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.
Genome-scale metabolic models (GEMs) computationally describe gene-protein-reaction associations for entire metabolic genes in an organism, and can be simulated to predict metabolic fluxes for ...various systems-level metabolic studies. Since the first GEM for Haemophilus influenzae was reported in 1999, advances have been made to develop and simulate GEMs for an increasing number of organisms across bacteria, archaea, and eukarya. Here, we review current reconstructed GEMs and discuss their applications, including strain development for chemicals and materials production, drug targeting in pathogens, prediction of enzyme functions, pan-reactome analysis, modeling interactions among multiple cells or organisms, and understanding human diseases.
SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary ...sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3′ tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.
Display omitted
•We provide a high-resolution map of SARS-CoV-2 transcriptome and epitranscriptome•The transcriptome is complex owing to numerous discontinuous transcription events•In addition to 10 canonical RNAs, SARS-CoV-2 produces RNAs encoding unknown ORFs•We discover at least 41 potential RNA modification sites with an AAGAA motif
The SARS-CoV-2 transcriptome and epitranscriptome reveal a complex array of canonical and non-canonical viral transcripts with RNA modifications.
We investigate Landau level structures of semimetals with nodal ring dispersions. When the magnetic field is applied parallel to the plane in which the ring lies, there exist almost nondispersive ...Landau levels at the Fermi level (E sub(F) = 0) as a function of the momentum along the field direction inside the ring. We show that the Landau levels at each momentum along the field direction can be described by the Hamiltonian for the graphene bilayer with fictitious interlayer couplings under a tilted magnetic field. Near the center of the ring where the in-terlayer coupling is negligible, we have Dirac Landau levels which explain the appearance of the zero modes. Although the interlayer hopping amplitudes become finite at higher momenta, the splitting of zero modes is exponentially small and they remain almost flat due to the finite artificial in-plane component of the magnetic field. The emergence of the density of states peak at the Fermi level would be a hallmark of the ring dispersion.
Obesity increases the risks of diabetes, hypertension, and cardiovascular diseases, ultimately contributing to mortality. Korean Society for the Study of Obesity (KSSO) was established to improve the ...management of obesity through research and education; to that end, the Committee of Clinical Practice Guidelines of KSSO reviews systemic evidence using expert panels to develop clinical guidelines. The clinical practice guidelines for obesity were revised in 2018 using National Health Insurance Service Health checkup data from 2006 to 2015. Following these guidelines, we added a category, class III obesity, which includes individuals with body mass index (BMI) ≥35 kg/m
. Agreeing with the International Federation for the Surgery of Obesity and Metabolic Disorders, Asian Pacific Chapter consensus, we determined that bariatric surgery is indicated for Korean patients with BMI ≥35 kg/m
and for Korean patients with BMI ≥30 kg/m
who have comorbidities. The new guidelines focus on guiding clinicians and patients to manage obesity more effectively. Our recommendations and treatment algorithms can serve as a guide for the evaluation, prevention, and management of overweight and obesity.
Display omitted
•Key factors for dry reforming of methane (DRM).•Comprehensive review on role of catalytic properties for DRM.•Rational and suitable design of catalysts for DRM.•Interaction, size, ...basicity, oxygen storage capacity, reducibility and porosity.
Because the whole world is under threat from climate change, 195 countries decided to reduce greenhouse gas (GHG) emissions by adopting the “Paris Agreement”. The mitigation and utilization of GHG have become the most significant challenges in the area of green energy research. One feasible solution is the reforming of methane with carbon dioxide (called dry reforming of methane, DRM) that converts the two main GHGs (CO2 and CH4) into synthesis gas (H2 and CO), which is a resource for the manufacture of useful value-added products. The main issue that needs to be addressed for DRM is the deactivation of catalysts by sintering and carbon formation. Design of a viable catalyst that exhibits high catalytic activity and stability, as well as resistance against deactivation, could be accomplished by making appropriate choices of active metal, support, promoter, structure and methods for preparation and activation. Numerous studies and reviews have dealt with various aspects of DRM. This review focuses on the physicochemical properties of the pertinent catalysts and their role in the catalytic performance needed for DRM. Specifically, the interaction between components, dispersion, particle size, basicity, oxygen storage capacity, reducibility, porosity and surface area are discussed. This study provides the understanding of catalytic properties and their correlation with catalytic performance needed for the rational design of catalysts and suitable for DRM.
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.
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.
Rational design of 2D materials is crucial for the realization of their profound implications in energy and environmental fields. The past decade has witnessed significant developments in 2D material ...research, yet a number of critical challenges remain for real‐world applications. Nanoscale assembly, precise control over the orientational and positional ordering, and complex interfaces among 2D layers are essential for the continued progress of 2D materials, especially for energy storage and conversion and environmental remediation. Herein, recent progress, the status, future prospects, and challenges associated with nanoscopic assembly of 2D materials are highlighted, specifically targeting energy and environmental applications. Geometric dimensional diversity of 2D material assembly is focused on, based on novel assembly mechanisms, including 1D fibers from the colloidal liquid crystalline phase, 2D films by interfacial tension (Marangoni effect), and 3D nanoarchitecture assembly by electrochemical processes. Relevant critical advantages of 2D material assembly are highlighted for application fields, including secondary batteries, supercapacitors, catalysts, gas sensors, desalination, and water decontamination.
Nanoscale assembly—the precise control over the complex interface between layers—is essential to promote continuous progress of 2D materials, especially in energy storage and conversion and environmental remediation. Recent progress, the status, future prospects, and challenges facing the nanoscopic assembly of 2D materials, mainly for energy and environmental applications, are discussed.
PDF
