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Hue Thi Mai,1 Giang Minh Le,1,2 Bach Xuan Tran,1,3,4 Ha Ngoc Do,5 Carl A Latkin,3 Luong Thanh Nguyen,6 Thao Phuong Thi Thai,7,8 Huong Thi Le,9 Anh Toan Ngo,10 Cuong Tat Nguyen,11 Cyrus SH Ho,12 Roger CM Ho13 1Institute for Preventive Medicine and Public Health, Hanoi Medical University, Hanoi, Vietnam; 2Center for Research and Training on HIV/AIDS (CREATA), Hanoi Medical University, Hanoi, Vietnam; 3Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 4Vietnam Young Physician Association, Hanoi, Vietnam; 5Youth Research Institute, Vietnam (YRI)-Ho Chi Minh Communist Youth Union, Hanoi, Vietnam; 6Center of Excellence in Evidence-based Medicine, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam; 7Department of General Planning, Friendship Hospital, Hanoi, Vietnam; 8Department of Cardiology, Friendship Hospital, Hanoi, Vietnam; 9Vietnam Administration of HIV/AIDS Control, Hanoi, Vietnam; 10National Hospital of Obstetrics and Gynecology, Hanoi, Vietnam; 11Institute for Global Health Innovations, Duy Tan University, Da Nang, Vietnam; 12Department of Psychological Medicine, National University Hospital, Singapore, Singapore; 13Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Purpose: This study aimed to assess the antiretroviral therapy (ART) compliance among patients with HIV/AIDS and its associated factors in the context of universal ART initiation in Vietnam. Patients and methods: A cross-sectional survey was conducted in five ART clinics located in three provinces, such as Hanoi, Thanh Hoa, and Lao Cai, from July to September 2017. Overall, adherence to ART in the last month was measured using a 100-point Visual Analog Scale (VAS). Besides, information about forgetting doses in the last 4 days and delaying taking pills in the last 7 days was also reported. Results: Among 482 patients, the suboptimal adherence rate was 54.5%. Noncurrent smoking (coefficient =4.19, 95% CI 0.42–7.97), higher baseline CD4 count (coefficient =4.35, 95% CI 0.58–8.13), and no traveling difficulties (coefficient =6.17, 95% CI 2.27–10.06) were predictors of higher VAS adherence score. Suboptimal adherence was associated with mountainous residence (OR =5.34, 95% CI 2.81–10.16). Female respondents were less likely to delay taking pills in the last 7 days (OR =0.19, 95% CI 0.07–0.52). Conclusion: Our study embraced early ART initiation in Vietnam; however, this approach should be parallel with appropriate resource allocation and service delivery. Keywords: HIV/AIDS, antiretroviral therapy, ART adherence, Visual Analog Scale, VAS

The combination of magnetic resonance imaging (MRI)/near-infrared (NIR) fluorescence signals and chemotherapy agents has been developed for cancer diagnosis and treatment. In this work, we investigated the impacts of NIR Cyanine 5.5 fluorescence and Doxorubicin on cell cycle arrest, magnetic resonance, and NIR fluorescence optical imaging for Fe3O4-encapsulated nanosystems based on poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymer. Although Cyanine 5.5 and Fe3O4 nanoparticles (NPs) are less cytotoxic than Doxorubicin, they present a cytostatic effect, inducing cell cycle arrest at the G2/M phase in human brain adenocarcinoma (CCF-STTG1) cells. For MRI applications, the permeability of the PLA-TPGS copolymer coating layer to water molecules might lengthen the translational diffusion time (τD), causing the high relaxivity ratio (r2/r1) in Fe3O4 bare NPs under an applied magnetic field (7 Tesla). Astonishingly, the chemical structures of Cyanine 5.5 and Doxorubicin significantly contribute to the enhancement of the T2 relaxivities of Fe3O4 NPs through π-π and p-π conjugation. Furthermore, the radiance ratio and signal-to-noise ratio enhancement and a slight blue shift in the optimal excitation and emission wavelengths were recorded. These findings show the potential for in vivo MRI and NIR bioimaging experiments of the nanoparticles., (© 2024 Wiley‐VCH GmbH.)

Agonists targeting α 2 -adrenergic receptors (ARs) are used to treat diverse conditions, including hypertension, attention-deficit/hyperactivity disorder, pain, panic disorders, opioid and alcohol withdrawal symptoms, and cigarette cravings. These receptors transduce signals through heterotrimeric Gi proteins. Here, we elucidated cryo-EM structures that depict α 2A -AR in complex with Gi proteins, along with the endogenous agonist epinephrine or the synthetic agonist dexmedetomidine. Molecular dynamics simulations and functional studies reinforce the results of the structural revelations. Our investigation revealed that epinephrine exhibits different conformations when engaging with α-ARs and β-ARs. Furthermore, α 2A -AR and β 1 -AR (primarily coupled to Gs, with secondary associations to Gi) were compared and found to exhibit different interactions with Gi proteins. Notably, the stability of the epinephrine-α 2A -AR-Gi complex is greater than that of the dexmedetomidine-α 2A -AR-Gi complex. These findings substantiate and improve our knowledge on the intricate signaling mechanisms orchestrated by ARs and concurrently shed light on the regulation of α-ARs and β-ARs by epinephrine., (© 2024. The Author(s).)

A fundamental understanding of how HIV-1 envelope (Env) protein facilitates fusion is still lacking. The HIV-1 fusion peptide, consisting of 15 to 22 residues, is the N-terminus of the gp41 subunit of the Env protein. Further, this peptide, a promising vaccine candidate, initiates viral entry into target cells by inserting and anchoring into human immune cells. The influence of membrane lipid reorganization and the conformational changes of the fusion peptide during the membrane insertion and anchoring processes, which can significantly affect HIV-1 cell entry, remains largely unexplored due to the limitations of experimental measurements. In this work, we investigate the insertion of the fusion peptide into an immune cell membrane mimic through multiscale molecular dynamics simulations. We mimic the native T-cell by constructing a 9-lipid asymmetric membrane, along with geometrical restraints accounting for insertion in the context of gp41. To account for the slow timescale of lipid mixing while enabling conformational changes, we implement a protocol to go back and forth between atomistic and coarse-grained simulations. Our study provides a molecular understanding of the interactions between the HIV-1 fusion peptide and the T-cell membrane, highlighting the importance of conformational flexibility of fusion peptides and local lipid reorganization in stabilizing the anchoring of gp41 into the targeted host membrane during the early events of HIV-1 cell entry. Importantly, we identify a motif within the fusion peptide critical for fusion that can be further manipulated in future immunological studies.

Predicting protein-peptide interactions is crucial for understanding peptide binding processes and designing peptide drugs. However, traditional computational modeling approaches face challenges in accurately predicting peptide-protein binding structures due to the slow dynamics and high flexibility of the peptides. Here, we introduce a new workflow termed "PepBinding" for predicting peptide binding structures, which combines peptide docking, all-atom enhanced sampling simulations using the Peptide Gaussian accelerated Molecular Dynamics (Pep-GaMD) method, and structural clustering. PepBinding has been demonstrated on seven distinct model peptides. In peptide docking using HPEPDOCK, the peptide backbone root-mean-square deviations (RMSDs) of their bound conformations relative to X-ray structures ranged from 3.8 to 16.0 Å, corresponding to the medium to inaccurate quality models according to the Critical Assessment of PRediction of Interactions (CAPRI) criteria. The Pep-GaMD simulations performed for only 200 ns significantly improved the docking models, resulting in five medium and two acceptable quality models. Therefore, PepBinding is an efficient workflow for predicting peptide binding structures and is publicly available at https://github.com/MiaoLab20/PepBinding.

