金属二聚体和氮共掺杂石墨烯(Gra)M_(2)N_(6)-Gra(M=Cr-Cu)的NO_(2)吸附特性理论研究

NO_(2)是空气污染物的主要成分之一,设计和开发高效的气敏传感器对NO_(2)进行检测具有重要意义.本工作利用基于密度泛函理论(DFT)的第一性原理计算方法对不同过渡金属原子形成的金属二聚体和氮共掺杂石墨烯(Gra)M_(2)N_(6)-Gra(M=Cr-Cu)的NO_(2)吸附特性进行了研究.结果表明,NO_(2)分子与M_(2)N_(6)-Gra之间均存在明显的化学吸附作用.其中,Ni_(2)N_(6)-Gra和Cu_(2)N_(6)-Gra体系具备较为适中的恢复时间(分别约为5秒和14分钟),这意味着这两个体系是开发新型NO_(2)气敏材料的潜在候选者.其它体系(M_(2)N_(6)-Gra,M=Cr-Co)强的吸附作用导致恢复时间过长,从而使得它们不适合作为NO_(2)气敏材料.这一研究不仅有望为设计和开发性能优异的新型NO_(2)气敏材料提供有益理论指导,还将有益于人们深入认识M_(2)N_(6)-Gra材料的NO_(2)电催化合成NO或NH 3性能.

Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy

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.

Overexpression pattern,function,and clinical value of proteasome 26S subunit non-ATPase 6 in hepatocellular carcinoma

BACKGROUND In recent years,many studies have shown that proteasome 26S subunit non-ATPase 6(PSMD6)plays an important role in the occurrence and development of malignant tumours.Unfortunately,there are no reports on the evaluation of the potential role of PSMD6 in hepatocellular carcinoma(HCC).AIM To comprehensively evaluate the overexpression pattern and clinical significance of PSMD6 in HCC tissues.METHODS This study integrated PSMD6 mRNA expression profiles from 4672 HCC and 3667 non-HCC tissues,along with immunohistochemical scores from 383 HCC and adjacent tissues,to assess PSMD6 overexpression in HCC.Clustered regularly interspaced short palindromic repeats knockout technology evaluated PSMD6’s essential role in HCC cell growth.Functional enrichment analysis explored the molecular mechanism of PSMD6 abnormalities in HCC.Drug sensitivity analysis and molecular docking analysed the effect of abnormal expression of PSMD6 on the drug sensitivity of HCC cells.RESULTS The results of 41 external and two internal datasets showed that PSMD6 mRNA(SMD=0.26,95%CI:0.09-0.42,P<0.05)and protein(SMD=2.85,95%CI:1.19-4.50,P<0.05)were significantly overexpressed in HCC tissues.The integrated analysis results showed that PSMD6 had a significant overexpression pattern in HCC tissues(SMD=0.40,95%CI:0.15-0.66,P<0.05).PSMD6 knockout inhibited HCC cell growth(chronos scores<-1).Functional enrichment implicated ribosome biogenesis and RNA splicing.Significant enrichment of signalling pathways such as RNA degradation,ribosomes,and chemical carcinogenesis—reactive oxygen species.Drug sensitivity analysis and a molecular docking model showed that high expression of PSMD6 was associated with the tolerance of HCC cells to drugs such as ML323,sepantronium bromide,and GDC0810.Overexpressed PSMD6 effectively distinguished HCC tissues(AUC=0.75,95%CI:0.71-0.79).CONCLUSION This study was the first to discover that PSMD6 was overexpressed in HCC tissues.PSMD6 is essential for the growth of HCC cells and may be involved in ribosome biogenesis and RNA splicing.

