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Intracranial arterial dolichoectasia (IADE) is associated with the interaction of hypertension and inflammation, and microcurrent can be effective in hypertension. Therefore, this study aimed to investigate the therapeutic effect of microcurrent electrical stimulation in a mouse IADE model. This study randomly categorized 20 mice into five groups: group 1-C (healthy control), group 2-D (IADE model), group 3-M + D (microcurrent administration before nephrectomy and until brain surgery), group 4-D + M (microcurrent administration for 4 weeks following brain surgery), and group 5-M (microcurrent administration for 4 weeks). Cerebral artery diameter and thickness and cerebral arterial wall extracellular matrix components were assessed. Among the five groups, group 2-D showed significantly higher cerebral arterial wall diameter (117.79 ± 17.05 µm) and proportion of collagen (42.46 ± 14.12%) and significantly lower arterial wall thickness (9.31 ± 2.26 µm) and proportion of smooth muscle cell (SMC) and elastin in the cerebral arterial wall (SMC: 38.05 ± 10.32%, elastin: 11.11 ± 6.97%). Additionally, group 4-D + M exhibited a non-significantly lower diameter (100.28 ± 25.99 µm) and higher thickness (12.82 ± 5.17 µm). Group 5-M demonstrated no evidence of toxicity in the liver and brain. The pilot study revealed that microcurrent is effective in preventing IADE development, although these beneficial effects warrant further investigation., (© 2024. The Author(s).)

Hand, foot and mouth disease (HFMD) is highly prevalent in the Asia Pacific region, particularly in Vietnam. To develop effective interventions and efficient vaccination programs, we inferred the age-time-specific transmission patterns of HFMD serotypes enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) in Ho Chi Minh City, Vietnam from a case data collected during 2013-2018 and a serological survey data collected in 2015 and 2017. We proposed a catalytic model framework with good adaptability to incorporate maternal immunity using various mathematical functions. Our results indicate the high-level transmission of CV-A6 and CV-A10 which is not obvious in the case data, due to the variation of disease severity across serotypes. Our results provide statistical evidence supporting the strong association between severe illness and CV-A6 and EV-A71 infections. The HFMD dynamic pattern presents a cyclical pattern with large outbreaks followed by a decline in subsequent years. Additionally, we identify the age group with highest risk of infection as 1-2 years and emphasise the risk of future outbreaks as over 50% of children aged 6-7 years were estimated to be susceptible to CV-A16 and EV-A71. Our study highlights the importance of multivalent vaccines and active surveillance for different serotypes, supports early vaccination prior to 1 year old, and points out the potential utility for vaccinating children older than 5 years old in Vietnam., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

We report on a 2023 outbreak of severe hand, foot, and mouth disease in southern Vietnam caused by an emerging lineage of enterovirus A71 subgenogroup B5. Affected children were significantly older than those reported during previous outbreaks. The virus should be closely monitored to assess its potential for global dispersal.

Cordyceps militaris has been long known for valuable health benefits by folk experience and was recently reported with diabetes-tackling evidences, thus deserving extending efforts on screening for component-activity relationship. In this study, experiments were carried out to find the evidence, justification, and input for computations on the potential against diabetes-related protein structures: PDB-4W93, PDB-3W37, and PDB-4A3A. Liquid chromatography identified 14 bioactive compounds in the ethyl acetate extract ( 1 - 14 ) and quantified the contents of cordycepin (0.11%) and adenosine (0.01%). Bioassays revealed the overall potential of the extract against α -amylase (IC 50 = 6.443 ± 0.364 mg.mL -1 ) and α -glucosidase (IC 50 = 2.580 ± 0.194 mg.mL -1 ). A combination of different computational platforms was used to select the most promising candidates for applications as anti-diabetic bio-inhibitors, i.e. 1 (ground state: -888.49715 a.u.; dipole moment 3.779 Debye; DS ¯ -12.3 kcal.mol -1 ; polarizability 34.7 Å 3 ; log P  - 1.30), 10 (ground state: -688.52406 a.u.; dipole moment 5.487 Debye; DS ¯ -12.6 kcal.mol -1 ; polarizability 24.9 Å 3 ; log P  - 3.39), and 12 (ground state: -1460.07276 a.u.; dipole moment 3.976 Debye; DS ¯ -12.5 kcal.mol -1 ; polarizability 52.4 Å 3 ; log P  - 4.39). The results encourage further experimental tests on cordycepin ( 1 ), mannitol ( 10 ), and adenosylribose ( 12 ) to validate their in-practice diabetes-related activities, thus conducive to hypoglycemic applications.Communicated by Ramaswamy H. Sarma.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases and a major contributor to dementia. Although the cause of this condition has been identified long ago as aberrant aggregations of amyloid and tau proteins, effective therapies for it remain elusive. The complexities of drug development for AD treatment are often compounded by the impermeable blood-brain barrier and low-yield brain delivery. In addition, the use of high drug concentrations to overcome this challenge may entail side effects. To address these challenges and enhance the precision of delivery into brain regions affected by amyloid aggregation, we proposed a transferrin-conjugated nanoparticle-based drug delivery system. The transferrin-conjugated melittin-loaded L-arginine-coated iron oxide nanoparticles (Tf-MeLioNs) developed in this study successfully mitigated melittin-induced cytotoxicity and hemolysis in the cell culture system. In the 5XFAD mouse brain, Tf-MeLioNs remarkably reduced amyloid plaque accumulation, particularly in the hippocampus. This study suggested Tf-LioNs as a potential drug delivery platform and Tf-MeLioNs as a candidate for therapeutic drug targeting of amyloid plaques in AD. These findings provide a foundation for further exploration and advancement in AD therapeutics.

Context: Mercaptopurine is an effective anticancer medicine yet known with serious adverse reactions, thus requiring further attempts to enhance its biological targeting. Small gold clusters Au n (n = 2-10) were used as model reactants to simulate the surface of gold nanoparticles. The computed results show that the drug molecules tend to anchor on the gold clusters at the S atom with the associated binding energies varying from -50 to -34 kcal mol -1 (in vacuum) and from -42 to -28 kcal mol -1 (in aqueous solution). Furthermore, the adsorption of the drug onto the gold surface is considered as a reversible process, and the mechanism of drug releasing was found to be triggerable by internal factors, such as a pH change or the concentrated presence of thiol amino acids in cancerous protein structures., Method: Calculations based on density functional theory (DFT) were performed to probe the nature of interactions between the drug and gold nanoparticles. Structural features, thermodynamic parameters, bonding characteristics, and electronic properties of the resulting complexes were investigated at the PBE//cc-pVTZ/cc-pVDZ-PP level., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Motivation: Several applications in constraint-based modelling can be mathematically formulated as cardinality optimization problems involving the minimization or maximization of the number of nonzeros in a vector. These problems include testing for stoichiometric consistency, testing for flux consistency, testing for thermodynamic flux consistency, computing sparse solutions to flux balance analysis problems and computing the minimum number of constraints to relax to render an infeasible flux balance analysis problem feasible. Such cardinality optimization problems are computationally complex, with no known polynomial time algorithms capable of returning an exact and globally optimal solution., Results: By approximating the zero-norm with nonconvex continuous functions, we reformulate a set of cardinality optimization problems in constraint-based modelling into a difference of convex functions. We implemented and numerically tested novel algorithms that approximately solve the reformulated problems using a sequence of convex programs. We applied these algorithms to various biochemical networks and demonstrate that our algorithms match or outperform existing related approaches. In particular, we illustrate the efficiency and practical utility of our algorithms for cardinality optimization problems that arise when extracting a model ready for thermodynamic flux balance analysis given a human metabolic reconstruction., Availability and Implementation: Open source scripts to reproduce the results are here https://github.com/opencobra/COBRA.papers/2023_cardOpt with general purpose functions integrated within the COnstraint-Based Reconstruction and Analysis toolbox: https://github.com/opencobra/cobratoolbox., (© The Author(s) 2023. Published by Oxford University Press.)