B-cell receptor complexes (BCR) are expressed on the surface of a B-cell and are the critical regulators of adaptive immune response. Even though the relevance of antibodies has been known for almost a hundred years, the antigen-dependent activation of antibody-producing B-cells has remained elusive. Several models have been proposed for BCR activation, including cross-linking, conformation-induced oligomerization, and dissociation activation models. Recently, the first cryo-EM structure of the human B-cell antigen receptor of the IgM isotype was published. Given the new asymmetric BCR complex, we have carried out extensive molecular dynamics simulations to probe the conformational changes upon antigen binding and the influence of the membrane. We identified two critical dynamical events that could be associated with antigen-dependent activation of BCR. First, antigen binding caused increased flexibility in regions distal to the antigen binding site. Second, this increased flexibility led to the rearrangement of helices in transmembrane helices, including the relative interaction of Igα/Igβ, which has been responsible for intracellular signaling. Further, these transmembrane rearrangements led to changes in localized lipid composition. Even though the simulations considered only a single BCR complex, our work indirectly supports the dissociation activation model.

Background: Respiratory infections have long been recognized as a primary cause of acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). Additionally, the emergence of antimicrobial resistance has led to an urgent and critical situation in developing countries, including Vietnam. This study aimed to investigate the distribution and antimicrobial resistance of bacteria in patients with AE-COPD using both conventional culture and multiplex real-time PCR. Additionally, associations between clinical characteristics and indicators of pneumonia in these patients were examined., Methods: This cross-sectional prospective study included 92 AE-COPD patients with pneumonia and 46 without pneumonia. Sputum specimens were cultured and examined for bacterial identification, and antimicrobial susceptibility was determined for each isolate. Multiplex real-time PCR was also performed to detect ten bacteria and seven viruses., Results: The detection rates of pathogens in AE-COPD patients with pneumonia were 92.39%, compared to 86.96% in those without pneumonia. A total of 26 pathogenic species were identified, showing no significant difference in distribution between the two groups. The predominant bacteria included Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, followed by Acinetobacter baumannii and Streptococcus mitis. There was a slight difference in antibiotic resistance between bacteria isolated from two groups. The frequency of H. influenzae was notably greater in AE-COPD patients who experienced respiratory failure (21.92%) than in those who did not (9.23%). S. pneumoniae was more common in patients with stage I (44.44%) or IV (36.36%) COPD than in patients with stage II (17.39%) or III (9.72%) disease. ROC curve analysis revealed that C-reactive protein (CRP) levels could distinguish patients with AE-COPD with and without pneumonia (AUC = 0.78)., Conclusion: Gram-negative bacteria still play a key role in the etiology of AE-COPD patients, regardless of the presence of pneumonia. This study provides updated evidence for the epidemiology of AE-COPD pathogens and the appropriate selection of antimicrobial agents in Vietnam., (© 2024. The Author(s).)

Introduction: For rational drug design, it is crucial to understand the receptor-drug binding processes and mechanisms. A new era for the use of computer simulations in predicting drug-receptor interactions at an atomic level has begun with remarkable advances in supercomputing and methodological breakthroughs., Areas Covered: End-point free energy calculation methods such as Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA) or Molecular-Mechanics/Generalized Born Surface Area (MM/GBSA), free energy perturbation (FEP), and thermodynamic integration (TI) are commonly used for binding free energy calculations in drug discovery. In addition, kinetic dissociation and association rate constants ( k off and k on ) play critical roles in the function of drugs. Nowadays, Molecular Dynamics (MD) and enhanced sampling simulations are increasingly being used in drug discovery. Here, the authors provide a review of the computational techniques used in drug binding free energy and kinetics calculations., Expert Opinion: The applications of computational methods in drug discovery and design are expanding, thanks to improved predictions of the binding free energy and kinetic rates of drug molecules. Recent microsecond-timescale enhanced sampling simulations have made it possible to accurately capture repetitive ligand binding and dissociation, facilitating more efficient and accurate calculations of ligand binding free energy and kinetics.

The chemical screening of an octocoral identifed as Junceella fragilis has led to the isolation of five chlorinated briarane-type diterpenoids, including three known metabolites, gemmacolide X (1), frajunolide I (2), and fragilide F (3), along with two new analogs, 12α-acetoxyfragilide F (4) and 12α-acetoxyjunceellin (5). Single-crystal X-ray diffraction analysis was carried out to determine the absolute configurations of 1 and 2, while the structures of new compounds 4 and 5 were ascertained with 2D NMR experiments. Briaranes 1 and 3-5 were active in enhancing alkaline phosphatase (ALP) activity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Bis(3-indolyl)methanes (BIMs) are known for their important bioactivities, which include anti-cancer, anti-inflammatory, antibacterial, and antioxidant properties. In this study, we are disclosing a metal catalyst-free synthesis of BIMs in high yields via the alkylation reaction of indoles and alcohols in the presence of lithium tert -butoxide base. Notably, oxygen in air played an important role as an oxidant for the facilitation of this transformation. Interestingly, unactivated aliphatic alcohols could be successfully used as alkylating reagents in the alkylation reactions of indole. Especially, several chemical intermediates detected by GC-MS gave important information about the mechanism insights. This method demonstrated cost and environmental advantages for the development of green processes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A new benzophenanthridine alkaloid 6-butanoyldihydrochelerythrine (1) and five known alkaloids 6-acetonyldihydronitidine (2) , 6-acetonyldihydrochelerythrine (3) , isocorydine (4) , (O)-methyltembamide (5) , N-(4-methoxyphenethyl)benzamide (6) were isolated from the stem barks of Zanthoxylum rhetsa . These structures were elucidated by 1D, 2D NMR spectroscopy and by mass spectrometry. This is the first time that compounds 2-6 were identified from Zanthoxylum rhetsa and the first time that compounds 4 and 6 were identified from the genus Zanthoxylum . Bioactivity results of isolated compounds showed that 1 , 2 , 5 and 6 exhibited inhibitory activity against MCF7 and A549 cell lines, while 3 showed the inhibitory activity against A549 cell line; all isolated compounds 1 - 6 inhibited at least two strain microorganisms; compound 4 showed angiotensin II converting enzyme inhibitory activity in vitro with IC 50 value of 65.58 µM and in silico with a docking score of -11.52 kcal/mol.