CaR调节TRPC6介导的自噬对软骨细胞SOD及NOX2的影响

目的观察钙敏感受体(CaR)调节瞬时感受器电位通道6(TRPC6)介导的自噬对软骨细胞超氧化物歧化酶(SOD)、NADPH氧化酶-2(NOX2)的影响。方法2023年7月将出生3~5 d SD大鼠关节软骨用胶原酶消化后进行传代培养,取第3代培养的细胞接种于96孔板,用白细胞介素-1β(10 ng/mL)诱导软骨细胞,分为对照组、CaR(10μg/L)组、U73122(5μg/L)组和CaR(10μg/L)+U73122(5μg/L)组,共培养24 h后应用酶联免疫吸附试验检测各组上清液SOD、NOX2水平,采用实时定量-聚合酶链反应检测各组SOD、NOX2、人自噬基因Beclin-1 mRNA表达,Western-blot检测SOD、NOX2、Beclin-1蛋白表达。结果原代关节软骨细胞在显微镜下呈三角形或不规则形或多角形,分布稀疏,培养24 h后可见贴壁生长;第3代软骨细胞显示其蓝染的细胞核,细胞间质及细胞质内偶见紫红色异染颗粒;细胞核染成蓝色,细胞质区呈棕黄色。对照组软骨细胞上清液SOD水平,SOD、Beclin-1 mRNA及其蛋白相对表达量,NOX2 mRNA相对表达量均明显低于CaR(10μg/L)组,NOX2水平、NOX2蛋白相对表达量均明显高于CaR(10μg/L)组,差异均有统计学意义(P<0.05);U73122(5μg/L)组和CaR(10μg/L)+U73122(5μg/L)组软骨细胞上清液SOD水平,SOD、Beclin-1 mRNA及蛋白相对表达量均明显低于对照组,NOX2水平、NOX2 mRNA及蛋白相对表达量均明显高于对照组,差异均有统计学意义(P<0.05)。结论CaR通过TRPC6介导的自噬降低软骨细胞氧化应激水平,可能是延缓骨关节炎发生、发展的重要机制。

水热反应条件对SnO_(2)/Bi_(2)WO_(6)复合材料光催化活性的影响

本文以不同水热条件制备了正交晶系结构的两种二氧化锡和一种钨酸铋,并制备出了两种由纳米片组成的花状团簇的二氧化锡/钨酸铋复合光催化材料。通过X射线衍射仪、扫描电子显微镜、比表面积孔隙度测试仪、紫外可见分光光度计等手段对三种样品的样貌、比表面积、孔隙度、孔体积及吸光度测试表征。用碘钨灯来模拟太阳光,研究对比以不同水热条件下制备的钨酸铋以及两种二氧化锡/钨酸铋复合材料作催化剂催化降解罗丹明B的光催化性能。综合实验数据分析,发现二氧化锡/钨酸铋复合样品的衍射峰与钨酸铋样品的衍射峰一致,不同的水热条件会影响产物的物相结构,但对晶体结构和结晶度无影响。光催化360 min时,水热条件为180℃、12 h的钨酸铋对罗丹明B的降解率是33%、水热条件为180℃、6 h的二氧化锡和180℃、12 h的钨酸铋制备的复合物样品1对罗丹明B的降解率是46%、水热条件为180℃、12 h的二氧化锡和180℃、12 h的钨酸铋制备的复合物样品2对罗丹明B的降解率是57%。二氧化锡/钨酸铋复合样品的催化效果优于纯钨酸铋,同时也说明不同水热反应条件对复合光催化材料的催化性能有一定的影响。

Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

17~45岁肥胖门诊患者的6分钟步行试验距离参考方程研究

背景 目前6分钟步行试验(6MWT)已经被广泛用于评估肥胖人群的运动能力,并为制订干预措施提供了参考依据。国外已有研究提出了其他人群的6MWT距离参考方程,但中国17~45岁且BMI≥30 kg/m^(2)肥胖受试者的6MWT距离参考方程研究较少。目的 为17~45岁门诊肥胖受试者制订6MWT距离参考方程,并评估其影响因素。方法 根据美国胸科学会指南,前瞻性选取2022年6月—2023年9月于江苏省苏北人民医院内分泌科肥胖门诊部就诊的143名年龄17~45岁且BMI≥30 kg/m^(2)的成年人(71名男性和72名女性),进行人体测量和6MWT。采用逐步多元回归模型建立6MWT距离参考方程,将新建立的6MWT距离参考方程与现有的预测方程进行比较。结果 143名受试者的平均6MWT距离为(506.1±49.8)m,其中男性平均6MWT距离为(515.7±50.1)m,大于女性的平均6MWT距离(496.6±47.9)m(P<0.05)。在年龄段17~23岁、24~30岁、31~37岁以及38~45岁中,男性与女性6MWT距离比较,差异均有统计学意义(P<0.05)。男性受试者的体质量、BMI、最大心率(HR_(max))、心率差(ΔHR)、腰围、舒张压差(ΔDBP)、Borg量表评分差(ΔBorg)与6MWT距离相关(P<0.05),女性受试者的体质量、BMI、腰围与6MWT距离相关(P<0.05)。以步进的方法将潜在的影响因素纳入多元线性回归方程中,最终建立6MWT距离参考公式:男性y=494.463+1.414×ΔHR-3.903×BMI+0.874×HR_(max),R^(2)=0.429,女性y=670.448+0.299×ΔHR-4.342×BMI-0.195×HR_(max),R^(2)=0.312。结论 17~45岁门诊肥胖受试者中,男性的平均6MWT距离长于女性,且在不同年龄段均有显著差异。男性的体质量、BMI、HR_(max)、ΔHR、腰围、ΔDBP、ΔBorg与6MWT距离相关,女性的体质量、BMI、腰围、ΔSBP与6MWT距离相关。通过多元线性回归分析,为男性和女性分别建立了预测6MWT距离的参考方程,这些公式可能为评估个体的体能水平提供有价值的参考。

Development and identification of two novel wheat-rye 6R derivative lines with adult-plant resistance to powdery mildew and high-yielding potential

Powdery mildew,caused by Blumeria graminis f.sp.tritici(Bgt),is a devastating disease that seriously threatens wheat yield and quality.To control this disease,host resistance is the most effective measure.Compared with the resistance genes from common wheat,alien resistance genes can better withstand infection of this highly variable pathogen.Development of elite alien germplasm resources with powdery mildew resistance and other key breeding traits is an attractive strategy in wheat breeding.In this study,three wheat-rye germplasm lines YT4-1,YT4-2,and YT4-3 were developed through hybridization between octoploid triticale and common wheat,out of which the lines YT4-1 and YT4-2 conferred adult-plant resistance(APR)to powdery mildew while the line YT4-3 was susceptible to powdery mildew during all of its growth stages.Using genomic in situ hybridization,multi-color fluorescence in situ hybridization,multi-color GISH,and molecular marker analysis,YT4-1,YT4-2,and YT4-3 were shown to be cytogenetically stable wheat-rye 6R addition and T1RS.1BL translocation line,6RL ditelosomic addition and T1RS.1BL translocation line,and T1RS.1BL translocation line,respectively.Compared with previously reported wheat-rye derivative lines carrying chromosome 6R,YT4-1 and YT4-2 showed stable APR without undesirable pleiotropic effects on agronomic traits.Therefore,these novel wheat-rye 6R derivative lines are expected to be promising bridge resources in wheat disease breeding.

Knockout of C6orf120 in Rats Alleviates Concanavalin A-induced Autoimmune Hepatitis by Regulating Macrophage Polarization

Objective The effect of the functionally unknown gene C6orf120 on autoimmune hepatitis was investigated on C6orf120 knockout rats(C6orf120^(-/-))and THP-1 cells.Method Six–eight-week-old C6orf120^(-/-)and wild-type(WT)SD rats were injected with Con A(16 mg/kg),and euthanized after 24 h.The sera,livers,and spleens were collected.THP-1 cells and the recombinant protein(rC6ORF120)were used to explore the mechanism in vitro.The frequency of M1 and M2 macrophages was analyzed using flow cytometry.Western blotting and PCR were used to detect macrophage polarization-associated factors.Results C6orf120 knockout attenuated Con A-induced autoimmune hepatitis.Flow cytometry indicated that the proportion of CD68^(+)CD86^(+)M1 macrophages from the liver and spleen in the C6orf120^(-/-)rats decreased.C6orf120 knockout induced downregulation of CD86 protein and the mRNA levels of related inflammatory factors TNF-α,IL-1β,and IL-6 in the liver.C6orf120 knockout did not affect the polarization of THP-1 cells.However,rC6ORF120 promoted the THP-1 cells toward CD68^(+)CD80^(+)M1 macrophages and inhibited the CD68^(+)CD206^(+)M2 phenotype.Conclusion C6orf120 knockout alleviates Con A-induced autoimmune hepatitis by inhibiting macrophage polarization toward M1 macrophages and reducing the expression of related inflammatory factors in C6orf120^(-/-)rats.

