoff,urban stormwater,and treated effluents presents significant challenges to aquatic ecosystems.Constructed wetlands(CWs)have gained recog-nition as an eco-friendly solution for removing pollutants from various wastewater sources and are increasingly applied for micro-polluted water treatment.By reviewing 78 full-scale CW studies from Web of Science,it is summarized that the ranges of ammonium nitrogen(NH4+-N)concentrations in runoff,wastewater treatment plant effluent and polluted river were 0.1–6.6,0.3–12.3,and 0.2–41.1 mg/L,respectively.The ranges of ni-trate nitrogen concentrations were 0.2–14.2,0–5.7,and 0–2.6 mg/L,respectively.Removal efficiencies of CWs for micro-polluted water varied by CW types.The total nitrogen removal efficiencies for subsurface-flow CWs,free-water surface-flow CWs,and hybrid CWs ranged from 27.4%to 66.5%,16.8%to 89.8%,and 19.4%to 88.2%,respectively.The NH4+-N removal efficiencies ranged from 34.2%to 73.6%,38.4%to 89.4%and 13.5%to 94.2%,respectively.Additionally,other factors influencing contaminant removal efficiency such as hydraulic retention time,vegetation types,redox micro-environment and influent water quality were evaluated.Based on these findings,two strategies for improving the purification performance of CWs were proposed:the selection of incorporating electron donor substrates and the optimization of operation parameters.This paper serves as a synthesis of information to guide future research and full-scale CW applications in micro-polluted water treatment.展开更多
BACKGROUND Lumbar interbody fusion(LIF)is the primary treatment for lumbar degenerative diseases.Elderly patients are prone to anxiety and depression after undergoing surgery,which affects their postoperative recovery...BACKGROUND Lumbar interbody fusion(LIF)is the primary treatment for lumbar degenerative diseases.Elderly patients are prone to anxiety and depression after undergoing surgery,which affects their postoperative recovery speed and quality of life.Effective prevention of anxiety and depression in elderly patients has become an urgent problem.AIM To investigate the trajectory of anxiety and depression levels in elderly patients after LIF,and the influencing factors.METHODS Random sampling was used to select 239 elderly patients who underwent LIF from January 2020 to December 2024 in Shenzhen Pingle Orthopedic Hospital.General information and surgery-related indices were recorded,and participants completed measures of psychological status,lumbar spine dysfunction,and quality of life.A latent class growth model was used to analyze the post-LIF trajectory of anxiety and depression levels,and unordered multi-categorical logistic regression was used to analyze the influencing factors.RESULTS Three trajectories of change in anxiety level were identified:Increasing anxiety(n=26,10.88%),decreasing anxiety(n=27,11.30%),and stable anxiety(n=186,77.82%).Likewise,three trajectories of change in depression level were identified:Increasing depression(n=30,12.55%),decreasing depression(n=26,10.88%),and stable depression(n=183,76.57%).Regression analysis showed that having no partner,female sex,elevated Oswestry dysfunction index(ODI)scores,and reduced 36-Item Short Form Health Survey scores all contributed to increased anxiety levels,whereas female sex,postoperative opioid use,and elevated ODI scores all contributed to increased depression levels.CONCLUSION During clinical observation,combining factors to predict anxiety and depression in post-LIF elderly patients enables timely intervention,quickens recovery,and enhances quality of life.展开更多
Alterations in RNA methylation may affect the initiation and development of Alzheimer’s disease.However,the exact nature of the relationship between RNA methylation and Alzheimer’s disease remains unclear.In this st...Alterations in RNA methylation may affect the initiation and development of Alzheimer’s disease.However,the exact nature of the relationship between RNA methylation and Alzheimer’s disease remains unclear.In this study,RNA methylation levels were analyzed by bulk transcriptomic and single-cell RNA sequencing.The expression levels of RNA methylation regulators were confirmed using molecular biology techniques.Co-expression network analysis was used to identify relevant long non-coding RNAs.Molecular subtypes related to RNA methylation were classified,and variations in clinical characteristics,biological behavior,and immune signatures between subtypes were assessed.Machine learning approaches were applied to identify methylation-associated long non-coding RNAs,which were used to construct a risk model and nomogram for Alzheimer’s disease.Potential therapeutic agents for different risk groups were predicted,and in vitro experiments were conducted to identify key RNA methylation events.Single-cell analysis demonstrated enhanced RNA methylation in patients with Alzheimer’s disease,particularly within T cells,B cells,and NK cells.Quantitative reverse transcription-polymerase chain reaction and western blot confirmed alterations in RNA methylation regulators in neurons treated with amyloid-βoligomers in vitro.This evidence supported the classification of patients with Alzheimer’s disease into heterogeneous subtypes.Specifically,subtype 1 was identified as the immune-active subtype,while subtype 2 was characterized by a metabolic phenotype.Machine learning algorithms identified five significant methylation-associated long non-coding RNAs-LINC01007,MAP4K3-DT,MIR302CHG,VAC14-AS1,and TGFB2-OT1-that accurately predict clinical outcomes for patients with Alzheimer’s disease.These patients were classified into low-and high-risk categories;the latter group displayed higher immune infiltration,upregulated immune regulatory gene expression,and elevated immune scores and responded better to treatment with arachidonic-trifluoroethane.These findings suggest that dysregulated RNA methylation alters the immune microenvironment in Alzheimer’s disease and is closely associated with its progression.This phenomenon provides novel insights into potential therapeutic strategies for Alzheimer’s disease that target RNA methylation.展开更多
Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and...Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.展开更多
N^(6)-methyladenosine RNA methylation,an essential post-transcriptional modification,dynamically regulates RNA metabolism and plays a crucial role in neuronal function.Growing evidence suggests that dysregulated N^(6)...N^(6)-methyladenosine RNA methylation,an essential post-transcriptional modification,dynamically regulates RNA metabolism and plays a crucial role in neuronal function.Growing evidence suggests that dysregulated N^(6)-methyladenosine modification contributes to the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and amyotrophic lateral sclerosis.However,the precise mechanisms by which N^(6)-methyladenosine modification influences these conditions remain unclear.This review summarizes the role of m6A modification and its associated regulators in neurodegeneration,focusing on their involvement in key pathological processes.In Alzheimer’s disease,m6A modification contributes to synaptic dysfunction,mitochondrial damage,and neuronal apoptosis.Evidence from APP/PS1,5xFAD,tau transgenic,and Drosophila models demonstrates that regulators such as methyltransferase-like 3 and fat mass and obesity-associated protein influence Alzheimer’s disease progression through neuroinflammation,circular RNAs dysregulation,and autophagy-related mechanisms.In Parkinson’s disease,altered N^(6)-methyladenosine regulator expression affects dopaminergic neuron survival and stress responses by modulating mRNA stability and autophagy-related lncRNAs.In multiple sclerosis and amyotrophic lateral sclerosis,N^(6)-methyladenosine affects immune activation,myelin repair,and the regulation of disease-associated genes such as TDP-43.Beyond N^(6)-methyladenosine,other RNA methylation modifications-such as m1A,m5C,m7G,uracil,and pseudouridine-are implicated in neurodegenerative diseases through their regulation of mitochondrial function,RNA metabolism,and neuronal stress responses.Additionally,N^(6)-methyladenosine exhibits cell type-specific functions:in microglia,it regulates inflammatory activation and phagocytic function;in astrocytes,it modulates metabolic homeostasis and glutamate-associated neurotoxicity;in neurons,it affects synaptic function and neurodegeneration-related gene expression;and in adult neural stem cells,it controls differentiation,neurogenesis,and cognitive plasticity.Recently,several small-molecule inhibitors targeting methyltransferase-like 3 or fat mass and obesity-associated protein have been developed to modulate N^(6)-methyladenosine modification,providing new opportunities for disease intervention,with the targeting of N⁶-methyladenosine-related pathways emerging as a promising therapeutic strategy.However,challenges persist in optimizing the specificity and delivery of these therapeutic approaches.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 At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affectin...BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affecting work and interpersonal communication,increasing the risk of recurrence,and adding to the burden on families.Studying the influencing factors of their social function is of great significance.AIM To explore the social function score and its influencing factors in patients with residual depressive symptoms.METHODS This observational study surveyed patients with residual depressive symptoms(case group)and healthy patients undergoing physical examinations(control group).Participants were admitted between January 2022 and December 2023.Social functioning was assessed using the Sheehan Disability Scale(SDS),and scores were compared between groups.Factors influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve,and these RESULTS The SDS scores of the 158 patients with depressive symptoms were 11.48±3.26.Compared with the control group,the SDS scores and all items in the case group were higher.SDS scores were higher in patients with relapse,discon-tinuous medication,drug therapy alone,severe somatic symptoms,obvious residual symptoms,and anxiety scores≥8.Disease history,medication compliance,therapy method,and residual symptoms correlated positively with SDS scores(r=0.354,0.414,0.602,and 0.456,respectively).Independent influencing factors included disease history,medication compliance,therapy method,somatic symptoms,residual symptoms,and anxiety scores(P<0.05).The areas under the curve for predicting social functional impairment using these factors were 0.713,0.559,0.684,0.729,0.668,and 0.628,respectively,with sensitivities of 79.2%,61.8%,76.8%,81.7%,63.6%,and 65.5%and specificities of 83.3%,87.5%,82.6%,83.3%,86.7%,and 92.1%,respectively.CONCLUSION The social function scores of patients with residual symptoms of depression are high.They are affected by disease history,medication compliance,therapy method,degree of somatic symptoms,residual symptoms,and anxiety.展开更多