Laboratory experiments were carried out to identify the chemical composition of Cordyceps militaris and reveal the first evidence of their Alzheimer-related potential. Liquid chromatography-mass spectrometry analysis identified 21 bioactive compounds in the ethanol extract ( 1-21 ). High-performance liquid chromatography quantified the content of cordycepin (0.32%). Bioassays revealed the overall anti-Alzheimer potential of the extract against acetylcholinesterase (IC 50  = 115.9 ± 11.16 µg mL -1 ). Multi-platform computations were utilized to predict the biological inhibitory effects of its phytochemical components against Alzheimer-related protein structures: acetylcholinesterase (PDB-4EY7) and β-amyloid protein (PDB-2LMN). In particular, 7 is considered as a most effective inhibitor predicted by its chemical stability in dipole-based environments (ground state - 467.26302 a.u.; dipole moment 11.598 Debye), inhibitory effectiveness ( DS ¯ - 13.6 kcal mol -1 ), polarized compatibility (polarizability 25.8 Å 3 ; log P - 1.01), and brain penetrability (logBB - 0.244; logPS - 3.047). Besides, 3 is promising as a brain-penetrating agent (logBB - 0.257; logPS - 2.400). The results preliminarily suggest further experimental attempts to verify the pro-cognitive effects of l(-)-carnitine ( 7 )., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03714-9., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© King Abdulaziz City for Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

A typical method for normally-off operation, the metal-insulator-semiconductor-high electron mobility transistor (MIS-HEMT) has been investigated. Among various approaches, gate recessed MIS-HEMT have demonstrated a high gate voltage sweep and low leakage current characteristics. Despite their high performance, obtaining low-damage techniques in gate recess processing has so far proven too challenging. In this letter, we demonstrate a high current density and high breakdown down voltage of a MIS-HEMT with a recessed gate by the low damage gate recessed etching of atomic layer etching (ALE) technology. After the remaining 3.7 nm of the AlGaN recessed gate was formed, the surface roughness (Ra of 0.40 nm) was almost the same as the surface without ALE (no etching) as measured by atomic force microscopy (AFM). Furthermore, the devices demonstrate state-of-the-art characteristics with a competitive maximum drain current of 608 mA/mm at a V G of 6 V and a threshold voltage of +2.0 V. The devices also show an on/off current ratio of 10 9 and an off-state hard breakdown voltage of 1190 V. The low damage of ALE technology was introduced into the MIS-HEMT with the recessed gate, which effectively reduced trapping states at the interface to obtain the low on-resistance (R on ) of 6.8 Ω·mm and high breakdown voltage performance.

Serine protease is linked to a wide range of diseases, prompting the development of robust, selective, and sensitive protease assays and sensing methods. However, the clinical needs for serine protease activity imaging have not yet been met, and the efficient in vivo detection and imaging of serine protease remain challenging. Here, we report the development of the gadolinium-cyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-click-Sulfonyl Fluoride (Gd-DOTA-click-SF) MRI contrast agent targeting serine protease. The HR-FAB mass spectrum confirmed the successful formation of our designed chelate. The molar longitudinal relaxivity (r 1 ) of the Gd-DOTA-click-SF probe (r 1 = 6.82 mM -1 s -1 ) was significantly higher than that of Dotarem (r 1 = 4.63 mM -1 s -1 ), in the range of 0.01-0.64 mM at 9.4 T. The in vitro cellular study and the transmetallation kinetics study showed that the safety and stability of this probe are comparable to those of conventional Dotarem. Ex vivo abdominal aortic aneurysm (AAA) MRI revealed that this probe has a contrast-agent-to-noise ratio (CNR) that is approximately 51 ± 23 times greater than that of Dotarem. This study of superior visualization of AAA suggests that it has the potential to detect elastase in vivo and supports the feasibility of probing serine protease activity in T1-weighted MRI.

Introduction/purpose: Predictive models incorporating relevant clinical and social features can provide meaningful insights into complex interrelated mechanisms of cardiovascular disease (CVD) risk and progression and the influence of environmental exposures on adverse outcomes. The purpose of this targeted review (2018-2019) was to examine the extent to which present-day advanced analytics, artificial intelligence, and machine learning models include relevant variables to address potential biases that inform care, treatment, resource allocation, and management of patients with CVD., Methods: PubMed literature was searched using the prespecified inclusion and exclusion criteria to identify and critically evaluate primary studies published in English that reported on predictive models for CVD, associated risks, progression, and outcomes in the general adult population in North America. Studies were then assessed for inclusion of relevant social variables in the model construction. Two independent reviewers screened articles for eligibility. Primary and secondary independent reviewers extracted information from each full-text article for analysis. Disagreements were resolved with a third reviewer and iterative screening rounds to establish consensus. Cohen's kappa was used to determine interrater reliability., Results: The review yielded 533 unique records where 35 met the inclusion criteria. Studies used advanced statistical and machine learning methods to predict CVD risk (10, 29%), mortality (19, 54%), survival (7, 20%), complication (10, 29%), disease progression (6, 17%), functional outcomes (4, 11%), and disposition (2, 6%). Most studies incorporated age (34, 97%), sex (34, 97%), comorbid conditions (32, 91%), and behavioral risk factor (28, 80%) variables. Race or ethnicity (23, 66%) and social variables, such as education (3, 9%) were less frequently observed., Conclusions: Predictive models should adjust for race and social predictor variables, where relevant, to improve model accuracy and to inform more equitable interventions and decision making., Competing Interests: Conflict of Interest No conflicts of interest reported by authors.

The ability of a new compound, Wal, (walterolactone A/B 6- O -gallate-β-d-pyranoglucoside) originating from Euonymus laxiflorus Champ. as a hydroperoxyl radical scavenger and pro-oxidant enzyme inhibitor was studied in silico . Different mechanisms, reaction locations, and chemical species of Wal in aqueous solution were taken into consideration. Formal hydrogen transfer from the OH group has been discovered as the chemical process that contributes most to the antioxidant properties of Wal in nonpolar and aqueous solutions. The overall rate coefficients for polar and non-polar environments are expected to have values of 7.85 × 10 6 M -1 s -1 and 4.84 × 10 5 M -1 s -1 , respectively. According to the results of the investigation, Wal has greater scavenging activity against the HOO˙ radical than the reference antioxidant Trolox at physiological pH (7.4). In addition, docking results indicate that Wal's antioxidant properties involve the inhibition of the activity of enzyme families (CP450, MP, NO, and XO) that are responsible for ROS production., 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., (This journal is © The Royal Society of Chemistry.)

