Search

The cation channel Piezo1, a crucial mechanotransducer found in various organs and tissues, has gained considerable attention as a therapeutic target in recent years. Following this trend, several Piezo1 inhibitors have been discovered and studied for potential pharmacological properties. This review provides an overview of the structural and functional importance of Piezo1, as well as discussing the biological activities of Piezo1 inhibitors based on their mechanism of action. The compounds addressed include the toxin GsMTx4, Aβ peptides, certain fatty acids, ruthenium red and gadolinium, Dooku1, as well as the natural products tubeimoside I, salvianolic acid B, jatrorrhzine, and escin. The findings revealed that misexpression of Piezo1 can be associated with a number of chronic diseases, including hypertension, cancer, and hemolytic anemia. Consequently, inhibiting Piezo1 and the subsequent calcium influx can have beneficial effects on various pathological processes, as shown by many in vitro and in vivo studies. However, the development of Piezo1 inhibitors is still in its beginnings, with many opportunities and challenges remaining to be explored., 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 Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In the Southern Central Highlands of Vietnam, droughts occur more frequently, causing significant damage and impacting the region's socio-economic development. During the dry season, rivers, streams, and reservoirs often face limited water availability, exacerbated in recent years by increasing drought severity. Recognizing the escalating severity of droughts, the study offers a novel contribution by conducting a comprehensive analysis of surface water resource distribution in Lam Dong province, focusing on assessing water demand for agricultural production, a crucial factor in ensuring sustainable crop growth. Two scenarios, Current-2020 (SC1) and Climate Change-2025 (SC2), are simulated, with SC2 based on climate change and sea level rise scenarios provided by the Ministry of Natural Resources and Environment (MONRE). These scenarios are integrated into the MIKE-NAM and MIKE-HYDRO basin models, allowing for a thorough assessment of the water balance of Lam Dong province. Furthermore, the study utilizes the Keetch-Byram Drought Index (KBDI) to measure drought severity, revealing prevalent dry and moderately droughty conditions in highland districts with rainfall frequency ranging from 50 to 85%. Severe drought conditions occur with a rainfall frequency of 95%, indicating an increased frequency and geographic scope of severe droughts. Additionally, the study highlights that under abnormally dry conditions, water demand for the winter-spring crop is consistently met at 100%, decreasing to 85%, 80%, and less than 75% for moderate, severe, and extreme droughts, respectively. These findings offer insights into future drought conditions in the Lam Dong province and their potential impact on irrigation capacity, crucial for adaptation strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Secondhand smoke (SHS) has detrimental effects on community health, including coronary heart diseases, stroke, lung cancer etc. This manuscript exploited data from the Vietnam Population-based Provincial Global Adult Tobacco Survey (PGATS) in 2022 to update the prevalence of adult exposure to SHS and associated socio-demographic factors. Methods: With the sample size of 71,981 adults aged 15+ throughout 30 provinces and cities in Vietnam, data was collected using the Global Adult Tobacco Survey (GATS) questionnaire. Bivariate analysis and multivariate logistic regression modelling were performed. Results: In the past 30 days, 44.4% (95% CI: 44.0%-44.9%) adults aged 15+ exposed to SHS at home while 23.1% (95% CI: 22.6%-23.6%) exposed to SHS at work. Female exposure to SHS in the past 30 days was higher at homes but lower at indoor workplaces. Participants aged 15-24 were likely to have higher odds of SHS exposure in the past 30 days to other age groups. Those living in the urban areas had 1.15 times higher odds (95% CI: 1.08-1.22) of exposure to SHS than those in the rural areas. Current smokers tended to have 2.2 times higher odds of exposure to SHS at the indoor workplaces compared to non-smokers (95% CI: 2.05-2.37). Conclusions: The prevalence of exposure to SHS at home was still relatively high amongst the adult population. While there was a significant reduction of SHS exposure at indoor workplaces, there was a higher prevalence of women being exposed to SHS at home. The Government of Vietnam should continue to strictly implement the smoke-free environment resolution at indoor workplaces and appropriate communication campaigns to protect people, especially women from SHS exposure at homes., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Volumetric modulated arc therapy (VMAT) and 3D image-guided brachytherapy (3D-IGBT) have recently been introduced in Vietnam for the treatment of locally advanced cervical cancer. This study aims to assess the outcomes and toxicities of chemoradiation using VMAT followed by 3D-IGBT in Vietnamese cervical cancer patients., Materials and Methods: A prospective interventional study on 72 patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB3-IIIC2 disease who underwent concurrent chemoradiation using VMAT, followed by 3D-IGBT according to EMBRACE-II protocol. Primary endpoints were locoregional control; secondary endpoints were systemic control and toxicity., Results: Median body volume received 43 Gy was 1589.1 cm 3 (range 1214.8-2574.8). Median high-risk clinical target volume (CTV-HR) was 18.8 cm 3 (range 8.6-61.2) with a median dose to 90% (D90) of CTV-HR of 90.6 Gy (range 86.8-99.6). Mean doses to 2cc (D2cc) of bladder, rectum, and sigmoid were 75.8, 55.2, and 62.1 Gy, respectively. At median 19-month follow-up (range 12-25), locoregional control and systemic control were 95.8% and 81.9%, respectively. Systemic control was the lowest in N2 disease (54.5%). Grade ≥ 3 acute toxicities were less than 10%, except neutropenia (31.9%). Extended-field radiation increased significantly nausea, fatigue, and thrombocytopenia. No grade ≥ 3 proctitis or cystitis; 8.3% had grade 3 vaginal stenosis., Conclusions: VMAT-based chemoradiation therapy followed by 3D-IGBT achieved high locoregional control with manageable toxicities in locally advanced cervical cancer. Systemic control correlated with disease stage., Competing Interests: Conflicts of interest: The authors declare no financial or other conflicts of interest., (© 2023 Greater Poland Cancer Centre.)

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles., Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies)., Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864., Conclusions: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

NaGdF 4 nanocrystalline doped with different concentrations of Eu 3+ ions were synthesized using the precipitation method. The structure and morphology of the material were investigated through the measurements of the XRD patterns and SEM images, respectively. The optical properties of the NaGdF 4 :Eu 3+ nanocrystalline were studied in the framework of the Judd-Ofelt theory in which the Ω λ parameters were calculated by two methods: the traditional method using the luminescence spectra and the self-referenced method using the luminescence excitation spectra. In NaGdF 4 :Eu 3+ nanocrystalline, the Gd 3+ ions in the lattice act as sensitizer centers for the luminescence of Eu 3+ ions under excitation at 272 and 310 nm. The energy transfer process from Gd 3+ to Eu 3+ causes the emission enhancement of Eu 3+ ions. Upon excitation by the characteristic wavelengths of Gd 3+ , the luminescence efficiency of the Eu 3+ ions in NaGdF 4 :Eu 3+ is affected by two mechanisms: the emission of Gd 3+ ions and the trapping of excited energy by the Eu 3+ ions. The energy transfer between Eu 3+ ions was also discussed in detail. This process leads to the enhancement of the luminescence bands originating from the 5 D 0 level. The dominant interaction between the Eu 3+ ions in the energy transfer process is the dipole-dipole mechanism, which is determined by fitting the decay curve of the 5 D 2 level to the Inokuti-Hirayama model.

