利什曼原虫感染树突状细胞早期基因表达差异分析及关键基因筛选

目的:分析利什曼原虫感染树突状细胞(DCs)早期的基因表达与信号通路变化,探究DCs感染后应答,寻找利什曼原虫感染后基于DCs的免疫治疗方法。方法:GEO数据库下载利什曼原虫感染前后DCs基因芯片数据,RStudio软件筛选差异表达基因(DEGs),STRING构建DEGs蛋白质相互作用网络(PPI),Cytoscape筛选差异表达蛋白质的核心模块,RStudio软件对DEGs进行GO和KEGG富集分析。结果:共筛选出DEGs 129个,其中IL12B与CXCL10差异最为显著,GO分析共富集23个过程,主要涉及病毒感染过程相关细胞反应及Ⅰ-IFN相关免疫反应;KEGG分析共富集3条信号通路,分别为甲型流感、麻疹及DNA复制信号通路。结论:利什曼原虫感染DCs前后Ⅰ-IFN信号通路和TLR4/NF-κB信号通路激活,影响IL12表达,提示Ⅰ-IFN/IL12信号通路与TLR4/NF-κB/IL12信号通路可作为利什曼原虫感染治疗的靶点,CXCL10也有望成为潜在的治疗靶点;利什曼原虫感染后,出现类似病毒感染现象,推测抗病毒免疫疗法可能在对抗利什曼原虫感染中具有一定疗效。     

A study on the self-assembly mode and supramolecular framework of complexes of cucurbit[6]urils and 1-(4-methoxyphenyl)piperazine

Self-assembly between symmetrical dicyclohexyl-substituted cucurbit[6]uril (abbreviated as (CyH)₂Q[6]) and cyclopentanocucurbit[6]uril (CyP₆Q[6]) as hosts and 1-(4-methoxyphenyl)piperazine (MeOPP) as a guest molecule has been studied by means of single-crystal X-ray diffraction analysis, NMR, MALDI-TOF mass spectrometry, and other characterization methods. The experimental results showed that the self-assembly was driven by the formation of exclusion complexes by the cucurbit[n]uril and the guest, that is, supramolecular interaction between the negative charge of the cucurbit[n]uril portals and a coordination polymer guest. Complexes were formed between the positive charge of the cucurbit[n]uril outer wall and inorganic anions, thus generating self-assemblies with multi-dimensional and multi-level supramolecular frameworks.

Complexes were formed between the positive charge of the cucurbit[n]uril outer wall and inorganic anions, thus generating self-assemblies with multi-dimensional and multi-level supramolecular frameworks.     

Synthesis of CdS-loaded (CuC10H26N6)3(PW12O40)2 for enhanced photocatalytic degradation of tetracycline under simulated solar light irradiation

Largely discharged and excreted medical pollutants pose huge threats to ecosystems. However, typical photocatalysts, such as the Keggin-typed H₃PW₁₂O₄₀, can hardly degrade these hazards under visible-light due to their broad bandgap and catalytic disability. In this work, the visible light harvesting was enabled by combining macrocyclic coordination compound CuC₁₀H₂₆N₆Cl₂O₈ with H₃PW₁₂O₄₀, and the resulting CuPW was loaded with CdS to reach robust catalytic ability to totally detoxify medicines. We prepared the CuPW–CdS composites through a facile precipitation method, and it showed excellent photocatalytic degradation for degrading tetracycline under visible-light irradiation. The (CuC₁₀H₂₆N₆)₃(PW₁₂O₄₀)₂ with 10 wt% load of CdS shows the highest performance and is ∼6 times more efficient than the pure CuPW counterpart. The heterojunctional CuPW–CdS composites promote the separation of electrons and holes, and consequentially enhance photocatalytic activity. Thanks to migration of electrons from CdS to CuPW, the photocorrosion of CdS is prohibited, resulting in a high chemical stability during photocatalysis. In this work we design a new route to the multi-structural composite photocatalysts for practical applications in medical pollutant decontamination.

We demonstrated the incorporation of (CuC₁₂H₃₀N₆)²⁺ into the a Keggin type H₃PW₁₂O₄₀ by a simple one-pot self-assembly process. A heterojunction structure was constructed by introducing CdS which has high photocatalytic activities.     