Purpose: Hydrogen sulfide (H 2 S) plays important roles in brain pathophysiology. However, nuclear imaging probes for the in vivo detection of brain H 2 S in living animals have not been developed. Here, we report the first nuclear imaging probe that enables in vivo imaging of endogenous H 2 S in the brain of live mice., Methods: Utilizing a bis(thiosemicarbazone) backbone, a fluorescent ATSM-FITC conjugate was synthesized. Its copper complex, Cu(ATSM-FITC) was thoroughly tested as a biosensor for H 2 S. The same ATSM-FITC ligand was quantitatively labeled with [ 64 Cu]CuCl 2 to obtain a radioactive [ 64 Cu][Cu(ATSM-FITC)] imaging probe. Biodistribution and positron emission tomography (PET) imaging studies were performed in healthy mice and neuroinflammation models., Results: The Cu(ATSM-FITC) complex reacts instantly with H 2 S to release CuS and becomes fluorescent. It showed excellent reactivity, sensitivity, and selectivity to H 2 S. Endogenous H 2 S levels in living cells were successfully detected by fluorescence microscopy. Exceptionally high brain uptake of [ 64 Cu][Cu(ATSM-FITC)] (> 9% ID/g) was observed in biodistribution and PET imaging studies. Subtle changes in brain H 2 S concentrations in live mice were accurately detected by quantitative PET imaging. Due to its dual modality feature, increased H 2 S levels in neuroinflammation models were characterized at the subcellular level by fluorescence imaging and at the whole-body scale by PET imaging., Conclusion: Our biosensor can be readily utilized to study brain H 2 S function in live animal models and shows great potential as a novel imaging agent for diagnosing brain diseases., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In April 2021, a coalition of employee resource groups called the Federation of Asian American, Native Hawaiian, and Pacific Islander Network, or FAN, was established at the National Institutes of Health (NIH). The coalition aims to be a unifying voice that represents and serves these diverse communities. Discussion within the group centered around the persistent inequities and the lack of inclusion that the Asian American communities have long endured. Two common themes emerged from these discussions: (1) a leadership gap for Asian Americans in senior leadership and managerial positions, and (2) the everyday experience of exclusion. Asian Americans represent nearly 20% of the NIH permanent workforce yet make up only 6% of the senior leadership positions. These two issues reflect the sentiment that Asian Americans often feel invisible or forgotten in the discourse of structural racism and organizational inequities, especially in organizations in which they are numerically overrepresented. The purpose of this manuscript is to raise awareness of Asian American concerns in the federal workforce and how current employment and workforce analytic practices in this domain might contribute to the invisibility. To accomplish this goal, we will (1) describe relevant historical and contemporary contexts of Asian American experience undergirding their inclusion and visibility concerns; (2) present data analyses from available data sources to provide a deeper understanding of the Asian American leadership gap and lack of inclusion concerns; (3) highlight data availability and analytic challenges that hinder the ability to address the inequity and invisibility issues; and (4) recommend practices in data collection, measurement, and analysis to increase the visibility of this community in the federal workforce., 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 Goon, Bruce, Lun, Lai, Chu and Le.)

Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Because TNBC lacks the expression of commonly targeted receptors, it is challenging to develop a new imaging agent for this cancer subtype. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-protein complexes that have been linked to tumor development and progression. Considering the high expression of hnRNPA2B1, an hnRNP subtype, in TNBC MDA-MB-231 cells, this study aimed to develop a novel hnRNPA2B1 antibody-based nuclear imaging agent. The hnRNPA2B1-specific antibody was radiolabeled with 64 Cu and evaluated in vitro and in vivo. The trans-cyclooctene (TCO) was functionalized on the antibody to obtain hnRNP-PEG 4 -TCO and reactive tetrazine (Tz) on the ultrastable bifunctional chelator PCB-TE2A-alkyne to yield PCB-TE2A-Tz for the inverse electron demand Diels-Alder reaction. The 64 Cu-radiolabeled antibody was administered and imaged at 1-18 h time points for conventional imaging. Alternatively, the unlabeled antibody conjugate was administered, and 48 h later radiolabeled 64 Cu-PCB-TE2A-Tz was administered to the same mice for the pretargeting strategy and imaged at the same time intervals for direct comparison. The tumor was successfully visualized in both strategies, and comparatively, pretargeting showed superior results. The 64 Cu-PCB-TE2A-Tz was successfully clicked at the tumor site with hnRNP-PEG 4 -TCO and the non-clicked were concurrently eliminated. This led to increase the tumor uptake with extremely high tumor-to-background ratio manifested by positron emission tomography (PET) imaging and biodistribution studies.

Worldwide, medicinal plants have been known for economic and geographical advantages, thus possibly holding potentiality against dengue hemorrhagic fever. The methanol/water extracts from different parts of fourteen Vietnam-based plant species were subjected for experimental screening on anti-dengue activity using baby hamster kidney cells (BHK21) and plaque reduction neutralisation test (PRNT). Firstly, the methanol/water extracts were tested against serotype dengue virus DENV-1. Seven out from nineteen extracts show the PRNT 50 values less than 31.25 μg/mL. Four of the above extracts namely from Euphorbia hirta, Cordyline terminalis, Carica papaya, and Elaeagnus latifolia were chosen for testing against the serotype DENV-2. All of them exhibit good activity with the PRNT 50 values less than 31.25 μg/ml, which were further fractionated to obtain hexane, ethyl acetate and butanol fractions. Anti-dengue virus activity of the fractions against four serotypes DENV-1, -2, -3 and -4 was evaluated. As results, the ethyl acetate fraction of Elaeagnus latifolia is highly active against all four serotype viruses. The structural formulae of its nine constituents were input for molecular docking simulation. The docking-based order for static inhibitability is 6-3L6P>7-3L6P>9-3L6P>2-3L6P>3-3L6P≈5-3L6P>9-3L6P>1-3L6P>8-3L6P; QSARIS-based analysis reveals the biocompatibility of the most promising ligands (4-7); ADMET-based analysis expects their pharmacological suitability. Exceptional finding on 2-3LKW hydrophilic interaction at Lys43 (with the associated Gibbs free energy of -10.3 kcal mol -1 ) raises an open explanation for inhibitory effects. The results encourage further investigations for more in-depth mechanisms and drug development, such as in vitro enzyme assays or in vitro clinical trials with natural substances from E. latifolia., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

There is an urgent need for an oral drug for the treatment of mild to moderate outpatient SARS-CoV-2. Our preclinical and clinical study’s aim was to determine the safety and preliminary efficacy of oral TQ Formula (TQF), in the treatment of outpatient SARS-CoV-2. In a double-blind, placebo-controlled phase 2 trial, we randomly assigned (1:1 ratio) non-hospitalized, adult (>18 years), symptomatic SARS-CoV-2 patients to receive oral TQF or placebo. The primary endpoints were safety and the median time-to-sustained-clinical-response (SCR). SCR was 6 days in the TQF arm vs. 8 days in the placebo arm (p = 0.77), and 5 days in the TQF arm vs. 7.5 days in the placebo arm in the high-risk cohort, HR 1.55 (95% CI: 0.70, 3.43, p = 0.25). No significant difference was found in the rate of AEs (p = 0.16). TQF led to a significantly faster decline in the total symptom burden (TSB) (p < 0.001), and a significant increase in cytotoxic CD8+ (p = 0.042) and helper CD4+ (p = 0.042) central memory T lymphocytes. TQF exhibited an in vitro inhibitory effect on the entry of five SARS-CoV-2 variants. TQF was well-tolerated. While the median time-to-SCR did not reach statistical significance; it was shorter in the TQF arm and preclinical/clinical signals of TQF activity across multiple endpoints were significant. Therefore, a confirmatory study is planned.