γ-Secretase is an intramembrane aspartyl protease complex that cleaves the transmembrane domain of over 150 peptide substrates, including amyloid precursor protein (APP) and the Notch family of receptors, via two conserved aspartates D257 and D385 in the presenilin-1 (PS1) catalytic subunit. However, while the activation of γ-secretase for cleavage of APP has been widely studied, the cleavage of Notch by γ-secretase remains poorly explored. Here, we combined Gaussian accelerated molecular dynamics (GaMD) simulations and mass spectrometry (MS) analysis of proteolytic products to present the first dynamic models for cleavage of Notch by γ-secretase. MS showed that γ-secretase cleaved the WT Notch at Notch residue G34, while cleavage of the L36F mutant Notch occurred at Notch residue C33. Initially, we prepared our simulation systems starting from the cryoEM structure of Notch-bound γ-secretase (PDB: 6IDF) and failed to capture the proper cleavages of WT and L36F Notch by γ-secretase. We then discovered an incorrect registry of the Notch substrate in the PS1 active site through alignment of the experimental structure of Notch-bound (PDB: 6IDF) and APP-bound γ-secretase (PDB: 6IYC). Every residue of the APP substrate was systematically mutated to the corresponding Notch residue to prepare a resolved model of Notch-bound γ-secretase complexes. GaMD simulations of the resolved model successfully captured γ-secretase activation for proper cleavages of both WT and L36F mutant Notch. Our findings presented here provided mechanistic insights into the structural dynamics and enzyme-substrate interactions required for γ-secretase activation for cleavage of Notch and other substrates.

Higher education strongly focuses on shifting from a more traditional teaching approach - "instructivist" to a more student-centered approach - known as "constructivist" to encourage learning imperative key skills in a future turbulent environment. This study examines the application of new learning environment creation, integrated from applying the Design Science approach and Constructivism learning environment, on two critical elements of student evaluation, namely, students' learning motivation and their learning strategy in higher institutions. Quantitative research was adopted for the study. To do so, a new teaching and learning approach was developed and implemented specifically for one cohort. Instead of regularly joining a regular classroom, students can actively attend workshops to gain the skills, knowledge, and action they need to complete the course successfully. Following three months of implementation, 193 questionnaires were collected from all students who took a Project Management course. The data show that a constructivist learning environment encourages intrinsic and extrinsic motivation. Additionally, the student's learning strategy significantly improved in the new learning environment. These findings demonstrate that further attention should be given to constructivist orientation and implementation in the higher education curriculum., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

G-protein-coupled receptors (GPCRs) make up the largest superfamily of human membrane proteins and represent primary targets of ∼1/3 of currently marketed drugs. Allosteric modulators have emerged as more selective drug candidates compared with orthosteric agonists and antagonists. However, many X-ray and cryo-EM structures of GPCRs resolved so far exhibit negligible differences upon the binding of positive and negative allosteric modulators (PAMs and NAMs). The mechanism of dynamic allosteric modulation in GPCRs remains unclear. In this work, we have systematically mapped dynamic changes in free energy landscapes of GPCRs upon binding of allosteric modulators using the Gaussian accelerated molecular dynamics (GaMD), deep learning (DL), and free energy prOfiling Workflow (GLOW). GaMD simulations were performed for a total of 66 μs on 44 GPCR systems in the presence and absence of the modulator. DL and free energy calculations revealed significantly reduced dynamic fluctuations and conformational space of GPCRs upon modulator binding. While the modulator-free GPCRs often sampled multiple low-energy conformational states, the NAMs and PAMs confined the inactive and active agonist-G-protein-bound GPCRs, respectively, to mostly only one specific conformation for signaling. Such cooperative effects were significantly reduced for binding of the selective modulators to "non-cognate" receptor subtypes. Therefore, GPCR allostery exhibits a dynamic "conformational selection" mechanism. In the absence of available modulator-bound structures as for most current GPCRs, it is critical to use a structural ensemble of representative GPCR conformations rather than a single structure for compound docking ("ensemble docking"), which will potentially improve structure-based design of novel allosteric drugs of GPCRs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Dialysis patients are more likely to die or become hospitalized from coronavirus disease 2019 (COVID-19). Currently, only a few studies have evaluated the efficacy of a fourth booster vaccination in hemodialysis (HD) patients and there is not enough evidence to recommend for or against a fourth booster vaccination. This study compared the humoral response and disease severity of patients on HD who received either three or four doses of COVID-19 vaccine. A total of 88 patients were enrolled. Humoral response to vaccination was measured by quantifying immunoglobulin G levels against the receptor binding domain of SARS-CoV-2 (anti-RBD IgG) at five different times and plaque reduction neutralization tests (PRNT) at two different times after vaccination over a period of 18 months. Antibody levels were measured at approximately two-month intervals after the first and second dose, then four months after the third dose, and then one to six months after the fourth dose of vaccine. PRNT was performed two months after the second and four months after the third dose of vaccine. We classified patients into four groups according to the number of vaccine doses and presence of COVID-19 infection. Severe infection was defined as hospital admission for greater than or equal to two weeks or death. There was no difference in antibody levels between naïve and infected patients except after a fourth vaccination, which was effective for increasing antibodies in infection-naïve patients. Age, sex, body mass index (BMI), dialysis vintage, and presence of diabetes mellitus (DM) did not show a significant correlation with antibody levels. Four patients who experienced severe COVID-19 disease tended to have lower antibody levels prior to infection. A fourth dose of SARS-CoV-2 vaccine significantly elevated antibodies in infection-naïve HD patients and may be beneficial for HD patients who have not been previously infected with SARS-CoV-2 for protection against severe infection.

Targeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family of receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib suppressed SARS-CoV-2 entry and later stages of the viral life cycle and showed synergistic effect with the direct-acting antiviral nirmatrelvir. We discovered that ErbB1, ErbB2, and ErbB4 bind SARS-CoV-2 S1 protein and regulate viral and ACE2 internalization, and they are required for VEEV infection. In human lung organoids, lapatinib protected from SARS-CoV-2-induced activation of ErbB-regulated pathways implicated in non-infectious lung injury, proinflammatory cytokine production, and epithelial barrier injury. Lapatinib suppressed VEEV replication, cytokine production, and disruption of blood-brain barrier integrity in microfluidics-based human neurovascular units, and reduced mortality in a lethal infection murine model. We validated lapatinib-mediated inhibition of ErbB activity as an important mechanism of antiviral action. These findings reveal regulation of viral replication, inflammation, and tissue injury via ErbBs and establish a proof of principle for a repurposed, ErbB-targeted approach to combat emerging viruses.

α 1 -adrenergic receptors (α 1 -ARs) play critical roles in the cardiovascular and nervous systems where they regulate blood pressure, cognition, and metabolism. However, the lack of specific agonists for all α 1 subtypes has limited our understanding of the physiological roles of different α 1 -AR subtypes, and led to the stagnancy in agonist-based drug development for these receptors. Here we report cryo-EM structures of α 1A -AR in complex with heterotrimeric G-proteins and either the endogenous common agonist epinephrine or the α 1A -AR-specific synthetic agonist A61603. These structures provide molecular insights into the mechanisms underlying the discrimination between α 1A -AR and α 1B -AR by A61603. Guided by the structures and corresponding molecular dynamics simulations, we engineer α 1A -AR mutants that are not responsive to A61603, and α 1B -AR mutants that can be potently activated by A61603. Together, these findings advance our understanding of the agonist specificity for α 1 -ARs at the molecular level, opening the possibility of rational design of subtype-specific agonists., (© 2023. Springer Nature Limited.)

