Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance

Prostate cancer (PCa) mortality remains a significant public health problem, as advanced disease has poor survivability due to the development of resistance in response to both standard and novel therapeutic interventions. Therapeutic resistance is a multifaceted problem involving the interplay of a number of biological mechanisms including genetic, signaling, and phenotypic alterations, compounded by the contributions of a tumor microenvironment that supports tumor growth, invasiveness, and metastasis. The androgen receptor (AR) is a primary regulator of prostate cell growth, response and maintenance, and the target of most standard PCa therapies designed to inhibit AR from interacting with androgens, its native ligands. As such, AR remains the main driver of therapeutic response in patients with metastatic castration-resistant prostate cancer (mCRPC). While androgen deprivation therapy (ADT), in combination with microtubule-targeting taxane chemotherapy, offers survival benefits in patients with mCRPC, therapeutic resistance invariably develops, leading to lethal disease. Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes and also to the development of biomarker signatures of predictive value. The interconversions between epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) navigate the prostate tumor therapeutic response, and provide a novel targeting platform in overcoming therapeutic resistance. Both microRNA (miRNA)- and long non-coding RNA (lncRNA)-mediated mechanisms have been associated with epigenetic changes in prostate cancer. This review discusses the current evidence-based knowledge of the role of the phenotypic transitions and novel molecular determinants (non-coding RNAs) as contributors to the emergence of therapeutic resistance and metastasis and their integrated predictive value in prostate cancer progression to advanced disease.     

Analysis of Sequence Divergence in Mammalian ABCGs Predicts a Structural Network of Residues That Underlies Functional Divergence

The five members of the mammalian G subfamily of ATP-binding cassette transporters differ greatly in their substrate specificity. Four members of the subfamily are important in lipid transport and the wide substrate specificity of one of the members, ABCG2, is of significance due to its role in multidrug resistance. To explore the origin of substrate selectivity in members 1, 2, 4, 5 and 8 of this subfamily, we have analysed the differences in conservation between members in a multiple sequence alignment of ABCG sequences from mammals. Mapping sets of residues with similar patterns of conservation onto the resolved 3D structure of ABCG2 reveals possible explanations for differences in function, via a connected network of residues from the cytoplasmic to transmembrane domains. In ABCG2, this network of residues may confer extra conformational flexibility, enabling it to transport a wider array of substrates.     

Molecular Mechanisms and Tumor Biological Aspects of 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells

5-Fluorouracil (5-FU) is a cornerstone drug used in the treatment of colorectal cancer (CRC). However, the development of resistance to 5-FU and its analogs remain an unsolved problem in CRC treatment. In this study, we investigated the molecular mechanisms and tumor biological aspects of 5-FU resistance in CRC HCT116 cells. We established an acquired 5-FU-resistant cell line, HCT116R^F10. HCT116R^F10 cells were cross-resistant to the 5-FU analog, fluorodeoxyuridine. In contrast, HCT116R^F10 cells were collaterally sensitive to SN-38 and CDDP compared with the parental HCT16 cells. Whole-exome sequencing revealed that a cluster of genes associated with the 5-FU metabolic pathway were not significantly mutated in HCT116 or HCT116R^F10 cells. Interestingly, HCT116R^F10 cells were regulated by the function of thymidylate synthase (TS), a 5-FU active metabolite 5-fluorodeoxyuridine monophosphate (FdUMP) inhibiting enzyme. Half of the TS was in an active form, whereas the other half was in an inactive form. This finding indicates that 5-FU-resistant cells exhibited increased TS expression, and the TS enzyme is used to trap FdUMP, resulting in resistance to 5-FU and its analogs.     