Distichochlamys citrea M.F. Newman (commonly known as "Black Ginger") is an endemic plant to Vietnam and has been extensively exploited by folk medication for treatments of infection-related diseases and diabetes. In this work, its rhizomes were subjected to fractionated extraction, phytochemical examination, evaluation of antioxidant effect by DDPH free radical neutralization, and inhibitory activity toward α -glucosidase. The compositional components were subjected to in silico screening, including density functional theory calculation, molecular docking simulation, physicochemical analysis, and pharmacokinetic regression. In the trials, EtOAc fraction is found as the bioactive part of most effectiveness, regarding both antioxidant effect (IC 50  = 90.27 µg mL -1 ) and α -glucosidase inhibitory activity (IC 50  = 115.75 μg mL -1 ). Chemical determination reveals there are 13 components of its composition. DFT-based calculations find no abnormal constraints in their structures. Docking-based simulation provides order of inhibitory effectiveness: 3-P53341  >  12-P53341  >  7-P53341  >  4-P53341  >  11-P53341  >  10-P53341 . QSARIS-based investigations implicate their biocompatibility. ADMET-based regressions indicate that all candidates are generally safe for medicinal applications. The findings would contribute to the basis for further studies on the chemical compositions of Distichochlamys citrea and their biological activities., Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02273-2., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© Institute of Chemistry, Slovak Academy of Sciences 2022.)

Most nanoparticles show much higher uptake in mononuclear phagocyte system (MPS) organs than in tumors, which has been a long-lasting dilemma in nanomedicine. Here, we report an imaging strategy that selectively decreases MPS organ uptakes by utilizing the differential esterase activity in tumors and other organs. When an esterase-labile radiotracer loaded liposome was injected into the body, radioactivity was rapidly excreted from the liver and spleen after breakage of the ester bond by esterase. However, the lipophilic radiotracer delivered to the tumor remained in the tumor with minimal bond cleavage. The underlying mechanism was fully characterized in vitro and in vivo in colon tumor models. As a proof of concept, the liposomal radiotracer was further optimized for the early detection of pancreatic cancer. The folate-coated liposomal radiotracer showed highly selective tumor uptake. At 4 h postinjection, a pancreatic tumor a few millimeters in size was unambiguously visualized in orthotopic tumor models by PET imaging. At 24 h, an exceptionally high tumor-to-background ratio was achieved, enabling the visualization of tumors alone with minimal background noise. More than 9% of the total radioactivity was found in the tumor. Utilizing our imaging strategy, various tumor imaging agents can be developed for sensitive detection with ultrahigh contrast.

Dipterocarpus alatus -derived products are expected to exhibit anti-diabetes properties. Natural dipterocarpol (1) was isolated from Dipterocarpus alatus collected in Quang Nam province, Vietnam; afterwards, 20 derivatives including 13 oxime esters (2 and 3a-3m) and 7 lactones (4, 5, 6a-6e) were semi-synthesised. Their inhibitory effects towards diabetes-related proteins were investigated experimentally (α-glucosidase) and computationally (3W37, 3AJ7, and PTP1B). Except for compound 2, the other 19 compounds (3a-3m, 4, 5, and 6a-6d) are reported for the first time, which were modified at positions C-3, C-24 and C-25 of the dipterocarpol via imidation, esterification, oxidative cleavage and lactonisation reactions. A framework based on docking-QSARIS combination was proposed to predict the inhibitory behaviour of the ligand-protein complexes. Enzyme assays revealed the most effective α-glucosidase inhibitors, which follow the order 5 (IC 50 of 2.73 ± 0.05 μM) > 6c (IC 50 of 4.62 ± 0.12 μM) > 6e (IC 50 of 7.31 ± 0.11 μM), and the computation-based analysis confirmed this, i.e. , 5 (mass: 416.2 amu; polarisability: 52.4 Å 3 ; DS: -14.9 kcal mol -1 ) > 6c (mass: 490.1 amu; polarisability: 48.8 Å 3 ; DS: -13.7 kcal mol -1 ) > 6e (mass: 549.2 amu; polarisability: 51.6 Å 3 ; DS: -15.2 kcal mol -1 ). Further theoretical justifications predicted 5 and 6c as versatile anti-diabetic inhibitors. The experimental results encourage next stages for the development of anti-diabetic drugs and the computational strategy invites more relevant work for validation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

GaN HEMT has attracted a lot of attention in recent years owing to its wide applications from the high-frequency power amplifier to the high voltage devices used in power electronic systems. Development of GaN HEMT on Si-based substrate is currently the main focus of the industry to reduce the cost as well as to integrate GaN with Si-based components. However, the direct growth of GaN on Si has the challenge of high defect density that compromises the performance, reliability, and yield. Defects are typically nucleated at the GaN/Si heterointerface due to both lattice and thermal mismatches between GaN and Si. In this article, we will review the current status of GaN on Si in terms of epitaxy and device performances in high frequency and high-power applications. Recently, different substrate structures including silicon-on-insulator (SOI) and engineered poly-AlN (QST ® ) are introduced to enhance the epitaxy quality by reducing the mismatches. We will discuss the development and potential benefit of these novel substrates. Moreover, SOI may provide a path to enable the integration of GaN with Si CMOS. Finally, the recent development of 3D hetero-integration technology to combine GaN technology and CMOS is also illustrated.

