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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.

In early 2000,large domestic shipyards introduced shipbuilding 3D computer-aided design （CAD） to the hull production design process to define manufacturing and assembly information.The production design process accounts for most of the man-hours （M/H） of the entire design process and is closely connected to yard production because designs must take into account the production schedule of the shipyard,the current state of the dock needed to mount the ship＇s block,and supply information.Therefore,many shipyards are investigating the complete automation of the production design process to reduce the M/H for designers.However,these problems are still currently unresolved,and a clear direction is needed for research on the automatic design base of manufacturing rules,batches reflecting changed building specifications,batch updates of boundary information for hull members,and management of the hull model change history to automate the production design process.In this study,a process was developed to aid production design engineers in designing a new ship＇s hull block model from that of a similar ship previously built,based on AVEVA Marine.An automation system that uses the similar ship＇s hull block model is proposed to reduce M/H and human errors by the production design engineer.First,scheme files holding important information were constructed in a database to automatically update hull block model modifications.Second,for batch updates,the database＇s table,including building specifications and the referential integrity of a relational database were compared.In particular,this study focused on reflecting the frequent modification of building specifications and regeneration of boundary information of the adjacent panel due to changes in a specific panel.Third,the rollback function is proposed in which the database （DB） is used to return to the previously designed panels.

This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol‐lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash‐out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low‐density lipoprotein‐C (LDL‐C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were −23.02 (3.04) versus −7.18 (3.09) mmHg in the TRE and RE groups, respectively (p < .0001), and −25.80 (2.74) versus −14.92 (2.65) mmHg in the TRE and T groups, respectively (p = .0005). The percentage changes in the mean (SD) LDL‐C at 8 weeks compared with baseline were −54.97% (3.49%) versus −0.17% (3.23%) in the TRE and T groups, respectively (p < .0001). No serious adverse events occurred, and no statistically significant differences in the incidence of overall AEs and adverse drug reactions occurred among the three groups. TRE therapy significantly decreased msSBP and LDL‐C compared to RE or T therapy with comparable safety and tolerability profiles.

The industrial potential of Saccharomyces cerevisiae has extended beyond its traditional use in fermentation to various applications, including recombinant protein production. Herein, comparative genomics was performed with three industrial S. cerevisiae strains and revealed a heterozygous diploid genome for the 98‐5 and KSD‐YC strains (exploited for rice wine fermentation) and a haploid genome for strain Y2805 (used for recombinant protein production). Phylogenomic analysis indicated that Y2805 was closely associated with the reference strain S288C, whereas KSD‐YC and 98‐5 were grouped with Asian and European wine strains, respectively. Particularly, a single nucleotide polymorphism (SNP) in FDC1 , involved in the biosynthesis of 4‐vinylguaiacol (4‐VG, a phenolic compound with a clove‐like aroma), was found in KSD‐YC, consistent with its lack of 4‐VG production. Phenotype microarray (PM) analysis showed that KSD‐YC and 98‐5 displayed broader substrate utilization than S288C and Y2805. The SNPs detected by genome comparison were mapped to the genes responsible for the observed phenotypic differences. In addition, detailed information on the structural organization of Y2805 selection markers was validated by Sanger sequencing. Integrated genomics and PM analysis elucidated the evolutionary history and genetic diversity of industrial S. cerevisiae strains, providing a platform to improve fermentation processes and genetic manipulation.

BackgroundThere is increasing interest in the influence of body composition on oncological outcomes. We evaluated the role of skeletal muscle and fat among patients with gastric cancer (GC) who underwent gastrectomy with or without adjuvant chemotherapy, as well as those changes’ associations with survival outcomes.MethodsThe present study evaluated 136 patients with GC who were enrolled in the CLASSIC Trial at Yonsei Cancer Center. Baseline body compositions including skeletal muscle area, Hounsfield units (HU), visceral fat area, and subcutaneous fat area were measured by preoperative computed tomography (CT). CT before and after the gastrectomy were used to determine the 6-month relative changes in body composition parameters. Continuous variables were dichotomized according to the best cutoff values by Contal and O’Quigley method.ResultsSeventy-three patients (53.7%) underwent surgery alone, and 63 patients (46.3%) underwent surgery followed by adjuvant chemotherapy. The baseline body composition parameters were not associated with disease-free survival (DFS) or overall survival (OS). Except for the HU, the marked loss of muscle, visceral fat, or subcutaneous fat significantly predicted shorter DFS and OS. Patients with a marked loss in at least one significant body composition parameter had significantly shorter DFS (hazard ratio 2.9, 95% confidence interval 1.7–4.8, P < 0.001) and OS (hazard ratio 2.9, 95% confidence interval 1.7–5.0, P < 0.001).ConclusionsMarked loss in body composition parameters significantly predicted shorter DFS and OS among patients with GC who underwent gastrectomy. Postoperative nutrition and active healthcare interventions could improve the prognosis of these GC patients.