We have developed a new deep boosted molecular dynamics (DBMD) method. Probabilistic Bayesian neural network models were implemented to construct boost potentials that exhibit Gaussian distribution with minimized anharmonicity, thereby allowing for accurate energetic reweighting and enhanced sampling of molecular simulations. DBMD was demonstrated on model systems of alanine dipeptide and the fast-folding protein and RNA structures. For alanine dipeptide, 30 ns DBMD simulations captured up to 83-125 times more backbone dihedral transitions than 1 μs conventional molecular dynamics (cMD) simulations and were able to accurately reproduce the original free energy profiles. Moreover, DBMD sampled multiple folding and unfolding events within 300 ns simulations of the chignolin model protein and identified low-energy conformational states comparable to previous simulation findings. Finally, DBMD captured a general folding pathway of three hairpin RNAs with the GCAA, GAAA, and UUCG tetraloops. Based on a deep learning neural network, DBMD provides a powerful and generally applicable approach to boosting biomolecular simulations. DBMD is available with open source in OpenMM at https://github.com/MiaoLab20/DBMD/.

Biomolecular binding kinetics including the association ( k on ) and dissociation ( k off ) rates are critical parameters for therapeutic design of small-molecule drugs, peptides, and antibodies. Notably, the drug molecule residence time or dissociation rate has been shown to correlate with their efficacies better than binding affinities. A wide range of modeling approaches including quantitative structure-kinetic relationship models, Molecular Dynamics simulations, enhanced sampling, and Machine Learning has been developed to explore biomolecular binding and dissociation mechanisms and predict binding kinetic rates. Here, we review recent advances in computational modeling of biomolecular binding kinetics, with an outlook for future improvements.

Background: The progression into the Digital Age has brought an array of novel skill requirements. Unlike traditional literacy, there are currently few measures that can reliably measure eHealth literacy. The Transactional Model of eHealth Literacy and subsequent Transactional eHealth Literacy Instrument may provide a feasible option for measuring eHealth literacy., Objective: This instrument has yet to be validated, which is the aim of this study. In particular, this article was conducted to validate the TeHLI to see which components of the tool (how many and which components included) would be the best fit statistically and whether the tool applies to groups of different characteristics., Methods: We conducted an online cross-sectional study among 236 Vietnamese young people. A exploratory factor analysis was used to identify the best fit model of the Transactional eHealth Literacy Instrument. A confirmatory factor analysis tested measurement invariance at four levels: configural, metric, scalar, and strict invariance. Only metric invariance was partially invariant, while the rest tested fully invariant. Even with partial metric invariance, there is reason to assume that functional, communicative, critical, and translational eHealth literacy (the four levels according to the transactional model) are consistently measured when deploying the Transactional eHealth Literacy Instrument across groups., Results: The study findings substantiate that the most optimal composition of the TeHLI consists of four factors: functional, communicative, critical, and translational eHealth literacy, with RMSEA = 0.116; CFI = 0.907, and the highest internal consistency (Cronbach's α = 0.91, 0.92, 0.88, and 0.92 for each factor respectively). After using measurement invariance, that gender, education, marital status, age, location, and household economy do not influence the way participants to respond to the TeHLI to the point that would introduce measurement bias. In other word, using TeHLI across population groups should not produce error margins that substantially differ from each other., Conclusions: This study suggests the instrument can be used for comparisons across groups and has the potential to generate high-quality data usable for informing change agents as to whether a particular population is proficient enough to adopt novel eHealth innovations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nguyen, Do, Do, Vu, van Kessel, Wong, Boyer, Fond, Auquier, Nguyen, Latkin, Ho and Ho.)

The immunogenicity of a heterologous vaccination regimen consisting of ChAdOx1 nCoV-19 (a chimpanzee adenovirus-vectored vaccine) followed by mRNA-1273 (a lipid-nanoparticle-encapsulated mRNA-based vaccine) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), specifically the omicron variant (B.1.1.529), is poorly studied. The aim of this study was to evaluate the neutralizing antibody activity and immunogenicity of heterologous ChAdOx1 nCoV-19 and mRNA-1273 prime-boost vaccination against wild-type (BetaCoV/Korea/KCDC03/2020), alpha, beta, gamma, delta, and omicron variants of SARS-CoV-2 in Korea. A 50% neutralizing dilution (ND50) titer was determined in serum samples using the plaque reduction neutralization test. Antibody titer decreased significantly at 3 months compared with that at 2 weeks after the 2nd dose. On comparing the ND50 titers for the above-mentioned variants of concerns, it was observed that the ND50 titer for the omicron variant was the lowest. This study provides insights into cross-vaccination effects and can be useful for further vaccination strategies in Korea., Competing Interests: No conflict of interest., (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

During the process of adapting to metal contamination, plants produce secondary metabolites that have the potential to modulate multidrug-resistant (MDR) phenotypes; this is achieved by inhibiting the activity of efflux pumps to reduce the minimum inhibitory concentrations (MICs) of antimicrobial substrates. Our study evaluated the effect of secondary metabolites of belowground parts of Pteris vittata L. and Fallopia japonica, two metal-tolerant plants from northern Vietnam, on six antibiotic-resistant Stenotrophomonas maltophilia strains possessing efflux pump resistance mechanisms that were isolated from soil and clinical samples. The chemical composition of aqueous and dichloromethane (DCM) fractions extracted from P. vittata and F. japonica was determined using UHPLC-DAD-ESI/QTOF analysis. The antibacterial and efflux pump inhibitory activities of the four fractions were evaluated for the six strains (K279a, 0366, BurA1, BurE1, PierC1, and 502) using a microdilution assay at fraction concentrations of 62.5, 125, and 250 μg/mL. The DCM fraction of F. japonica exhibited remarkable antibacterial activity against strain 0366, with a MIC of 31.25 μg/mL. Furthermore, this fraction also significantly decreased gentamicin MIC: four-fold and eight-fold reductions for BurA1 and BurE1 strains, respectively (when tested at 250 μg/mL), and two-fold and eight-fold reductions for K279a and BurE1 strains, respectively (when tested at 125 μg/mL). Pure emodin, the main component identified in the DCM fraction of F. japonica , and sennidine A&B only reduced by half the MIC of gentamicin (when tested at 30 μg/mL). Our results suggest that the DCM fraction components of F. japonica underground parts may be potential candidates for new bacterial efflux pump inhibitors (EPIs).

Presenilin-1 (PS1) is the catalytic subunit of γ-secretase which cleaves within the transmembrane domain of over 150 peptide substrates. Dominant missense mutations in PS1 cause early-onset familial Alzheimer's disease (FAD); however, the exact pathogenic mechanism remains unknown. Here we combined Gaussian accelerated molecular dynamics (GaMD) simulations and biochemical experiments to determine the effects of six representative PS1 FAD mutations (P117L, I143T, L166P, G384A, L435F, and L286V) on the enzyme-substrate interactions between γ-secretase and amyloid precursor protein (APP). Biochemical experiments showed that all six PS1 FAD mutations rendered γ-secretase less active for the endoproteolytic (ε) cleavage of APP. Distinct low-energy conformational states were identified from the free energy profiles of wildtype and PS1 FAD-mutant γ-secretase. The P117L and L286V FAD mutants could still sample the "Active" state for substrate cleavage, but with noticeably reduced conformational space compared with the wildtype. The other mutants hardly visited the "Active" state. The PS1 FAD mutants were found to reduce γ-secretase proteolytic activity by hindering APP residue L49 from proper orientation in the active site and/or disrupting the distance between the catalytic aspartates. Therefore, our findings provide mechanistic insights into how PS1 FAD mutations affect structural dynamics and enzyme-substrate interactions of γ-secretase and APP., (© 2023. The Author(s).)