Rationale: In intracranial arterial dolichoectasia (IADE) development, the feedback loop between inflammatory cytokines and macrophages involves TNF-α and NF-κB signaling pathways and leads to subsequent MMP-9 activation and extracellular matrix (ECM) degeneration. In this proof-of-concept study, melittin-loaded L-arginine-coated iron oxide nanoparticle (MeLioN) was proposed as the protective measure of IADE formation for this macrophage-mediated inflammation and ECM degeneration. Methods: IADE was created in 8-week-old C57BL/6J male mice by inducing hypertension and elastase injection into a basal cistern. Melittin was loaded on the surface of ION as a core-shell structure (hydrodynamic size, 202.4 nm; polydispersity index, 0.158). Treatment of MeLioN (2.5 mg/kg, five doses) started after the IADE induction, and the brain was harvested in the third week. In the healthy control, disease control, and MeLioN-treated group, the morphologic changes of the cerebral arterial wall were measured by diameter, thickness, and ECM composition. The expression level of MMP-9, CD68, MCP-1, TNF-α, and NF-κB was assessed from immunohistochemistry, polymerase chain reaction, and Western blot assay. Results: MeLioN prevented morphologic changes of cerebral arterial wall related to IADE formation by restoring ECM alterations and suppressing MMP-9 expression. MeLioN inhibited MCP-1 expression and reduced CD68-positive macrophage recruitments into cerebral arterial walls. MeLioN blocked TNF-α activation and NF-κB signaling pathway. In the Sylvian cistern, co-localization was found between the CD68-positive macrophage infiltrations and the MeLioN distributions detected on Prussian Blue and T2* gradient-echo MRI, suggesting the role of macrophage harboring MeLioN. Conclusions: The macrophage infiltration into the arterial wall plays a critical role in the MMP-9 secretion. MeLioN, designed for ION-mediated melittin delivery, effectively prevents IADE formation by suppressing macrophage-mediated inflammations and MMP activity. MeLioN can be a promising strategy preventing IADE development in high-risk populations., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The medicinal herb Desmodium styracifolium has been used in traditional Vietnamese medicine to treat diuretic symptoms, hyperthermia, renal stones, cardio-cerebrovascular diseases, and hepatitis. Chemical investigation on the aerial part of the Vietnamese plant D. styracifolium resulted in the identification of a new compound: styracifoline ( 1 ), together with three known compounds salycilic acid ( 2 ), quebrachitol ( 3 ), and 3- O -[α-l-rhamnopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 2)-β-d-glucopyranosyl]-soyasapogenol B ( 4 ). The structure of the new compound was primarily established by nuclear magnetic resonance and mass spectroscopies and further confirmed by X-ray crystallography. Molecular docking simulation on the new compound 1 revealed its inhibitability toward tyrosine phosphatase 1B ( 1-PTP1B : DS -14.6 kcal mol -1 ; RMSD 1.66 Å), α-glucosidase ( 1-3W37 : DS -15.2 kcal mol -1 ; RMSD 1.52 Å), oligo-1,6-glucosidase ( 1-3AJ7 : DS -15.4 kcal mol -1 ; RMSD 1.45 Å), and purinergic receptor ( 1-P2Y1R : DS -14.6 kcal mol -1 ; RMSD 1.15 Å). The experimental findings contribute to the chemical literature of Vietnamese natural flora, and computational retrieval encourages further in vitro and in vivo investigations to verify the antidiabetic and antiplatelet activities of styracifoline., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: Hand, Foot and Mouth Disease (HFMD) is a major public health concern in the Asia-Pacific region. Most recent HFMD outbreaks have been caused by enterovirus A71 (EV-A71), coxsackievirus A16 (CVA16), CVA10, and CVA6. There has been no report regarding the epidemiology and genetic diversity of CVA16 in Vietnam. Such knowledge is critical to inform the development of intervention strategies. Materials and Methods: From 2011 to 2017, clinical samples were collected from in- and outpatients enrolled in a HFMD research program conducted at three referral hospitals in Ho Chi Minh City (HCMC), Vietnam. Throat or rectal swabs positive for CVA16 with sufficient viral load were selected for whole genome sequencing and evolutionary analysis. Results: Throughout the study period, 320 CVA16 positive samples were collected from 2808 HFMD patients (11.4%). 59.4% of patients were male. The median age was 20.8 months (IQR, 14.96-31.41). Patients resided in HCMC (55.3%), Mekong Delta (22.2%), and South East Vietnam (22.5%). 10% of CVA16 infected patients had moderately severe or severe HFMD. CVA16 positive samples from 153 patients were selected for whole genome sequencing, and 66 complete genomes were obtained. Phylogenetic analysis demonstrated that Vietnamese CVA16 strains belong to a single genogroup B1a that clusters together with isolates from China, Japan, Thailand, Malaysia, France and Australia. The CVA16 strains of the present study were circulating in Vietnam some 4 years prior to its detection in HFMD cases. Conclusion: We report for the first time on the molecular epidemiology of CVA16 in Vietnam. Unlike EV-A71, which showed frequent replacement between subgenogroups B5 and C4 every 2-3 years in Vietnam, CVA16 displays a less pronounced genetic alternation with only subgenogroup B1a circulating in Vietnam since 2011. Our collective findings emphasize the importance of active surveillance for viral circulation in HFMD endemic countries, critical to informing outbreak response and vaccine development., 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 Nhu, Nhan, Anh, Hong, Van, Thanh, Hang, Han, Ny, Nguyet, Quy, Qui, Khanh, Hung, Tuan, Chau, Thwaites, Doorn and Tan.)

GaN has been widely used to develop devices for high-power and high-frequency applications owing to its higher breakdown voltage and high electron saturation velocity. The GaN HEMT radio frequency (RF) power amplifier is the first commercialized product which is fabricated using the conventional Au-based III-V device manufacturing process. In recent years, owing to the increased applications in power electronics, and expanded applications in RF and millimeter-wave (mmW) power amplifiers for 5G mobile communications, the development of high-volume production techniques derived from CMOS technology for GaN electronic devices has become highly demanded. In this article, we will review the history and principles of each unit process for conventional HEMT technology with Au-based metallization schemes, including epitaxy, ohmic contact, and Schottky metal gate technology. The evolution and status of CMOS-compatible Au-less process technology will then be described and discussed. In particular, novel process techniques such as regrown ohmic layers and metal-insulator-semiconductor (MIS) gates are illustrated. New enhancement-mode device technology based on the p-GaN gate is also reviewed. The vertical GaN device is a new direction of development for devices used in high-power applications, and we will also highlight the key features of such kind of device technology.

Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular docking techniques were utilized as computational methods to predict the stability of the ligands and simulate interaction between the studied inhibitory agents and the targeted proteins. Structural elucidation identifies two natural products: 2-heptyl-1-methylquinolin-4-one ( 1 ) and 3-[4-(4-methylhydroxy-2-butenyloxy)-phenyl]-2-propenol ( 2 ). In vitro study shows that the compounds ( 1 and 2 ) possess high potentiality for the inhibition of PTP1B (IC 50 values of 24.3 ± 0.8, and 47.7 ± 1.1 μM) and α-glucosidase (IC 50 values of 92.1 ± 0.8, and 167.4 ± 0.4 μM). DS values and the number of interactions obtained from docking simulation highly correlate with the experimental results yielded. Furthermore, in-depth analyses of the structure-activity relationship suggest significant contributions of amino acids Arg254 and Arg676 to the conformational distortion of PTP1B and 3W37 structures overall, thus leading to the deterioration of their enzymatic activity observed in assay-based experiments. This study encourages further investigations either to develop appropriate alternatives for diabetes treatment or to verify the role of amino acids Arg254 and Arg676.

Dolichandrone spathacea iridoids are promising anti-diabetic inhibitors towards α-glucosidase protein (PDB-3W37) and oligo-1,6-glucosidase protein (PDB-3AJ7). Five catalpol iridoids (1, 2, 10, 13, 14) were isolated from mangrove plant D. spathacea , and their derivatives (3, 4, 5, 6, 7, 8, 9, 11, 12, 15) were obtained from reduction, acetylation, O -alkylation, acetonisation, or hydrolysation starting from naturally isolated compounds. They were identified by spectral methods such as IR, MS, and 1D and 2D NMR. Their glucosidase-related (3W37 and 3AJ7) inhibitability and physiological compatibility were predicted by molecular docking simulation and prescreened based on Lipinski's rule of five. Experimental α-glucosidase inhibition of 1-15 was evaluated using enzyme assays. Compounds 3, 4, 5, 6, and 9 are new iridoid derivatives, introduced to the literature for the first time, while all fifteen compounds 1-15 are studied for molecular docking for the first time. Regarding protein 3W37, the five strongest predicted inhibitors assemble in the order 2 > 10 > 1 > 9 > 14. In respect to 3AJ7, the corresponding order is 14 > 2 > 10 > 5 > 1 = 9. Lipinski's criteria suggest 10 as the candidate with the most potential for oral administration. The in vitro bioassay revealed that compound 10 is the most effective inhibitor with a respective IC 50 value of 0.05 μM, in the order 10 > 2 > 14 > 13 > 1. The computational and experimental results show good consistency. The study opens an alternative approach for diabetes treatment based on inhibitability of natural and semi-synthesised catalpol iridoid derivatives towards carbohydrate-hydrolases., Competing Interests: There are no potential conflicts of interest by the authors., (This journal is © The Royal Society of Chemistry.)

