Asymmetric imidazole-4,5-dicarboxamide derivatives as SARS-CoV-2 main protease inhibitors: design, synthesis and biological evaluation.

The SARS-CoV-2 main protease, a vital enzyme for virus replication, is a potential target for developing drugs in COVID-19 treatment. Until now, three SARS-CoV-2 main protease inhibitors have been approved for COVID-19 treatment. This study explored the inhibitory potency of asymmetric imidazole-4,5-dicarboxamide derivatives against the SARS-CoV-2 main protease. Fourteen derivatives were designed based on the structure of the SARS-CoV-2 main protease active site, the hydrolysis mechanism, and the experience gained from the reported inhibitor structures. They were synthesized through a four-step procedure from benzimidazole and 2-methylbenzimidazole. SARS-CoV-2 main protease inhibition was evaluated in vitro by fluorogenic assay with lopinavir, ritonavir, and ebselen as positive references. N-(4-Chlorophenyl)-2-methyl-4-(morpholine-4-carbonyl)-1H-imidazole-5-carboxamide (5a2) exhibited the highest potency against the SARS-CoV-2 main protease with an IC50 of 4.79 ± 1.37 µM relative to ebselen with an IC50 of 0.04 ± 0.013 µM. Enzyme kinetic and molecular docking studies were carried out to clarify the inhibitory mechanism and to prove that the compound interacts at the active site. We also performed cytotoxicity assay to confirm that these compounds are not toxic to human cells.

Exchange rate pass-through for European Union countries.

Exchange rate pass-through (ERPT) represents a degree to which changes in nominal exchange rates are transmitted into domestic prices. European Union (EU) countries have experienced the unprecedented inflationary pressure due to high geopolitical risk events. As such, understanding the ERPT plays a crucial role. This study provides a comprehensive and up-to-date analysis of ERPT to import prices for 16 EU countries from January 2006 to December 2022. Using the panel autoregressive distributed lag (ARDL) model, our findings confirm the linear, rather than nonlinear, ERPT pattern characterized by a diminishing trend over time in the EU countries. However, the degree of pass-through varies depending on country characteristics. Specifically, countries that are highly dependent on imports experience a larger ERPT. Furthermore, the degree of pass-through to import prices is more significant and persistent during periods of high uncertainty. These findings are robust across various robust analyses including sub periods. Our findings provide that help policymakers evaluate the trade-offs between exchange rate risks and macroeconomic stability during times of high uncertainty.

AlphaFold accelerated discovery of psychotropic agonists targeting the trace amine-associated receptor 1.

Artificial intelligence is revolutionizing protein structure prediction, providing unprecedented opportunities for drug design. To assess the potential impact on ligand discovery, we compared virtual screens using protein structures generated by the AlphaFold machine learning method and traditional homology modeling. More than 16 million compounds were docked to models of the trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor of unknown structure and target for treating neuropsychiatric disorders. Sets of 30 and 32 highly ranked compounds from the AlphaFold and homology model screens, respectively, were experimentally evaluated. Of these, 25 were TAAR1 agonists with potencies ranging from 12 to 0.03 µM. The AlphaFold screen yielded a more than twofold higher hit rate (60%) than the homology model and discovered the most potent agonists. A TAAR1 agonist with a promising selectivity profile and drug-like properties showed physiological and antipsychotic-like effects in wild-type but not in TAAR1 knockout mice. These results demonstrate that AlphaFold structures can accelerate drug discovery.

The short- and long-run effect of human capital on income inequality: Empirical evidence in the ASEAN region.

Human capital is a nation's primary source of inner strength to achieve sustainable economic growth and development. Meanwhile, income inequality is a critical issue preventing sustainable economic growth and social transformation, especially in developing countries. This paper investigates the effect of human capital on income inequality in both the short and long term using the mean group, pooled mean group, and threshold regressions for the ASEAN-7 (including Indonesia, Laos, Malaysia, the Philippines, Singapore, Thailand, and Vietnam) from 1992 to 2018. The paper develops a theoretical linkage between human capital and income inequality by combining the learning theory and the Kuznets hypothesis. This linkage is then tested using data from the ASEAN countries. Findings from the paper indicate that human capital reduces income inequality in the short run in the ASEAN countries. However, the effect is reverted in the long run, suggesting that human capital may increase the income gap in these countries. Particularly, the inverted U-shaped relationship between human capital and income inequality is established for the ASEAN countries whose GDP per capita is lower than USD 8.2 thousand per year. In contrast, the U-shaped relationship is found for the countries with income per capital of more than USD 8.2 thousand. All these findings suggest that social policies targeting reducing income inequality should be prioritized and stay at the centre of any economic policies to achieve sustainable economic growth and development in the ASEAN countries.

