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
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
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
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
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
Objective Accurately identifying the key influencing factors of psychological birth trauma in primiparous women is crucial for implementing effective preventive and intervention measures.This study aimed to develop an...Objective Accurately identifying the key influencing factors of psychological birth trauma in primiparous women is crucial for implementing effective preventive and intervention measures.This study aimed to develop and validate an interpretable machine learning prediction model for identifying the key influencing factors of psychological birth trauma in primiparous women.Methods A multicenter cross-sectional study was conducted on primiparous women in four tertiary hospitals in Sichuan Province,southwestern China,from December 2023 to March 2024.The Childbirth Trauma Index was used in assessing psychological birth trauma in primiparous women.Data were collected and randomly divided into a training set(80%,n=289)and a testing set(20%,n=73).Six different machine learning models were trained and tested.Training and prediction were conducted using six machine learning models included Linear Regression,Support Vector Regression,Multilayer Perceptron Regression,eXtreme Gradient Boosting Regression,Random Forest Regression,and Adaptive Boosting Regression.The optimal model was selected based on various performance metrics,and its predictive results were interpreted using SHapley Additive exPlanations(SHAP)and accumulated local effects(ALE).Results Among the six machine learning models,the Multilayer Perceptron Regression model exhibited the best overall performance in the testing set(MAE=3.977,MSE=24.832,R2=0.507,EVS=0.524,RMSE=4.983).In the testing set,the R2 and EVS of the Multilayer Perceptron Regression model increased by 8.3%and 1.2%,respectively,compared to the traditional linear regression model.Meanwhile,the MAE,MSE,and RMSE decreased by 0.4%,7.3%,and 3.7%,respectively,compared to the traditional linear regression model.The SHAP analysis indicated that intrapartum pain,anxiety,postpartum pain,resilience,and planned pregnancy are the most critical influencing factors of psychological birth trauma in primiparous women.The ALE analysis indicated that higher intrapartum pain,anxiety,and postpartum pain scores are risk factors,while higher resilience scores are protective factors.Conclusions Interpretable machine learning prediction models can identify the key influencing factors of psychological birth trauma in primiparous women.SHAP and ALE analyses based on the Multilayer Perceptron Regression model can help healthcare providers understand the complex decision-making logic within a prediction model.This study provides a scientific basis for the early prevention and personalized intervention of psychological birth trauma in primiparous women.展开更多
BACKGROUND Patients with middle and advanced hepatocellular carcinoma(HCC)frequently experience significant anxiety and depression,severely affecting their quality of life.AIM To examine the anxiety and depression sta...BACKGROUND Patients with middle and advanced hepatocellular carcinoma(HCC)frequently experience significant anxiety and depression,severely affecting their quality of life.AIM To examine the anxiety and depression status of patients with middle and advanced HCC,the influencing factors,and the correlation between these psychological factors and quality of life.METHODS We collected baseline data from 100 patients with HCC,assessing anxiety and depression levels using the Hamilton Anxiety Rating Scale(HAMA)and Hamilton Depression Rating Scale(HAMD).Quality of life was evaluated with the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire.Multivariate logistic regression analyzed clinical and psychosocial factors affecting anxiety and depression,while Pearson correlation assessed relationships among HAMA,HAMD,and Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire scores.RESULTS Results indicated that 64%of patients exhibited anxiety and 65%showed depression symptoms.Key influencing factors included Barcelona Clinic Liver Cancer C stage,multiple tumors,social support,prior treatments(such as liver resection and transcatheter arterial chemoembolization/hepatic artery infusion chemotherapy),as well as HAMA and HAMD scores.Anxiety and depression correlated negatively with quality of life,with coefficients of-0.671 and-0.575 for HAMA and HAMD,respectively.CONCLUSION Anxiety and depression are prevalent among patients with middle and advanced HCC,impacting quality of life.This underscores the need for psychological health considerations in liver cancer treatment and establishing psychological interventions is essential.展开更多
Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This s...Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This study demonstrates that tenacissoside I(TI),a compound isolated from Marsdenia tenacissima(Roxb.)Wight et Arn,traditionally used in clinical practice as an ethnic medicine for cancer treatment,exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells.TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin(DOX)and paclitaxel(PAC)by downregulating ABCB1 expression and reducing ABCB1 drug transport function.Mechanistically,protein arginine methyltransferase 1(PRMT1),whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues,was differentially expressed in TI-treated SW620/AD300 cells.SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine(aDMA)and enhanced PRMT1-EGFR interaction compared to their parental cells.Moreover,TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR,PRMT1-EGFR interaction,and EGFR downstream signaling in SW620/AD300 and KBV200 cells.These effects were significantly reversed by PRMT1 overexpression.Additionally,TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities.This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR,suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.展开更多
