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.

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.

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。

符号与隐喻:解析拉赫玛尼诺夫音画练习曲Op.39 No.6

乐谱是作曲家与演奏者之间的重要介质,也是一种视觉符号的呈现。从结构主义的视角来看,符号的背后有一套表意系统,掌握这套系统有利于理解符号的意义。借用该观点分析拉赫玛尼诺夫的音画练习曲Op.39 No.6,有助于找寻一种理解音乐作品的路径。理解作品除了要从音乐符号的角度出发进行分析,更重要的是站在作曲家的意义系统中探寻隐藏在其背后的意义。

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.

Non-isothermal Crystallization Kinetics of Polyamide 6/Diaminemodified MWNTs Nanocomposite

The non-isothermal crystallization kinetics of polyamide 6/diamine-modified multi-walled carbon nanotube （PA6/D-MWNT） nanocomposite was investigated by differential scanning calorimetry （DSC）. The modified Avrami equation, the Ozawa equation and the combined Avrami/Ozawa equation were employed to analyze the non-isothermal crystallization data. The crystallization activation energies were also evaluated by the Kissinger method. It was found that the combined Avrami/Ozawa equation could successfully describe the non-isothermal crystallization process. The results showed that D-MWNTs not only acted as effective heterogeneous nucleating agents for PA6 and noticeably increased the crystallization temperature of PA6, but also influenced the mechanism of nucleation and crystal growth of PA6 and then reduced the overall crystallization rate of the neat PA6 matrix. The crystallization activation energy for the nanocomposite sample was greater than that of the neat PA6, which indicated that the addition of D-MWNTs hindered the mobility of PA6 chain segments.

Synthesis,Structure Characterization and Photoluminescence of a Novel Complex with(6,4,4)-Network [Ce_2(2,5-pydc)_3(H_2O)_2](2,5-pydc = Pyridine-2,5-dicarboxylic Acid)

A new three-dimensional supramolecular [Ce2（2,5-pydc）3（H2O）2]（1） has been hydrothermally synthesized at 180 ℃ and characterized by single-crystal X-ray diffraction.X-ray crystal analyses reveal that the compound belongs to the monoclinic system,space group P21/c,C21H13Ce2N3O14,a = 6.561（1）,b = 17.986（5）,c = 9.411（3） ,β = 95.558（5）° and Z = 2.In the structure of 1,each Ce（1） center is surrounded by 2,5-pydc ligands,forming the 6-connected node,and the 2,5-pydc ligand coordinates to the Ce（Ⅲ） in two different coordination modes.In mode 1,the four oxygen atoms of two carboxyl groups connect neighboring Ce（Ⅲ） ions,giving 4-connected（4-c） second building unit（SBU-1）.Furthermore,the structure is extended into a 2-D layer from SBU-1 by sharing Ce（1） atoms.In mode 2,the ligand coordinates to the Ce（Ⅲ） ion from the adjacent chain with the 4-connected（4-c） second building unit（SBU-2）,generating a 1-D ladder from SBU-2 by sharing Ce（1） atoms.Finally,the structure is extended into a 6,4,4-c network.Its photoluminescence property was also investigated.

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。

Silicoaluminophosphate molecular sieve DNL-6: Synthesis with a novel template, N,N'-dimethylethylenediamine, and its catalytic application

DNL-6, a silicoaluminophosphate（SAPO） molecular sieve with RHO topology, was hydrothermally synthesized using a new structure-directing agent（SDA）, N,N＇-dimethylethylenediamine. The obtained samples were characterized by X-ray diffraction, X-ray fluorescence, X-ray photoelectron spectroscopy, scanning electron microscopy, and N2 adsorption, which indicated that the synthesized DNL-6 s have high crystallinity and relatively high Si content ranging from 20% to 35%. Solid-state magic-angle-spinning（MAS） nuclear magnetic resonance（13 C, 29 Si, 27 Al, 31 P, and 27 Al multiple-quantum（MQ）） was conducted to investigate the status of the SDA and local atomic environment in the as-synthesized DNL-6. Thermal analysis revealed the presence of a large amount of amines in the DNL-6 crystals（about 4.4 SDAs per α-cage）, which was the reason for the formation of DNL-6 with an ultrahigh Si content（36.4% Si per mole）. Interestingly, DNL-6 exhibited excellent catalytic performance for methanol amination. More than 88% methanol conversion and 85% methylamine plus dimethylamine selectivity could be achieved due to the combined contribution of strong acid sites, suitable acid distribution, and narrow pore dimensions of DNL-6.

Luminol-K_3Fe(CN)_6 chemiluminescence system for the determination of glipizide

A rapid and sensitive flow-injection chemiluminescence（CL） method for the determination of glipizide was developed on the basis of finding that glipizide can enhance the CL intensity of the luminol-K3Fe（CN）6 system.In optimum condition,the increased CL intensity was directly proportional to the concentration of glipizide in the range from 4.0×108 g/mL to 1.0×106 g/mL and the detection limit was 1.0×108 g/mL glipizide.The relative standard deviation（RSD） of the developed method was 2.1% with 11 repeated measurements of 1.0×107 g/mL glipizide.The developed method has been successfully applied to the analysis of glipizide in its pharmaceutical preparations.

Differences in brain pathological changes between rotenone and 6-hydroxydopamine Parkinson＇s disease models

Rotenone and 6-hydroxydopamine are two drugs commonly used to generate Parkinson＇s disease animal models.They not only achieve degenerative changes of dopaminergic neurons in the substantia nigra,but also satisfy the requirements for iron deposition.However,few studies have compared the characteristics of these two models by magnetic resonance imaging.In this study,rat models of Parkinson＇s disease were generated by injection of 3 μg rotenone or 10 μg 6-hydroxydopamine into the right substantia nigra.At 1,2,4,and 6 weeks after injection,coronal whole-brain T2-weighted imaging,transverse whole-brain T2-weighted imaging,and coronal diffusion tensor weighted imaging were conducted to measure fractional anisotropy and T2＊ values at the injury site.The fractional anisotropy value on the right side of the substantia nigra was remarkably lower at 6 weeks than at other time points in the rotenone group.In the 6-hydroxydopamine group,the fractional anisotropy value was decreased,but T2＊ values were increased on the right side of the substantia nigra at 1 week.Our findings confirm that the 6-hydroxydopamine-induced model is suitable for studying dopaminergic neurons over short periods,while the rotenone-induced model may be appropriate for studying the pathological and physiological processes of Parkinson＇s disease over long periods.

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.