One of the major crucial issues that need worldwide attention is open stubble burning, which imposes a variety of adverse impacts on nature and human society, destroying the world's biodiversity. Many earth observation satellites render information to monitor and assess agricultural burning activities. In this study, different remotely sensed data (Sentinel-2A, VIIRS) has been employed to estimate the quantitative measurements of agricultural burned areas of the Purba Bardhaman district from October-December 2018. The multi-temporal image differencing techniques and indices (NDVI, NBR, and dNBR) and VIIRS active fires data (VNP14IMGT) have been utilized to spot agricultural burned areas. In the case of the NDVI technique, a prominent area, 184.82 km 2 of agricultural burned area (7.85% of the total agriculture), was observed. The highest (23.04 km 2 ) burned area was observed in the Bhatar block, located in the middle part of the district, and the lowest (0.11 km 2 ) burned area was observed in the Purbasthali-II block, which is located in the eastern part of the district. On the other hand, the dNBR technique revealed that the agricultural burned areas enwrap 8.18% of the total agricultural area, which is 192.45 km 2 . As per the earlier NDVI technique, the highest agricultural burned areas (24.82 km 2 ) were observed in the Bhatar block, and the lowest (0.13 km 2 ) burn area occurred in the Purbashthali-II block. In both cases, it is observed that agricultural residue burning is high in the western part of the Satgachia block and the adjacent areas of the Bhatar block, which is in the middle part of Purba Bardhaman. The agricultural burned area was extracted using different spectral separability analyses, and the performance of dNBR was the most effective in spectral discrimination of burned and unburned surfaces. This study manifested that agricultural residue burning started in the central part of Purba Bardhaman. Later it spread all over the district due to the trend of early harvesting rice crops in this region. The performance of different indices for mapping the burned areas was evaluated and compared, revealing a strong correlation (R2) = 0.98. To estimate the campaign's effectiveness against the dangerous practice and plan the control of the menace, regular monitoring of crop stubble burning using satellite data is required., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: Two major avoidable reasons for adverse events in hospital are medication errors and intravenous therapy-induced infections or complications. Training for clinical staff and compliance to patient safety principles could address these., Methods: Joint Commission International (JCI) consultants created a standardised, 6-month training programme for clinical staff in hospitals. Twenty-one tertiary care hospitals from across south-east Asia took part. JCI trained the clinical consultants, who trained hospital safety champions, who trained nursing staff. Compliance and knowledge were assessed, and monthly audits were conducted., Results: There was an overall increase of 29% in compliance with parameters around medication preparation and vascular access device management., Conclusion: The programme improved safe practice around preparing medications management and managing vascular access devices. The approach could be employed as a continuous quality improvement initiative for the prevention of medication errors and infusion-associated complications.

Chemical adsorption of non-metal atoms may lead to the emergence of novel features in two-dimensional (2D) materials. In this work, the electronic and magnetic properties of graphene-like XC (X = Si and Ge) monolayers with adsorbed H, O, and F atoms are investigated using spin-polarized first-principles calculations. Deeply negative adsorption energies suggest strong chemical adsorption on XC monolayers. Despite the non-magnetic nature of both host monolayer and adatom, SiC is significantly magnetized by H adsorption inducing the magnetic semiconductor nature. Similar features are observed in GeC monolayers upon adsorbing H and F atoms. In all cases, an integer total magnetic moment of 1 μ B is obtained, originating mainly from adatoms and their neighbor X and C atoms. In contrast, O adsorption preserves the non-magnetic nature of SiC and GeC monolayers. However, the electronic band gaps exhibit significant reduction of the order of 26% and 18.84%, respectively. These reductions are consequences of the middle-gap energy branch generated by the unoccupied O-p z state. The results introduce an efficient approach to develop d 0 2D magnetic materials to be applied in spintronic devices, as well as to widen the working region of XC monolayers in optoelectronic applications., 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.)

Machine learning is considered a potential aid to support human decision making in disease prediction. In this study, we determined the utility of various machine learning algorithms in classifying peripheral vestibular (PV) and non-PV diseases based on the results of equilibrium function tests. A total of 1009 patients who had undergone our standardized neuro-otological examinations were recruited. We applied five supervised machine learning algorithms (random forest, adaboost, gradient boosting, support vector machine, and logistic regression). After preprocessing the data, optimizing the hyperparameters using GridSearchCV, and performing a final evaluation on the test set using scikit-learn, we evaluated the predictive capability using various performance metrics, namely, accuracy, F1-score, area under the receiver operating characteristic curve, precision, recall, and Matthews correlation coefficient (MCC). All five machine learning algorithms yielded satisfactory results; the accuracy of the algorithms ranged from 76 to 79%, with the support vector machine classifier having the highest accuracy. In cases where the predictions of the five models were consistent, the accuracy of the PV diagnostic results was improved to 83%, whereas it increased to 85% for the non-PV diagnostic results. Future research should increase the number of patients and optimize the classification methods to obtain the highest diagnostic accuracy., (© 2022. The Author(s).)

Surgical sperm retrieval (SSR) is currently one of the most common procedures in in vitro fertilization (IVF). However, a gap between the guidelines and routine clinical practice regarding antibiotic use in SSR, which might lead to antibiotic resistance, is a challenging problem worldwide. A cross-sectional survey was conducted from May 1, 2021, to July 15, 2021, to investigate antibiotic usage by medical professionals when performing SSR in IVF centers in Vietnam. The confidential questionnaire comprised 12 items, including characteristics of the study population, awareness of antimicrobial resistance, attitude toward prescribing antibiotics, and current practice of prescribing antibiotics when performing SSR. Surveys were completed by 30 of 45 registered IVF centers (66.7%). Among 67 physicians working at those centers, the age and work-experience years (mean ± standard deviation [s.d.]) were 38.6 ± 6.6 years and 11.2 ± 7.0 years, respectively. Over 60% of them held a degree in Obstetrics and Gynecology, and over four-fifths were men. Most respondents "often/very often/always" raised awareness of antimicrobial resistance to their patients (83.3%), but only half of them "often/occasionally" prescribed antibiotics to patients with SSR in cases where the prescription would be optional. About one-tenth of respondents followed the recommendation from the American Urological Association using "prophylaxis only" for SSR patients. For more invasive SSR, physicians tended to prescribe more complicated and sometimes inappropriate regimens. In conclusion, antibiotic usage in SSR was not always appropriate among IVF centers. Further studies may define specific recommendations for regimens, intervention strategies, and programs to promote appropriate antibiotic use for SSR patients among IVF specialists., Competing Interests: None

This article presents a review of many types of SERS sensors for food safety and environmental pollution monitoring based on detecting rhodamine. It introduces the basic concepts of substrates, enhancement factors, and mechanisms, devices' sensors integrated with the microstructure. Here, we review the state-of-the-art research in the field of rhodamine monitoring and highlight the applications of SERS sensors. The trends in the development of substrates for different applications have been mentioned with the aim of providing an overview of the development of different SERS substrates. Thus, an efficient approach for rhodamine detection has a good perspective for application in environmental monitoring.