Cross-border e-commerce,as a new form of international trade,has shown great development potential in the context of the“Belt and Road”initiative.Based on the cross-border e-commerce export data from 2015 to 2024,th...Cross-border e-commerce,as a new form of international trade,has shown great development potential in the context of the“Belt and Road”initiative.Based on the cross-border e-commerce export data from 2015 to 2024,this paper analyzes the influencing factors of China's cross-border e-commerce exports to countries along the“Belt and Road”by constructing an econometric model.The study found that factors such as the perfection of digital infrastructure,the efficiency of logistics and transportation,the convenience of payment and settlement,and the penetration rate of consumers online shopping significantly affect the export scale of cross-border e-commerce.Institutional factors such as the development level of e-commerce platforms in countries along the route,market access thresholds,and tariff policies also play an important role.Based on the research results,suggestions are put forward to strengthen the construction of cross-border payment system,optimize the logistics distribution network,promote customs clearance facilitation,and deepen cooperation in the field of e-commerce,to provide references for promoting the development of China's crossborder e-commerce exports to countries along the“Belt and Road.”展开更多
BACKGROUND China has recently encountered severe challenges associated with population aging.Parents of first-generation only children face significant challenges regarding elderly care needs and the associated negati...BACKGROUND China has recently encountered severe challenges associated with population aging.Parents of first-generation only children face significant challenges regarding elderly care needs and the associated negative emotions.AIM To analyze the elderly care needs of first-generation only child parents in China and identify factors that influence negative emotions.METHODS This study used a cross-sectional design.Convenience sampling was used to select 1580 elderly individuals who met the inclusion criteria in a Chinese city between June and September 2022.A questionnaire was administered to collect general information about participants.Depression and anxiety were assessed using the patient health questionnaire-9 and generalized anxiety disorder-7 scale,respectively.A logistic regression analysis was performed to evaluate the relevant correlations.RESULTS Among 1580 first-generation only child parents,1120(70.89%)preferred family based care,324(20.51%)opted for community care,and 136(8.61%)chose institutional care,with 460(29.11%)reporting negative emotions.Significant differences in the distribution of negative emotions among only child parents were observed based on age,marital status,living conditions,disability,type of chronic disease,frailty status,and family support(P<0.05).The regression analysis indicated that disability,type of chronic disease,living environment,frailty status,and level of family support were independent risk factors for negative emotions among parents with only children(P<0.05).CONCLUSION Elderly care for parents of only children is primarily family-based.Independent risk factors for negative emotions in this group include disability,chronic disease type,and living environment.展开更多
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 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 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.
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.
基金supported by the Sichuan Province Nursing Scientific Research Project Plan(H23022)the 2022 Municipal-University Science and Technology Strategic Cooperation Special Fund of Nanchong Science and Technology Bureau(22SXQT0222)。
文摘Objective Accurately identifying the key influencing factors of psychological birth trauma in primiparous women is crucial for implementing effective preventive and intervention measures.This study aimed to develop and validate an interpretable machine learning prediction model for identifying the key influencing factors of psychological birth trauma in primiparous women.Methods A multicenter cross-sectional study was conducted on primiparous women in four tertiary hospitals in Sichuan Province,southwestern China,from December 2023 to March 2024.The Childbirth Trauma Index was used in assessing psychological birth trauma in primiparous women.Data were collected and randomly divided into a training set(80%,n=289)and a testing set(20%,n=73).Six different machine learning models were trained and tested.Training and prediction were conducted using six machine learning models included Linear Regression,Support Vector Regression,Multilayer Perceptron Regression,eXtreme Gradient Boosting Regression,Random Forest Regression,and Adaptive Boosting Regression.The optimal model was selected based on various performance metrics,and its predictive results were interpreted using SHapley Additive exPlanations(SHAP)and accumulated local effects(ALE).Results Among the six machine learning models,the Multilayer Perceptron Regression model exhibited the best overall performance in the testing set(MAE=3.977,MSE=24.832,R2=0.507,EVS=0.524,RMSE=4.983).In the testing set,the R2 and EVS of the Multilayer Perceptron Regression model increased by 8.3%and 1.2%,respectively,compared to the traditional linear regression model.Meanwhile,the MAE,MSE,and RMSE decreased by 0.4%,7.3%,and 3.7%,respectively,compared to the traditional linear regression model.The SHAP analysis indicated that intrapartum pain,anxiety,postpartum pain,resilience,and planned pregnancy are the most critical influencing factors of psychological birth trauma in primiparous women.The ALE analysis indicated that higher intrapartum pain,anxiety,and postpartum pain scores are risk factors,while higher resilience scores are protective factors.Conclusions Interpretable machine learning prediction models can identify the key influencing factors of psychological birth trauma in primiparous women.SHAP and ALE analyses based on the Multilayer Perceptron Regression model can help healthcare providers understand the complex decision-making logic within a prediction model.This study provides a scientific basis for the early prevention and personalized intervention of psychological birth trauma in primiparous women.
