Identification of Inhibitors and Drug Targets for Human Adenovirus Infections

Adenoviruses can cause infections in people of all ages at all seasons of the year. Adenovirus infections cause mild to severe illnesses. Children, immunocompromised patients, or those with existing respiratory or cardiac disease are at higher risk. Unfortunately, there are no commercial drugs or vaccines available on the market for adenovirus infections. Therefore, there is an urgent need to discover new antiviral drugs or drug targets for adenovirus infections. To identify potential antiviral agents for adenovirus infections, we screened a drug library containing 2138 compounds, most of which are drugs with known targets and past phase I clinical trials. On a cell-based assay, we identified 131 hits that inhibit adenoviruses type 3 and 5. A secondary screen confirmed the antiviral effects of 59 inhibitors that inhibit the replication of adenoviruses type 3 or 5. Most of the inhibitors target heat shock protein, protein tyrosine kinase, the mTOR signaling pathway, and other host factors, suggesting that these host factors may be essential for replicating adenoviruses. Through this study, the newly identified adenovirus inhibitors may provide a start point for developing new antiviral drugs to treat adenovirus infections. Further validation of the identified drug targets can help the development of new therapeutics against adenovirus infections.     

Multi-Step Forming Simulation and Quality Control of Aluminum Alloy Automobile Rear Upper Control Arm

Aluminum alloy is widely used in automobile parts because of its light weight and good process performance. In view of the complex structure of aluminum alloy automobile rear upper control arms, multiple forming processes and the difficulty in quality control, in this paper, we propose a rolling-forging composite process to produce a rear upper control arm. Based on the reasonable volume distribution of the blank by cross-wedge rolling, multi-step forging was carried out. Finite element simulation of thermomechanically coupled multi-step forming was carried out using DEFORM software. Based on a comparison of the traditional process and the proposed rolling-forging composite forming process, we concluded that the rolling-forging composite process can greatly reduce the material cost and the forming force, resulting in superior product performance. The coarse-grain structure of products at different process temperatures was analyzed by a crystal-phase experiment. The results show that the process temperature of the multi-step process, as well as the heat treatment temperature and time have an important influence on the coarse-grain structure of the product. The optimal preheating temperatures for preforging and final forging dies were determined to be 335 °C and 350 °C, respectively; a preheating temperature of 530 °C and a solution time of 45 min resulted in the least coarse-grain surface structure. The research results provide a theoretical basis for improving the multi-step forming quality of automobile rear upper control arms.     

Magnetic Properties and Washability of Roasted Suspended Siderite Ores

Steel is one of the most important industrial materials, which mainly comes from the smelting of iron ore. In view of the huge steel consumption every year, the exploitation of vast reserves of siderite ores is significant for improving the self-sufficiency rate of iron ore resources and ensuring the strategic security of the iron and steel industries. This paper investigated the influence of temperature, time, and other parameters on the magnetic properties of roasted siderite ores using the method of suspended roasting and analyzed the washability of roasted ores under weak-magnetic-field conditions using the magnetic separation tube experiment. The findings of the study explained the iron phase transformation process, i.e., FeCO₃ was transformed into Fe₃O₄ by suspension magnetization roasting. Furthermore, the saturation magnetization of the roasted ore increased in due time at a constant temperature range of 550–750 °C and a roasting time of less than 5 s. It also increased with increasing temperature and constant time. The roasted ore achieved the best magnetic characteristics after roasting at 750 °C for 5 s. After low-intensity magnetic separation, the iron grade of the concentrate changed to 55.12%, with a recovery rate of 90.34%. The study results provide a reference for the development and application of siderite suspension magnetization roasting technology.     

Resistance of Xanthomonas oryzae pv. oryzae to Lytic Phage X2 by Spontaneous Mutation of Lipopolysaccharide Synthesis-Related Glycosyltransferase

Phage therapy is a promising biocontrol management on plant diseases caused by bacterial pathogens due to its specificity, efficiency and environmental friendliness. The emergence of natural phage-resistant bacteria hinders the application of phage therapy. Xanthomonas oryzae pv. oryzae (Xoo) is the causal agent of the devastating bacterial leaf blight disease of rice. Here, we obtained a spontaneous mutant C2R of an Xoo strain C2 showing strong resistance to the lytic phage X2. Analysis of the C2R genome found that the CDS2289 gene encoding glycosyltransferase acquired a frameshift mutation at the 180th nucleotide site, which also leads to a premature stop mutation at the 142nd amino acid. This mutation confers the inhibition of phage adsorption through the changes in lipopolysaccharide production and structure and bacterial surface morphology. Interestingly, glycosyltransferase-deficient C2R and an insertional mutant k2289 also showed reduced virulence, suggesting the trade-off costs of phage resistance. In summary, this study highlights the role of glycosyltransferase in interactions among pathogenic bacteria, phages and plant hosts, which provide insights into balanced coevolution from environmental perspectives.     

Burst Pressure Prediction of Subsea Supercritical CO2 Pipelines

To improve transportation efficiency, a supercritical CO₂ pipeline is the best choice for large-scale and long-distance transportation inshore and offshore. However, corrosion of the pipe wall will occur as a result of the presence of free water and other impurities present during CO₂ capture. Defects caused by corrosion can reduce pipe strength and result in pipe failure. In this paper, the burst pressure of subsea supercritical CO₂ pipelines under high pressure is investigated. First, a mechanical model of corroded CO₂ pipelines is established. Then, using the unified strength theory (UST), a new burst pressure equation for subsea supercritical CO₂ pipelines is derived. Next, analysis of the material’s intermediate principal stress parameters is conducted. Lastly, the accuracy of the burst pressure equation of subsea supercritical CO₂ pipelines is proven to meet the engineering requirement by experimental data. The results indicate that the parameter b of UST plays a significant role in determining burst pressure of pipelines. The study can provide a theoretical basis and reference for the design of subsea supercritical CO₂ pipelines.     

