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关键词： miRNA治疗   癌症   肝炎   心血管疾病   糖尿病  

摘要： microRNAs(miRNAs)是一类内源性、非编码小分子RNAs(约22 nt),在基因表达调控中发挥关键作用。已有研究表明,miRNAs失调是造成多种人类疾病的原因,如癌症、病毒感染及自身免疫性疾病等。补充或抑制miRNAs功能与活性已成为多种疾病治疗的新策略,抗肿瘤miR-34mimics、治疗HCV感染的anti-miR-122等基于miRNAs的治疗方案已进入临床试验。重点就miRNAs治疗在癌症及其他疾病中的最新研究进展进行综述,并对目前开发安全有效miRNAs治疗策略所面临的挑战进行分析。

关键词： Organic acids   Catalysts   Metals   Ligands   Organic reactions  

摘要： The reaction of the hexahydride OsH6(PiPr(3))(2) with a P,Ge,P-germylene-diphosphine affords an osmium tetrahydride derivative bearing a Ge,P-chelate, which arises from the hydrogenolysis of a P-C(sp(3)) bond. This Os(IV)-Ge(II) compound is a pioneering example of a bifunctional catalyst based on the coordination of a sigma-donor acid, which is active in the dehydrogenation of formic acid to H-2 and CO2. The kinetics of the dehydrogenation, the characterization of the resting state of the catalysis, and DFT calculations point out that the hydrogen formation (the fast stage) exclusively occurs on the coordination sphere of the basic metal center, whereas both the metal center and the sigma-donor Lewis acid cooperatively participate in the CO2 release (the rate-determining step). During the process, the formate group pivots around the germanium to approach its hydrogen atom to the osmium center, which allows its transfer to the metal and the CO2 release.

关键词： composite materials   mechanical strength   turbine engine fuel   carbon fiber   alternative jet fuel  

摘要： New commercial and military aircraft components are often manufactured using advanced composite materials. Fuel is stored in the wing and horizontal tail structures of aircraft for prolonged periods of time. The use of alternative turbine engine fuels as substitutes for such kerosene-based fuels as Jet-A is increasing steadily. However, the studies related to effects of the fuels on the composite structure of aircraft are limited in number. This research was meant to investigate the effects that contacting alternative turbine fuels might have on the mechanical properties of a composite structure. Three different test settings were prepared - 0 and 90 degrees orientation tensile and a modified wedge ones. An IM7 8552 unidirectional carbon fiber/epoxy prepreg was used to manufacture test specimens. They were soaked in various kinds of turbine engine fuels: neat Jet-A, 50/50 blend of Jet-A and hydroprocessed renewable jet (HRJ) (Jet-A/HRJ), Fischer-Tropsch (FT), 50/50 blend of synthetic jet fuel S8 and Fischer-Tropsch (FT) (S8/FT), hydrogenated esters and fatty acids (HEFA) fuels, and synthesized iso-paraffin fuels (SIP) for a period of 45 days and then tested. The test data obtained were analyzed to detect any significant degradation of the mechanical properties of test specimens.

关键词： dysregulation of RNA processing   alternative splicing   therapeutic targeting of alternative splicing   cancer   gastrointestinal malignancies  

摘要： Recent comprehensive genomic studies including single-cell RNA sequencing and characterization have revealed multiple processes by which protein-coding and noncoding RNA processing are dysregulated in many cancers. More specifically, the abnormal regulation of mRNA and precursor mRNA (pre-mRNA) processing, which includes the removal of introns by splicing, is frequently altered in tumors, producing multiple different isoforms and diversifying protein expression. These alterations in RNA processing result in numerous cancer-specific mRNAs and pathogenically spliced events that generate altered levels of normal proteins or proteins with new functions, leading to the activation of oncogenes or the inactivation of tumor suppressor genes. Abnormally spliced pre-mRNAs are also associated with resistance to cancer treatment, and certain cancers are highly sensitive to the pharmacological inhibition of splicing. The discovery of these alterations in RNA processing has not only provided new insights into cancer pathogenesis but identified novel therapeutic vulnerabilities and therapeutic opportunities in targeting these aberrations in various ways (e.g., small molecules, splice-switching oligonucleotides (SSOs), and protein therapies) to modulate alternative RNA splicing or other RNA processing and modification mechanisms. Some of these strategies are currently progressing toward clinical development or are already in clinical trials. Additionally, tumor-specific neoantigens produced from these pathogenically spliced events and other abnormal RNA processes provide a potentially extensive source of tumor-specific therapeutic antigens (TAs) for targeted cancer immunotherapy. Moreover, a better understanding of the molecular mechanisms associated with aberrant RNA processes and the biological impact they play might provide insights into cancer initiation, progression, and metastasis. Our goal is to highlight key alternative RNA splicing and processing mechanisms and their roles