Analysis of temporal patterns of high-dimensional time-series water quality data is essential for pollution management worldwide. This study has applied dynamic factor analysis (DFA) and cluster analysis (CA) to analyze time-series water quality data monitored at the five stations installed along the La Buong river in Southern Vietnam. Application of the DFA identified two types of temporal patterns, one of the run-off driven parameters (total suspended solid (TSS), turbidity, and iron) and the other of diffuse source pollution. The association of the variables like BOD 5 and COD at most stations to the run-off-driven parameters revealed their sharing of drivers. On the contrary, separating variables like phosphate (PO 4 3 ) at the three upstream stations from the run-off patterns suggested their local point-source origin. The DFA-derived factors were later used in the time-point CA to explore the seasonality of water quality parameters and their pollution intensities compared to regulatory levels. The result suggested intensification in wet season of Fe, TSS, BOD 5 , and COD concentrations at most sites, which are unobservable in run-off detached parameters like reactive nitrogen, phosphate (PO 4 3- ), and E. coli. These findings generated robust insights to support water quality management for river habitat conservation., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Ca Mau and Kien Giang, the two provinces of the Mekong Delta bordering the Gulf of Thailand, are facing major environmental challenges affecting the agriculture and aquaculture sectors upon which many livelihoods in this region depend on. This study maps the suitability of these two provinces for paddy rice cultivation and shrimp farming according to soil characteristics and current and future environmental conditions for variables found to significantly influence the yield of those two sectors, i.e., the level of saltwater intrusion, water availability for rainfed agriculture, and the length of the growing period. Future environmental conditions were simulated using the MIKE 11 hydrodynamic model forced by four hydrodynamic scenarios, each one representing different extents of saltwater intrusion during both the dry and rainy seasons, while also considering the availability of water resources for rainfed agriculture. The suitability zoning was performed using a GIS-based analytic hierarchy process (AHP) approach, resulting in the categorisation of the land according to four suitability levels for each sector. The analysis reveals that paddy rice cultivation will become more suitable to Kien Giang province while shrimp farming will be more suitable to Ca Mau province if the simulated future environmental conditions materialise. A suitability analysis is essential for optimal utilisation of the land. The approach presented in this study will inform the regional economic development master plan and provide guidance to other delta regions experiencing severe environmental changes and wishing to consider potential future climatic and sea level changes, and their associated impacts, in their land use planning., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Electronic cigarette use among adolescents has increased in the past decade. Little is known about the perception and use of e-cigarettes in Vietnam, especially among young people. This study examines the perceptions and use of electronic cigarettes among young adults in Vietnam. The study uses data from a survey of adult tobacco consumption among adults at the provincial level in 2020, which was funded and managed by the Vietnam Tobacco Control Fund-Ministry of Health. Data were collected from 34 provinces and cities throughout Vietnam and managed using REDCap software. The survey engaged 80,166 participants, of which 9478 were young adults aged 15-24 were selected and reported in this paper. The results show that, at the time of the survey, 2.4% of young Vietnamese adults were smoking e-cigarettes. Many survey participants cited more than one reason for smoking e-cigarettes. These reasons included preferring the taste of e-cigarettes (64.0%), disliking the odour of other cigarettes (46.2%), following the example of family members (44.9%), and believing e-cigarettes threatened fewer health risks (39.1%). Almost half of the e-cigarette users wanted to quit (48%). E-cigarette use was associated with males living in urban areas who are aware of the Law on Prevention and Control of Tobacco Harms. The findings of this study provide evidential data that support public health policies aimed at reducing and ceasing e-cigarette use among young people., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Vietnam is one of the countries most impacted by disasters in Asia- Pacific. Floods, droughts and storms are the most common catastrophes. These risks endanger millions of lives and create massive financial and production losses., Objective: This study aims at reviewing the disaster risk management (DRM) system in Vietnam, identifying progress and challenges of this system, hence making recommendations for improving the system for better responding with natural hazards., Method: The study uses PSR model (Pressure- State- Response) in combination with DRM management framework by United Nations Development Program (UNDP) to evaluate DRM system in Vietnam with 5 aspects: (i) DRM regulatory framework (ii) DRM organization (iii) DRM financial resources (iv) DRM integration in to plans at central and local levels (v) Disaster warning and education. The data collection consists of reviewing existing literature and interviewing key informants in DRM., Results: Disasters is a serious threat to Vietnam's socio economic development. To respond, Vietnam has made many efforts including develop a comprehensive legal framework for DRM which Law on Disaster Prevention and Control takes the key role. Vietnam has also established a fairly well organized DRM system from the central to local levels. The financial sources for DRM are arranged from State budget and sources outside State budget. Vietnam has developed major policies for integrating DRM into development plans centrally and locally. The disaster information and warning system is being modernized with the integration of disaster education in training programs. Challenges in DRM are identified, including institutional, financial and information issues. In addition, Vietnam is facing the increase of disasters and extreme climate events due to climate change. Covid 19 and its socio-economic consequences also lead to a lack of resources for DRM. Economic development moreover results in the decline of ecosystem-based disaster mitigation works and put more pressures on DRM., Recommendations: In the future, Vietnam should develop an information-sharing network between ministries, sectors, localities and NGOs to support the policy formulation process and enhance the coordination of multi-stakeholders. The country should also establish more proper funding allocation mechanisms to fulfill DRM's demands, especially for disaster preparedness and reconstruction phases., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

In this work, the structural, electronic, and magnetic properties of arsenene monolayer doped with germanium (Ge) and nitrogen (N) atoms are investigated using density functional theory calculations. Pristine monolayer is dynamically stable and it possesses a wide indirect band gap. Ge doping induces magnetic semiconductor (MS) nature generated by the semiconductor behavior in both spin channels with significant spin asymmetry around the Fermi level. The dopant produces mainly magnetic properties. Upon increasing the doping concentration, different doping configurations along armchair, zigzag edges, and hexagonal ring have been proposed. The MS nature is retained with an odd number of Ge atoms, meanwhile an eVen number leads to the disappearance of magnetism. In contrast, N doping induces a gap reduction of 11.80%, preserving the non-magnetic nature. At higher doping level, different electronic features including semiconductor, nearly semimetallic, and metallic natures are obtained depending on the doping concentration and configurations. In addition, the formation energy and cohesive energy are calculated to analyze the systems' stability. Our results show that different doping arrangements induce novel features in arsenene monolayer for applications in spintronic and optoelectronic devices., (© 2022 IOP Publishing Ltd.)

The delta of the Mekong River is one of the largest in the world, with the Mekong River carrying a large amount of sediments in its Region of Freshwater Influence (ROFI). This study investigates the flow structure and movement of both suspended and bedload sediments in the ROFI of the Lower Mekong Delta (LMD) in order to identify areas prone to sediment accretion and erosion. This is accomplished by applying the three-dimensional Coastal and Regional Ocean COmmunity (CROCO) model and then calculating the sediment budget of different stretches of the coastline. The model outputs, depicting areas experiencing sediment accretion and erosion along the coastline of the LMD, are then compared against observations obtained during the period 1990-2015 and demonstrate the ability of the model to identify areas particularly prone to erosion and where preventive actions against coastal erosion should focus., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Smoking leads to many smoking-attributable diseases. The promotion of quitting tobacco smoking is urgent as it has significant and immediate health benefits and improves the impacts of other tobacco control strategies. Intention to quit smoking is considered the first step before quitting smoking., Methodology: This paper used data from Vietnam provincial GATS 2020 on 80,166 participants who were 15-year-old or older. Data were collected from 34 provinces and cities throughout Vietnam and managed using REDCap., Results: Among those who were current smokers, 50.3% (95% CI: 49.1%-51.4%) had the intention to quit smoking. Some predictive factors found to be positively associated with the intention to quit smoking were age (from 45-64), education level, received information about harmful effects or encouragement to quit smoking from media channels (from 6 channels), hearing about the Tobacco Control Law and noticing health warnings on the cigarette package. There was no significant difference in intention to quit smoking between current smokers from urban and rural areas or among different age groups to start smoking., Conclusions: Interventions or health promotion programs on smoking cessation should be focused on current smokers who have low education levels as they have a higher smoking rate and are less motivated to stop smoking. Received information about harmful effects or encouragement to quit smoking from media channels is also associated with stopping smoking in the future. The importance of health warning pictures on tobacco packages should be maintained and promoted as it has a specific effect on one's intention to stop smoking., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

The quality of groundwater in the study watershed has worsened because of industrial effluents and residential wastes from the urbanized cities; therefore, there is an important need to explore the aquifer vulnerability to pollution for sustainable groundwater management in the Irrigated Indus Basin (IIB). This study proposed a novel methodology to quantify groundwater vulnerability using two fully independent methodologies: the first by reintroducing an improved recharge factor (R) map and the second by incorporating three different weight and rating schemes into a traditional DRASTIC framework to improve the performance of the DRASTIC approach. In the current study, we composed a recharge map from Soil and Water Assessment Tool (SWAT) output (namely SWAT recharge map) with a drainage density map to retrieve an improved composite recharge map (SWAT-CRM). SWAT-CRM along with other thematic layers was combined using weightage overlay analysis to prepare the maps of groundwater vulnerability index (VI). The weight scale (w) and rating scale (r) were assigned based on a survey of available literature, and we then amended them using the analytical hierarchy process (AHP) and a probability frequency ratio (PFR) technique. Results depicted that the region under high groundwater vulnerability was found to be 5-22% using traditional recharge maps, while those are 9-23% using improved SWAT-CRM. The area under the curve (AUC) revealed that groundwater vulnerability zones predicted with SWAT-CRM outperformed the DRASTIC model applied with the traditional recharge map. Groundwater electrical conductivity (EC) was>2500 mS/cm in the high groundwater vulnerability zones, while it was <1000 mS/cm in the low groundwater vulnerability zones. The outcomes of this study can be used to improve the sustainability of the groundwater resources in IIB through proper land-use management practices., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nitrate is a major pollutant in groundwater whose main source is municipal wastewater and agricultural activities. In the present study, Bayesian approaches such as Bayesian generalized linear model (BGLM), Bayesian regularized neural network (BRNN), Bayesian additive regression tree (BART), and Bayesian ridge regression (BRR) were used to model groundwater nitrate contamination in a semiarid region Marvdasht watershed, Fars province, Iran. Eleven groundwater (GW) nitrate conditioning factors have been taken as input parameters for predictive modeling. The results showed that the Bayesian models used in this study were all competent to model groundwater nitrate and the BART model with R 2  = 0.83 was more efficient than the other models. The result of variable importance showed that potassium (K) has the highest importance in the models followed by rainfall, altitude, groundwater depth, and distance from the residential area. The results of the study can support the decision-making process to control and reduce the sources of nitrate pollution., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In our search for novel small molecules activating procaspase-3, we have designed and synthesized two series of novel (E)-N'-arylidene-2-(2-oxoindolin-1-yl)acetohydrazides (4) and (Z)-2-(5-substituted-2-oxoindolin-1-yl)-N'-(2-oxoindolin-3-ylidene)acetohydrazides (5). Cytotoxic evaluation revealed that the compounds showed notable cytotoxicity toward three human cancer cell lines: colon cancer SW620, prostate cancer PC-3, and lung cancer NCI-H23. Especially, six compounds, including 4f-h and 4n-p, exhibited cytotoxicity equal or superior to positive control PAC-1, the first procaspase-3 activating compound. The most potent compound 4o was three- to five-fold more cytotoxic than PAC-1 in three cancer cell lines tested. Analysis of compounds effects on cell cycle and apoptosis demonstrated that the representative compounds 4f, 4h, 4n, 4o and 4p (especially 4o) accumulated U937 cells in S phase and substantially induced late cellular apoptosis. The results show that compound 4o would serve as a template for further design and development of novel anticancer agents., (© 2022. The Author(s).)