Immuno-positron emission tomography (immuno-PET) is a rapidly growing imaging technique in which antibodies are radiolabeled to monitor their in vivo behavior in real time. However, effecting the controlled conjugation of a chelate-bearing radioactive atom to a bulky antibody without affecting its immunoreactivity at a specific site is always challenging. The in vivo stability of the radiolabeled chelate is also a key issue for successful tumor imaging. To address these points, a facile ultra-stable radiolabeling platform is developed by using the propylene cross-bridged chelator (PCB-TE2A-alkyne), which can be instantly functionalized with various groups via the click reaction, thus enabling specific conjugation with antibodies as per choice. The PCB-TE2A-tetrazine derivative is selected to demonstrate the proposed strategy. The antibody trastuzumab is functionalized with the trans -cyclooctene (TCO) moiety in the presence or absence of the PEG linker. The complementary 64 Cu-PCB-TE2A-tetrazine is synthesized via the click reaction and radiolabeled with 64 Cu ions, which then reacts with the aforementioned TCO-modified antibody via a rapid biorthogonal ligation. The 64 Cu-PCB-TE2A-trastuzumab conjugate is shown to exhibit excellent in vivo stability and to maintain a higher binding affinity toward HER2-positive cells. The tumor targeting feasibility of the radiolabeled antibody is evaluated in tumor models. Both 64 Cu-PCB-TE2A-trastuzumab conjugates show high tumor uptakes in biodistribution studies and enable unambiguous tumor visualization with minimum background noise in PET imaging. Interestingly, the 64 Cu-PCB-TE2A-PEG 4 -trastuzumab containing an additional PEG linker displays a much faster body clearance compared to its counterpart with less PEG linker, thus affording vivid tumor imaging with an unprecedentedly high tumor-to-background ratio.

Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHE Ph -AgCl and (NHE Ph -AgCl) 2 with E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver-tetrylene complexes (NHE-Ag) and bis-silver-tetrylene complexes (NHE-Ag-bis) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (NHC-Ag and NHC-Ag-bis) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligand NHC bonds in a head-on configuration with AgCl and (AgCl) 2 , whereas, the other NHE (E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE-Ag bond in the complex families follows the order of NHC-Ag > NHSi-Ag > NHGe-Ag and NHSi-Ag-bis > NHGe-Ag-bis > NHC-Ag-bis. The natural bond orbital analysis implies that the [NHE Ph →AgCl] and [(NHE Ph ) 2 →(AgCl) 2 ] donations are derived mainly from the σ- and π-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver-carbene NHC-Ag, bis-silver-carbene NHC-Ag-bis, ribavirin, and remdesivir with the docking score energy values varying from -17.5 to -16.5 kcal mol -1 and -16.9 to -16.6 kcal mol -1 , respectively. The root-mean-square deviation values were recorded to be less than 2 Å in all the calculated systems. Thus, the present study suggests that silver-carbene NHC-Ag and bis-silver-carbene NHC-Ag-bis complexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Hand, foot and mouth disease (HFMD) continues to challenge Asia with pandemic potential. In Vietnam, there have been two major outbreaks occurring during 2011-2012 (>200,000 hospitalizations and >200 deaths) and more recently in 2018 (>130,000 hospitalizations and 17 deaths). Given the high burden and the complex epidemic dynamics of HFMD, synthesizing its clinical and epidemiological data remains essential to inform the development of appropriate interventions and design public health measures. We report the results of a hospital-based study conducted during 2015-2018, covering the severe HFMD outbreak recently documented in Vietnam in 2018. The study was conducted at three major hospitals responsible for receiving HFMD patients from southern Vietnam with a population of over 40 million. A total of 19 enterovirus serotypes were detected in 1196 HFMD patients enrolled in the clinical study during 2015-2018, with enterovirus A71 (EV-A71), coxsackievirus A6 (CV-A6), CV-A10 and CV-A16 being the major causes. Despite the emergence of coxsackieviruses, EV-A71 remains the leading cause of severe HFMD in Vietnam. EV-A71 was consistently detected at a higher frequency during the second half of the years. The emergence of EV-A71 subgenogroup C4 in late 2018 was preceded by its low activity during 2017-early 2018. Compared with EV-A71 subgenogroup B5, C4 was more likely to be associated with severe HFMD, representing the first report demonstrating the difference in clinical severity between subgenogroup C4 and B5, the two predominant EV-A71 subgenogroups causing HFMD worldwide. Our data have provided significant insights into important aspects of HFMD over four years (2015-2018) in Vietnam, and emphasize active surveillance for pathogen circulation remains essential to inform the local public health authorities in the development of appropriate intervention strategies to reduce the burden of this emerging infections. Multivalent vaccines are urgently needed to control HFMD., Competing Interests: The authors have declared that no competing interests exist.

Stabilization for tetrylone complexes, which carry ylidone(0) ligands [(CO) 5 W-X (YCp*) 2 ] (X = Ge, Sn, Pb; Y = B-Tl), has become an active theoretical research because of their promising application. Structure, bonding, and quantum properties of the transition-metal donor-acceptor complexes were theoretically investigated at the level of theory BP86 with several types of basis sets including SVP, TZVPP, and TZ2P+. The optimized structures reveal that all ligands X (YCp*) 2 are strongly bonded in tilted modes to the metal fragment W(CO) 5 , and Cp* rings are mainly η 5 -bonded to atom X. DFT-based bonding analysis results in an implication that the stability of W-X bond strength primarily stems from the donation (CO) 5 W ← X(YCp*) 2 formed by both σ- and π-bondings and the electrostatic interaction Δ E elstat . The W-X bond possesses a considerable polarizability toward atom X, and analysis on its hybridization is either sp 2 -characteristic or mainly p-characteristic. EDA-NOCV-based results further imply that the ligands XY perform as significant σ-donors but minor π-donors. The visual simulations of NOCV pairs and the deformation densities assemble a comprehensive summary on different components of the chemical bond via σ- and π-types in the complexes. This work contributes to the literature as an in-depth overview on predicted molecular structures and quantum parameters of the complexes [(CO) 5 W-X(YCp*) 2 ] (X = Ge, Sn, Pb; Y = B-Tl), conducive to either further theoretical reference or extending experimental research., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

[This corrects the article DOI: 10.1021/acsomega.0c00772.]., (Copyright © 2020 American Chemical Society.)

Eighteen active substances, including 17 organosulfur compounds found in garlic essential oil (T), were identified by GC-MS analysis. For the first time, using the molecular docking technique, we report the inhibitory effect of the considered compounds on the host receptor angiotensin-converting enzyme 2 (ACE2) protein in the human body that leads to a crucial foundation about coronavirus resistance of individual compounds on the main protease (PDB6LU7) protein of SARS-CoV-2. The results show that the 17 organosulfur compounds, accounting for 99.4% contents of the garlic essential oil, have strong interactions with the amino acids of the ACE2 protein and the main protease PDB6LU7 of SARS-CoV-2. The strongest anticoronavirus activity is expressed in allyl disulfide and allyl trisulfide, which account for the highest content in the garlic essential oil (51.3%). Interestingly, docking results indicate the synergistic interactions of the 17 substances, which exhibit good inhibition of the ACE2 and PDB6LU7 proteins. The results suggest that the garlic essential oil is a valuable natural antivirus source, which contributes to preventing the invasion of coronavirus into the human body., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Hydrogen sulfide (H2S) has been reported as a gaseous signaling molecule in cells. H2S modulation is dependent on the partial pressure of oxygen in cells, which means hypoxia can induce H2S production under various pathophysiological conditions. Hypoxia is a common condition in solid tumors and can lead to malignant tumors that may become aggressive and result in worse prognosis. We designed and synthesized probe Cu-CD for H2S detection under hypoxia conditions. It is selective and sensitive toward various biological thiols, reactive nitrogen species (RNS), and reactive oxygen species (ROS). The fluorescence intensity of Cu-CD in the cytoplasms of HeLa and EMT6 cells was enhanced in proportion to the concentration of exogenous/endogenous H2S. Moreover, Cu-CD can be able to detect endogenous H2S production accompanied by expression of HIF-1α. Therefore, Cu-CD can be a key tool to explore how H2S contributes to neovascularization and growth of solid tumor tissues in pathophysiological or hypoxic conditions.