多孔纤维型重整微反应器的等效电阻网络建模

针对应用于重整制氢微反应器的复杂多孔金属纤维载体（PFS）的流速场高效分析难题,建立载体中随机微通道的等效电阻网络分析模型. 基于复杂随机纤维结构的统计网络模型,将纤维载体中三维联通的随机微通道结构及与之相连的进出口腔简化为规则的网络通道结构.借鉴基尔霍夫定律,建立纤维载体的等效电阻网络模型,并确定求解方法. 纤维载体流速场实例分析的结果表明,基于等效电阻网络模型求解的纤维载体流速场与计算流体力学(CFD)方法的结果之间的皮尔森相关系数约为98%,且求解效率约为CFD方法的2.9×10⁴倍. 研究成果为多孔纤维型重整制氢微反应器的设计制造提供了新的支撑方案.     

Corrosion resistance of electroplated Zn-Co alloy coating

By the NSS test and the test in SO2 gas atmosphere and detecting the φcorr-t curves, Rp-t curves and the cyclic voltammogram curves, the corrosion resistance of the electroplated Zn-Co alloy coating was studied. The corrosion resistance of the electroplated Zn-Co alloy coating is three times higher than that of the galvanized coating. Because the corrosion resistance of the Zn-Co alloy coating is especially remarkable in SO2 gas atmosphere, it is particularly fit to be used as a protective coating in industrial atmosphere. The reason why the Zn-Co alloy coating has such a high corrosion resistance is that its corrosive product has a comparatively great role in depressing the corrosive process.     

铈对中铝耐热铸铁抗氧化性能的影响

采用氧化增重法测定了含Ce中铝耐热铸铁在850℃时氧化动力学曲线，用SEM，X－ray对氧化膜表面的形貌，结构及氧化层－基体界面进行了观察分析，结果表明：Ce改变了中铝耐热铸铁氧化膜的结构和组成，提高了中铝耐热铸铁的抗氧化性能。     

2＋2×0.32ST超高强度钢丝帘线在半钢子午线轮胎带束层中的应用

研究2+2×0.32ST钢丝帘线替代2+2×0.35HT钢丝帘线在半钢子午线轮胎带束层中的应用。结果表明:与2+2×0.35HT钢丝帘线相比,2+2×0.32ST钢丝帘线的强度更高、直径更小、耐疲劳性能更好;在轮胎带束层中用2+2×0.32ST钢丝帘线替代2+2×0.35HT钢丝帘线后,工艺性能良好,成品轮胎的充气外缘尺寸变化不大,强度性能、高速性能、耐久性能和耐水压性能均能满足设计和国家标准要求,滚动阻力降低,同时有效减小了轮胎中的钢丝帘线和胶料用量,降低了生产成本。     

阻燃OMMT/WPU纳米复合材料的制备及性能研究

采用端羟基聚丁二烯（HTPB）剥离层状有机蒙脱土（OMMT）为纳米片层,并与异佛尔酮二异氰酸酯（IPDI）、二羟甲基丙酸（DMPA）等单体通过原位聚合法制备了OMMT纳米片改性的水性聚氨酯（OWPU）纳米乳液及胶膜。利用小角XRD、TEM、DLS、EDS、TGA、LOI、CONE以及SEM对样品的结构和性能进行了表征。结果表明,HTPB剥离的OMMT纳米片的衬度均匀,完整性较好;改性后OWPU的乳液粒径增大,胶膜的弹性模量、热稳定性、抗熔滴性和阻燃性能均得到明显地改善,其中弹性模量可提高59.4%,热释放速率峰值可降低36.9%;燃烧炭渣表面形貌显示,瓦片状蒙脱土相互穿插形成了具有团簇结构的蒙脱土覆盖层。     

金属陶瓷防腐蚀涂层替代镀镉或镉−钛工艺的研究

针对钢制零件采用镀镉、镀镉?钛工艺存在氢脆、镉脆风险及不利于环境保护的现状,研究采用涂覆IPcote9183或IPcote9183+IPseal9184形成金属陶瓷防腐蚀涂层(MCAC)的替代工艺。对比结果表明:上述2种金属陶瓷涂层的氢脆性和耐蚀性优于镉及镉?钛镀层,其他性能相当,能够完全替代它们应用于起落架钢制零件的表面防护。     

The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.