我国放射卫生学学科建设与放射卫生工作回顾

随着人们对电离辐射对人类健康危害的认识,以及随之开展的电离辐射生物效应及防护措施的研究,逐步形成了放射卫生学。因此作为传统的公共卫生体系下的五大卫生之一,放射卫生主要围绕电离辐射对人体健康有害影响及其综合防护措施开展工作。从上世纪三、四十年代起,经过近百年的蓬勃发展,现阶段我国的放射卫生学学科水平和放射卫生工作成效等有了很大提升。本文就放射卫生学研究与我国放射卫生工作的历史、现状、工作内容等情况进行简单的概述,以期为我国放射卫生工作今后的发展提供助力。     

Human Retrovirus Genomic RNA Packaging

Two non-covalently linked copies of the retrovirus genome are specifically recruited to the site of virus particle assembly and packaged into released particles. Retroviral RNA packaging requires RNA export of the unspliced genomic RNA from the nucleus, translocation of the genome to virus assembly sites, and specific interaction with Gag, the main viral structural protein. While some aspects of the RNA packaging process are understood, many others remain poorly understood. In this review, we provide an update on recent advancements in understanding the mechanism of RNA packaging for retroviruses that cause disease in humans, i.e., HIV-1, HIV-2, and HTLV-1, as well as advances in the understanding of the details of genomic RNA nuclear export, genome translocation to virus assembly sites, and genomic RNA dimerization.     

Moderate Hypofractionated Helical Tomotherapy for Older Patients with Localized Prostate Cancer: Long-term Outcomes of a Phase I–II Trial

BackgroundOur previous study showed that two different regimens of moderate hypofractionated radiotherapy (HFRT) delivered with helical tomotherapy (HT) are well tolerated in older prostate cancer patients. We provide a longterm efficacy and toxicity after > 7 years of follow-up.Patients and methodsThe study recruited 33 patients from February 2009 to July 2011 (76 Gy/34F; Group-1); and 34 from July 2011 to February 2014 (71.6 Gy/28F; 50.4 Gy/25F for the risk of pelvic lymph nodes involvement (LNI) >15%; Group-2). The primary outcomes were biochemical failure (BF), biochemical failure and clinical disease failure (BCDF), progression-free survival (PFS), overall survival (OS), late genitourinary (GU) and gastrointestinal (GI) toxicity.ResultsThe average ages of two groups were 80 and 77 years and the proportions of patients with LNI > 15% were 69.7% and 73.5%, respectively. At the final follow-up in February 2020, 27.3% and 20.6% cases experienced BF, with a median time until BF of 3.3 years. A total of 38.8% patients reached primary endpoints, in which 18 deaths were reported BCDF events (45.5% vs. 32.4%, p = 0.271). There was no significant difference in 7-year PFS (68.6% vs. 74.8%, p = 0.591), BCDF (45.5% vs. 32.4%, p = 0.271) and OS (71.9% vs. 87.5%, p = 0.376) for full set analysis and for subgroup analysis (all p > 0.05). The incidence of grade ≥ 2 late GU (6.2% vs. 6.3%, p = 0.127) and GI toxicities (9.4% vs. 15.6%, p = 0.554) was comparable.ConclusionsIn older patients with localized prostate cancer, two moderate hypofractionated regimens were all well tolerated with similar, mild late toxicities and satisfactory survival, without necessity of prophylactic pelvic node irradiation.Key words: helical tomotherapy, radiation dose hypofractionation, progression-free survival, follow-up studies, prostatic neoplasms, adenocarcinoma     

软组织损伤超声治疗研究现状

尽管超声广泛用于治疗软组织损伤,而且超声的生物物理学效应通过体外研究也得以证实,但超声对软组织损伤的治疗效果仍受到质疑。很少有确切的证据表明超声治疗软组织损伤有效,其原因可能与多种因素有关,如技术方面的变数,临床研究中方法学的局限与缺陷,或者超声确实缺少治疗作用。     

Anticholinergic treatment for sialorrhea in children: A systematic review

BackgroundSialorrhea in children can be associated with adverse physical and social effects. Treatment using anticholinergic medications has been shown to offer symptomatic relief, but there is no consensus regarding which treatment is the most efficacious.ObjectiveTo examine the effectiveness of anticholinergic medications for sialorrhea in children.MethodsA systematic review was carried out in Medline, EMBASE, Cochrane, Scopus, and the Web of Science from inception until April 29, 2020. Studies reporting original data on the efficacy of anticholinergic medications in the management of sialorrhea in children aged 0 to 17 years of age were included. This review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. Data on study design, setting, population, pharmacologic intervention(s), comparator(s), outcomes, and results were extracted and summarized.ResultsThe search strategy identified 2,800 studies of which 27 articles were included in the synthesis, including five randomized controlled trials. Each anticholinergic undergoing experimental study (glycopyrrolate, scopolamine/hyoscine, trihexyphenidyl/benzhexol, benztropine, and atropine) showed evidence of efficacy. Adverse side effects were common. Significant heterogeneity exists in the studies’ methodology and the variability of outcome measures used between studies precluded a meta-analysis.ConclusionsGlycopyrrolate, scopolamine/hyoscine, trihexyphenidyl/benzhexol, benztropine, and atropine have all shown efficacy in the treatment of sialorrhea in children. The small number of reports and the variability in study design precluded a meta-analysis. More studies are needed with uniformity in outcome measures to help guide evidence-based decision making. A guidance table is presented.