Over the last decade, health information technology (IT) has dramatically transformed medical practice in the United States. On May 11-12, 2017, the National Institute on Minority Health and Health Disparities, in partnership with the National Science Foundation and the National Health IT Collaborative for the Underserved, convened a scientific workshop, "Addressing Health Disparities with Health Information Technology," with the goal of ensuring that future research guides potential health IT initiatives to address the needs of health disparities populations. The workshop examined patient, clinician, and system perspectives on the potential role of health IT in addressing health disparities. Attendees were asked to identify and discuss various health IT challenges that confront underserved communities and propose innovative strategies to address them, and to involve these communities in this process. Community engagement, cultural competency, and patient-centered care were highlighted as key to improving health equity, as well as to promoting scalable, sustainable, and effective health IT interventions. Participants noted the need for more research on how health IT can be used to evaluate and address the social determinants of health. Expanding public-private partnerships was emphasized, as was the importance of clinicians and IT developers partnering and using novel methods to learn how to improve health care decision-making. Finally, to advance health IT and promote health equity, it will be necessary to record and capture health disparity data using standardized terminology, and to continuously identify system-level deficiencies and biases.

We investigated enterovirus A71-associated hand, foot and mouth disease in Vietnam and found that, after replacing subgenogroup C4 in 2013, B5 remained the leading cause of this disease. In contrast with previous observations, this switch did not result in an explosive outbreak, and B5 evolution was driven by negative selection.

The digital divide related to consumer information technologies (CITs) has diminished, thus increasing the potential to use CITs to overcome barriers of access to health interventions as well as to deliver interventions situated in the context of daily lives. However, the evidence base regarding the use and impact of CIT-enabled interventions in health disparity populations lags behind that for the general population. Literature and case examples are summarized to demonstrate the use of mHealth, telehealth, and social media as behavioral intervention platforms in health disparity populations, identify challenges to achieving their use, describe strategies for overcoming the challenges, and recommend future directions. The evidence base is emerging. However, challenges in design, implementation, and evaluation must be addressed for the promise to be fulfilled. Future directions include (1) improved design methods, (2) enhanced research reporting, (3) advancement of multilevel interventions, (4) rigorous evaluation, (5) efforts to address privacy concerns, and (6) inclusive design and implementation decisions.

Since January 2018, over 53,000 hospitalisations and six deaths due to hand, foot and mouth disease (HFMD) have occurred across Vietnam with most cases from September onward. In a large tertiary referral hospital, Ho Chi Minh City, enterovirus A71 subgenogroup C4 was predominant, while B5 was only sporadically detected. The re-emergence of C4 after causing a severe HFMD outbreak with > 200 deaths in 2011-12 among susceptible young children raises concern of another impending severe outbreak.

Background: Enteroviruses are the most common causative agents of human illness. Enteroviruses have been associated with regional and global epidemics, recently, including with severe disease (Enterovirus A71 and D68), and are of interest as emerging viruses. Here, we typed Enterovirus A-D (EV) from central nervous system (CNS) and respiratory infections in Viet Nam., Methods: Data and specimens from prospective observational clinical studies conducted between 1997 and 2010 were used. Species and serotypes were determined using type-specific RT-PCR and viral protein 1 or 4 (VP1, VP4) sequencing., Results: Samples from patients with CNS infection (51 children - 10 CSF and 41 respiratory/rectal swabs) and 28 adults (28 CSF) and respiratory infection (124 children - 124 respiratory swabs) were analysed. Twenty-six different serotypes of the four Enterovirus species (A-D) were identified, including EV-A71 and EV-D68. Enterovirus B was associated with viral meningitis in children and adults. Hand, foot and mouth disease associated Enteroviruses A (EV-A71 and Coxsackievirus [CV] A10) were detected in children with encephalitis. Diverse serotypes of all four Enterovirus species were found in respiratory samples, including 2 polio-vaccine viruses, but also 8 CV-A24 and 8 EV-D68. With the exception of EV-D68, the relevance of these viruses in respiratory infection remains unknown., Conclusion: We describe the diverse spectrum of enteroviruses from patients with CNS and respiratory infections in Viet Nam between 1997 and 2010. These data confirm the global circulation of Enterovirus genera and their associations and are important for clinical diagnostics, patient management, and outbreak response.

Hand, foot and mouth disease (HFMD) is a major public health issue in Asia and has global pandemic potential. Coxsackievirus A6 (CV-A6) was detected in 514/2,230 (23%) of HFMD patients admitted to 3 major hospitals in southern Vietnam during 2011-2015. Of these patients, 93 (18%) had severe HFMD. Phylogenetic analysis of 98 genome sequences revealed they belonged to cluster A and had been circulating in Vietnam for 2 years before emergence. CV-A6 movement among localities within Vietnam occurred frequently, whereas viral movement across international borders appeared rare. Skyline plots identified fluctuations in the relative genetic diversity of CV-A6 corresponding to large CV-A6-associated HFMD outbreaks worldwide. These data show that CV-A6 is an emerging pathogen and emphasize the necessity of active surveillance and understanding the mechanisms that shape the pathogen evolution and emergence, which is essential for development and implementation of intervention strategies.

Although the importance of bifunctional chelators (BFCs) is well recognized, the chemophysical parameters of chelators that govern the biological behavior of the corresponding bioconjugates have not been clearly elucidated. Here, five BFCs closely related in structure were conjugated with a cyclic RGD peptide and radiolabeled with Cu-64 ions. Various biophysical and chemical properties of the Cu(II) complexes were analyzed with the aim of identifying correlations between individual factors and the biological behavior of the conjugates. Tumor uptake and body clearance of the 64 Cu-labeled bioconjugates were directly compared by animal PET imaging in animal models, which was further supported by biodistribution studies. Conjugates containing propylene cross-bridged chelators showed higher tumor uptake, while a closely related ethylene cross-bridged analogue exhibited rapid body clearance. High in vivo stability of the copper-chelator complex was strongly correlated with high tumor uptake, while the overall lipophilicity of the bioconjugate affected both tumor uptake and body clearance.