Purpose: Mental wellbeing and life satisfaction play an important role in the development of adolescents, yet factors potentially influencing these states have not been sufficiently studied, especially in Vietnam. This study aims to fill the research gaps by exploring the associations of the parent-child relationship, self-esteem, and resilience on the mental wellbeing and satisfaction with life of adolescents., Methods: A cross-sectional study was conducted from June to July 2020 on 1,023 adolescents from 10 to 18 years old living in Vietnam. To assess the satisfaction with life as well as the mental wellbeing of participants, this study used the Satisfaction with life and The World Health Organization-Five Wellbeing Index scale., Results: More than 70% of participants reported having conflicts with their parents (74.6% of those conflicted with their father ad 73.9% of those conflicted with their mother), while 26.3% stated dissatisfaction with life. The mean score of mental wellbeing was 61.5 (SD = 23.0). Higher academic performance, self-esteem, resilience, encounter loneliness and isolation within own family, and having support and sharing from family members had a positive effect on life satisfaction and mental wellbeing. Female participants had higher satisfaction with life score (Coef = 0.77; 95%CI = 0.10; 1.44) but they had a lower mental wellbeing score (Coef = -6.00; 95%CI = -8.57; -3.44) than male participants. High school students had lower both satisfaction with life and mental wellbeing scores than secondary students., Conclusion: The results highlight the importance of being aware of the influence that expectations (of higher grades) and bias (toward male children) imposed by parents, teachers, and society on the mental wellbeing of youths, especially in Asian cultures. Strengthening the family bond and encouraging young people to share their feeling is also crucial to enhancing the mental health condition of adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Trong Dam, Do, Thi Vu, Vu, Do, Thi Nguyen, Nguyen, Thi Vu, Thi Nguyen, Auquier, Boyer, Fond, Latkin, Ho and Ho.)

Introduction: This study aimed to determine latent profiles from the Problematic Internet Use Questionnaire Short Form-6 (PIUQ-SF-6) score of Vietnamese youths and adolescents, which supports the diagnosis of problematic internet use among a large sample size. Moreover, it also explored factors that affect each latent profile of the PIUQ-SF-6 score among participants., Methods: A sample of 1477 Vietnamese people, aged 14 to 24, across five provinces participated in the study. Multinomial logistic regression determined factors related to the levels of the Problematic Internet Use Questionnaire Short Form-6 (PIUQ-SF-6) after using latent profile analysis., Results: Participants were divided into three profiles, including those at low, moderate, and high risk of internet addiction. The high-risk latent profile was obtained for 23.1% of adolescents, and the remaining percentages were, respectively, 40.2% and 36.7% of adolescents belonging to the moderate and low-risk groups. Moreover, factors including age, living alone, high Kessler psychological distress scale, excessive time on the internet, living in central cities, and high neighborhood disorder scores were found to be related to moderate- and high-risk internet addiction profiles., Conclusions: Factors analyzed according to individual and social characteristics further explore the reasons underlying increasing internet addiction among Vietnamese youths and inform early interventions.

Background: Delayed childbearing has become a concern among policymakers across the world. In Vietnam, population policies have been adjusted to cope with this issue. In 2020, Decision 588/QD-TTg was ratified to encourage people to marry and give birth before the age of 30. This study reviewed recent changes in Vietnam's population policies and assessed the intention of giving birth before 30 in young Vietnamese to provide insights into the potential effectiveness of the policy changes among young people. Methods: This study combined two approaches: a desk review and a survey of a group of youths. An online cross-sectional study was conducted on 116 respondents aged 16 to 30 in Vietnam from June to July 2020. The intention of childbearing before 30 and the importance and responsiveness of different social-environmental factors were asked using a structured questionnaire. We used multivariate logistic regression to identify associated factors of such intention. Results: The incentives set out by the Vietnamese government shared similarities with those of other countries. The plan of childbearing before the age of 30 among young adults in Vietnam was demonstrated to correlate with age, socioeconomic and biological characteristics, resources of the local health systems, as well as a clean and safe living environment. Conclusion: This study highlighted the recent crucial shift in Vietnam's population policy. However, the quantitative analysis suggested that measures relating to environmental factors should be incorporated under this policy, implying that further interventions need to be taken into account to cope with delayed childbearing.

Background: Concerning rates of psychological disorders are increasingly recognized in young adults during the COVID-19 pandemic. This study aimed to examine the associations of different structural and functional social supports on depression, anxiety, and stress among young adults in Vietnam., Methods: An online cross-sectional study was performed on 236 respondents aged 16 to 30 years in Vietnam from June to July 2020. The Depression, Anxiety and Stress Scale-21 Items (DASS-21); the Multidimensional Scale of Perceived Social Support (MSPSS), and the LUBBEN Social Network Scale (LSNS-6) was used to measure psychological health, functional and structural social support characteristics. Multi-level mixed-effect logistic regression was used to identify associations between social support and anxiety, depression, and stress., Results: The rate of at least mild depression, anxiety, and stress were 30.1%, 34.8%, and 35.6%, respectively. Structural supports measured by LSNS-6 were not associated with the likelihood of having depression, anxiety, and stress (p>0.05). Respondents having friends with whom they could share joys and sorrows were less likely to have anxiety (aOR = 0.61, 95%CI = 0.41-0.90) and stress (aOR = 0.66, 95%CI = 0.45-0.96). Having family support in decision-making was also negatively associated with depression, anxiety, and stress. Meanwhile, those having family and friends who tried to help them were more likely to suffer stress (aOR = 1.94, 95%CI = 1.16-3.24) and depression (aOR = 2.09; 95%CI = 1.11-3.92), respectively., Conclusion: This study highlighted a high rate of psychological problems among young adults during the COVID-19 pandemic in Vietnam. Emotional support from friends and advice support from family were important components that should be considered in further interventions to mitigate the psychological problems in young adults., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Doan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Although the pathogenesis of depressive disorders is not fully elucidated, untreated adolescent depression can lead to serious sequelae such as impaired academic performance and social functioning, substance use disorders, poor self-esteem, and increased risk for suicidal ideation and attempts. Literature on adolescent mental health in Vietnam is limited, despite increased international awareness of this critical issue. This study aimed to investigate the prevalence and associations of depressive symptoms in Vietnamese adolescents., Methods: A cross-sectional, self-administered survey was conducted in five provinces of Vietnam among adolescents aged 14 to 24 years. In addition to collecting participants' demographics, a structured questionnaire was developed to examine depressive symptoms, suicidal ideation, loneliness, and cyberbullying victimization. Depressive symptoms and loneliness were assessed via the PHQ-9 and UCLA Loneliness Scale, respectively. Two-tailed Chi-squared, Mann-Whitney, and Kruskal-Wallis tests were performed to examine associations between variables. Multivariate Logistic regression models were conducted to examine the associations between prior-defined variables and positive depressive symptoms., Results: Among 1,600 respondents, 31.8% of participants reported having mild-moderate or severe depressive symptoms. Participants within the moderate-severe depressive symptom group had significantly lower community cohesion scores than those of participants in normal and mild depressive symptom groups ( p < 0.05). Youths living alone were more likely to have moderate-severe depressive symptoms (OR 2.16; 95% CI: 1.09-4.25). Cyberbullying had significant associations with depressive severity (OR 1.93; 95% CI 1.38-2.70)., Conclusion: The findings of this study characterize various risk and protective factors for depression in Vietnamese youths and adolescents. The results highlight the importance of raising awareness and increasing access to educational resources for depression and other mental health illnesses. With the rising prevalence of depression, parents, teachers, and community leaders play a vital role in addressing mental health problems in adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Phan, Chau, Do, Vu, Vu, Nguyen, Nguyen, Do, Nguyen, La, Dam, Nguyen, Nguyen, Do, Vu, Vu Le, Vu, Le, Latkin, Ho and Ho.)