Synthesis and biological activities of novel trifluoromethylpyridine amide derivatives containing sulfur moieties

A series of trifluoromethylpyridine amide derivatives containing sulfur moieties (thioether, sulfone and sulfoxide) was designed and synthesized. Their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo), Ralstonia solanacearum (R. solanacearum) and insecticidal activities against P. xylostella were evaluated. Notably, the half-maximal effective concentration (EC₅₀) value of sulfone-containing compound F10 is 83 mg L⁻¹ against Xoo, which is better than that of commercial thiodiazole copper (97 mg L⁻¹) and bismerthiazol (112 mg L⁻¹). Thioether-containing compounds E1, E3, E5, E6, E10, E11 and E13 showed much higher activities against R. solanacearum with the EC₅₀ value from 40 to 78 mg L⁻¹, which are much lower than that of thiodiazole copper (87 mg L⁻¹) and bismerthiazol (124 mg L⁻¹). Generally, most of the sulfone-containing compounds and sulfoxide-containing compounds showed higher activities against Xoo than that of the corresponding thioether-containing compound, but most of the thioether-containing compounds contributed higher antibacterial activities against R. solanacearum. Furthermore, title compounds E3, E11, E24 and G2 showed good insecticidal activities of 75%, 70%, 70% and 75%, respectively.

Novel trifluoromethylpyridine amide derivatives containing sulfur moieties were synthesized, which exhibited good antibacterial and insecticidal activities for potential crop protection agents.     

整合素αvβ3抑制剂Cyclo-RGDfK对纤连蛋白诱导乳腺上皮细胞间质转化的影响

目的本研究探讨整合素αvβ3抑制剂(Cyclo-RGDfK)对纤连蛋白(fibronectin,FN)诱导人乳腺上皮细胞MCF-10A上皮间质转化的影响。方法体外传代培养MCF-10A细胞,采用FN诱导建立上皮间质转化(EMT)模型。Western blot实验检测αv integrin、β3 integrin、上皮标志物E-cadherin和间充质标志物N-cadherin、Vimentin的蛋白表达;划痕修复实验和Transwell小室实验检测细胞的迁移和侵袭能力。结果 Western blot结果显示FN作用48 h后可明显增强αv integrin、β3 integrin、N-cadherin、Vimentin的蛋白表达,下调E-cadherin蛋白表达,在给予Cyclo-RGDfK作用后,FN诱导的N-cadherin和Vimentin表达上调和E-cadherin表达下调被明显逆转;划痕修复实验和Transwell小室实验结果表明,FN能显著增强MCF-10A细胞迁移和侵袭能力,Cyclo-RGDfK能显著抑制FN的诱导作用。结论 Cyclo-RGDfK能抑制FN诱导乳腺上皮细胞MCF-10A的EMT过程,降低细胞的侵袭和迁移能力,其可能是治疗乳腺癌转移的潜在药物。     

中国南方与北方地区2013-2018年骨质疏松流行病学对比分析

目的对比分析我国南方地区和北方地区骨质疏松的流行病学特点。 方法利用万方数据库、中国知网数据库检索2013年1月至2018年12月报道的关于骨质疏松流行病学文献,按照纳入及排除标准选择其中具有区域性代表（以北京市、甘肃省、河南省、山西省和山东省代表北方地区,以广东省、广西省、四川省、贵州省和江西省代表南方地区）的文献。然后人工提取各文献中的相关数据,包括研究对象样本量、性别、年龄、骨质疏松患病人数等。率的比较采用χ²检验。 结果共筛选出符合标准的文献10篇,从中收集到研究对象38 941例,其中骨质疏松患者8 334例（21.4%）。南方地区和北方地区骨质疏松患病情况呈现出一致的流行病学特征：无论男性还是女性,骨质疏松患病率均随增龄逐渐增高;除20～29岁外的其他各年龄段,女性骨质疏松患病率均明显高于男性（P<0.05或0.01）;老年人骨质疏松患病率普遍较高（其中南方地区80～89岁女性患病率更是高达73.46%）,老年男性、女性骨质疏松患病率均显著高于非老年人（北方地区：χ²=960.180、1 315.400,均P<0.01;南方地区：χ²=773.290、1 482.720,均P<0.01）。与南方地区比较,北方地区男性、女性骨质疏松患病率均明显更高（非老年人：χ²=39.740、44.660,P<0.01;老年人：χ²=34.540、16.140）。与南方地区对应年龄段比较,北方地区40～49岁、50～59岁及60～69岁人群骨质疏松患病率更高（男性：χ²=29.300、8.000、3.900,P<0.05或0.01;女性：χ²=15.580、50.590、5.860,P<0.05或0.01）,但70～79、80～89岁人群骨质疏松患病率更低（男性：χ²=21.570、90.240,P<0.01;女性：χ²=4.430、97.200,P<0.05或0.01）。 结论南方地区总体发病率高于北方,两个地区均为70～80岁年龄段患者所占比例最高,并且各个年龄段女性患者均多于男性。南北两地区骨质疏松患病率均随年龄增加而升高,且两地区50岁年龄段人口骨质疏松患病率较前明显升高,临床上应在此时间段予以干预,预防骨质丢失及骨质疏松的发生。     