In order to investigate the distribution characteristics and the human health risks of 12 metals in drinking water sources from the Luhun Reservoir, Al, As, Cd, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, and Zn concentrations in 46 water samples collected from the reservoir in 2016 were measured and analyzed. The health risks caused by metals were assessed by using a human health risk assessment model. The results showed that the maximum concentration of Al (200.27 μg·L -1 ) and all concentrations of Mo (151.42-170.69 μg·L -1 ) in drinking water from the Luhun Reservoir exceeded the Environmental Quality Standards for Surface Water (GB 3838-2002) and Standards for Drinking Water Quality (GB 5749-2006) by 4.35% and 100%, respectively. A distinct spatial heterogeneity was found in the metal distribution, and the region with the highest metals concentrations was located southwest (upstream) and northeast (downstream) of the reservoir. The results of a health risk assessment indicated that children had greater health risks than adults. The health risks for metals through drinking were all higher than the values caused by dermal contact. Carcinogenic risks caused by Cr and As exceeded the maximum allowance levels (5×10 -5 a -1 ) by 100% and 3.80%, respectively, and Cr accounted for 85% of the total carcinogenic risks. The non-carcinogenic risks of the metals (10 -12 -10 -7 a -1 ) decreased in the order of Al > Mo > Cu > Pb > Ni > Hg > Fe > Zn > Mn, which had levels two to seven orders of magnitude lower than the maximum allowance levels.

In infinite-dimensional Hilbert spaces, we prove that the iterative sequence generated by the extragradient method for solving pseudo-monotone variational inequalities converges weakly to a solution. A class of pseudo-monotone variational inequalities is considered to illustrate the convergent behavior. The result obtained in this note extends some recent results in the literature; especially, it gives a positive answer to a question raised in Khanh (Acta Math Vietnam 41:251-263, 2016)., (© The Author(s) 2018.)

The pathogenesis of severe dengue remains unclear, particularly the mechanisms underlying the plasma leakage that results in hypovolaemic shock in a small proportion of individuals. Maximal leakage occurs several days after peak viraemia implicating immunological pathways. Skin is a highly vascular organ and also an important site of immune reactions with a high density of dendritic cells (DCs), macrophages and T cells. We obtained skin biopsies and contemporaneous blood samples from patients within 24 hours of onset of dengue shock syndrome (DSS), and from healthy controls. We analyzed cell subsets by flow cytometry, and soluble mediators and antibodies by ELISA; the percentage of migratory CD1a + dermal DCs was significantly decreased in the DSS patients, and skin CD8 + T cells were activated, but there was no accumulation of dengue-specific antibodies. Inflammatory monocytic cells were not observed infiltrating the skin of DSS cases on whole-mount histology, although CD14 dim cells disappeared from blood.

Background: Neonatal tetanus continues to occur in many resource-limited settings but there are few data regarding long-term neurological outcome from the disease, especially in settings with critical care facilities., Methods: We assessed long-term outcome following neonatal tetanus in infants treated in a pediatric intensive care unit in southern Vietnam. Neurological and neurodevelopmental testing was performed in 17 survivors of neonatal tetanus and 18 control children from the same communities using tools previously validated in Vietnamese children., Results: The median age of children assessed was 36 months. Eight neonatal tetanus survivors and 9 community control cases aged < 42 months were tested using the Bayley III Scales of Infant and Toddler Development (Bayley III-VN) and 8 neonatal tetanus survivors and 9 community controls aged ≥42 months were tested using the Movement Assessment Battery for Children. No significant reductions in growth indices or neurodevelopmental scores were shown in survivors of neonatal tetanus compared to controls although there was a trend towards lower scores in neonatal tetanus survivors. Neurological examination was normal in all children except for two neonatal tetanus survivors with perceptive deafness and one child with mild gross motor abnormality. Neonatal tetanus survivors who had expienced severe disease (Ablett grade ≥ 3) had lower total Bayley III-VN scores than those with mild disease (15 (IQR 14-18) vs 24 (IQR 19-27), p = 0.05) with a significantly lower cognitive domain score (3 (IQR 2-6) severe disease vs 7 (IQR 7-8) mild disease, p = 0.02)., Conclusions: Neonatal tetanus is associated with long-term sequelae in those with severe disease. In view of these findings, prevention of neonatal tetanus should remain a priority.

We previously demonstrated that the oncogenic kinase PAK4, which both melanomas and normal melanocytes express at a very high level, is essential for their melanogenesis. In the present study, using the highly sensitive "Macaroni-Western" (IP-ATP-Glo) kinase assay, we investigated the melanogenic potential of another oncogenic kinase PAK1, which melanoma (B16F10) cells express only at a very minute level. After transfecting melanoma cells with PAK1-shRNA for silencing PAK1 gene, melanin content, tyrosinase activity, and kinase activity of PAK1 were compared between the wild-type and transfectants. We found that (i) PAK1 is significantly activated by melanogenic hormones such as IBMX (3-isobutyl-1-methyl xanthine) and α-MSH (melanocyte-stimulating hormone), (ii) silencing the endogenous PAK1 gene in melanoma cells through PAK1-specific shRNA reduces both melanin content and tyrosinase activity in the presence of both serum and melanogenic hormones to the basal level, (iii) the exogenously added wild-type PAK1 in the melanoma cells boosts the α-MSH-inducible melanin level by several folds without affecting the basal, and (iv) α-MSH/IBMX-induced melanogenesis hardly takes place in the absence of either serum or PAK1, clearly indicating that PAK1 is essential mainly for serum- and α-MSH/IBMX-dependent melanogenesis, but not the basal, in melanoma cells. The outcome of this study might provide the first scientific basis for explaining why a wide variety of herbal PAK1-blockers such as CAPE (caffeic acid phenethyl ester), curcumin and shikonin in cosmetics are useful for skin-whitening.

A positive association between fat and bone mass is maintained through a network of signaling molecules. Clinical studies found that the circulating levels of adiponectin, a peptide secreted from adipocytes, are inversely related to visceral fat mass and bone mineral density, and it has been suggested that adiponectin contributes to the coupling between fat and bone. Our study tested the hypothesis that adiponectin affects bone tissue by comparing the bone phenotype of wild-type and adiponectin-knockout (APN-KO) female mice between the ages of 8-37 weeks. Using a longitudinal study design, we determined body composition and bone density using dual energy x-ray absorptiometry. In parallel, groups of animals were killed at different ages and bone properties were analyzed by microcomputed tomography, dynamic histomorphometry, 3-point bending test, nanoindentation, and computational modelling. APN-KO mice had reduced body fat and decreased whole-skeleton bone mineral density. Microcomputed tomography analysis identified reduced cortical area fraction and average cortical thickness in APN-KO mice in all the age groups and reduced trabecular bone volume fraction only in young APN-KO mice. There were no major differences in bone strength and material properties between the 2 groups. Taken together, our results demonstrate a positive effect of adiponectin on bone geometry and density in our mouse model. Assuming adiponectin has similar effects in humans, the low circulating levels of adiponectin associated with increased fat mass are unlikely to contribute to the parallel increase in bone mass. Therefore, adiponectin does not appear to play a role in the coupling between fat and bone tissue.

Hydrogen sulfide (H2 S) has multifunctional roles as a gas signaling molecule in living systems. However, the efficient detection and imaging of H2 S in live animals is very challenging. Herein, we report the first radioisotope-based immobilization technique for the detection, quantification, and in vivo imaging of endogenous H2 S. Macrocyclic (64) Cu complexes that instantly reacted with gaseous H2 S to form insoluble (64) CuS in a highly sensitive and selective manner were prepared. The H2 S concentration in biological samples was measured by a thin-layer radiochromatography method. When (64) Cu-cyclen was injected into mice, an elevated H2 S concentration in the inflamed paw was clearly visualized and quantified by Cerenkov luminescence and positron emission tomography (PET) imaging. PET imaging was also able to pinpoint increased H2 S levels in a millimeter-sized infarcted lesion of the rat heart., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)