Application of Echocardiography Combined with Blood SAA, IL-6, PCT, and CRP Detection in the Diagnosis and Treatment of Kawasaki Disease in Children

Objective: To understand the application of echocardiography combined with blood SAA, IL-6, PCT, and CRP detection in the diagnosis and treatment of Kawasaki disease in children. Methods: 56 children with Kawasaki disease were selected as the study subjects as the treatment group, and 54 children with other diseases during the same period were selected as the control group. Echocardiography, blood SAA, IL-6, PCT and CRP were detected before and after treatment to observe the results of the two groups. A database was established to compare the changes of various indicators between the two groups, as well as the application value of each indicator in the clinical diagnosis and treatment of Kawasaki disease, and the pros and cons of the application of each indicator in the diagnosis and treatment of children with Kawasaki disease were analyzed, so as to provide a clearer early warning mechanism for the clinical diagnosis and treatment of children with Kawasaki disease. Results: There was no significant difference in the results of related imaging indexes in the control group before and after treatment (P > 0.05). There was no significant difference in the results of relevant imaging indicators in the treatment group before and after treatment (P > 0.05), except for LMCA (P < 0.05). The comparison of imaging related indicators before and after treatment between the two groups showed that except for no statistically significant difference in LMCA and RMCA before treatment (P > 0.05), all other indicators had statistical significance (P < 0.05). The results of relevant laboratory indexes in control group before and after treatment were statistically significant (P < 0.05). The results of relevant laboratory indexes before and after treatment in the treatment group were statistically significant (P < 0.05). The results of relevant laboratory indicators were compared between the two groups, except for the results of SAA, IL-6 and PCT before treatment, which were not statistically significant (P > 0.05), the differences in all other indicators were statistically significant (P Conclusion: The combination of echocardiography with blood SAA, IL-6, PCT, and CRP detection can establish the optimal evaluation plan for accurate and effective diagnosis, treatment, and prognosis of Kawasaki disease in children, providing more accurate and reliable diagnostic and treatment methods and laboratory data for clinical practice, and thus providing strong protection for children’s health.

联合检测GR、NO、IL-6对儿童病毒性心肌炎的评价

目的联合几项免疫介导的血清学指标来提高对儿童儿童病毒性心肌炎(VMC)的诊断效率,为临床提供早期的诊断价值,避免漏检对患儿引起的不良结局。方法收集泗洪医院2018年1月至2022年6月在儿科住院就诊符合条件的45例VMC病例纳入VMC组,45例单纯病毒感染患儿纳入NVMC组以及体检的50名正常儿童纳入对照组。收集研究对象一般资料,包括白细胞介素6(IL-6)、谷胱甘肽还原酶(GR)、一氧化氮(NO)以及心肌酶谱、肌钙蛋白结果。用受试者工作特征(ROC)曲线各单项指标对VMC的价值分析,并采用Logistic回归模型构建模型来预判VMC。结果VMC组的肌酸激酶同工酶(CK-MB)、天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、肌钙蛋白I(cTnI)、NO、IL-6含量明显高于NVMC组和对照组,而GR含量则明显低于后两组;用各单项指标来对VMC进行ROC曲线分析,结果显示特异性最高的是cTnI的0.907,敏感性最高的是IL-6的0.912,AUC面积最大的是NO,为0.883;由cTnI、CK-MB、GR、NO、IL-6等5项指标联合建立的回归模型,当诊断界值定为0.55时,模型对VMC的AUC为0.976,敏感性为0.977,特异性为0.982,此时约登指数最大为0.959。结论用NO、GR、IL-6联合cTnI、CK-MB构建的回归模型对VMC的诊断特异性以及敏感性明显高于其他的单一指标。能够为临床医生及早的诊断儿童VMC提供有力的依据和辅助。