In our continuing search for novel small-molecule anticancer agents, we designed and synthesized a series of novel (E)-N'-(3-allyl-2-hydroxy)benzylidene-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides (5), focusing on the modification of substitution in the quinazolin-4(3H)-one moiety. The biological evaluation showed that all 13 designed and synthesized compounds displayed significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5l displayed cytotoxicity up to 213-fold more potent than 5-fluorouracil and 87-fold more potent than PAC-1, the first procaspase-activating compound. Structure-activity relationship analysis revealed that substitution of either electron-withdrawing or electron-releasing groups at positions 6 or 7 on the quinazolin-4(3H)-4-one moiety increased the cytotoxicity of the compounds, but substitution at position 6 seemed to be more favorable. In the caspase activation assay, compound 5l was found to activate the caspase activity by 291% in comparison to PAC-1, which was used as a control. Further docking simulation also revealed that this compound may be a potent allosteric inhibitor of procaspase-3 through chelation of the inhibitory zinc ion. Physicochemical and ADMET calculations for 5l provided useful information of its suitable absorption profile and some toxicological effects that need further optimization to be developed as a promising anticancer agent., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

Background: Herein, we have designed and synthesized a series of the novel (E)-N'-((1-(4-chlorobenzyl)- 1H-indol-3-yl)methylene)-2-(4-oxoquinazolin-3(4H)-yl)acetohydrazides (5) as potent small molecules activating procaspase- 3. The compounds were designed by the amalgamation of structural features of PAC-1 (the first procaspase-3 activator) and oncrasin-1, one potential anticancer agent., Methods: The target acetohydrazides (5a-m) were prepared via the Niementowski condensation of anthranilic acid (1a) or 5-substituted-2-aminobenzoic acid (1b-m) and formamide. The compound libraries were evaluated for their cytotoxicity, caspase-3 activation, cell cycle analysis, and apoptosis. In addition, computational chemistry is also performed., Results: A biological evaluation revealed that all thirteen compounds designed and synthesized showed strong cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer) with eight compounds (5a, 5c-i, 5k), which were clearly more potent than both PAC-1 and oncrasin-1. In this series, four compounds, including 5c, 5e, 5f, and 5h, were the most potent members with approximately 4- to 5-fold stronger than the reference compounds PAC-1 and oncrasin-1 in terms of IC50. In comparison to 5-FU, these compounds were even 18- to 29-fold more potent in terms of cytotoxicity in three human cell lines tested. In the caspase activation assay, the caspase activity was activated to 285% by compound 5e compared to PAC-1, the first procaspase activating compound, which was used as a control. Our docking simulation revealed that compound 5e was a potent allosteric inhibitor of procaspase-3 through chelation of inhibitory zinc ion. Physicochemical and ADMET calculations for 5e provided useful information of its suitable absorption profile and some toxicological effects that need further optimization to be developed as a promising anticancer agent., Conclusion: Compound 5e has emerged as a potential hit for further design and development of caspases activators and anticancer agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The ecological sustainability of rivers is in question due to severe pollution and lack of stringent regulations. Long term (1990-2016) water quality data of five stations namely Haridwar, Bareilly, Kanpur, Prayagraj and Varanasi of Upper Ganga river, India was considered for analysis using fuzzy analytical process (FAHP) based water quality index (WQI) to assess surface water quality. The value of water physical, biological and chemical parameters of temporal resolution (monthly, seasonal and yearly) indicate that value of electrical conductivity (EC), total dissolved solids (TDS), biological oxygen demand (BOD), chemical oxygen demand (COD), total alkalinity (Mg CaCO 3 ), total hardness (Mg CaCO 3 ), calcium (Ca), magnesium (Mg), sodium (Na), chlorine (Cl) and bicarbonate (HCO 3 ) were observed very high compared to recommended value of Bureau of Indian Standards (BIS) and World Health Organization (WHO) at Kanpur, Prayagraj and Varanasi stations. However, low value of parameters is observed at Haridwar and Bareilly stations. Also, the high deviation was observed in water quality parameters during 1990-2010 whereas the deviation of parameters is decreased in 2011-2016. It is observed from the piper diagram that magnesium and bicarbonate at Haridwar, sodium, potassium and bicarbonate in Bareilly, Kanpur, Prayagraj and Varanasi stations are dominant during monthly and seasonal periods. The fuzzy based WQI value indicate that water quality is excellent to poor at Haridwar, while poor to unsuitable in Bareilly, Kanpur, Prayagraj and Varanasi during monthly and seasonal periods. The water quality ranges from poor to unsuitable during the 1990-2010 period and good to very poor during the 2011-2016 period at Bareilly, Kanpur, Prayagraj and Varanasi stations. Whereas very good to good during 1990-2010 and excellent to good during 2011-2016 at Haridwar. It was also determined that water quality parameters (Ca, Na+K, SO 4 , Hardness, Cl and Mg) and WQI values were increased with length of the stream. It indicates that drain discharge, urban growth, urban functions, ecological footprints and crop area increment were key sources of pollution., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Objectives: There is little data regarding the characteristics of young Vietnamese patients (<40 years old) who get acute coronary syndrome (ACS). This study aimed to compare the risk factors, clinical-subclinical characteristics, coronary lesions, and mortality prediction (based on the GRACE and TIMI scores) of young ACS patients with their older counterparts., Methods: A cross-sectional descriptive study was conducted amongst 69 patients with ACS at the Cardiovascular Center of Hue Central Hospital from May 2017 to December 2018. These patients were divided into two groups: 33 patients were < 40 years old (group 1), and 36 patients were ≥ 40 years old (group 2). Demographic data, risk factors profile, clinical-subclinical characteristics, coronary lesions, and mortality prediction were compared between the two groups., Results: Compared with group 2, group 1 had a higher proportion of severe angina (the prevalence of angina graded III-IV by CCS classification was 69.7% in group 1 versus 36.1% in group 2, P = 0.0108) and lower systolic pressure (median was 120 mmHg in group 1 versus 135 mmHg in group 2, P = 0.006). The prevalence of unstable angina and STEMI was higher in group 1 (51.5% and 36.4% in group 1 versus 30.6% and 11.1% in group 2, respectively), while NSTEMI was higher in group 2 (58.3% in group 2 versus 12.1% in group 1, P = 0.0002). The prevalence of single-vessel CAD, normal coronary angiography (CAG), nonobstructive CAD in group 1 was also higher and multi-vessel CAD was lower than group 2 (45.5%, 33.3%, 12.1% and 9.1% in group 1 versus 33.3%, 2.8%, 2.8% and 61.2% in group 2, respectively). The Gensini, GRACE, and TIMI scores were lower in group 1 (median was 5; medium was 78.55 and median was 2 in group 1 versus 37.5, 130.22 and 3 in group 2, respectively). Smoking was a risk factor for obstructive CAD in group 1 (OR = 7.12, 95% CI: 1.25-40.63, P < 0.05)., Conclusion: Young patients with ACS tended to be males, smokers, and with positive familial history; the grade of angina was more severe, and systolic pressure was lower; the prevalence of unstable angina and STEMI was higher. Smoking was a risk factor for obstructive CAD in young patients., Competing Interests: Conflicts of Interest The authors declare no conflict of interest, (© 2021 Dinh The Anh, Huynh Van Minh, Ho Anh Binh, Tran Quang Bao, Nguyen Thi Thai Hai, Le Xuan Nam, Tran Duc Anh, published by Sciendo.)