Water use efficiency(WUE),as a pivotal indicator of the coupling degree within the carbon–water cycle of ecosystems,holds considerable importance in assessment of the carbon–water balance within terrestrial ecosyste...Water use efficiency(WUE),as a pivotal indicator of the coupling degree within the carbon–water cycle of ecosystems,holds considerable importance in assessment of the carbon–water balance within terrestrial ecosystems.However,in the context of global warming,WUE evolution and its primary drivers on the Tibetan Plateau remain unclear.This study employed the ensemble empirical mode decomposition method and the random forest algorithm to decipher the nonlinear trends and drivers of WUE on the Tibetan Plateau in 2001–2020.Results indicated an annual mean WUE of 0.8088 gC/mm·m^(2)across the plateau,with a spatial gradient reflecting decrease from the southeast toward the northwest.Areas manifesting monotonous trends of increase or decrease in WUE accounted for 23.64%and 9.69%of the total,respectively.Remarkably,66.67%of the region exhibited trend reversals,i.e.,39.94%of the area of the Tibetan Plateau showed transition from a trend of increase to a trend of decrease,and 26.73%of the area demonstrated a shift from a trend of decrease to a trend of increase.Environmental factors accounted for 70.79%of the variability in WUE.The leaf area index and temperature served as the major driving forces of WUE variation.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 The development of hepatocellular carcinoma(HCC)is influenced by multiple factors.Interventional therapy offers an effective treatment option for patients with unresectable intermediate-to-advanced HCC.Inte...BACKGROUND The development of hepatocellular carcinoma(HCC)is influenced by multiple factors.Interventional therapy offers an effective treatment option for patients with unresectable intermediate-to-advanced HCC.Interventional therapy can induce electrocardiographic(ECG)abnormalities that may be associated with liver dysfunction,electrolyte disorders,and cardiac injury.AIM To explore the ECG alterations and determinants following interventional therapy in patients with HCC.METHODS Sixty patients undergoing interventional treatment for liver cancer were selected as study participants.According to the results of the dynamic ECG examination 1 day after surgery,the patients were divided into an abnormal group(n=21)and a nonabnormal group(n=39).With the help of dynamic ECG examination,the ECG parameters were compared and the baseline data of patients was recorded in the two groups.RESULTS The 24 hours QT interval variability,24 hours normal atrial polarization to ventricular polarization(R-R)interval(standard deviation),24 hours consecutive 5 minutes normal R-R interval,and 24 hours continuous 5 minutes normal R-R interval(standard deviation mean)were lower than patients in the nonabnormal group(P<0.05).The logistic analysis showed that age>60 years,liver function grade B,and postoperative body temperature 38°C were risk factors for abnormal dynamic electrocardiogram in patients with liver cancer intervention(P<0.05).CONCLUSION Interventional therapy for HCC can lead to ECG abnormalities,underscoring the clinical need for enhanced cardiac monitoring to mitigate myocardial complications.展开更多
BACKGROUND Fear-related disorders,such as post-traumatic stress disorder(PTSD),significantly impact patients and families.Exposure therapy is a common treatment,but imp-roving its effectiveness remains a key challenge...BACKGROUND Fear-related disorders,such as post-traumatic stress disorder(PTSD),significantly impact patients and families.Exposure therapy is a common treatment,but imp-roving its effectiveness remains a key challenge.Fear conditioning and extinction in animal models offer insights into its mechanisms.Our previous research indi-cates that DNA methyltransferases play a role in fear memory renewal.AIM To investigate the role of DNA methylation in the extinction of fear memory,with the goal of identifying potential strategies to enhance the efficacy of exposure therapy for fear-related disorders.METHODS This study investigated the role of DNA methylation in fear memory extinction in mice.DNA methylation was manipulated using N-phthalyl-L-tryptophan(RG108)to reduce methylation and L-methionine injections to enhance it.Neuronal activity,and dendritic spine density was measured following extinction training.RESULTS RG108 suppressed extinction,reduced spine density,and inhibited neuronal activity.Methionine injections facilitated extinction.CONCLUSION DNA methylation is crucial for fear memory extinction.Enhancing methylation may improve the efficacy of exposure therapy,offering a potential strategy to treat fear-related disorders.展开更多
基金Project supported by the University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province(No.UNPYSCT-2017124)。
文摘The development of methylation protocol has attracted intense attention owing to"magic methyl effect"in drug discovery.Meanwhile,the indole scaffold is prevalence in the natural products and pharmacophores.Despite the advances in other site selective methylation,there is scarce reports for C4 methylation of indoles and combination of a carbonyl group rearrangement with C—H methylation on indole ring.Herein,the C4 methylation of indoles and the steric controlled C4-methylation/carbonyl group migration are reported.The large steric hindrance at carbonyl group facilitates the carbonyl group migration,which provides a straightforward protocol for the synthesis of C2/C4 disubstituted indoles.