文摘BACKGROUND Patients with middle and advanced hepatocellular carcinoma(HCC)frequently experience significant anxiety and depression,severely affecting their quality of life.AIM To examine the anxiety and depression status of patients with middle and advanced HCC,the influencing factors,and the correlation between these psychological factors and quality of life.METHODS We collected baseline data from 100 patients with HCC,assessing anxiety and depression levels using the Hamilton Anxiety Rating Scale(HAMA)and Hamilton Depression Rating Scale(HAMD).Quality of life was evaluated with the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire.Multivariate logistic regression analyzed clinical and psychosocial factors affecting anxiety and depression,while Pearson correlation assessed relationships among HAMA,HAMD,and Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire scores.RESULTS Results indicated that 64%of patients exhibited anxiety and 65%showed depression symptoms.Key influencing factors included Barcelona Clinic Liver Cancer C stage,multiple tumors,social support,prior treatments(such as liver resection and transcatheter arterial chemoembolization/hepatic artery infusion chemotherapy),as well as HAMA and HAMD scores.Anxiety and depression correlated negatively with quality of life,with coefficients of-0.671 and-0.575 for HAMA and HAMD,respectively.CONCLUSION Anxiety and depression are prevalent among patients with middle and advanced HCC,impacting quality of life.This underscores the need for psychological health considerations in liver cancer treatment and establishing psychological interventions is essential.
基金supported by the National Natural Science Foundation of China(Nos.82274211 and 82474190)the Natural Science Foundation of Tianjin(Nos.24JCZDJC00120 and 24PTLYHZ00280)Liaoning Provincial Department of Education Basic Research Projects for Higher Education Institutions(No.LJ212510163021)。
文摘Cancer multidrug resistance(MDR)impairs the therapeutic efficacy of various chemotherapeutics.Novel approaches,particularly the development of MDR reversal agents,are critically needed to address this challenge.This study demonstrates that tenacissoside I(TI),a compound isolated from Marsdenia tenacissima(Roxb.)Wight et Arn,traditionally used in clinical practice as an ethnic medicine for cancer treatment,exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells.TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin(DOX)and paclitaxel(PAC)by downregulating ABCB1 expression and reducing ABCB1 drug transport function.Mechanistically,protein arginine methyltransferase 1(PRMT1),whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues,was differentially expressed in TI-treated SW620/AD300 cells.SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine(aDMA)and enhanced PRMT1-EGFR interaction compared to their parental cells.Moreover,TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR,PRMT1-EGFR interaction,and EGFR downstream signaling in SW620/AD300 and KBV200 cells.These effects were significantly reversed by PRMT1 overexpression.Additionally,TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities.This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR,suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
文摘Cross-border e-commerce,as a new form of international trade,has shown great development potential in the context of the“Belt and Road”initiative.Based on the cross-border e-commerce export data from 2015 to 2024,this paper analyzes the influencing factors of China's cross-border e-commerce exports to countries along the“Belt and Road”by constructing an econometric model.The study found that factors such as the perfection of digital infrastructure,the efficiency of logistics and transportation,the convenience of payment and settlement,and the penetration rate of consumers online shopping significantly affect the export scale of cross-border e-commerce.Institutional factors such as the development level of e-commerce platforms in countries along the route,market access thresholds,and tariff policies also play an important role.Based on the research results,suggestions are put forward to strengthen the construction of cross-border payment system,optimize the logistics distribution network,promote customs clearance facilitation,and deepen cooperation in the field of e-commerce,to provide references for promoting the development of China's crossborder e-commerce exports to countries along the“Belt and Road.”
基金Supported by General Projects of Henan Province Universities Humanities and Social Sciences Research in 2023,No.2023-ZDJH-533.
文摘BACKGROUND China has recently encountered severe challenges associated with population aging.Parents of first-generation only children face significant challenges regarding elderly care needs and the associated negative emotions.AIM To analyze the elderly care needs of first-generation only child parents in China and identify factors that influence negative emotions.METHODS This study used a cross-sectional design.Convenience sampling was used to select 1580 elderly individuals who met the inclusion criteria in a Chinese city between June and September 2022.A questionnaire was administered to collect general information about participants.Depression and anxiety were assessed using the patient health questionnaire-9 and generalized anxiety disorder-7 scale,respectively.A logistic regression analysis was performed to evaluate the relevant correlations.RESULTS Among 1580 first-generation only child parents,1120(70.89%)preferred family based care,324(20.51%)opted for community care,and 136(8.61%)chose institutional care,with 460(29.11%)reporting negative emotions.Significant differences in the distribution of negative emotions among only child parents were observed based on age,marital status,living conditions,disability,type of chronic disease,frailty status,and family support(P<0.05).The regression analysis indicated that disability,type of chronic disease,living environment,frailty status,and level of family support were independent risk factors for negative emotions among parents with only children(P<0.05).CONCLUSION Elderly care for parents of only children is primarily family-based.Independent risk factors for negative emotions in this group include disability,chronic disease type,and living environment.