Two series of novel 4-oxoquinazoline-based N -hydroxypropenamides ( 9a - m and 10a - m ) were designed, synthesized, and evaluated for their inhibitory and cytotoxicity activities against histone deacetylase (HDAC). The compounds showed good to potent HDAC inhibitory activity and cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung cancer). In this series, compounds with the N -hydroxypropenamide functionality impeded at position 7 on the 4-oxoquinazoline skeleton ( 10a - m ) were generally more potent than compounds with the N -hydroxypropenamide moiety at position 6 ( 9a - m ). Also, the N 3 -benzyl-substituted derivatives ( 9h - m , 10h - m ) exhibited stronger bioactivity than the N 3 -alkyl-substituted ones ( 9a - e , 10a - e ). Two compounds 10l and 10m were the most potent ones. Their HDAC inhibitory activity (IC 50 values, 0.041-0.044 μM) and cytotoxicity (IC 50 values, 0.671-1.211 μM) were approximately 2- to 3-fold more potent than suberoylanilide hydroxamic acid (SAHA). Some compounds showed up to 10-fold more potent HDAC6 inhibition compared to their inhibitory activity in total HDAC extract assay. Analysis of selected compounds 10l and 10m revealed that these compounds strongly induced both early and late apoptosis and arrested SW620 cells at the G2/M phase. Docking studies were carried out on the HDAC6 isoform for series 10a - m and revealed some important features contributing to the inhibitory activity of synthesized compounds., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Sanitary landfill is still considered as one of the most significant and least expensive methods of waste disposal. It is essential to consider environmental impacts while selecting a suitable landfill site. Thus, the site selection for sanitary landfill is a complex and time-consuming task needing an assessment of multiple criteria. In the present study, a decision support system (DSS) was prepared for selecting a landfill site in a growing urban region. This study involved two steps of analysis. The first step of analysis involved the application of spatial data to prepare the thematic maps and derive their weight. The second step employed a fuzzy multicriteria decision-making (FMCDM) technique for prioritizing the identified landfill sites. Thus, initially, the analytic hierarchy process (AHP) was used for weighting the selected criteria, while the fuzzy technique for order of preference by similarity to ideal solution (FTOPSIS) was applied for addressing the uncertainty associated with decision-making and prioritizing the most suitable site. A case study was conducted in the city of Memari Municipality. The main goal of this study was the initial evaluation and acquisition of landfill candidate sites by utilizing GIS and the following decision criteria: (1) environmental criteria consisting of surface water, groundwater, land elevation, land use land cover, distance from urban residence and buildup, and distance from sensitive places; and (2) socioeconomic criteria including distance from the road, population density, and land value. For preparing the final suitability map, the integration of GIS layers and AHP was used. On output, 7 suitable landfill sites were identified which were further ranked using FTOPSIS based on expert's views. Finally, candidate site-7 and site-2 were selected as the most suitable for proposing new landfill sites in Memari Municipality. The results from this study showed that the integration of GIS with the MCDM technique can be highly applied for site suitability. The present study will be helpful to local planners and municipal authorities for proposing a planning protocol and suitable sites for sanitary landfill in the near future.

Actinoplanes sp. A1094 strain had been selected for its high production of acarbose from 20 different strains of Actinoplanes sp. can be found in wild. The content for glucosidase inhibitor of acarbose concentration was recorded at 1.12 g/L. The conducted analysis of 16S rRNA sequence of Actinoplanes sp. A1094 showed 99% similar identity to the corresponding sequence of Actinoplanes hulinensis. Acarbose was purified from Actinoplanes hulinensis 1094 with a yield of 8.48%, purity of 98% and further identified by LC/MS and NMR methods (C 25 H 43 NO 18 ; m/z: 645.6 g/mol). The purified acarbose was used to evaluate the hypoglycemia in streptozotocin (STZ)-induced diabetic mice model. The purified acarbose reduced postprandial blood glucose level in comparison with Glucobay® as medication for control type 2 diabetes in a combination therapy. Notably, the outcomes of native acarbose on fasting blood glucose levels in mice resemble akin to the commercial product and the acarbose accumulating fermentation and metabolic engineering from the cell gene in which would reduce in production cost. Therefore, acarbose from Actinoplanes hulinensis 1094 could be potentially used to make products for the treatment of type II diabetes., Competing Interests: Declaration of competing interest The authors declare that they have not known of any competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Breast cancer is one of the most common cancers and a major cause of death in women worldwide. Chemotherapy is mainly used to treat and control the progression of breast cancer. Leukopenia is the most common side effect of chemotherapy which may decrease immune function and further lead to serious fatal infections. The purpose of this study was to evaluate the effect of acupuncture on regulating hematopoietic function in chemotherapy-induced leukopenia among patients with breast cancer., Methods: PubMed, Embase, Cochrane Library, CINAHL Plus, Web of Science, and Chinese articles in the Airiti Library and China National Knowledge Infrastructure (CNKI) databases were searched to August 2021 for papers to include in a systematic review and meta-analysis. A random-effects model was applied. The effect size was calculated by Hedges' g. Heterogeneity was determined using Cochran's Q test. Moderator analyses were performed to examine potential sources of heterogeneity. A trial sequential analysis (TSA) was conducted to determine whether the current sample size was sufficient., Results: Ten randomized controlled trials involving 650 participants were eligible for inclusion. Analysis by the random-effects model showed a significant effect by acupuncture of ameliorating leukopenia during chemotherapy. Levels of white blood cells (WBCs) were increased (Hedges' g = 0.70, P < .001, I 2 = 34%), neutrophil counts (Hedges' g = 0.80, P < .001, I 2 = 0%) were significantly enhanced. Moreover, regardless of the manner through which acupuncture was applied, overall values of WBCs increased., Conclusions: The current meta-analysis supports acupuncture possibly ameliorating chemotherapy-induced leukopenia, as WBC and neutrophil values significantly increased after acupuncture in patients undergoing chemotherapy. Additionally, regardless of the type of acupuncture, values of WBCs increased. These findings are actionable and support both the clinical use of acupuncture to relieve chemotherapy-induced leukopenia and further research regarding the use of acupuncture in patients experiencing immunosuppression when undergoing chemotherapy. Trial Registration: PROSPERO-CRD42020215759.

Prediction of water quality is a critical issue because of its significant impact on human and ecosystem health. This research aims to predict water quality index (WQI) for the free surface wetland using three soft computing techniques namely, adaptive neuro-fuzzy system (ANFIS), artificial neural networks (ANNs), and group method of data handling (GMDH). Seventeen wetland points for a period of 14 months were considered for monitoring water quality parameters including conductivity, suspended solid (SS), biochemical oxygen demand (BOD), ammoniacal nitrogen (AN), chemical oxygen demand (COD), dissolved oxygen (DO), temperature, pH, phosphate nitrite, and nitrate. The sensitivity analysis performed by ANFIS indicates that the significant parameters to predict WQI are pH, COD, AN, and SS. The results indicated that ANFIS with Nash-Sutcliffe Efficiency (NSE = 0.9634) and mean absolute error (MAE = 0.0219) has better performance to predict the WQI comparing with ANNs (NSE = 0.9617 and MAE = 0.0222) and GMDH (NSE = 0.9594 and MAE = 0.0245) models. However, ANNs provided a comparable prediction and the GMDH can be considered as a technique with an acceptable prediction for practical purposes. The findings of this study could be used as an effective reference for policy makers in the field of water resource management. Decreasing variables, reduction of running time, and high speed of these approaches are the most important reasons to employ them in any aquatic environment worldwide.

