Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is currently spreading globally. To overcome the COVID-19 pandemic, preclinical evaluations of ...vaccines and therapeutics using K18-hACE2 and CAG-hACE2 transgenic mice are ongoing. However, a comparative study on SARS-CoV-2 infection between K18-hACE2 and CAG-hACE2 mice has not been published. In this study, we compared the susceptibility and resistance to SARS-CoV-2 infection between two strains of transgenic mice, which were generated in FVB background mice. K18-hACE2 mice exhibited severe weight loss with definitive lethality, but CAG-hACE2 mice survived; and differences were observed in the lung, spleen, cerebrum, cerebellum, and small intestine. A higher viral titer was detected in the lungs, cerebrums, and cerebellums of K18-hACE2 mice than in the lungs of CAG-hACE2 mice. Severe pneumonia was observed in histopathological findings in K18-hACE2, and mild pneumonia was observed in CAG-hACE2. Atrophy of the splenic white pulp and reduction of spleen weight was observed, and hyperplasia of goblet cells with villi atrophy of the small intestine was observed in K18-hACE2 mice compared to CAG-hACE2 mice. These results indicate that K18-hACE2 mice are relatively susceptible to SARS-CoV-2 and that CAG-hACE2 mice are resistant to SARS-CoV-2. Based on these lineage-specific sensitivities, we suggest that K18-hACE2 mouse is suitable for highly susceptible model of SARS-CoV-2, and CAG-hACE2 mouse is suitable for mild susceptible model of SARS-CoV-2 infection.
Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the ...receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.
Introduction
The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor ...in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea.
Materials and Methods
Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at −80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate.
Results
The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate.
Conclusion
The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.
Direct chemical vapor deposition (CVD) growth of single‐layer graphene on CVD‐grown hexagonal boron nitride (h‐BN) film can suggest a large‐scale and high‐quality graphene/h‐BN film hybrid structure ...with a defect‐free interface. This sequentially grown graphene/h‐BN film shows better electronic properties than that of graphene/SiO2 or graphene transferred on h‐BN film, and suggests a new promising template for graphene device fabrication.
CO2 emitted from calcination processes in kilns comprises 60% of all emissions from cement production. The chemical components of building materials, demolished inorganic building materials (DIBMs), ...and waste concrete powder (WCP) are similar to those of cement minerals. Therefore, if DIBMs are used as a cement substitute material along with limestone, the quantity of disposed waste and the use of limestone will likely be reduced, as will CO2 emissions during cement production. This study proposes a recycling method for recycled cement, using DIBMs and WCP as cement substitute materials, and the properties of trial recycled cement were evaluated. The mortar specimen using recycled cement showed a high compressive strength, as did the ordinary Portland cement mortar. According to the proposed composition, the producible recycled cement was derived from 0.5% to 9.1% of annual cement production (about 57.6 million tons) in Japan. Additionally, the CO2 reduction by usage of recycled cement ranged from 0.06 million tons to 0.72 million tons from the total annual CO2 emissions from cement production (about 29.4 million tons), using natural resources in Japan.
This retrospective cohort study investigated the risk and mortality rate due to aspiration pneumonia in patients with Parkinson's disease (PD) using a nationwide database. We identified 10,159 newly ...diagnosed PD patients between 2004 and 2006, and four age- and sex-matched controls for each PD patient from the National Health Insurance Service database in Korea. We analyzed the relative risk of aspiration pneumonia and mortality after the first occurrence of aspiration pneumonia until 2017. Throughout the study period, PD patients showed a higher incidence of aspiration pneumonia than their matched controls (3.01 vs. 0.59 events per 1,000 person-years), and they were at an increased risk of aspiration pneumonia (hazard ratio = 4.21; 95% confidence interval, 3.87-4.58). After the first occurrence of aspiration pneumonia, the mortality rate of PD patients was 23.9% after one month, 65.2% after 1 year, and 91.8% after 5 years, while that of controls was 30.9%, 67.4%, and 88.9%, respectively. Patients with PD are at an increased risk of aspiration pneumonia, and approximately two-thirds of the patients die within a year after experiencing aspiration pneumonia. Further studies are warranted to prevent aspiration pneumonia and implement proper treatments to prevent death after aspiration pneumonia in patients with PD.