Large‑scale transcriptomic and genomic analyses reveal a novel functional gene SERPINB6 for chicken carcass traits

Background Carcass traits are crucial indicators of meat production efficiency.However,the molecular regulatory mechanisms associated with these traits remain unclear.Results In this study,we conducted comprehensive transcriptomic and genomic analyses on 399 Tiannong partridge chickens to identify key genes and variants associated with carcass traits and to elucidate the underlying regulatory mechanisms.Based on association analyses with the elastic net(EN)model,we identified 12 candidate genes(AMY1A,AP3B2,CEBPG,EEF2,EIF4EBP1,FGFR1,FOXD3,GOLM1,LOC107052698,PABPC1,SERPINB6 and TBC1D16)for 4 carcass-related traits,namely live weight,dressed weight,eviscerated weight,and breast muscle weight.SERPINB6 was identified as the only overlapping gene by 3 analyses,EN model analysis,weighted gene co-expression network analysis and differential expression analysis.Cell-level experiments confirmed that SERPINB6 promotes the proliferation of chicken DF1 cells and primary myoblasts.Further expression genome-wide association study and association analysis indicated that rs317934171 is the critical site that enhances SERPINB6 expression.Furthermore,a dual-luciferase reporter assay proved that gga-miR-1615 targets the 3′UTR of SERPINB6.Conclusions Collectively,our findings reveal that SERPINB6 serves as a novel gene for chicken carcass traits by promoting fibroblast and myoblast proliferation.Additionally,the downstream variant rs317934171 regulates SERPINB6 expression.These results identify a new target gene and molecular marker for the molecular mechanisms of chicken carcass traits.

Learning Sequential and Structural Dependencies Between Nucleotides for RNA N6-Methyladenosine Site Identification

N6-methyladenosine(m6A)is an important RNA methylation modification involved in regulating diverse biological processes across multiple species.Hence,the identification of m6A modification sites provides valuable insight into the biological mechanisms of complex diseases at the post-transcriptional level.Although a variety of identification algorithms have been proposed recently,most of them capture the features of m6A modification sites by focusing on the sequential dependencies of nucleotides at different positions in RNA sequences,while ignoring the structural dependencies of nucleotides in their threedimensional structures.To overcome this issue,we propose a cross-species end-to-end deep learning model,namely CR-NSSD,which conduct a cross-domain representation learning process integrating nucleotide structural and sequential dependencies for RNA m6A site identification.Specifically,CR-NSSD first obtains the pre-coded representations of RNA sequences by incorporating the position information into single-nucleotide states with chaos game representation theory.It then constructs a crossdomain reconstruction encoder to learn the sequential and structural dependencies between nucleotides.By minimizing the reconstruction and binary cross-entropy losses,CR-NSSD is trained to complete the task of m6A site identification.Extensive experiments have demonstrated the promising performance of CR-NSSD by comparing it with several state-of-the-art m6A identification algorithms.Moreover,the results of cross-species prediction indicate that the integration of sequential and structural dependencies allows CR-NSSD to capture general features of m6A modification sites among different species,thus improving the accuracy of cross-species identification.