基金supported by funding from the National Natural Science Foundation of China(81971349 and 81300456).
文摘In vitro maturation(IvM)of human oocytes offers cost efficiency and minimal invasiveness,serving as a valuable supplementary tool in assisted reproduction for fertility preservation,ovarian hyperstimulation syndrome prevention,and other reproductive strategies.Despite its availability for three decades,the clinical use of IVM remains limited due to efficacy and safety concerns.This study examines the DNA methylation profile of IVM oocytes collected during laparoscopic/hysteroscopic surgeries compared to in vivo matured oocytes via reduced representation bisulfite sequencing.Results indicate IVM oocytes exhibit a higher global methylation level.Differentially methylated regions(DMRs)analysis reveals that the in vitro group displays more hypermethylated and fewer hypomethylated DMRs compared to the in vivo group.Additionally,the in vitro group exhibits a higher level of non-CpG methylation than the in vivo group.However,no significant correlation between methylation levels and transcriptional activity in these oocytes is found,especially for those specific imprinted genes or genes related to embryonic development.These findings shed light on the epigenetic landscape of IvM oocytes,contributing to the ongoing assessment of their clinical feasibility and safety in assisted reproduction.
基金financially supported by the Natural Science Foundation of Wuhan City (Chenguang Project) (No.2024040801020331)the Natural Science Foundation of Hubei Province of China (No.2023AFB402)+1 种基金the National Key Research and Development Program of China (No.2023YFE0210200)Interdisciplinary Research Program of HUST。
文摘DNA methylation is an important promising biomarker for cancer diagnosis and monitoring.Therefore,the assessment of DNA methylation levels is helpful for the prognosis and diagnosis of cancer.However,it is still a huge challenge to sensitively and accurately quantify the levels of DNA methylation in clinical sample.In this work,we proposed a protospacer adjacent motif(PAM)-free mediated CRISPR-Cas12a ultra-sensitive and quantitative DNA methylation detection method.Through recognizing the ds DNA with toehold region,CRISPR-Cas12a not only got rid of the limitation of PAM,but also improved its distinction ability for single Cp G site methylation,nearly 5-fold that of conventional PAM-containing ds DNA.We further introduced assist-strand and design an artificial mismatch to greatly improve the ability to distinguish single Cp G methylation site.Our results showed that the discrimination factor was >200.Then,we constructed toe-ds DNA by using “heating and freezing”,which made our method universally applicable and feasible.In addition,we greatly simplified the difficulty of primer design.Our method detected four highly methylated genes acyl carrier protein(ACP),CLV3/ESR-related(CLE),Disabled(DAB) and Homeobox(HOX) with a detection limit of 0.01 % and excellent linearity in DNA methylation standards.Then,we verified the clinical utility of this method in 29 hepatocellular carcinomas,11 ovarian cancers and4 health people.In conclusion,we have successfully constructed a PAM-free CRISPR-Cas12a DNA methylation quantification method,which achieves high congruence in sensitivity,specificity and universality,fully demonstrating its significant clinical application value.
基金funded by the National Natural Science Foundation of China(No.42061012)the Open Project of Yunnan Province’s First Class Discipline of Soil and Water Conservation and Desertification Control(SBK20240019)。
文摘Major chemical ionic components in water serve as indicators of natural factors in the areas traversed by water bodies,and are thus widely used to elucidate key hydrogeochemical processes,including rock weathering,aquatic evaporation-crystallization,and the input of precipitation-derived materials into river basins.A total of 208 water samples were collected between August 2021 and August 2022 to investigate the hydrochemical characteristics and their influencing factors of the surface water and the groundwater in the Mingyong River Basin.To systematically analyze the data,we combined hydrogeochemical and statistical methods:descriptive statistics characterized ion concentration and physicochemical parameter distributions;Piper trilinear diagrams classified hydrochemical types;Pearson correlation analysis assessed ion-ion and ionTDS dependencies;Gibbs diagrams and ion ratio analysis identified solute sources;and the absolute principal component score-multiple linear regression(APCS-MLR)model quantified the contribution rates of different influencing factors.The results revealed that the dominant cations in the surface water and groundwater are Ca^(2+)and Mg^(2+),while the dominant anions are HCO_(3)^(-)and SO_(4)^(2-).The groundwater exhibits an extended residence time within rock strata,facilitating prolonged interaction with soluble minerals and intensifying the water-rock reaction process,thereby resulting in higher levels of electrical conductivity(EC),pH,and total dissolved solids(TDS)than those in the surface water.Secondly,the parameters of the surface water and groundwater indicate positive correlation.The weathering of rocks constitutes the primary solute source in the water of the basin.The hydrochemical composition of the basin water is primarily influenced by both carbonate and silicate rocks,with a minor contribution from evaporite rocks.The water bodies in the basin are affected by anthropogenic activities.The surface water is influenced by four sources,namely lixiviation-enrich,human activities,geological environmental,and unknown sources.The groundwater is influenced by five sources,namely lixiviation-enrich,primary geological,human activities,geological environmental,and unknown sources.