Gaussian accelerated molecular dynamics (GaMD) is a computational technique that provides both unconstrained enhanced sampling and free energy calculations of biomolecules. Here, we present the implementation of GaMD in the OpenMM simulation package and validate it on model systems of alanine dipeptide and RNA folding. For alanine dipeptide, 30 ns GaMD production simulations reproduced free energy profiles of 1000 ns conventional molecular dynamics (cMD) simulations. In addition, GaMD simulations captured the folding pathways of three hyperstable RNA tetraloops (UUCG, GCAA, and CUUG) and binding of the rbt203 ligand to the HIV-1 Tar RNA, both of which involved critical electrostatic interactions such as hydrogen bonding and base stacking. Together with previous implementations, GaMD in OpenMM will allow for wider applications in simulations of proteins, RNA, and other biomolecules.

G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies, and transduce to heterotrimeric G-proteins to generate different degrees of physiological responses. Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. We report the cryo-EM structures of β 1 -adrenergic receptor (β 1 -AR) in complex with Gs (Gα s Gβ 1 Gγ 2 ) and a partial agonist or a very weak partial agonist, and compare them to the β 1 -AR-Gs structure in complex with a full agonist. Analyses reveal similar overall complex architecture, with local conformational differences. Cellular functional studies with mutations of β 1 -AR residues show effects on the cellular signaling from β 1 -AR to the cAMP response initiated by the three different ligands, with residue-specific functional differences. Biochemical investigations uncover that the intermediate state complex comprising β 1 -AR and nucleotide-free Gs is more stable when binding a full agonist than a partial agonist. Molecular dynamics simulations support the local conformational flexibilities and different stabilities among the three complexes. These data provide insights into the ligand efficacy in the activation of GPCRs and G-proteins., (© 2022. The Author(s).)

The membrane-embedded γ-secretase complex processively cleaves within the transmembrane domain of amyloid precursor protein (APP) to produce 37-to-43-residue amyloid β-peptides (Aβ) of Alzheimer's disease (AD). Despite its importance in pathogenesis, the mechanism of processive proteolysis by γ-secretase remains poorly understood. Here, mass spectrometry and Western blotting were used to quantify the efficiency of tripeptide trimming of wild-type (WT) and familial AD (FAD) mutant Aβ49. In comparison to WT Aβ49, the efficiency of tripeptide trimming was similar for the I45F, A42T, and V46F Aβ49 FAD mutants but substantially diminished for the I45T and T48P mutants. In parallel with biochemical experiments, all-atom simulations using a novel peptide Gaussian accelerated molecular dynamics (Pep-GaMD) method were applied to investigate the tripeptide trimming of Aβ49 by γ-secretase. The starting structure was the active γ-secretase bound to Aβ49 and APP intracellular domain (AICD), as generated from our previous study that captured the activation of γ-secretase for the initial endoproteolytic cleavage of APP (Bhattarai, A., ACS Cent. Sci. 2020, 6, 969-983). Pep-GaMD simulations captured remarkable structural rearrangements of both the enzyme and substrate, in which hydrogen-bonded catalytic aspartates and water became poised for tripeptide trimming of Aβ49 to Aβ46. These structural changes required a positively charged N-terminus of endoproteolytic coproduct AICD, which could dissociate during conformational rearrangements of the protease and Aβ49. The simulation findings were highly consistent with biochemical experimental data. Taken together, our complementary biochemical experiments and Pep-GaMD simulations have enabled elucidation of the mechanism of tripeptide trimming of Aβ49 by γ-secretase.

G protein-coupled receptors (GPCRs) represent the largest family of human membrane proteins. Four subtypes of adenosine receptors (ARs), the A 1 AR, A 2A AR, A 2B AR and A 3 AR, each with a unique pharmacological profile and distribution within the tissues in the human body, mediate many physiological functions and serve as critical drug targets for treating numerous human diseases including cancer, neuropathic pain, cardiac ischemia, stroke and diabetes. The A 1 AR and A 3 AR preferentially couple to the G i/o proteins, while the A 2A AR and A 2B AR prefer coupling to the G s proteins. Adenosine receptors were the first subclass of GPCRs that had experimental structures determined in complex with distinct G proteins. Here, we will review recent studies in molecular simulations and computer-aided drug discovery of the adenosine receptors and also highlight their future research opportunities.

We introduce a Gaussian-accelerated molecular dynamics (GaMD), deep learning (DL), and free energy profiling workflow (GLOW) to predict molecular determinants and map free energy landscapes of biomolecules. All-atom GaMD-enhanced sampling simulations are first performed on biomolecules of interest. Structural contact maps are then calculated from GaMD simulation frames and transformed into images for building DL models using a convolutional neural network. Important structural contacts are further determined from DL models of attention maps of the structural contact gradients, which allow us to identify the system reaction coordinates. Finally, free energy profiles are calculated for the selected reaction coordinates through energetic reweighting of the GaMD simulations. We have also successfully demonstrated GLOW for the characterization of activation and allosteric modulation of a G protein-coupled receptor, using the adenosine A 1 receptor (A 1 AR) as a model system. GLOW findings are highly consistent with previous experimental and computational studies of the A 1 AR, while also providing further mechanistic insights into the receptor function. In summary, GLOW provides a systematic approach to mapping free energy landscapes of biomolecules. The GLOW workflow and its user manual can be downloaded at http://miaolab.org/GLOW.

Objective: The goal of the study was to explore the relationship between parent-children relationships related to using the internet among kids and potentially associated factors., Materials and Methods: A sample of 1.216 Vietnamese students between the ages of 12 and 18 agreed to participate in the cross-sectional online survey. Data collected included socioeconomic characteristics and internet use status of participants, their perceived changes in relationship and communication between parents and children since using the internet, and parental control toward the child's internet use. An Ordered Logistic Regression was carried out to determine factors associated with parent-children relationship since using the internet., Results: The characteristics of the relationship between children and their parents since using the Internet were divided into three levels: deterioration (7.0%), stability (78.2%), and improvement (14.8%). The topics that children most often communicate with their parents include learning, housework, and future directions. Two-way interactive activities, such as supporting parents to use the Internet, have a positive impact on the parent-child relationship. Stubborn parental control, such as establishing rules about contact or allowing Internet access and setting up global positioning system (GPS) to track negatively affecting parent-child relationships., Conclusion: Findings indicated that changes in the quality of the parent-child relationship were self-assessed by participants regard to kids' internet use, especially in the COVID-19 epidemic context. Educational campaigns and programs to raise awareness of parents as to the dangers and negative influences that their children may encounter online, psychology of children's behaviors and effects of different responding strategies are recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nguyen, Nguyen, Do, Vu, Vu, Do, Nguyen, Doan, Vu, Do, Nguyen, Latkin, Ho and Ho.)