自噬与心肌病相关性的研究进展

自噬这个词来源于希腊语,原意为“吃自己”和“精确的细胞作用”。自噬从最初发现到如今经历了近50年,研究发现自噬可以被许多刺激所激活,包括饥饿、毒素、氧化应激和感染。在正常情况下,心肌细胞自噬维持在较低的情况,但在应激反应的高度激活下,自噬活动增强并在调节心脏稳态和功能中起重要作用。该文对自噬与心肌病相关性的研究进展进行综述。     

Modeling and Composition Design of Low-Alloy Steel’s Mechanical Properties Based on Neural Networks and Genetic Algorithms

Accurately improving the mechanical properties of low-alloy steel by changing the alloying elements and heat treatment processes is of interest. There is a mutual relationship between the mechanical properties and process components, and the mechanism for this relationship is complicated. The forward selection-deep neural network and genetic algorithm (FS-DNN&GA) composition design model constructed in this paper is a combination of a neural network and genetic algorithm, where the model trained by the neural network is transferred to the genetic algorithm. The FS-DNN&GA model is trained with the American Society of Metals (ASM) Alloy Center Database to design the composition and heat treatment process of alloy steel. First, with the forward selection (FS) method, influencing factors—C, Si, Mn, Cr, quenching temperature, and tempering temperature—are screened and recombined to be the input of different mechanical performance prediction models. Second, the forward selection-deep neural network (FS-DNN) mechanical prediction model is constructed to analyze the FS-DNN model through experimental data to best predict the mechanical performance. Finally, the FS-DNN trained model is brought into the genetic algorithm to construct the FS-DNN&GA model, and the FS-DNN&GA model outputs the corresponding chemical composition and process when the mechanical performance increases or decreases. The experimental results show that the FS-DNN model has high accuracy in predicting the mechanical properties of 50 furnaces of low-alloy steel. The tensile strength mean absolute error (MAE) is 11.7 MPa, and the yield strength MAE is 13.46 MPa. According to the chemical composition and heat treatment process designed by the FS-DNN&GA model, five furnaces of Alloy1–Alloy5 low-alloy steel were smelted, and tensile tests were performed on these five low-alloy steels. The results show that the mechanical properties of the designed alloy steel are completely within the design range, providing useful guidance for the future development of new alloy steel.     

Site-specific functionalization with amino,guanidinium, and imidazolyl groups enabling the activation of 10–23 DNAzyme

10–23 DNAzyme has been extensively explored as a therapeutic and biotechnological tool, as well as in DNA computing. Faster cleavage or transformation is always needed. The present research displays a rational modification approach for a more efficient DNAzyme. In the catalytic core, amino, guanidinium and imidazolyl groups were introduced for its chemical activation through the adenine base. Among the six adenine residues, A9 is the unique residue that realizes all the positive effects; the 6-amino and 8-position of adenine and the 7-position of 8-aza-7-deaza-adenine could be used for the introduction of the functional groups. A12 is a new choice for catalytic improvement with an 8-substituent. Therefore, more active DNAzymes could be expected by this nucleobase-modified activation approach.

Chemical activation of 10–23 DNAzyme was realized at A9 modified with active functional groups amino, guanidinium, and imidazolyl groups.     

A functional modified graphene oxide/nanodiamond/nano zinc oxide composite for excellent vulcanization properties of natural rubber

A modified graphene oxide/nanodiamond/nanozinc oxide (MGO/ND/nanoZnO) functional hybrid filler is designed and prepared to improve the vulcanization efficiency of a rubber composite and to reduce the use of ZnO. ND was grafted onto graphite oxide with the aid of 4,4′-methylene diphenyl diisocyanate (MDI). NanoZnO, with high surface activity, was then loaded onto the MGO/ND complex through the wet chemical method, in order to synthesize the MGO/ND/nanoZnO functional hybrid filler. Rubber composites were prepared using the rubber latex composite method and their vulcanization behaviors were investigated. Our results show that the MGO/ND/nanoZnO functional hybrid filler can remarkably improve the vulcanization behaviors of the rubber composite. Compared with that of pure natural rubber (NR), the vulcanization activation energy of the rubber composite was reduced by approximately 16%. Moreover, the vulcanization efficiency can be improved by 63% (i.e., the optimum cure time is shortened from the original 405 s to 150 s) after the same amount of traditional ZnO was replaced by the functional hybrid filler loaded with 1 wt% nanoZnO. The prepared MGO/ND/nanoZnO functional hybrid filler thus provides a promising alternative to improve the vulcanization efficiency of rubber composites.

A modified graphene oxide/nanodiamond/nanozinc oxide (MGO/ND/nanoZnO) functional hybrid filler is designed and prepared to improve the vulcanization efficiency of a rubber composite and to reduce the use of ZnO.