基金China Health and Retirement Longitudinal Study(CHARLS)the 2022-2023 Nursing Research Project of Chinese Medical Association Publishing House(Grant No.CMAPH-NRD2022024)。
文摘Background:The trajectory of intrinsic capacity(IC)among the older population is characterized by its diversity and is predictive of adverse health outcomes such as disability,nursing home admission,decline in quality of life,and mortality.Gaining an understanding of the trajectory of IC and the factors that influence it is of paramount importance for fostering healthy aging.This research is focused on exploring the trajectory of IC among older adults in China and examining the factors that influence it.Methods:This observational longitudinal cohort study leveraged data from the China Health and Retirement Longitudinal Study(CHARLS),which was conducted in the years 2011,2013,and 2015.For the purpose of this analysis,a total of 2,233 participants who were aged 60 and over were included.A Growth Mixture Model(GMM)was utilized to define trajectory categories for IC.Influential factors were ascertained based on the health ecology model,and binary logistic regression analysis was utilized to investigate the factors linked with the different trajectory categories.Results:Two distinct trajectory classes of IC were identified:Class 1,the normal-stable group,encompassed 90.4%of the elderly population,while Class 2,the declining group,made up 9.6%.Advanced age and a history of stroke were found to be significantly associated with Class 2.High scores in activities of daily living(ADL),employment status,receiving primary or junior high school education,and residence in the East or Central regions of China were significantly linked with Class 1.Conclusion:The trajectory of IC among older Chinese adults is marked by its heterogeneity.Advanced age and a history of stroke are significant risk factors for a declining IC trajectory,while higher ADL scores,being employed,receiving primary or junior high school education,and residing in the East or Central regions of China are protective factors associated with a stable IC trajectory.Healthcare institutions must closely monitor IC levels and understand these trajectory patterns to implement personalized and targeted interventions promptly to maintain IC at a healthy level and advocate for healthy aging.
基金supported by 111 Project(Grant No.B17043)China Postdoctoral Science Foundation(Grant No.2022M723425).
文摘Fig(Ficus carica L.)with purple-red peel cultivars are popular among consumers and exhibit better storability.While DNA methylation influences fruit ripening and color development,its specific role in fig fruit remains unclear.This study explores the impact of DNA methylation on the fig peel coloration.Enzymatic colorimetric detection revealed that the level of‘Purple Peel’fig DNA methylation decreases with fig fruit ripening and coloring.Treatment of young fruit with the DNA-methylation inhibitor azacytidine induced peel coloration,suggesting that a decrease in DNA-methylation level promotes fig peel coloration.Seven members of DNA methyltransferases and three members of DNA demethylases were identified from a high-level fig genome,highlighting FcMET1 and FcDRM2 as stable proteins,ensuring functional expression.Reference to the Arabidopsis protein interaction network map predicted that FcMET1 is in a central position,suggesting a crucial regulatory role in multiple biological processes.Correlation analysis revealed a positive correlation between FcMET1 expression during peel development and the level of total DNA methylation.Weighted gene co-expression network analysis identified co-expression of FcMET1 with the color-related transcription factors MYB,bHLH and WD40,as well as with eight structural genes in the flavonoid-biosynthesis pathway.The expression of FcUFGT3 was negatively correlated with that of FcMET1.McrBC-PCR and Bisulfite Sequencing detection showed that a low methylation level of the FcUFGT3 promoter corresponds with its high expression in colored fig.This investigation of the mechanism of DNA methylation provides a theoretical basis for understanding the role of DNA-methylation modifications in fig ripening and coloring.
基金Supported by Open Fund Project of the Engineering Technology Research Center of Characteristic Medicinal Plants of Fujian(PP202003).
文摘This paper provides a systematic review of the histochemical localization,content characteristics,and influencing factors of saponins in Pseudostellaria heterophylla based on an extensive literature survey.It provides an in-depth analysis and summary of the effects of biological factors,environmental conditions,agronomic practices,processing methods,and continuous cropping obstacles on the synthesis of P.heterophylla saponins,as well as their underlying mechanisms.Based on identified gaps in the current literature,future research directions and prospects are proposed.The findings of this review offer valuable insights for advancing the understanding of the saponin biosynthesis mechanisms in P.heterophylla and for enhancing its quality.
基金supported by the Natural Science Foundation of China(No.52470105)the Young Taishan Scholars Program of Shandong Province(No.358202103017).
