An antibody targeting the N-terminal domain of SARS-CoV-2 disrupts the spike trimer

The protective human antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) focuses on the spike (S) protein, which decorates the virion surface and mediates cell binding and entry. Most SARS-CoV-2 protective antibodies target the receptor-binding domain or a single dominant epitope (“supersite”) on the N-terminal domain (NTD). Using the single B cell technology called linking B cell receptor to antigen specificity through sequencing (LIBRA-Seq), we isolated a large panel of NTD-reactive and SARS-CoV-2–neutralizing antibodies from an individual who had recovered from COVID-19. We found that neutralizing antibodies against the NTD supersite were commonly encoded by the IGHV1-24 gene, forming a genetic cluster representing a public B cell clonotype. However, we also discovered a rare human antibody, COV2-3434, that recognizes a site of vulnerability on the SARS-CoV-2 S protein in the trimer interface (TI) and possesses a distinct class of functional activity. COV2-3434 disrupted the integrity of S protein trimers, inhibited the cell-to-cell spread of the virus in culture, and conferred protection in human angiotensin-converting enzyme 2–transgenic (ACE2-transgenic) mice against the SARS-CoV-2 challenge. This study provides insight into antibody targeting of the S protein TI region, suggesting this region may be a site of virus vulnerability.     

Association of Dietary Fish and n-3 Unsaturated Fatty Acid Consumption with Diabetic Nephropathy from a District Hospital in Northern Taiwan

Nephropathy caused by diabetes mellitus (DM) is the main cause of end-stage renal disease (ESRD). To understand the association of dietary intake with renal function indicators among patients with diabetic nephropathy (DN), this cross-sectional study was conducted at the dietetic consultation clinic of the Taoyuan Armed Forces General Hospital in Taiwan. In total, 317 participants were recruited for this study. Patients with diabetes who had a urinary albumin–creatinine ratio (UACR) of ≥30 mg/g were defined as having DN. The anthropometric characteristics, blood biochemistry, and renal function of the participants were assessed. Furthermore, a semiquantitative food frequency questionnaire (SQFFQ) was administered to investigate the dietary intake of the participants in the DM and DN groups. The result showed that participants in the DN group were older, had longer diabetes duration and poorer glycemic control and renal function than those in the DM group. Logistic regression models revealed that intake of high-fat marine fishes had the lowest odds ratio (OR) for DN risk compared with other fishes (OR: 0.868; 95% CI: 0.781–0.965, p = 0.009). Shellfish, soybean products, and skim milk also provided better protective effects to decrease the risk of DN. A further analysis of polyunsaturated fatty acids revealed that Σn-3 PUFAs significantly reduced DN risk, while Σn-6 PUFAs did not, especially EPA (OR: 0.821; 95% CI: 0.688–0.979, p = 0.029) and DHA (OR: 0.903; 95% CI: 0.823–0.992, p = 0.033) regardless of whether the variables were adjusted, including diabetes duration, age, and HbA1c. Our findings suggest that a diet that incorporates high-fat fish, shellfish, soybean products, and a lower Σn-6/Σn-3 ratio can mitigate DN risk.     

A Novel Herbal Extract Blend Product Prevents Particulate Matters-Induced Inflammation by Improving Gut Microbiota and Maintaining the Integrity of the Intestinal Barrier

Air pollutants of PM2.5 can alter the composition of gut microbiota and lead to inflammation in the lung and gastrointestinal tract. The aim of this study was to evaluate the protective effect of a novel herbal extract blend, FC, composed of Lonicera japonica extract, Momordica grosvenori extract, and broccoli seed extract, on PM2.5-induced inflammation in the respiratory and intestinal tract. A549 cells and THP-1 cells, as well as C57BL/6 mice, were stimulated with PM2.5 to establish in vitro and in vivo exposure models. The models were treated with or without FC. The expression of inflammatory cytokines and tight junction proteins were studied. Proteomic analysis was performed to elucidate mechanisms. Mouse feces were collected for gut microbiota analysis. FC was shown to modulate the upregulation of pro-inflammatory cytokines mRNA expression in A549 and THP-1 cells and downregulated tight junction proteins mRNA expression in A549 cells due to PM2.5 stimulation. In animal models, the decreased expression of the anti-inflammatory factor il-10, tight junction protein ZO-1, and the elevated expression of COX-2 induced by PM2.5 were improved by FC intervention, which may be associated with zo-1 and cox-2 signaling pathways. In addition, FC was shown to improve the gut microbiota by increasing the abundance of beneficial bacteria.     

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。