Pseudothrombosis due to blood-contrast level in the infrarenal vena cava.

Filling defects within the inferior vena cava (IVC) are common findings on computed tomography (CT); nevertheless, a majority of these defects are attributed to artifacts. The documentation pertaining to pseudothrombosis specifically affecting the infrarenal vena cava is notably insufficient in current literature. The aim of this study is to present a case demonstrating a blood-contrast level in the infrarenal vena cava, resembling an intraluminal filling defect.

Drivers of domestic migration in Vietnam: The characteristics of the households and their heads, environmental factors and living conditions.

Vietnam has achieved significant economic growth, poverty reduction, and social transformation since its 1986 major economic reform. However, industrialization, a key pillar supporting this achievement, has resulted in massive domestic migration from certain parts of the country into industrialized provinces mainly located in the south of Vietnam, leading to various challenges for society. This study investigates the effects of the characteristics of Vietnamese households and their heads, environmental factors, and living conditions of the households in the regions where they have decided to leave behind for a migration decision on domestic migration. Our study also compares the migration trends in the past decade using the Vietnamese Household Living Standard Surveys (VHLSS) in 2010 and 2020, together with a logit model. We find that the average probability that a household and their members migrate is about 10 per cent in 2010, reduced to approximately 6.8 per cent in 2020. Our empirical findings also confirm that a migration decision is strongly associated with the characteristics of the households and their heads, particularly for the household size and the educational level of the household head. The average radiation and rainfall are also associated with a migration decision. Weather temperature, water sources, and electricity supply also play an essential role in Vietnamese households' migration decisions. Policy implications have emerged based on these empirical findings that the Vietnamese government should consider.

Acute acalculous cholecystitis with portal cavernoma: A case report with literature review.

Portal cavernoma cholangiopathy (PCC) refers to morphological changes in the intrahepatic, extrahepatic biliary system, along with the gallbladder (GB), induced by portal cavernoma (PC). Acute acalculous cholecystitis (AAC) represents an infrequent clinical manifestation of PCC. Given the inadequacy of documentation within medical literature, AAC may go undiagnosed among patients with PC presenting symptoms of right upper quadrant pain. The current study aims to report a case of acute acalculous cholecystitis secondary to portal cavernoma, focusing on radiological findings, with a brief review of literature.

Urbanization and renewable energy consumption in the emerging ASEAN markets: A comparison between short and long-run effects.

The emerging markets in the ASEAN region, such as Indonesia, Malaysia, the Philippines, Thailand and Vietnam, have put great effort into achieving dual objectives: (i) supporting economic growth and (ii) combating environmental degradation simultaneously. These objectively depend on the fast urbanization taking place in these countries. While increased energy consumption from urbanization supports economic growth, urbanization is a key driver of environmental degradation. This paper examines a potential link between urbanization and renewable energy consumption, primarily ignored in current literature, particularly in the ASEAN-5 countries. Findings from this paper indicate that, despite the adverse effect of urbanization on renewable energy consumption in the short run, a positive effect is found in the long run for these emerging ASEAN markets, except Malaysia. The Philippines appears to balance well between urbanization and renewable energy consumption in the short and long run. Policy implications have emerged based on the findings of this paper.

Corporate restructuring and firm performance in Vietnam: The moderating role of digital transformation.

In the digital age, firms should continually innovate and adapt to remain competitive and enhance performance. Innovation and adaptation require firms to take a holistic approach to their corporate structuring to ensure efficiency and effectiveness to stay competitive. This study examines how corporate restructuring impacts firm performance in Vietnam. We then investigate the moderating role of digital transformation in the corporate restructuring-firm performance nexus. We use content analysis, with a focus on particular terms, including "digitalization," "big data," "cloud computing," "blockchain," and "information technology" for 11 years, from 2011 to 2021. The frequency index from these keywords is developed to proxy the digital transformation for the Vietnamese listed firms. A final sample includes 118 Vietnamese listed firms with sufficient data for the analysis using the generalized method of moments (GMM) approach. The results indicate that corporate restructuring, including financial, portfolio, and operational restructuring, has a negative effect on firm performance in Vietnam. Digital transformation also negatively affects firm performance. However, corporate restructuring implemented in conjunction with digital transformation improves the performance of Vietnamese listed firms. These findings largely remain unchanged across various robustness analyses.