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DDT (dichlorodiphenyltrichloroethane) is a commonly used insecticide that is recalcitrant and highly stable in the environment. Currently, DDT residue contamination, especially in agricultural soil, is still a concern in many countries, threatening human health and the environment. Among the approaches to resolve such an issue, novel biodegradation-based methods are now preferred to physicochemical methods, due to the sustainability and the effectiveness of the former. In this study, we explored the possibility of building mixed microbial cultures that can offer improved DDT-degrading efficiencies and be more environmentally transilient, based on genome annotation using the KEGG database and prediction of interactions between single strains using the obtained metabolic maps. We then proposed 10 potential DDT-degrading mixed cultures of different strain combinations and evaluated their DDT degradation performances in liquid, semi-solid and solid media. The results demonstrated the superiority of the mixtures over the single strains in terms of degrading DDT, particularly in a semi-solid medium, with up to 40-50% more efficiency. Not only did the mixed cultures degrade DDT more efficiently, but they also adapted to broader spectra of environmental conditions. The three best DDT-degrading and transilient mixtures were selected, and it turned out that their component strains seemed to have more metabolic interactions than those in the other mixtures. Thus, our study demonstrates the effectiveness of exploiting genome-mining techniques and the use of constructed mixed cultures in improving biodegradation., (© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

Coronary artery disease requiring surgical revascularization is prevalent in United States Veterans. We aimed to investigate preoperative predictors of 30-day mortality following coronary artery bypass grafting (CABG) in the Veteran population. The Veterans Affairs Surgical Quality Improvement (VASQIP) national database was queried for isolated CABG cases between 2008 and 2018. The primary outcome was 30-day mortality. A multivariable logistic regression was performed to assess for independent predictors of the primary outcome. A P-value of <0.05 was considered statistically significant. A total of 32,711 patients were included. The 30-day mortality rate was 1.37%. Multivariable analysis identified the following predictors of 30-day mortality: African-American race (OR 1.46, 95% CI 1.09-1.96); homelessness (OR 6.49, 95% CI 3.39-12.45); female sex (OR 2.15, 95% CI 1.08-4.30); preoperative myocardial infarction within 7 days (OR 1.49, 95% CI 1.06-2.10) or more than 7 days before CABG (OR 1.34, 95% CI 1.04-1.72); partially/fully dependent functional status (OR 1.44, 95% CI 1.07-1.93); chronic obstructive pulmonary disease (OR 1.54, 95% CI 1.24-1.92); mild (OR 1.48, 95% CI 1.04-2.11) and severe aortic stenosis (OR 2.06, 95% CI 1.37-3.09); moderate (OR 1.88, 95% CI 1.31-2.72), or severe (OR 2.99, 95% CI 1.71-5.22) mitral regurgitation; cardiomegaly (OR 1.73, 95% CI 1.35-2.22); NYHA Class III/IV heart failure (OR 2.05, 95% CI 1.10-3.83); and urgent/emergent operation (OR 1.42, 95% CI 1.08-1.87). The 30-day mortality rate in US Veterans undergoing isolated CABG between 2008 and 2018 was 1.37%. In addition to established clinical factors, African-American race and homelessness were independent demographic predictors of 30-day mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Children with congenital tracheal stenosis born in the developing world face a high risk of mortality due to limited access to proper treatment. Patients who required preoperative respiratory support were suspected to have poor survival after slide tracheoplasty; however, this was not clearly demonstrated in the previous studies. This study aims to investigate the impact of preoperative respiratory conditions on outcomes of slide tracheoplasty., Methods: From 2016 to 2022, children who underwent slide tracheoplasty were retrospectively reviewed. Patients with respiratory distress requiring emergency operations (group A) were compared with patients in stable condition who were scheduled for surgery (group B)., Results: Perioperative results revealed that group A (n = 43) had a longer bypass time (P < 0.001), operation time (P = 0.01), postoperative ventilation time (P < 0.001) and length of intensive care unit stay (P = 0.00125) than group B (n = 60). The early mortality rate was 7.8%, and the actuarial 5-year survival rate was 85.3%. The cumulative incidence test revealed that group A was highly significant for overall mortality [sudistribution (SHR) 4.5; 95% confidence interval (CI) 1.23-16.4; P = 0.023]. Risk factors for overall mortality were prolonged postoperative ventilation time (hazard ratio 3.86; 95% CI 1.20-12.48; P = 0.024), bronchial stenosis (hazard ratio 5.77; 95% CI 1.72-19.31; P = 0.004), and preoperative tracheal mucositis (hazard ratio 5.67; 95% CI 1.51-21.31; P = 0.01). Four patients needed reintervention during a follow-up of 28.4 months (interquartile range 15.3-47.3)., Conclusions: Preoperative respiratory distress negatively affected the outcomes of patients who required slide tracheoplasty. Therefore, early detection of congenital tracheal stenosis and aggressive slide tracheoplasty are crucial and obligatory to enhance long-term survival in this lethal congenital airway disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Fat-soluble vitamins (vitamin A, D, E, and K) assume a pivotal role in maintaining human homeostasis by virtue of their enzymatic functions. The daily inclusion of these vitamins is imperative to the upkeep of various physiological processes including vision, bone health, immunity, and protection against oxidative stress. Current research highlights fat-soluble vitamins as potential therapeutics for human diseases, especially cancer. Fat-soluble vitamins exert their therapeutic effects through multiple pathways, including regulation of matrix metalloproteinases' (MMPs) expression and enzymatic activity. As MMPs have been reported to be involved in the pathology of various diseases, such as cancers, cardiovascular diseases, and neurological disorders, regulating the expression and/or activity of MMPs could be considered as a potent therapeutic strategy. Here, we summarize the properties of fat-soluble vitamins and their potential as promising candidates capable of effectively modulating MMPs through multiple pathways to treat human diseases.