This study examined the effects of increasing concrete unit water content and artificially controlling water content on concrete performance in the production process of ready-mixed concrete. Results ...showed that changes in the unit water content of 20 concrete mix proportions without air-entraining significantly reduced concrete compressive strength, increased porosity, and in-creased occurrence of bleeding. A unit water content increase of 25 kg/m
or more may reduce the compressive strength of concrete below the design standard and significantly affect the occurrence of bleeding water. Moreover, an extra unit water content of at least 25 kg/m
could significantly affect the diffusion of chloride ions in the concrete. The carbonation depth of concrete was extremely high with the increase in unit water content and water addition. In the production of concrete requiring at least normal strength or durability, the extra water change to total unit water content should be maintained at 15 kg/m
or less. And a water-cement ratio of 48% or less and a unit water content of 155 kg/m
or less are considered effective for management of concrete quality. Considering the aggregate type, absorption rate, and moisture state, the management of unit water content error in concrete production processes requires greater.
Translational regulation in tissue environments during in vivo viral pathogenesis has rarely been studied due to the lack of translatomes from virus-infected tissues, although a series of translatome ...studies using in vitro cultured cells with viral infection have been reported. In this study, we exploited tissue-optimized ribosome profiling (Ribo-seq) and severe-COVID-19 model mice to establish the first temporal translation profiles of virus and host genes in the lungs during SARS-CoV-2 pathogenesis. Our datasets revealed not only previously unknown targets of translation regulation in infected tissues but also hitherto unreported molecular signatures that contribute to tissue pathology after SARS-CoV-2 infection. Specifically, we observed gradual increases in pseudoribosomal ribonucleoprotein (RNP) interactions that partially overlapped the trails of ribosomes, being likely involved in impeding translation elongation. Contemporaneously developed ribosome heterogeneity with predominantly dysregulated 5 S rRNP association supported the malfunction of elongating ribosomes. Analyses of canonical Ribo-seq reads (ribosome footprints) highlighted two obstructive characteristics to host gene expression: ribosome stalling on codons within transmembrane domain-coding regions and compromised translation of immunity- and metabolism-related genes with upregulated transcription. Our findings collectively demonstrate that the abrogation of translation integrity may be one of the most critical factors contributing to pathogenesis after SARS-CoV-2 infection of tissues.
Existing deicing technologies involving chloride and heating wires have limitations such as reduced durability of roads and surrounding structures, and high labor requirements and maintenance costs. ...Hence, in this study, we performed indoor experiments, numerical analyses, and field tests to examine the efficiency of deicing using carbon nanotubes (CNTs) to overcome these limitations. For indoor experiments, a CNT was inserted into the center of a concrete sample and then heated to 60 °C while maintaining the ambient and internal temperatures of the sample at −10 °C using a refrigeration chamber. Numerical analysis considering thermal conductivity was performed based on the indoor experimental results. Using the calculation results, field tests were conducted, and the thermal conduction performance of the heating element was examined. Results showed that the surface temperature between the heating elements exceeded 0 °C. Moreover, we found that the effective heating distance of the heating elements should be 20–30 cm for effective thermal overlap through the indoor experiments. Additionally, the numerical analysis results indicated that the effective heating distance increased to 100 cm when the heating element temperature and experiment time were increased. Field test results showed that 62 cm-deep snow melted between the heating elements (100 cm), thus, verifying the possibility of deicing.
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. Several genome sequencing studies have provided comprehensive CRC genomic datasets. Likewise, in our previous ...study, we performed genome-wide Sleeping Beauty transposon-based mutagenesis screening in mice and provided comprehensive datasets of candidate CRC driver genes. However, functional validation for most candidate CRC driver genes, which were commonly identified from both human and mice, has not been performed. Here, we describe a platform for functionally validating CRC driver genes that utilizes CRISPR-Cas9 in mouse intestinal tumor organoids and human CRC-derived organoids in xenograft mouse models. We used genetically defined benign tumor-derived organoids carrying 2 frequent gene mutations (Apc and Kras mutations), which act in the early stage of CRC development, so that we could clearly evaluate the tumorigenic ability of the mutation in a single gene. These studies showed that Acvr1b, Acvr2a, and Arid2 could function as tumor suppressor genes (TSGs) in CRC and uncovered a role for Trp53 in tumor metastasis. We also showed that co-occurrent mutations in receptors for activin and transforming growth factor-β (TGF-β) synergistically promote tumorigenesis, and shed light on the role of activin receptors in CRC. This experimental system can also be applied to mouse intestinal organoids carrying other sensitizing mutations as well as organoids derived from other organs, which could further contribute to identification of novel cancer driver genes and new drug targets.
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