Overexpression of proteasome 26S subunit non-ATPase 6 protein and its clinicopathological significance in intrahepatic cholangiocarcinoma

BACKGROUND Currently,intrahepatic cholangiocarcinoma(ICC)poses a continuing,significant health challenge,but the relationship has yet to be established between ICC and the proteasome 26S subunit non-ATPase 6(PSMD6).AIM To investigate the protein expression and clinicopathological significance of PSMD6 in ICC.METHODS The potential impact of the PSMD6 gene on the growth of ICC cell lines was analyzed using clustered regularly interspaced short palindromic repeat knockout screening technology.Forty-two paired specimens of ICC and adjacent noncancerous tissues were collected.PSMD6 protein expression was determined by immunohistochemistry.Receiver operating characteristic curve analysis was performed to validate PSMD6 expression level,and its association with ICC patients’various clinicopathological characteristics was investigated.RESULTS The PSMD6 gene was found to be essential for the growth of ICC cell lines.PSMD6 protein was significantly overexpressed in ICC tissues(P<0.001),but showed no significant association with patient age,gender,pathological grade,or tumor-node-metastasis stage(P>0.05).CONCLUSION PSMD6 can promote the growth of ICC cells,thus playing a pro-oncogenic role.

Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer

BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.

Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in Chinese Aniridia Families

Objective To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency.Methods A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives.The clinical feature analysis included the evaluation of visual acuity,intraocular pressure,slit-lamp anterior segment examination,fundus photography,and spectral domain optical coherence tomography.To identify the mutation responsible for aniridia,targeted next-generation sequencing was used as a beneficial technique.Results A total of 4 mutations were identified,consisting of two novel frameshift mutations(c.314delA,p.K105Sfs*33 and c.838_845dup AACACACC,p.S283Tfs*85),along with two recurring nonsense mutations(c.307C>T,p.R103X and c.619A>T,p.K207*).Complete iris absence,macular foveal hypoplasia,and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families,while corneal lesions,cataracts,and glaucoma exhibited heterogeneity both among the families and within the same family.Conclusion In our study,two novel PAX6 mutations associated with aniridia were identified in Chinese families,which expanded the phenotypic and genotypic spectrum of PAX6 mutations.We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.

定向电场下W_(6)C_(6)团簇的超卤素调制及非线性光学特性

本文采用密度泛函(DFT)方法研究了定向外电场(OEEF)对W_(6)C_(6)团簇几何结构、电子性质以及非线性光学响应(NLO)的影响.计算结果表明W_(6)C_(6)的结构在一定OEEF强度下可以保持稳定.OEEF可以增大W_(6)C_(6)团簇的电子亲和能(EA值),且在特定强度下,OEEF可以将W_(6)C_(6)团簇转变为超卤素.通过对EA值的非线性拟合可以实现对W_(6)C_(6)团簇的连续调制.进一步对不同外电场下W_(6)C_(6)团簇的最高占据分子轨道(HOMO)和最低未占据分子轨道(LUMO)能级进行分析,发现OEEF降低了W_(6)C_(6)团簇LUMO能级是其EA值增大的主因.此外,OEEF可以显著增大W_(6)C_(6)团簇的平均极化率和第一超极化率,尤其是第一超极化率,改变其非线性光学性质.

Imprinting at the KBTBD6 locus involves species-specific m ternal methylation and monoallelic expression in livestock animals

Background The primary differentially methylated regions(DMRs) which are maternally hypermethylated serve as imprinting control regions(ICRs) that drive monoallelic gene expression, and these ICRs have been investigated due to their implications in mammalian development. Although a subset of genes has been identified as imprinted, in-depth comparative approach needs to be developed for identification of species-specific imprinted genes. Here, we examined DNA methylation status and allelic expression at the KBTBD6 locus across species and tissues and explored potential mechanisms of imprinting.Results Using whole-genome bisulfite sequencing and RNA-sequencing on parthenogenetic and normal porcine embryos, we identified a maternally hypermethylated DMR between the embryos at the KBTBD6 promoter Cp G island and paternal monoallelic expression of KBTBD6. Also, in analyzed domesticated mammals but not in humans, non-human primates and mice, the KBTBD6 promoter Cp G islands were methylated in oocytes and/or allelically methyl-ated in tissues, and monoallelic KBTBD6 expression was observed, indicating livestock-specific imprinting. Further analysis revealed that these Cp G islands were embedded within transcripts in porcine and bovine oocytes which coexisted with an active transcription mark and DNA methylation, implying the presence of transcription-dependent imprinting.Conclusions In this study, our comparative approach revealed an imprinted expression of the KBTBD6 gene in domesticated mammals, but not in humans, non-human primates, and mice which implicates species-specific evolution of genomic imprinting.