African swine fever (ASF) is a lethal and highly contagious transboundary animal disease with the potential for rapid international spread. Currently, there is no ASF vaccine commercially available. All infected animals must be isolated and culled immediately upon the confirmation of the presence of the virus. Studies leading to the rational development of protective ASF vaccines are urgently needed. Here, we generated a safe and efficacious live-attenuated vaccine (LAV) VNUA-ASFV-LAVL2 by serially passaging a field isolate (VNUA-ASFV-05L1, genotype II) in porcine alveolar macrophages (PAMs, 65 passages) and an immortalized porcine alveolar macrophage cell line (3D4/21, 55 passages). VNUA-ASFV-LAVL2 can efficiently replicate in both PAMs and 3D4/21 cells. It provides 100% protection, even with the low dose of 10 2 HAD 50 , to the vaccinated pigs against the challenge of contemporary pandemic ASFV field isolate. Pigs vaccinated with this LAV in a dose range of 10 2 to 10 5 HAD 50 remained clinically healthy during both the 28-day observation period of immunization and the 28-day observation period of challenge. VNUA-ASFV-LAVL2 was eliminated from blood by 28 days post-inoculation (DPI), and from feces or oral fluids by 17 DPI. Although the vaccine strain in serum remained a safe and attenuated phenotype after five passages in swine, a reversion-to-virulence study using blood or tissue homogenates at peak viremia will be conducted in the future. ASFV-specific IgG antibodies and significant cellular immunity were detected in vaccinated pigs before the ASFV challenge. These results indicate that the VNUA-ASFV-LAVL2 strain is a safe and efficacious LAV against the genotype II ASFV strain responsible for current ASF outbreaks in Asia.

Objective: Alcohol abuse can cause developing cirrhosis, even liver cancer. Several single nucleotide polymorphisms (SNPs) of ADH1B, ADH1C, and ALDH2 genes have been reported to be associated with alcohol abuse and alcoholic cirrhosis (ALC). This study investigated the association between three SNPs of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with alcohol abuse and ALC in people living in the Northeast region of Vietnam., Methods: 306 male participants were recruited including 206 alcoholics (106 ALC, 100 without ALC) and 100 healthy non-alcoholics. Clinical characteristics were collected by clinicians. Genotypes were identified by Sanger sequencing. Chi-Square (χ2) and Fisher-exact tests were used to assess the differences in age and clinical characteristics, Child-Pugh score, frequencies of alleles and genotypes., Result: Our data showed that the frequency of ALDH2*1 was significantly higher in alcoholics (88.59%) and ALC groups (93.40%) than that of healthy non-alcoholics (78.50%) with p=0.0009 and non-ALC group (83.50%) with p=0.002, respectively. We detected opposite results when examined ALDH2*2. Frequency of combined genotypes with high acetaldehyde accumulation were significantly lower in alcoholics and ALC group than those of control groups with p=0.005 and p=0.008, respectively. Meanwhile, the proportion of combined genotypes with non-acetaldehyde accumulation were significantly two times higher in the ALC group (19.98%) than those of the non-ALC group (8%) with p=0.035. These combined genotypes showed a decreasing trend in the Child-Pugh score from likely phenotype causing risk for non-acetaldehyde accumulation to high acetaldehyde accumulation., Conclusion: The ALDH2*1 allele was found as a risk factor for alcohol abuse and ALC, and combined genotypes of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with non-acetaldehyde accumulation increase ALC risk. In contrast, ALDH2*2 and the genotype combinations related to high acetaldehyde accumulation were protective factors against alcohol abuse and ALC.