关键词： Constrained multi-objective optimization   Evolutionary algorithm   Dual population  

摘要： It is challenging to solve constrained multi-objective optimization problems (CMOPs). Different from the traditional multi-objective optimization problem, the feasibility, convergence, and diversity of the population must be considered in the optimization process of a CMOP. How these factors are balanced will affect the performance of the constrained multi-objective optimization algorithm. To solve this problem, we propose a dual population multi-objective optimization evolutionary algorithm. The proposed algorithm can make good use of its secondary population and alternative between evolution and degeneration according to the state of the secondary population to provide better information for the main population. The test results of three benchmark constrained multi objective optimization problem suites, and four real-world constrained multi-objective optimization problems show that the algorithm is better than existing dual-population multi-objective optimization, especially when there is a distance between the unconstrained PF and the constrained PF. (c) 2021 Elsevier Inc. All rights reserved.

关键词： diabetes mellitus   glucose metabolism   gastrointestinal endoscopy   duodenal mucosa   fatty liver  

摘要： Correspondence to Professor Jacques J G H M Bergman, Gastroenterology and Hepatology, Amsterdam UMC Location AMC, Amsterdam 1105 AZ, The Netherlands; ***@*** Key messages Despite important and promising advances in oral and injectable glucose-lowering medications for type 2 diabetes, overall control of blood glucose remains suboptimal in most patients. Abstract Introduction The number of patients with type 2 diabetes (T2D) worldwide is expected to increase from 463 million in 2019 to 700 million in 2045, with a prevalence of more than 10% in Europe. Besides a role for genetics, causative factors include obesity, diet high in refined sugar and fat, and sedentary lifestyle. [...]for the majority of patients with T2D (about 60%), metformin monotherapy is not sufficient to achieve euglycaemia.9 As a next step, the most recent guidelines by the American Diabetes Association and the European Association for the Study of Diabetes10 advise to add either a glucagon-like peptide-1 receptor agonist (GLP-1RA), a dipeptidyl peptidase-4 inhibitor (DPP-4i) or a sodium-glucose cotransporter 2 inhibitor (SGLT2i) in patients with T2D and established cardiovascular disease, heart failure, or when there is a compelling need to minimise hypoglycaemia or to control weight. In patients with T2D, the incretin response is blunted and circulating GLP-1 levels are reduced.11 GLP-1RAs improve insulin sensitivity and lower blood glucose, induce 2–6 kg of weight loss on average, reduce apoptosis of beta cells and increase their proliferation.

关键词： Augmentative and alternative communication   Speech production   Autism spectrum disorder  

摘要： This review evaluated the effects of augmentative and alternative communication (AAC) on speech development in children with autism spectrum disorders (ASD);replicated, updated, and extended the systematic review by Schlosser and Wendt (American Journal of Speech-Language Pathology 17:212-230, 2008). Twenty-five single case design articles and three group design articles published between 1975 and May 2020 met inclusion criteria related to participant characteristics, intervention type, design, and visual analysis of dependent variable outcomes. Overall, AAC resulted in improved speech production;however, speech gains that did occur did not surpass AAC use.

关键词： horse   thymoma   thoracic mass   neoplasia   thoracoscopy  

摘要： Thymoma is a rare condition in horses. This case of a 24-year-old Warmblood gelding that was presented with oedema and signs of vascular congestion of the left forelimb caused by a thoracic mass is described. The diagnostic work-up included blood chemistry, cytology of pleural effusion, ultrasonography, radiography and the visualisation and collection of a tissue sample by thoracoscopy. Finally, post-mortem findings and histopathology revealed thymic epithelial neoplasia with histomorphologic features previously unreported in horses. The unique mixture of spindle-shaped and epithelioid tumour cells in combination with clear features of malignancy suggested the application of the Moran and Suster histological classification system for thymomas in humans (Moran and Suster, 2008, Curr. Treat. Options Oncol., 9, 288), which has not been reported in an equine case before and fits well to the present case.

关键词： dry reforming   catalysts   metal carbides   molybdenum   tungsten   titanium  

摘要： Dry reforming of hydrocarbons (DRH) is a pro-environmental method for syngas production. It owes its pro-environmental character to the use of carbon dioxide, which is one of the main greenhouse gases. Currently used nickel catalysts on oxide supports suffer from rapid deactivation due to sintering of active metal particles or the deposition of carbon deposits blocking the flow of gases through the reaction tube. In this view, new alternative catalysts are highly sought after. Transition metal carbides (TMCs) can potentially replace traditional nickel catalysts due to their stability and activity in DR processes. The catalytic activity of carbides results from the synthesis-dependent structural properties of carbides. In this respect, this review presents the most important methods of titanium, molybdenum, and tungsten carbide synthesis and the influence of their properties on activity in catalyzing the reaction of methane with carbon dioxide.