New insights into developmental biology of Eimeria tenella revealed by comparative analysis of mRNA N6-methyladenosine modification between unsporulated oocysts and sporulated oocysts

Evidence showed that N6-methyladenosine(m^(6)A)modification plays a pivotal role in influencing RNA fate and is strongly associated with cell growth and developmental processes in many species.However,no information regarding m^(6)A modification in Eimeria tenella is currently available.In the present study,we surveyed the transcriptome-wide prevalence of m^(6)A in sporulated oocysts and unsporulated oocysts of E.tenella.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)analysis showed that m^(6)A modification was most abundant in the coding sequences,followed by stop codon.There were 3,903 hypermethylated and 3,178 hypomethylated mRNAs in sporulated oocysts compared with unsporulated oocysts.Further joint analysis suggested that m^(6)A modification of the majority of genes was positively correlated with mRNA expression.The mRNA relative expression and m^(6)A level of the selected genes were confirmed by quantitative reverse transcription PCR(RT-qPCR)and MeRIP-qPCR.GO and KEGG analysis indicated that differentially m^(6)A methylated genes(DMMGs)with significant differences in mRNA expression were closely related to processes such as regulation of gene expression,epigenetic,microtubule,autophagy-other and TOR signaling.Moreover,a total of 96 DMMGs without significant differences in mRNA expression showed significant differences at protein level.GO and pathway enrichment analysis of the 96 genes showed that RNA methylation may be involved in cell biosynthesis and metabolism of E.tenella.We firstly present a map of RNA m^(6)A modification in E.tenella,which provides significant insights into developmental biology of E.tenella.

ALKBH5 suppresses autophagic flux via N6-methyladenosine demethylation of ZKSCAN3 mRNA in acute pancreatitis

BACKGROUND Increasing evidence has demonstrated that N6-methyladenosine(m6A)RNA modification plays an essential role in a wide range of pathological conditions.Impaired autophagy is a critical hallmark of acute pancreatitis(AP).AIM To explore the role of the m6A modification of ZKSCAN3 in the regulation of autophagy in AP.METHODS The AP mouse cell model was established by cerulein-treated mouse pancreatic acinar cells(MPC-83),and the results were confirmed by the levels of amylase and inflammatory factors.Autophagy activity was evaluated by specific identification of the autophagy-related microstructure and the expression of autophagy-related genes.ZKSCAN3 and ALKBH5 were knocked down to study the function in AP.A m6A RNA binding protein immunoprecipitation assay was used to study how the m6A modification of ZKSCAN3 mRNA is regulated by ALKBH.RESULTS The increased expression of amylase and inflammatory factors in the supernatant and the accumulation of autophagic vacuoles verified that the AP mouse cell model was established.The downregulation of LAMP2 and upregulation of LC3-II/I and SQSTM1 demonstrated that autophagy was impaired in AP.The expression of ZKSCAN3 was upregulated in AP.Inhibition of ZKSCAN3 increased the expression of LAMP2 and decreased the expression of the inflammatory factors,LC3-II/I and SQSTM1.Furthermore,ALKBH5 was upregulated in AP.Knockdown of ALKBH5 downregulated ZKSCAN3 expression and restored decreased autophagic flux in AP.Notably,the bioinformatic analysis revealed 23 potential m6A modification sites on ZKSCAN3 mRNA.The m6A modification of ZKSCAN3 mRNA was significantly decreased in AP.Knockdown of ALKBH5 increased the modification of ZKSCAN3 mRNA,which confirmed that ALKBH5 upregulated ZKSCAN3 expression in a m6A-dependent manner.CONCLUSION ALKBH5 inhibits autophagic flux through m6A demethylation of ZKSCAN3 mRNA in AP,thereby aggravating the severity of the disease.