文摘The discharge of micro-polluted water from sources such as agricultural runoff,urban stormwater,and treated effluents presents significant challenges to aquatic ecosystems.Constructed wetlands(CWs)have gained recog-nition as an eco-friendly solution for removing pollutants from various wastewater sources and are increasingly applied for micro-polluted water treatment.By reviewing 78 full-scale CW studies from Web of Science,it is summarized that the ranges of ammonium nitrogen(NH4+-N)concentrations in runoff,wastewater treatment plant effluent and polluted river were 0.1–6.6,0.3–12.3,and 0.2–41.1 mg/L,respectively.The ranges of ni-trate nitrogen concentrations were 0.2–14.2,0–5.7,and 0–2.6 mg/L,respectively.Removal efficiencies of CWs for micro-polluted water varied by CW types.The total nitrogen removal efficiencies for subsurface-flow CWs,free-water surface-flow CWs,and hybrid CWs ranged from 27.4%to 66.5%,16.8%to 89.8%,and 19.4%to 88.2%,respectively.The NH4+-N removal efficiencies ranged from 34.2%to 73.6%,38.4%to 89.4%and 13.5%to 94.2%,respectively.Additionally,other factors influencing contaminant removal efficiency such as hydraulic retention time,vegetation types,redox micro-environment and influent water quality were evaluated.Based on these findings,two strategies for improving the purification performance of CWs were proposed:the selection of incorporating electron donor substrates and the optimization of operation parameters.This paper serves as a synthesis of information to guide future research and full-scale CW applications in micro-polluted water treatment.
基金Supported by the Scientific Research Projects of the Health System in Pingshan District,No.2023122.
文摘BACKGROUND Lumbar interbody fusion(LIF)is the primary treatment for lumbar degenerative diseases.Elderly patients are prone to anxiety and depression after undergoing surgery,which affects their postoperative recovery speed and quality of life.Effective prevention of anxiety and depression in elderly patients has become an urgent problem.AIM To investigate the trajectory of anxiety and depression levels in elderly patients after LIF,and the influencing factors.METHODS Random sampling was used to select 239 elderly patients who underwent LIF from January 2020 to December 2024 in Shenzhen Pingle Orthopedic Hospital.General information and surgery-related indices were recorded,and participants completed measures of psychological status,lumbar spine dysfunction,and quality of life.A latent class growth model was used to analyze the post-LIF trajectory of anxiety and depression levels,and unordered multi-categorical logistic regression was used to analyze the influencing factors.RESULTS Three trajectories of change in anxiety level were identified:Increasing anxiety(n=26,10.88%),decreasing anxiety(n=27,11.30%),and stable anxiety(n=186,77.82%).Likewise,three trajectories of change in depression level were identified:Increasing depression(n=30,12.55%),decreasing depression(n=26,10.88%),and stable depression(n=183,76.57%).Regression analysis showed that having no partner,female sex,elevated Oswestry dysfunction index(ODI)scores,and reduced 36-Item Short Form Health Survey scores all contributed to increased anxiety levels,whereas female sex,postoperative opioid use,and elevated ODI scores all contributed to increased depression levels.CONCLUSION During clinical observation,combining factors to predict anxiety and depression in post-LIF elderly patients enables timely intervention,quickens recovery,and enhances quality of life.
基金supported by the Elderly Health Research Project of Jiangsu Province,No.LKM2023043(to XZ).
文摘Alterations in RNA methylation may affect the initiation and development of Alzheimer’s disease.However,the exact nature of the relationship between RNA methylation and Alzheimer’s disease remains unclear.In this study,RNA methylation levels were analyzed by bulk transcriptomic and single-cell RNA sequencing.The expression levels of RNA methylation regulators were confirmed using molecular biology techniques.Co-expression network analysis was used to identify relevant long non-coding RNAs.Molecular subtypes related to RNA methylation were classified,and variations in clinical characteristics,biological behavior,and immune signatures between subtypes were assessed.Machine learning approaches were applied to identify methylation-associated long non-coding RNAs,which were used to construct a risk model and nomogram for Alzheimer’s disease.Potential therapeutic agents for different risk groups were predicted,and in vitro experiments were conducted to identify key RNA methylation events.Single-cell analysis demonstrated enhanced RNA methylation in patients with Alzheimer’s disease,particularly within T cells,B cells,and NK cells.Quantitative reverse transcription-polymerase chain reaction and western blot confirmed alterations in RNA methylation regulators in neurons treated with amyloid-βoligomers in vitro.This evidence supported the classification of patients with Alzheimer’s disease into heterogeneous subtypes.Specifically,subtype 1 was identified as the immune-active subtype,while subtype 2 was characterized by a metabolic phenotype.Machine learning algorithms identified five significant methylation-associated long non-coding RNAs-LINC01007,MAP4K3-DT,MIR302CHG,VAC14-AS1,and TGFB2-OT1-that accurately predict clinical outcomes for patients with Alzheimer’s disease.These patients were classified into low-and high-risk categories;the latter group displayed higher immune infiltration,upregulated immune regulatory gene expression,and elevated immune scores and responded better to treatment with arachidonic-trifluoroethane.These findings suggest that dysregulated RNA methylation alters the immune microenvironment in Alzheimer’s disease and is closely associated with its progression.This phenomenon provides novel insights into potential therapeutic strategies for Alzheimer’s disease that target RNA methylation.