The thermo-mechanical response of shock-initiated energetic materials (EMs) is highly influenced by their microstructures, presenting an opportunity to engineer EM microstructures in a "materials-by-design" framework. However, the current design practice is limited, as a large ensemble of simulations is required to construct the complex EM structure-property-performance linkages. We present the physics-aware recurrent convolutional (PARC) neural network, a deep learning algorithm capable of learning the mesoscale thermo-mechanics of EM from a modest number of high-resolution direct numerical simulations (DNS). Validation results demonstrated that PARC could predict the themo-mechanical response of shocked EMs with comparable accuracy to DNS but with notably less computation time. The physics-awareness of PARC enhances its modeling capabilities and generalizability, especially when challenged in unseen prediction scenarios. We also demonstrate that visualizing the artificial neurons at PARC can shed light on important aspects of EM thermos-mechanics and provide an additional lens for conceptualizing EM.

Nowadays, cancers and dementia, such as Alzheimer's disease, are the most fatal causes of death. Many studies tried to understand the pathogenesis of those diseases clearly and develop a promising way to treat the diseases. Matrix metalloproteinases (MMPs) have been reported to be involved in the pathology of cancers and AD through tumor cell movement and amyloid degradation. Therefore, control of the levels and actions of MMPs, especially MMP-2 and MMP-9, is necessary to care for and/or cure cancer and AD. Various molecules have been examined for their potential application as regulators of MMPs expression and activity. Among the molecules, multiple metal complexes have shown advantages, including simple synthesis, less toxicity and specificity toward MMPs in cancer cells or in the brain. In this review, we summarize the recent studies and knowledge of metal complexes (e.g., Pt-, Ru-, Au-, Fe-, Cu-, Ni-, Zn-, and Sn-complexes) targeting MMPs and their potentials for treating and/or caring the most fatal human diseases, cancers and AD.

Objective: ADH1B, ADH1C and ALDH2 genes are mainly responsible for alcohol metabolism in the body. Several single nucleotide polymorphisms (SNPs) of these genes have been reported to be associated with alcohol dependence and are considered risk factors for various human diseases. This study aims to identify the prevalence of three SNPs of ADH1B (rs1229984), ADH1C (rs698) and ALDH2 (rs671) in 235 unrelated individuals living in Thai Nguyen province, the northeast region of Vietnam., Methods: The target genotypes were identified by using PCR direct sequencing, and their frequencies were compared to previous reports., Result: Our data showed that allele frequencies of ADH1B*2, ADH1C*2 and ALDH2*2 were 68.8%, 8.3% and 20.4%, respectively. The ADH1B*2 and ADH1C*2 frequencies were similar to those of the Kinh ethnic individuals living in the south region of Vietnam, while the ALDH2*2 frequency was higher. Compared to data from other countries, ADH1B*2 frequency is similar to the Philippines (60.5%) and Mongolia (62.9%) but significantly different from the other populations. The ADH1C*2 frequency is not so different compared to Japanese (5.7%) and Chinese (7.1%) but is quite different in other populations. ALDH2*2 frequency was lower than Japanese (29.3%), Indonesian (30%) and higher than other countries. Regarding the risk of alcoholism, the percentage of Vietnamese people in this study with genotypes related to alcohol dependence is 8.1%. In contrast, the carrier has genotypes protecting against alcoholism with high frequency, 91.9%. Among them, the individuals can cause high acetaldehyde accumulation accounting for 33.2%., Conclusion: This study helps to understand the genetic polymorphisms of alcohol metabolism genes in the community living in Thai Nguyen province, northeast of Vietnam, and provides valuable scientific data relating to alcohol consumption behavior as well as public health protection.