BackgroundVarious parameters are used to predict perioperative surgical outcomes. However, no comprehensive studies in gastrectomy have been conducted. This study aimed to compare the performance of each parameter in patients with gastric cancer.MethodsThe medical records of 1032 gastric cancer patients who underwent curative gastrectomy between 2009 and 2015 were reviewed. Laboratory values and associated parameters (neutrophil count, lymphocyte count, platelet count, albumin level, Prognostic Nutritional Index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and Systemic Immune-Inflammation Index) as well as body weight-related data and associated parameters [body mass index (BMI), percentage of weight loss, Nutritional Risk Screening 2002 assessment, the Malnutrition Universal Screening Tool, and the Nutritional Risk Index] were measured and calculated. The study end points were major complications, operative mortality, prolonged hospital stay, overall survival (OS), and recurrence-free survival (RFS).ResultsMultivariable logistic regression analysis showed that male gender, total gastrectomy, advanced-stage gastric cancer, and low albumin level were risk factors for major complications. Old age, total gastrectomy, advanced-stage cancer, and high BMI were risk factors for operative mortality. Old age, open approach, and total gastrectomy were risk factors for prolonged hospital stay. Multivariable Cox proportional hazards models showed that old age, total gastrectomy, advanced-stage cancer, and high neutrophil count were unfavorable risk factors for OS. Old age, advanced-stage cancer, high neutrophil count, and high BMI were unfavorable risk factors for RFS.ConclusionsAlbumin level, BMI, and neutrophil count are the most useful parameters for predicting short- and long-term surgical outcomes. Compared with complex parameters, simple-to-measure parameters are better for predicting surgical outcomes for gastric cancer patients.

Metastable phases—kinetically favoured structures—are ubiquitous in nature 1 , 2 . Rather than forming thermodynamically stable ground-state structures, crystals grown from high-energy precursors often initially adopt metastable structures depending on the initial conditions, such as temperature, pressure or crystal size 1 , 3 , 4 . As the crystals grow further, they typically undergo a series of transformations from metastable phases to lower-energy and ultimately energetically stable phases 1 , 3 , 4 . Metastable phases sometimes exhibit superior physicochemical properties and, hence, the discovery and synthesis of new metastable phases are promising avenues for innovations in materials science 1 , 5 . However, the search for metastable materials has mainly been heuristic, performed on the basis of experiences, intuition or even speculative predictions, namely ‘rules of thumb’. This limitation necessitates the advent of a new paradigm to discover new metastable phases based on rational design. Such a design rule is embodied in the discovery of a metastable hexagonal close-packed (hcp) palladium hydride (PdH x ) synthesized in a liquid cell transmission electron microscope. The metastable hcp structure is stabilized through a unique interplay between the precursor concentrations in the solution: a sufficient supply of hydrogen (H) favours the hcp structure on the subnanometre scale, and an insufficient supply of Pd inhibits further growth and subsequent transition towards the thermodynamically stable face-centred cubic structure. These findings provide thermodynamic insights into metastability engineering strategies that can be deployed to discover new metastable phases. A metastable palladium hydride is synthesized where the unique environment in the liquid cell, namely the limited quantity of Pd precursors and the continuous supply of H, resulted in the formation of the hcp phase.

Despite the development of multidimensional state‐of‐the‐art electrode materials for constructing better lithium metal anodes (LMAs), the key factors influencing the electrochemical performance of LMAs are still poorly understood. Herein, it is demonstrated that the local lithium ion concentration at the interface between the electrode and electrolyte exerts significant influence on the electrochemical performance of LMAs. The local ion concentration is multiplied by introducing pseudocapacitive nanocarbons (PNCs) containing numerous heteroatoms, because PNCs can store large numbers of lithium ions in a pseudocapacitive manner, and promote the formation of an electrochemical double layer. The high interfacial lithium ion concentration induces the formation of lithium‐rich inorganic solid–electrolyte–interface layers with high ionic conductivities, and facilitates sustainable and stable supplies of lithium ion charge carriers on the overall active surfaces of the PNCs. Accordingly, the PNC‐induced LMA exhibits high Coulombic efficiencies, high rate capabilities, and stable cycling performance. The local lithium ion concentration at the interface between the electrode and electrolyte is a key factor in determining the electrochemical performance of lithium metal anodes. A high interfacial lithium ion concentration induces the formation of lithium‐rich inorganic solid–electrolyte–interface layers with high ionic conductivities, and facilitates sustainable and stable supplies of lithium ion charge carriers.

Face-centered-cubic crystallized super-fine (~ 2 nm in size) wet-ceria-abrasives are synthesized using a novel wet precipitation process that comprises a Ce 4+ precursor, C 3 H 4 N 2 catalyst, and NaOH titrant for a synthesized termination process at temperature of at temperature of 25 °C. This process overcomes the limitations of chemical–mechanical-planarization (CMP)-induced scratches from conventional dry ceria abrasives with irregular surfaces or wet ceria abrasives with crystalline facets in nanoscale semiconductor devices. The chemical composition of super-fine wet ceria abrasives depends on the synthesis termination pH, that is, Ce(OH) 4 abrasives at a pH of 4.0–5.0 and a mixture of CeO 2 and Ce(OH) 4 abrasives at a pH of 5.5–6.5. The Ce(OH) 4 abrasives demonstrate better abrasive stability in the SiO 2 -film CMP slurry than the CeO 2 abrasives and produce a minimum abrasive zeta potential (~ 12 mV) and a minimum secondary abrasive size (~ 130 nm) at the synthesis termination pH of 5.0. Additionally, the abrasive stability of the SiO 2 -film CMP slurry that includes super-fine wet ceria abrasives is notably sensitive to the CMP slurry pH; the best abrasive stability (i.e., a minimum secondary abrasive size of ~ 130 nm) is observed at a specific pH (6.0). As a result, a maximum SiO 2 -film polishing rate (~ 524 nm/min) is achieved at pH 6.0, and the surface is free of stick-and-slip type scratches.