基金supported by the National Natural Science Foundation of China(82574173,82003516)Jiangsu Provincial Natural Science Foundation(BK20251958)+2 种基金Jiangsu Provincial Medical Key Discipline(ZDXK202250)Top Talent Awards Project Fund(RDF-TP-0023,RDF-TP-0030)Postgraduate Research Fund(PGRS2112022)at Xi'an Jiaotong-Liverpool University.
文摘Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.
基金supported by the National Nature Science Foundation of China(General Program),Nos.82271237,82071218(both to JC),and 82230042(to ZY)the Foundation of Key Laboratory of Neurology,Hebei Medical University,Ministry of Education,China,No.2023001(to JC).
文摘N^(6)-methyladenosine RNA methylation,an essential post-transcriptional modification,dynamically regulates RNA metabolism and plays a crucial role in neuronal function.Growing evidence suggests that dysregulated N^(6)-methyladenosine modification contributes to the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,and amyotrophic lateral sclerosis.However,the precise mechanisms by which N^(6)-methyladenosine modification influences these conditions remain unclear.This review summarizes the role of m6A modification and its associated regulators in neurodegeneration,focusing on their involvement in key pathological processes.In Alzheimer’s disease,m6A modification contributes to synaptic dysfunction,mitochondrial damage,and neuronal apoptosis.Evidence from APP/PS1,5xFAD,tau transgenic,and Drosophila models demonstrates that regulators such as methyltransferase-like 3 and fat mass and obesity-associated protein influence Alzheimer’s disease progression through neuroinflammation,circular RNAs dysregulation,and autophagy-related mechanisms.In Parkinson’s disease,altered N^(6)-methyladenosine regulator expression affects dopaminergic neuron survival and stress responses by modulating mRNA stability and autophagy-related lncRNAs.In multiple sclerosis and amyotrophic lateral sclerosis,N^(6)-methyladenosine affects immune activation,myelin repair,and the regulation of disease-associated genes such as TDP-43.Beyond N^(6)-methyladenosine,other RNA methylation modifications-such as m1A,m5C,m7G,uracil,and pseudouridine-are implicated in neurodegenerative diseases through their regulation of mitochondrial function,RNA metabolism,and neuronal stress responses.Additionally,N^(6)-methyladenosine exhibits cell type-specific functions:in microglia,it regulates inflammatory activation and phagocytic function;in astrocytes,it modulates metabolic homeostasis and glutamate-associated neurotoxicity;in neurons,it affects synaptic function and neurodegeneration-related gene expression;and in adult neural stem cells,it controls differentiation,neurogenesis,and cognitive plasticity.Recently,several small-molecule inhibitors targeting methyltransferase-like 3 or fat mass and obesity-associated protein have been developed to modulate N^(6)-methyladenosine modification,providing new opportunities for disease intervention,with the targeting of N⁶-methyladenosine-related pathways emerging as a promising therapeutic strategy.However,challenges persist in optimizing the specificity and delivery of these therapeutic approaches.
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.
文摘BACKGROUND At present,the influencing factors of social function in patients with residual depressive symptoms are still unclear.Residual depressive symptoms are highly harmful,leading to low mood in patients,affecting work and interpersonal communication,increasing the risk of recurrence,and adding to the burden on families.Studying the influencing factors of their social function is of great significance.AIM To explore the social function score and its influencing factors in patients with residual depressive symptoms.METHODS This observational study surveyed patients with residual depressive symptoms(case group)and healthy patients undergoing physical examinations(control group).Participants were admitted between January 2022 and December 2023.Social functioning was assessed using the Sheehan Disability Scale(SDS),and scores were compared between groups.Factors influencing SDS scores in patients with residual depressive symptoms were analyzed by applying multiple linear regression while using the receiver operating characteristic curve,and these RESULTS The SDS scores of the 158 patients with depressive symptoms were 11.48±3.26.Compared with the control group,the SDS scores and all items in the case group were higher.SDS scores were higher in patients with relapse,discon-tinuous medication,drug therapy alone,severe somatic symptoms,obvious residual symptoms,and anxiety scores≥8.Disease history,medication compliance,therapy method,and residual symptoms correlated positively with SDS scores(r=0.354,0.414,0.602,and 0.456,respectively).Independent influencing factors included disease history,medication compliance,therapy method,somatic symptoms,residual symptoms,and anxiety scores(P<0.05).The areas under the curve for predicting social functional impairment using these factors were 0.713,0.559,0.684,0.729,0.668,and 0.628,respectively,with sensitivities of 79.2%,61.8%,76.8%,81.7%,63.6%,and 65.5%and specificities of 83.3%,87.5%,82.6%,83.3%,86.7%,and 92.1%,respectively.CONCLUSION The social function scores of patients with residual symptoms of depression are high.They are affected by disease history,medication compliance,therapy method,degree of somatic symptoms,residual symptoms,and anxiety.
