Hereditary Prostate Cancer: Genes Related,Target Therapy and Prevention

Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5–15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and homologous recombination genes (BRCA1/2, ATM, PALB2, CHEK2). Additional genes are also recommended to be integrated into specific research, including HOXB13, BRP1 and NSB1. Importantly, BRCA1/BRCA2 and ATM mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed.     

Metabolic Profiling of VOCs Emitted by Bacteria Isolated from Pressure Ulcers and Treated with Different Concentrations of Bio-AgNPs

Considering the advent of antibiotic resistance, the study of bacterial metabolic behavior stimulated by novel antimicrobial agents becomes a relevant tool to elucidate involved adaptive pathways. Profiling of volatile metabolites was performed to monitor alterations of bacterial metabolism induced by biosynthesized silver nanoparticles (bio-AgNPs). Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis were isolated from pressure ulcers, and their cultures were prepared in the presence/absence of bio-AgNPs at 12.5, 25 and 50 µg mL⁻¹. Headspace solid phase microextraction associated to gas chromatography–mass spectrometry was the employed analytical platform. At the lower concentration level, the agent promoted positive modulation of products of fermentation routes and bioactive volatiles, indicating an attempt of bacteria to adapt to an ongoing suppression of cellular respiration. Augmented response of aldehydes and other possible products of lipid oxidative cleavage was noticed for increasing levels of bio-AgNPs. The greatest concentration of agent caused a reduction of 44 to 80% in the variety of compounds found in the control samples. Pathway analysis indicated overall inhibition of amino acids and fatty acids routes. The present assessment may provide a deeper understanding of molecular mechanisms of bio-AgNPs and how the metabolic response of bacteria is untangled.     

石峡遗址玉琮形制与纹饰设计流变解读

通过梳理石峡遗址玉琮不同阶段形制与纹饰设计的变化,以及良渚文化和同时期其他地区玉琮的形制、纹饰和功能的分析,发现广东境内出土的玉琮与良渚文化关系极为密切,石峡遗址的多节玉琮更是直接来自于太湖地区,而那些纹饰设计出现颠倒或发生较大改变者应为本地仿制品。龙山时代,玉琮虽然传播和辐及的范围十分广泛,但是在大部分地区其功能都发生了变化,只有广东地区的玉琮仍最大程度地坚守着传统与信仰。石峡遗址玉琮形制与纹饰设计流变,所反映出的这种文化传播方式、接收程度与再创作,突出地体现了一种强势文化在对外传播和扩散的过程中,因地因时而制宜。这或许可以提示我们,利用传统文化元素进行再设计,欲意达到传统与现代的融合与契合,更理应如此。     

基于乙酰胆碱酯酶和氧化应激研究海胆酮对阿尔茨海默症的作用机制

海胆酮是一种酮式类胡萝卜素，主要从海胆及藻类等海洋生物中提取。本文研究海胆酮对乙酰胆碱酯酶（acetylcholinesterase，AChE）的抑制作用，应用酶动力学、荧光光谱、圆二色光谱和分子对接技术研究海胆酮对AChE的抑制机理，并用淀粉样β蛋白片段25～35（amyloid beta-peptide 25-35，Aβ25-35）诱导大鼠肾上腺嗜铬细胞瘤细胞（PC12细胞）建立阿尔茨海默症（Alzheimer’s disease，AD）模型，研究海胆酮对AD细胞模型氧化应激损伤的作用。结果表明，海胆酮有很强的AChE抑制活性，其半抑制质量浓度为（16.29±0.97）μg/mL，抑制常数Ki为3.82 μg/mL，表现为竞争性抑制；海胆酮可诱导AChE二级结构改变，更容易与AChE活性中心氨基酸Ser200、His440、Trp84和Tyr121结合，阻碍底物碘代硫代乙酰胆碱（acetylthiocholine iodide，ATCI）与酶结合，从而引起酶活力降低。海胆酮能有效抑制Aβ25-35诱导PC12细胞的AChE活力，降低丙二醛含量，增加超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活力，减轻Aβ25-35诱导的PC12细胞氧化应激损伤。本研究基于AChE和氧化应激阐明了海胆酮对AD的潜在作用机制，为海胆酮在功能食品、生物医药等领域的应用提供了数据支持和理论根据。     

Development of structurally modified OER catalysts with enhanced performance and longevity for PEM-based electrolytic air dehumidification

PEM-based electrolytic air dehumidification is innovative in dehumidification that requires high precision and small space due to its high efficiency, compactness, and cleanness. However, the system dehumidification performance and durability are limited by using commercial Anatase-IrO₂ catalysts. In this study, two types of structurally modified OER catalyst materials, ATO-IrO₂ and ND-MnO₂-IrO₂, are developed to improve the performance of the system. System experiments showed that, compared to the commercial catalysts, the use of ATO-IrO₂ and ND-MnO₂-IrO₂ as the anode catalyst can improve the dehumidification performance by 45% and 20%, respectively. Furthermore, in 50-h accelerated aging tests, the attenuation rates of the ATO-IrO₂ and ND-MnO₂-IrO₂ systems are 3% and 8% respectively, which are far lower than the 35% attenuation of commercial catalyst. The results indicate that, as catalysts with a classic core-shell structure, ATO-IrO₂ and ND-MnO₂-IrO₂ still have a significant impact on improving the performance of the electrolytic dehumidification systems.     

解脂耶氏酵母作为微生物细胞工厂的应用研究进展

解脂耶氏酵母（Yarrowia lipolytica）是一种重要的工业微生物菌种，被公认为食品级安全微生物。近年来，随着合成生物学和基因编辑技术的快速发展，科学家们利用合成生物学及基因编辑技术已经成功构建出了能够生产生物化学品、生物燃料、香料、药物、工业酶和药用蛋白等多种高附加值工业产品的解脂耶氏酵母细胞工厂，使得该酵母在食品、药品和生化能源等领域均具有巨大的应用潜力。本文将重点介绍解脂耶氏酵母表达系统、合成生物学元件和基因编辑方法的最新研究进展和应用情况，并对近年来以解脂耶氏酵母作为微生物细胞工厂生产高附加值产品的应用实例进行总结，希望为研究人员进一步利用解脂耶氏酵母进行底盘细胞设计、构建和优化相关合成途径并最终实现目的产物的高效合成提供有用的信息。