In continuity of our search for novel anticancer agents acting as procaspase activators, we have designed and synthesised two series of ( E )- N ' - benzylidene-carbohydrazides ( 4a-m ) and (Z)-N' -(2-oxoindolin-3-ylidene)carbohydrazides ( 5a-g ) incorporating 1-(4-chlorobenzyl)-1 H -indole core. Bioevaluation showed that the compounds, especially compounds in series 4a-m , exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). Within series 4a-m , compounds with 2-OH substituent ( 4g-i ) exhibited very strong cytotoxicity in three human cancer cell lines assayed with IC 50 values in the range of 0.56-0.83 µM. In particular, two compounds 4d and 4f bearing 4-Cl and 4-NO 2 substituents, respectively, were the most potent in term of cytotoxicity with IC 50 values of 0.011-0.001 µM. In caspase activation assay, compounds 4b and 4f were found to activate caspase activity by 314.3 and 270.7% relative to PAC-1. This investigation has demonstrated the potential of these simple acetohydrazides, especially compounds 4b , 4d , and 4f , as anticancer agents.

Several novel indirubin-based N-hydroxybenzamides, N-hydropropenamides and N-hydroxyheptanamides (4a-h, 7a-h, 10a-h) were designed using a fragment-based approach with structural features extracted from several previously reported HDAC inhibitors, such as SAHA (vorinostat), MGCD0103 (mocetinostat), nexturastat A and PXD-101 (belinostat). The biological results reveal that our compounds showed excellent cytotoxicity toward three common human cancer cell lines (SW620, PC-3 and NCI-H23) with IC 50 values ranging from 0.09 to 0.007 µM. The cytotoxicity of the compounds was equipotent or even up to 10-times more potent than adriamycin and up to 205-times more potent than SAHA. Among the series of N-hydroxypropenamides, compounds 10a-d were the most potent HDAC inhibitors as well as cytotoxicity toward the cell lines tested. In addition, the strong inhibitory activites toward HDAC of our compounds were observed with IC 50 values of below-micromolar range. Especially, compound 4a inhibited HDAC6 with an IC 50 value of 29-fold lower than that against HDAC2 isoform. Representative compounds 4a and 7a were found to significantly arrest SW620 cells at G0/G1 phase. Compounds 7a and 10a were found to strongly induce apoptosis in SW620 cells. Docking studies revealed some important features affecting the selectivity against HDAC6 isoform. The results clearly demonstrate the potential of the indirubin-hydroxamic acid hybrids and these compounds should be very promising for further development., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Many stresses induce the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum, a phenomenon known as ER stress. In response to ER stress, cells initiate a protective response, known as unfolded protein response (UPR), to maintain cellular homeostasis. The UPR sensor, inositol-requiring enzyme 1 (IRE1), catalyzes the cytoplasmic splicing of bZIP transcription factor-encoding mRNAs to activate the UPR signaling pathway. Recently, we reported that pretreatment of Arabidopsis thaliana plants with tunicamycin, an ER stress inducer, increased their susceptibility to bacterial pathogens; on the other hand, IRE1 deficient mutants were susceptible to Pseudomonas syringae pv. maculicola (Psm) and failed to induce salicylic acid (SA)-mediated systemic acquired resistance. However, the functional relationship of IRE1 with the pathogen and TM treatment remains unknown. In the present study, we showed that bacterial pathogen-associated molecular patterns (PAMPs) induced IRE1 expression; however, PAMP-triggered immunity (PTI) response such as callose deposition, PR1 protein accumulation, or Pst DC3000 hrcC growth was not altered in ire1 mutants. We observed that IRE1 enhanced plant immunity against the bacterial pathogen P. syringae pv. tomato DC3000 (Pst DC3000) under ER stress. Moreover, TM-pretreated ire1 mutants were more susceptible to the avirulent strain Pst DC3000 (AvrRpt2) and showed greater cell death than wild-type plants during effector-triggered immunity (ETI). Additionally, Pst DC3000 (AvrRpt2)-mediated RIN4 degradation was reduced in ire1 mutants under TM-induced ER stress. Collectively, our results reveal that IRE1 plays a pivotal role in the immune signaling pathway to activate plant immunity against virulent and avirulent bacterial strains under ER stress., (Copyright © 2020. Published by Elsevier Masson SAS.)

The complement system may be crucial during dengue virus infection and progression to severe dengue. This study investigates the role of MBL2 genetic variants and levels of MBL in serum and complement proteins in Vietnamese dengue patients. MBL2 genotypes (- 550L/H, MBL2 codon 54), MBL2 diplotypes (XA/XO, YA/XO) and MBL2 haplotypes (LXPB, HXPA, XO) were associated with dengue in the study population. The levels of complement factors C2, C5, and C5a were higher in dengue and dengue with warning signs (DWS) patients compared to those in healthy controls, while factor D levels were decreased in dengue and DWS patients compared to the levels determined in healthy controls. C2 and C5a levels were associated with the levels of AST and ALT and with WBC counts. C9 levels were negatively correlated with ALT levels and WBC counts, and factor D levels were associated with AST and ALT levels and with platelet counts. In conclusions, MBL2 polymorphisms are associated with dengue in the Vietnamese study population. The levels of the complement proteins C2, C4b, C5, C5a, C9, factor D and factor I are modulated in dengue patients during the clinical course of dengue.

The clinical outcome of dengue is due to a complex interplay between dengue virus (DENV) and host immune factors, including complement and cytokine systems. Proinflammatory cytokines are mainly produced by monocytes in response to infectious pathogens. This study investigated the levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), and IL-12 in Vietnamese patients with dengue, and their correlations with the clinical outcome of dengue infection in 156 patients clinically classified as dengue without warning signs (DWS-, n  = 87), dengue with warning signs (DWS+, n  = 62), and severe dengue (SD, n  = 7) patients as well as in 60 healthy controls (HCs). Serum TNF-α, IL-1β, and IL-12 levels were quantified by enzyme-linked immunosorbent assay (ELISA). The results showed that TNF-α, IL-1β, and IL-12 levels were significantly increased in dengue patients compared with HCs ( p  < 0.0001). TNF-α levels were significantly correlated with white blood cells and platelet counts ( r s  = 0.52, 0.2; p  < 0.0001, p  = 0.018, respectively). IL-1β levels were correlated with red blood cells counts and the levels of aspartate aminotransferase and alanine aminotransferase ( r s  = 0.23, 0.21, 0.23; p  = 0.004, 0.012, 0.005, respectively). The results suggest that these three proinflammatory cytokines are associated with the clinical outcome of dengue and could play roles in the pathogenesis of the disease.

Several novel series of hydroxamic acids bearing 2-benzamidooxazole/thiazole (5a-g, 6a-g) or 2-phenylsulfonamidothiazole (8a-c) were designed and synthesized. The compounds were obtained straightforwards via a two step pathway, starting from commercially available ethyl 2-aminooxazole-4-carboxylate or ethyl 2-aminothiazole-4-carboxylate. Biological evaluation showed that these hydroxamic acids generally exhibited good cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung cancer), with IC 50 values in low micromolar range and comparable to that of SAHA. These compounds also comparably inhibited HDACs with IC 50 values in sub-micromolar range (0.010-0.131 µM) and some compounds (e.g 5f, IC 50 , 0.010 µM) were even more potent than SAHA (IC 50 , 0.025 µM) in HDAC inhibition. Representative compounds 6a and 8a appeared to arrest the SW620 cell cycle at G2 phase and significantly induced both early and late apoptosis of SW620 colon cancer cells. Docking experiments on HDAC2 and HDAC6 isozymes revealed favorable interactions at the tunnel of the HDAC active site which positively contributed to the inhibitory activity of synthesized compound. The binding affinity predicted by docking program showed good correlation with the experimental IC 50 values. This study demonstrates that simple 1,3-oxazole- and 1,3-thiazole-based hydroxamic acids are also promising as antitumor agents and HDAC inhibitors and these results should provide valuable information for further design of more potent HDAC inhibitors and antitumor agents., 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 © 2020 Elsevier Inc. All rights reserved.)

Quantification of plasma cell-free Epstein Barr virus DNA (cf EBV DNA) has been suggested as a promising liquid biopsy assay for screening and early detection of nasopharyngeal carcinoma (NPC). However, the diagnostic value of this assay is currently not known in the population of Vietnam, one of the countries which contributed the most to the NPC cases. Herein, we have reported a highly sensitive quantitative polymerase chain reaction (qPCR)-based assay targeting cf EBV DNA for the detection of NPC. A standard curve with linear regression, R 2 = 0.9961 (range: 25-150 000 copies/mL) and a detection limit of 25 copies/mL were obtained using an EBV standard panel provided by the Chinese University of Hong Kong. The clinical performance of this assay was assessed using plasma samples obtained from 261 Vietnamese individuals. The optimized qPCR assay detected cf EBV DNA in plasma with a sensitivity of 97.4% and a specificity of 98.2%. The absolute quantitative results of pretreatment cf EBV DNA and patient overall clinical stages were statistically correlated ( P < .05). In summary, the remarkably high sensitivity and specificity of our optimized qPCR assay strongly supports the wide use of cf EBV DNA quantification as a routine noninvasive method in early diagnosis and management of patients with NPC.