G-protein-coupled receptors (GPCRs) are the largest family of human membrane proteins and represent the primary targets of about one third of currently marketed drugs. Despite the critical importance, experimental structures have been determined for only a limited portion of GPCRs and functional mechanisms of GPCRs remain poorly understood. Here, we have constructed novel sequence coevolutionary models of the A and B classes of GPCRs and compared them with residue contact frequency maps generated with available experimental structures. Significant portions of structural residue contacts were successfully detected in the sequence-based covariational models. "Exception" residue contacts predicted from sequence coevolutionary models but not available structures added missing links that were important for GPCR activation and allosteric modulation. Moreover, we identified distinct residue contacts involving different sets of functional motifs for GPCR activation, such as the Na + pocket, CWxP, DRY, PIF, and NPxxY motifs in the class A and the HETx and PxxG motifs in the class B. Finally, we systematically uncovered critical residue contacts tuned by allosteric modulation in the two classes of GPCRs, including those from the activation motifs and particularly the extracellular and intracellular loops in class A GPCRs. These findings provide a promising framework for rational design of ligands to regulate GPCR activation and allosteric modulation., (© 2021 Wiley Periodicals LLC.)

Biomolecular recognition including binding of small molecules, peptides and proteins to their target receptors plays a key role in cellular function and has been targeted for therapeutic drug design. However, the high flexibility of biomolecules and slow binding and dissociation processes have presented challenges for computational modeling. Here, we review the challenges and computational approaches developed to characterize biomolecular binding, including molecular docking, Molecular Dynamics (MD) simulations (especially enhanced sampling) and Machine Learning. Further improvements are still needed in order to accurately and efficiently characterize binding structures, mechanisms, thermodynamics and kinetics of biomolecules in the future.

Background: Seroprevalence studies of coronavirus disease 2019 (COVID-19) cases, including asymptomatic and past infections, are important to estimate the scale of the disease outbreak and to establish quarantine measures. We evaluated the clinical performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays available in Korea for use in seroprevalence studies., Methods: The sensitivity, specificity, cross-reactivity, and interference of five SARS-CoV-2 antibody assays were evaluated using the following: 398 serum samples from confirmed COVID-19 patients, 510 negative control samples from before 2018 (pre-pandemic), 163 serum samples from patients with SARS, Middle East respiratory syndrome (MERS), and other viral infections, and five samples for the interference study., Results: The sensitivities of the five assays ranged from 92.2% to 98%, and their specificities, including cross-reactivity and interference, ranged from 97.5% to 100%. The agreement rates were excellent (kappa >0.9). Adjustment of the cutoff values could be considered through ROC curve analysis. The positive predictive values of the individual assays varied from 3.5% to 100% at a 0.1% prevalence but were as high as ≥95% when two assays were combined., Conclusions: The prevalence of COVID-19 in Korea is considered to be exceptionally low at present; thus, we recommend using a combination of two or more SARS-CoV-2 antibody assays rather than a single assay. These results could help select SARS-CoV-2 antibody assays for COVID-19 seroprevalence studies in Korea.

Objectives: The Korea National Health and Nutrition Examination Survey (KNHANES) is a nationwide cross-sectional surveillance system that assesses the health and nutritional status of the Korean population. To evaluate the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the community, we investigated the prevalence of anti-SARS-CoV-2 antibodies in the sera of KNHANES participants., Methods: Subjects were recruited between April 24 and December 12, 2020. In total, 5,284 subjects aged 10-90 years from 17 regions participated. SARS-CoV-2 antibodies were screened using the Elecsys Anti-SARS-CoV-2 assay. Positive samples were verified using 4 different SARS-CoV-2 antibody assays and the plaque reduction neutralizing test. The final seropositivity criteria were a positive screening test and at least 1 positive result from the 5 additional tests., Results: Almost half (49.2%; 2,600/5,284) of participants were from metropolitan areas, 48.9% were middle-aged (40-69 years), and 20.5% were in their 20s or younger. The seropositivity rate was 0.09% (5/5,284). Three of the 5 antibody-positive subjects had a history of infection, of whom 2 were infected abroad and 1 was infected in a local cluster outbreak., Conclusions: The low SARS-CoV-2 antibody seroprevalence in Korea indicates that there have been few coronavirus disease 2019 (COVID-19) cases due to successful COVID-19 management measures (e.g., diagnostic tests for overseas arrivals, national social distancing, and strict quarantine measures). Moreover, asymptomatic infections were uncommon due to active polymerase chain reaction testing. However, hidden infections may exist in the community, requiring the continuation of quarantine and vaccination measures.

Objectives: After the third wave of coronavirus disease 2019 (COVID-19), by mid-February 2021, approximately 0.16% of the Korean population was confirmed positive, which appeared to be among the lowest rates worldwide at that time. However, asymptomatic transmission is challenging for COVID-19 surveillance. Therefore, a community-based serosurvey of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was conducted to understand the effectiveness of Korea's strong containment strategy., Methods: We collected 5,002 residual sera samples from January 30 to March 3, 2021, from 265 medical facilities in Seoul, 346 in Gyeonggi Province, and 57 in Incheon. Sixty samples from tertiary institutions were excluded. We defined the sub-regions according to the addresses of the medical facilities where the specimens were collected. Elecsys Anti-SARS-CoV-2 was used for screening, and positivity was confirmed using the SARS-CoV-2 sVNT Kit. Prevalence was estimated using sampling weights and the Wilson score interval for a binomial proportion with a 95% confidence interval., Results: Among the 4,942 specimens, 32 and 25 tested positive for COVID-19 in the screening and confirmatory tests, respectively. The overall crude prevalence of SARS-CoV-2 antibodies was 0.51%. The population-adjusted overall prevalence was 0.55% in women and 0.38% in men. The region-specific estimation was 0.67% and 0.30% in Gyeonggi Province and Seoul, respectively. No positive cases were detected in Incheon., Conclusions: The proportion of undetected cases in Korea remained low as of early 2021. Therefore, an infection control strategy with exhaustive tracing and widespread pre-emptive testing appears to be effective in containing community spread of COVID-19.

The multifunctional nano drug delivery system (MNDDS) has much revolutionized in cancer treatment, aiming to eliminate many disadvantages of conventional formulations. This paper herein proposes and demonstrates MNDDS inspired by poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymer co-loaded Doxorubicin and magnetic iron oxide nanoparticles (MIONs) with a 1 : 1 (w/w) optimal ratio. In vitro drug release kinetics of Doxorubicin from this nanosystem fitted best to the Weibull kinetic model and can be described by the classical Fickian diffusion mechanism under acidic pH conditions. The combination of MIONs and Doxorubicin in the PLA-TPGS copolymer has maintained the fluorescence properties of Doxorubicin and good cell penetration, especially inside the nucleus and its vicinity. Moreover, different cell cycle profiles were observed in HeLa cell lines treated with MNDDSs., (© 2021 Wiley-VCH GmbH.)