基金National Nonprofit Institute Research Grant of CAF,No.CAFYBB2018ZA004,No.CAFYBB2023ZA009Fengyun Application Pioneering Project,No.FY-APP-ZX-2023.02。
文摘Water use efficiency(WUE),as a pivotal indicator of the coupling degree within the carbon–water cycle of ecosystems,holds considerable importance in assessment of the carbon–water balance within terrestrial ecosystems.However,in the context of global warming,WUE evolution and its primary drivers on the Tibetan Plateau remain unclear.This study employed the ensemble empirical mode decomposition method and the random forest algorithm to decipher the nonlinear trends and drivers of WUE on the Tibetan Plateau in 2001–2020.Results indicated an annual mean WUE of 0.8088 gC/mm·m^(2)across the plateau,with a spatial gradient reflecting decrease from the southeast toward the northwest.Areas manifesting monotonous trends of increase or decrease in WUE accounted for 23.64%and 9.69%of the total,respectively.Remarkably,66.67%of the region exhibited trend reversals,i.e.,39.94%of the area of the Tibetan Plateau showed transition from a trend of increase to a trend of decrease,and 26.73%of the area demonstrated a shift from a trend of decrease to a trend of increase.Environmental factors accounted for 70.79%of the variability in WUE.The leaf area index and temperature served as the major driving forces of WUE variation.
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.
文摘BACKGROUND The development of hepatocellular carcinoma(HCC)is influenced by multiple factors.Interventional therapy offers an effective treatment option for patients with unresectable intermediate-to-advanced HCC.Interventional therapy can induce electrocardiographic(ECG)abnormalities that may be associated with liver dysfunction,electrolyte disorders,and cardiac injury.AIM To explore the ECG alterations and determinants following interventional therapy in patients with HCC.METHODS Sixty patients undergoing interventional treatment for liver cancer were selected as study participants.According to the results of the dynamic ECG examination 1 day after surgery,the patients were divided into an abnormal group(n=21)and a nonabnormal group(n=39).With the help of dynamic ECG examination,the ECG parameters were compared and the baseline data of patients was recorded in the two groups.RESULTS The 24 hours QT interval variability,24 hours normal atrial polarization to ventricular polarization(R-R)interval(standard deviation),24 hours consecutive 5 minutes normal R-R interval,and 24 hours continuous 5 minutes normal R-R interval(standard deviation mean)were lower than patients in the nonabnormal group(P<0.05).The logistic analysis showed that age>60 years,liver function grade B,and postoperative body temperature 38°C were risk factors for abnormal dynamic electrocardiogram in patients with liver cancer intervention(P<0.05).CONCLUSION Interventional therapy for HCC can lead to ECG abnormalities,underscoring the clinical need for enhanced cardiac monitoring to mitigate myocardial complications.
基金Supported by National Natural Science Foundation of China,No.82360231Yunnan Basic Research Program General Project,No.202401AT070075+1 种基金Dali Basic Research Program Key Project,No.202301A020021Youth Special Project for Basic Research of Local Universities in Yunnan Province,No.202301BA070001-127.
文摘BACKGROUND Fear-related disorders,such as post-traumatic stress disorder(PTSD),significantly impact patients and families.Exposure therapy is a common treatment,but imp-roving its effectiveness remains a key challenge.Fear conditioning and extinction in animal models offer insights into its mechanisms.Our previous research indi-cates that DNA methyltransferases play a role in fear memory renewal.AIM To investigate the role of DNA methylation in the extinction of fear memory,with the goal of identifying potential strategies to enhance the efficacy of exposure therapy for fear-related disorders.METHODS This study investigated the role of DNA methylation in fear memory extinction in mice.DNA methylation was manipulated using N-phthalyl-L-tryptophan(RG108)to reduce methylation and L-methionine injections to enhance it.Neuronal activity,and dendritic spine density was measured following extinction training.RESULTS RG108 suppressed extinction,reduced spine density,and inhibited neuronal activity.Methionine injections facilitated extinction.CONCLUSION DNA methylation is crucial for fear memory extinction.Enhancing methylation may improve the efficacy of exposure therapy,offering a potential strategy to treat fear-related disorders.