Two series of 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-ones and N-(1-benzylpiperidin-4-yl)quinazolin-4-amines were designed initially as potential acetylcholine esterase inhibitors. Biological evaluation demonstrated that N-(1-benzylpiperidin-4-yl)quinazolin-4-amines significantly inhibited AChE activity. Especially, two compounds of them were found to be the most potent with relative AChE inhibition percentages of 87 % in comparison to donepezil. The docking studies with AChE showed similar interactions between donepezil and four derivatives. N-(1-Benzylpiperidin-4-yl)quinazolin-4-amines also exhibited significant DPPH scavenging effects. The two series of compound also exerted moderate to good cytotoxicity against three human cancer cell lines, including SW620 (human colon cancer), PC-3 (prostate cancer), and NCI-H23 (lung cancer), with 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one being the most cytotoxic agent. 3-[(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one significantly induced early apoptosis and arrested the SW620 cells at G2/M phase. From this study, two compounds of N-(1-benzylpiperidin-4-yl)quinazolin-4-amines could serve as new leads for further design and AChE inhibitors, while 3-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]quinazolin-4(3H)-one could serve as a new lead for the design and development of more potent anticancer agents., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Background and Objective: The human ficolin-2, encoded by FCN2, recognizes pathogen-associated acetylated residues on their cell surfaces and activates the lectin complement cascade. This study aimed to investigate the contribution of human ficolin-2 and the functional FCN2 genetic variants in dengue virus (DENV) infection and in clinical progression., Methods: FCN2 genetic polymorphisms in the promoter, intron 7 and exon 8 were genotyped in 279 patients with dengue fever and in 200 healthy controls by direct Sanger sequencing. The ficolin-2 levels were measured in serum samples by ELISA and correlated with clinical data., Results: The frequencies of +6031GG, +6220GG and +6424TT genotypes were significantly higher in dengue patients compared to healthy controls indicating an increased risk of dengue fever. The SNPs rs11103563 (+6031A/G), rs7872508 (+6220 T/G), and rs7851696 (+6424G/T) significantly regulated ficolin-2 levels in dengue patients (P < 0.0001). Ficolin-2 levels were increased in patients with dengue and Dengue with Warning Signs (DWS) compared to healthy controls (P < 0.0001 and P = 0.038, respectively). Ficolin-2 levels were significantly increased after 10-14 days of admission in both dengue and DWS patients and then slightly decreased after three weeks of discharge, indicating that ficolin-2 levels were modulated during the progression of dengue fever. In addition, ficolin-2 levels were negatively correlated with AST levels and positively correlated with platelet counts., Conclusions: FCN2 polymorphisms are associated with dengue fever in the Vietnamese population. Ficolin-2 levels are modulated during the progression of dengue fever and correlated with clinical parameters and thus may play a possible role in the pathogenesis of DENV infection., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In our search for new small molecules activating procaspase-3, we have designed and synthesized a series of new acetohydrazides incorporating both 2-oxoindoline and 4-oxoquinazoline scaffolds. Biological evaluation showed that a number of these acetohydrazides were comparably or even more cytotoxic against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer) in comparison to PAC-1, a first procaspase-3 activating compound, which was used as a positive control. One of those new compounds, 2-(6-chloro-4-oxoquinazolin-3(4H)-yl)-N'-[(3Z)-5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]acetohydrazide activated the caspase-3 activity in U937 human lymphoma cells by 5-fold higher than the untreated control. Three of the new compounds significantly induced necrosis and apoptosis in U937 cells., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Objectives: During dengue fever, a pronounced gamma-interferon immune response produces neopterin and promotes tryptophan degradation by the enzyme indoleamine-2,3-dioxygenase 1 (IDO-1). Activated IDO-1 is indicated by an increased kynurenine to tryptophan ratio (Kyn/Trp) in patients., Methods: Plasma levels of neopterin, kynurenine, and tryptophan were measured in 72 hospitalized dengue virus (DENV) patients and 100 healthy individuals. Plasma levels of neopterin, kynurenine, and tryptophan were also measured prospectively in a second cohort of 13 DENV patients; on the day of hospitalization, on day 2-3 at discharge, and 7-10 days after discharge. DENV RNA positivity was determined by qualitative and quantitative methodologies., Results: DENV RNA-positive patients presented significantly higher levels of neopterin (mean 36.5nmol/l) and Kyn/Trp ratios (mean 102μmol/mmol) compared to DENV RNA-negative individuals. A significant correlation between neopterin levels and Kyn/Trp ratios was observed in both DENV RNA-positive (Spearman's rho=0.37, p< 0.01) and DENV RNA-negative (Spearman's rho=0.89, p<0.001) patients. Kyn/Trp ratios were negatively correlated with platelet counts (Spearman's rho=-0.43, p<0.01) and positively correlated with liver enzymes: AST (Spearman's rho=0.68, p<0.01) and ALT (Spearman's rho=0.51, p<0.05). In addition, the follow-up data presented a significant decrease in neopterin levels and Kyn/Trp ratios within 10 days after hospital entry., Conclusions: Neopterin levels and Kyn/Trp ratios were significantly increased in DENV patients and subsequently decreased after recovery., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Vitamin D derivatives and their receptor (VDR) are potent modulators of immune responses in various diseases including malignancies as well as in metabolic and infectious disorders. The impact of vitamin D receptor polymorphisms on clinical outcomes of hepatitis B virus (HBV) infection is not well understood. This study aims to investigate the potential role of VDR polymorphisms (TaqI, FokI, ApaI, and BsmI) in Vietnamese HBV infected patients and to correlate these polymorphisms with the progression of HBV-related liver disease., Methods: Four hundred forty-three HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 183), liver cirrhosis (LC, n = 89) and hepatocellular carcinoma (HCC, n = 171) and 238 healthy individuals (HC) were enrolled. VDR polymorphisms were genotyped by DNA sequencing and in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of VDR polymorphisms with manifest HBV infection as well as with progression of related liver diseases mulin different genetic models., Results: The VDR ApaI CA genotype was less frequent in HCC than in CHB patients in different genetic models (codominant model, OR = 0.5, 95%CI = 0.3-0.84, P = 0.004; dominant model, OR = 0.46, 95%CI = 0.27-0.76, P = 0.0023). In the recessive model, the genotype ApaI AA was found more frequently among HCC compared to CHB patients (OR = 2.56, 95%CI = 1.01-6.48, P = 0.04). Similarly, the ApaI CA genotype was less frequent in HCC than in non-HCC group codominant model, OR = 0.6, 95%CI = 0.4-0.98, dominant model, P = 0.04 and OR = 0.6, 95%CI = 0.38-0.90, P = 0.017). The ApaI genotypes CA and AA was significantly associated with higher levels of liver enzymes, bilirubin, and HBV DNA (P < 0.05). No association between TaqI, FokI and BsmI polymorphisms and any clinical outcome as well as liver disease progression was found., Conclusions: Among the four investigated VDR polymorphisms, ApaI is associated with clinical outcome and liver disease progression in Vietnamese HBV infected patients.