Background: While internal migrants in Vietnam have been a key driving force in the country's rapid economic development, they also face many vulnerabilities. Our study seeks to explore possible inequalities in housing and working conditions between local and internal migrant industrial workers in Vietnam., Methods: Cross-sectional surveys were conducted with 1200 industrial workers in four regions of Vietnam. Dependent variables included housing conditions (satisfaction with convenience of accommodation, sanitation and water of accommodation, and accommodation in general) and working conditions (satisfaction with income, monthly income, number of hazardous working conditions, and work-related stress measured through the modified Effort-Reward Imbalance Questionnaire). The primary independent variable is migrant status. Covariates included region, gender, education, marital status, accommodation status, living arrangements, industry, age, monthly income, experience, and working hours., Results: Of the sample, 24.7% (n=296) were migrants. Overall, no differences were found regarding housing conditions by migrant status. In adjusted regression models, migrants reported higher numbers of hazardous working conditions (β=0.07, 95%CI=0.01-0.13, p=.01) and higher monthly income (β=0.05, 95%CI=0.01-0.09, p=.02)., Discussion: Recent state-level changes in the Vietnamese household registration system may explain the lack of differences in housing conditions by migrant status. Future research should utilize longitudinal designs to examine impacts over time of state policy on migrants' housing conditions as well as well-being. Regarding working conditions, findings highlight the need for stronger social protection policy and better information channels on occupational health and safety for migrants. Further research, including qualitative studies, is needed to explore why migrants face more hazardous working conditions.

Purpose: The mainstay of treatment for basal cell carcinoma (BCC) is surgical excision, which can result in significant associated morbidity, particularly for patients with recurrent tumors. We previously conducted a drug repositioning screen using molecular data from human BCCs and identified histone deacetylase (HDAC) inhibitors as a potential treatment for BCC. Here we conduct the first proof-of-principle study of a topical pan-HDAC inhibitor, remetinostat, in human BCC., Patients and Methods: We conducted a phase II, open-label, single-arm, single-institution trial of a topical HDAC inhibitor. Participants with at least one BCC were recruited. All participants applied 1% remetinostat gel three times daily for 6 weeks, with measurements of tumor diameter conducted at baseline and week 8. Surgical excision of the remaining tumor was conducted at the end of the study and microscopic evaluation was performed., Results: Thirty-three per-protocol tumors from 25 participants were included in the analysis. The overall response rate, defined as the proportion of tumors achieving more than 30% decrease in the longest diameter from baseline to week 8, was 69.7% [90% confidence interval (CI), 54%-82.5%]. On pathologic examination, 54.8% of tumors demonstrated complete resolution. Pharmacodynamic analysis demonstrated similar levels of acetylated histone H3 in skin tissue before and after treatment, however, phosphorylation was increased. No systemic adverse events were reported., Conclusions: The HDAC inhibitor remetinostat is a well-tolerated and effective topical treatment for reducing BCC disease burden in a clinically significant manner. This provides in-human validation of HDAC inhibitors as a therapy for BCC., (©2021 American Association for Cancer Research.)

This study was performed to evaluate the measurement properties of Youth Quality of Life-Short Form (YQOL-SF) in assessing the quality of life (QOL) among general youths in Vietnam. An online cross-sectional study was conducted to validate the YQOL-SF. Factor analysis (including exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) was utilized to determine the factorial structure of this tool. The psychometric properties (reliability and validity) of the new factorial model were assessed. The factor analysis revealed the two-factor model of YQOL-SF including factor 1 "Belief in self and family", and factor 2 "Environment and relationships". Cronbach's alpha value showed excellent internal consistency in both factors (0.911 and 0.910, respectively). Results also indicated good convergent, divergent, concurrent, and know-group validity of the two-factor model. Our study provided a promising model with different domains that were proved to be essential for the assessment of quality of life among Vietnamese youth aged 16-24. Our two-factor model affirmed that a balance between detail and length of the assessment is important to consider when selecting YQOL-SF for youths' QOL assessment. It helped reduce the risk of redundancy and encourages high survey completion rates among participants., Competing Interests: The authors have declared that no competing interests exist.

Caffeine (CFF) is a common antagonist to the four subtypes of adenosine G-protein-coupled receptors (GPCRs), which are critical drug targets for treating heart failure, cancer, and neurological diseases. However, the pathways and mechanism of CFF binding to the target receptors remain unclear. In this study, we have performed all-atom-enhanced sampling simulations using a robust Gaussian-accelerated molecular dynamics (GaMD) method to elucidate the binding mechanism of CFF to human adenosine A 2A receptor (A 2A AR). Multiple 500-1,000 ns GaMD simulations captured both binding and dissociation of CFF in the A 2A AR. The GaMD-predicted binding poses of CFF were highly consistent with the x-ray crystal conformations with a characteristic hydrogen bond formed between CFF and residue N6.55 in the receptor. In addition, a low-energy intermediate binding conformation was revealed for CFF at the receptor extracellular mouth between ECL2 and TM1. While the ligand-binding pathways of the A 2A AR were found similar to those of other class A GPCRs identified from previous studies, the ECL2 with high sequence divergence serves as an attractive target site for designing allosteric modulators as selective drugs of the A 2A AR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Do, Akhter and Miao.)

IL-38 is an IL-1 family receptor antagonist that restricts IL-17-driven inflammation by limiting cytokine production from macrophages and T cells. In the current study, we aimed to explore its role in experimental autoimmune encephalomyelitis in mice, which is, among others, driven by IL-17. Unexpectedly, IL-38-deficient mice showed strongly reduced clinical scores and histological markers of experimental autoimmune encephalomyelitis. This was accompanied by reduced inflammatory cell infiltrates, including macrophages and T cells, as well as reduced expression of inflammatory markers in the spinal cord. IL-38 was highly expressed by infiltrating macrophages in the spinal cord, and in vitro activated IL-38-deficient bone marrow-derived macrophages showed reduced expression of inflammatory markers, accompanied by altered cellular metabolism. These data suggest an alternative cell-intrinsic role of IL-38 to promote inflammation in the CNS., (Copyright © 2021 by The American Association of Immunologists, Inc.)

Many of today's online services are designed specifically to encourage impulse buying. Moreover, many studies have shown that with the assistance of Mobile Augmented Reality, retailers have the potential to significantly improve their sales. However, the effects of Mobile AR on consumer impulse buying behavior have yet to be examined, particularly in the tourism field. Consequently, the present study integrates the Technology Acceptance Model (TAM), Stimulus-Organism-Response (SOR) framework, and flow theory to examine the effects of Mobile AR apps on tourist impulse buyingbehavior. The research model is implemented using an online questionnaire, with the results analyzed by Partial-Least-Squares Structural Equation Modeling (PLS-SEM) approach. The results obtained from 479 valid samples show that the characteristics of Mobile AR apps play an important role in governing tourist behavior in making unplanned purchases. In particular, as the utility, ease-of-use, and interactivity of the apps increase, the perceived enjoyment and satisfaction of the user also increase and give rise to a stronger impulse buying behavior. The results also reveal a mediating effect of the flow experience on the relationship between the perceived ease of use of the Mobile AR app and the user satisfaction in using the app. Overall, the findings presented in this study provide a useful source of reference for Mobile AR app developers, retailers, and tourism marketers in better understanding users' preferences for Mobile AR apps and strengthening their impulse buying behavior in the tourism context as a result., (© 2020 The Author(s).)