The thermophilic biomass-degrader Malbranchea cinnamomea exhibits poor growth on cellulose but excellent growth on hemicelluloses as the sole carbon source. This is surprising considering that its genome encodes eight lytic polysaccharide monooxygenases (LPMOs) from auxiliary activity family 9 (AA9), enzymes known for their high potential in accelerating cellulose depolymerization. We characterized four of the eight ( M. cinnamomea AA9s) Mc AA9s, namely, Mc AA9A, Mc AA9B, Mc AA9F, and Mc AA9H, to gain a deeper understanding about their roles in the fungus. The characterized Mc AA9s were active on hemicelluloses, including xylan, glucomannan, and xyloglucan, and furthermore, in accordance with transcriptomics data, differed in substrate specificity. Of the Mc AA9s, Mc AA9H is unique, as it preferentially cleaves residual xylan in phosphoric acid-swollen cellulose (PASC). Moreover, when exposed to cellulose-xylan blends, Mc AA9H shows a preference for xylan and for releasing (oxidized) xylooligosaccharides. The cellulose dependence of the xylan activity suggests that a flat conformation, with rigidity similar to that of cellulose microfibrils, is a prerequisite for productive interaction between xylan and the catalytic surface of the LPMO. Mc AA9H showed a similar trend on xyloglucan, underpinning the suggestion that LPMO activity on hemicelluloses strongly depends on the polymers' physicochemical context and conformation. Our results support the notion that LPMO multiplicity in fungal genomes relates to the large variety of copolymeric polysaccharide arrangements occurring in the plant cell wall. IMPORTANCE The Malbranchea cinnamomea LPMOs ( Mc AA9s) showed activity on a broad range of soluble and insoluble substrates, suggesting their involvement in various steps of biomass degradation besides cellulose decomposition. Our results indicate that the fungal AA9 family is more diverse than originally thought and able to degrade almost any kind of plant cell wall polysaccharide. The discovery of an AA9 that preferentially cleaves xylan enhances our understanding of the physiological roles of LPMOs and enables the use of xylan-specific LPMOs in future applications., (Copyright © 2019 Hüttner et al.)

In search for novel small molecules with antitumor cytotoxicity via activating procaspase-3, we have designed and synthesized three series of novel (E)-N'-benzylidene-4-oxoquinazolin-3(4H)-yl)acetohydrazides (5a-j, 6a-h, and 7a-h). On the phenyl ring ò the benzylidene part, three different substituents, including 2-OH-4-OCH 3 , 4-OCH 3 , and 4-N(CH 3 ) 2 , were introduced, respectively. Biological evaluation showed that the acetohydrazides in series 5a-j, in which the phenyl ring of the benzylidene part was substituted by 2-OH-4-OCH 3 substituent, exhibited potent cytotoxicity against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). Most of the compounds, in this series, especially compounds 5c, 5b and 5h, also significantly activated caspase-3 activity. Among these, compound 5c displayed 1.61-fold more potent than PAC-1 as caspase-3 activator. Cell cycle analysis showed that compounds 5b, 5c, and 5h significantly arrested the cell cycle in G1 phase. Further apoptotic studies also demonstrated compounds 5b, 5c, and 5h as strong apoptotic cell death inducers. The docking simulation studies showed that these compounds could activate procaspase via chelating Zn 2+ ion bound to the allosteric site of the zymogen., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin-4(3H)-ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N-hydroxy-7-(7-methyl-4-oxoquinazolin-3(4H)-yl)heptanamide (5b) and N-hydroxy-7-(6-methyl-4-oxoquinazolin-3(4H)-yl)heptanamide (5c) (IC 50 values, 0.10-0.16 μm) were found to be approximately 30-fold more cytotoxic than SAHA (IC 50 values of 3.29-3.67 μm). N-Hydroxy-7-(4-oxoquinazolin-3(4H)-yl)heptanamide (5a; IC 50 values of 0.21-0.38 μm) was approximately 10- to 15-fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC 50 values in sub-micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c, strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA., (© 2019 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Histone Deacetylase (HDAC) inhibitors represent an extensive class of targeted anticancer agents. Among the most explored structure moieties, hydroxybenzamides and hydroxypropenamides have been demonstrated to have potential HDAC inhibitory effects. Several compounds of these structural classes have been approved for clinical uses to treat different types of cancer, such as givinostat (ITF2357) and belinostat (PXD-101)., Aims: This study aims at developing novel HDAC inhibitors bearing N-hydroxybenzamides and Nhydroxypropenamides scaffolds with potential cytotoxicity against different cancer cell lines., Methods: Two new series of N-hydroxybenzamides and N-hydroxypropenamides analogues (4a-j, 6a-j) designed based on the structural features of nexturastat A, AR-42, and PXD-101, were synthesized and evaluated for HDAC inhibitory potency as well as cytotoxicity against three human cancer cell lines (SW620 (colorectal adenocarcinoma), PC3 (prostate adenocarcinoma), and NCI-H23 (adenocarcinoma, non-small cell lung cancer). Molecular simulations were finally carried out to gain more insight into the structure-activity relationships., Results: It was found that the N-hydroxypropenamides (6a-e) displayed very good HDAC inhibitory potency and cytotoxicity. Various compounds, e.g. 6a-e, especially compound 6e, were up to 5-fold more potent than suberanilohydroxamic acid (SAHA) in terms of cytotoxicity. These compounds also comparably inhibited HDACs with IC50 values in the sub-micromolar range. Docking experiments showed that these compounds bound to HDAC2 at the enzyme active binding site with the same binding mode of SAHA, but with higher binding affinities., Conclusions: The two series of N-hydroxybenzamides and N-hydroxypropenamides designed and synthesized were potential HDAC inhibitors and antitumor agents. Further development of these compounds should be warranted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N-hydroxybenzamides incorporating quinazoline heterocycles (4a - 4i, 6a - 6i). Bioevaluation showed that these quinazoline-based hydroxamic acids and N-hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). In term of cytotoxicity, several compounds, e.g., 4g, 4c, 4g - 4i, 6c, and 6h, displayed from 5- up to 10-fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC 50 values in sub-micromolar range. Some compounds, e.g., 4g, 6c, 6e, and 6h, were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g, 6c, and 6g, while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates., (© 2018 Wiley-VHCA AG, Zurich, Switzerland.)

In our search for novel small molecules targeting histone deacetylases, we have designed and synthesized several series of novel N-hydroxybenzamides/N-hydroxypropenamides incorporating quinazolin-4(3H)-ones (4a-h, 8a-d, 10a-d). Biological evaluation showed that these hydroxamic acids were generally cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung cancer). It was found that the N-hydroxypropenamides (10a-d) were the most potent, both in term of HDAC inhibition and cytotoxicity. Several compounds, e.g. 4e, 8b-c, and 10a-c, displayed up to 4-fold more potent than SAHA (suberoylanilide hydroxamic acid, vorinostat) in term of cytotoxicity. These compounds also comparably inhibited HDACs with IC 50 values in sub-micromolar range. Docking experiments on HDAC2 isozyme revealed some important features contributing to the inhibitory activity of synthesized compounds, especially for propenamide analogues. Importantly, the free binding energy computed was found to have high quantitative correlation (R 2  ∼ 95%) with experimental results., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In this study, we attempted to isolate Escherichia coli from healthy adults in Ho Chi Minh City, Vietnam, and characterized its antimicrobial resistance profile, extended-spectrum β-lactamase (ESBL) genotype, phylogenetic grouping and virulence gene profile. A total of 103 E. coli isolates were obtained, and most of them were antimicrobial resistant such to streptomycin (80.6%), tetracycline (67.0%), ampicillin (65.0%), sulfamethoxsazole/trimethoprim (48.5%), nalidixic acid (43.7%), chloramphenicol (34.0%), cefotaxime (15.5%), ciprofloxacin (15.5%), kanamycin (12.6%), ceftazidime (10.7%), fosfomycin (4.9%) and gentamicin (2.9%). However, all these E. coli strains were susceptible to imipenem. Surprisingly, of 103 strains, 74 (71.8%) and 43 (41.7%) strains showed resistance to more than 3 and 5 classes of antimicrobials, respectively. Furthermore, 10 E. coli strains were ESBL-producers and positive for bla CTX-M genes (7 for bla CTX-M-9 and 3 for bla CTX-M-1 ), while five were additionally positive for bla TEM genes. S1-nuclease pulsed-field gel electrophoresis analysis revealed that 7 and 3 strains of E. coli carry bla CTX-M genes on their large plasmid and chromosome, respectively. Phylogenetic analysis exhibited that majority of the E. coli strains was grouped into A (44.7%), followed by B1 (23.3%), B2 (18.4%) and D (13.6%). Virulence genes associated with diarrheagenic E. coli, such as astA, EAF, eaeA, elt and eagg were also detected in ESBL-producing E. coli as well as antimicrobial resistant strains. These data suggest that commensal E. coli of healthy human could be a reservoir for antimicrobial resistance determinants and some of them might be harmful to human.