The heterodimer of human ubiquitin fusion degradation 1 (hUfd1) and human nuclear protein localization 4 (hNpl4) is a major cofactor of human p97 adenosine triphosphatase (ATPase). The p97-Ufd1-Npl4 complex translocates the ubiquitin-conjugated proteins from the endoplasmic reticulum membrane to the cytoplasm. Ubiquitinated proteins are then degraded by the proteasome. The structures of Npl4 and Ufd1-Npl4 (UN) complex in Saccharomyces cerevisiae have been recently reported; however, the structures of hNpl4 and the human UN complex remain unknown. Here, we report the crystal structures of the human UN complex at a resolution of 2.7 Å and hNpl4 at a resolution of 3.0 Å. We also present atomic details and characterization of the human UN complex. Crystallographic studies and site-directed mutagenesis of the hUfd1 residues involved in the interaction with hNpl4 revealed the atomic details of the two proteins., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Due to the overuse of antibiotics in treatment and regional variation in disease factors, community-acquired pneumonia (CAP) has a relatively high morbidity and mortality rate. This study determined the prevalence of bacteria that cause CAP and the rate of antibiotic resistance. From April 2018 to May 2019, a cross-sectional study was conducted on 254 CAP patients at hospitals and medical centers in the province of Vinh Long. Based on interviews and medical records, SPSS 18.0 was used to analyze the data. CAP-causing bacteria, antibiotic susceptibility, and extended-spectrum β-lactamase production of bacteria were determined by performing Identification and Antibiotic Susceptibility Testing on sputum specimens using the VITEK 2 Automated instrument. With a total of 254 patients, the age of 60s accounted for the highest prevalence. Streptococcus pneumonia was the leading factor, accounting for 12.6%, followed by Klebsiella pneumonia and Pseudomonas aeruginosa at 12.2% and 8.3%, respectively. The Enterobacteriaceae group was the highest at 36.5%, followed by other gram-negative bacteria (34%) and gram-positive bacteria (29.5%). Amoxicillin/clavulanic acid ranked the highest in antibiotic resistance, accounting for 31.4% of Enterobacteriaceae and 91.7% of non-Enterobacteriaceae. S. pneumonia resisted erythromycin at a high prevalence (84.4%), followed by clindamycin (71.9%) and tetracycline (78.1%). The age of 60s was the leading group in community pneumonia and had increased resistance to amoxicillin/clavulanic acid and cefuroxime., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Targeting cancer stem cell metabolism has emerged as a promising therapeutic strategy for cancer treatment. Breast cancer stem cells (BCSCs) exert distinct metabolism machinery, which plays a major role in radiation and multidrug resistance. Therefore, exploring the mechanisms involved in energy utilization of BCSCs could improve the effectiveness of therapeutic strategies aimed at their elimination. This study was conducted to clarify the glucose metabolism machinery and the function of nootkatone, a bioactive component of grapefruit, in regulating glucose metabolism and stemness characteristics in human breast carcinoma MCF-7 stem cells (MCF-7SCs). In vivo experiments, transcriptomic analysis, seahorse XF analysis, MTT assay, Western blotting, mammosphere formation, wound healing, invasion assay, flow cytometric analysis, reverse transcription-quantitative polymerase chain reaction, and in silico docking experiments were performed. MCF-7SCs showed a greater tumorigenic capacity and distinct gene profile with enrichment of the genes involved in stemness and glycolysis signaling pathways compared to parental MCF-7 cells, indicating that MCF-7SCs use glycolysis rather than oxidative phosphorylation (OXPHOS) for their energy supply. Nootkatone impaired glucose metabolism through AMPK activation and reduced the stemness characteristics of MCF-7SCs. In silico docking analysis demonstrated that nootkatone efficiently bound to the active site of AMPK. Therefore, this study indicates that regulation of glucose metabolism through AMPK activation could be an attractive target for BCSCs.

To provide preliminary insights into metabolic and lipidomic characteristics in radioresistant triple-negative breast cancer (TNBC) cells and suggest potential therapeutic targets, we performed a comprehensive metabolic and lipidomic profiling of radioresistant MDA-MB-231 (MDA-MB-231/RR) TNBC cells and their parental cells using gas chromatography-mass spectrometry and nano electrospray ionization-mass spectrometry, followed by multivariate statistical analysis. Buthionine sulfoximine (BSO) and radiation were co-treated to radioresistant TNBC cells. The level of glutathione (GSH) was significantly increased, and the levels of GSH synthesis-related metabolites, such as cysteine, glycine, and glutamine were also increased in MDA-MB-231/RR cells. In contrast, the level of lactic acid was significantly reduced. In addition, reactive oxygen species (ROS) level was decreased in MDA-MB-231/RR cells. In the lipidomic profiles of MDA-MB-231/RR cells, the levels of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were significantly increased, whereas those of most of the phosphatidylinositol species were significantly decreased. BSO sensitized MDA-MB-231/RR cells to radiotherapy, which resulted in decreased GSH level and increased ROS level and apoptosis. Radioresistant TNBC cells showed distinct metabolic and lipidomic characteristics compared to their parental cells. We suggested activated GSH, PC, and PE biosynthesis pathways as potential targets for treating radioresistant TNBC cells. Particularly, enhanced radiosensitivity was achieved by inhibition of GSH biosynthesis in MDA-MB-231/RR cells., 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 © 2021 Elsevier B.V. All rights reserved.)

Ampelopsin, also known as dihydromyricetin, is a commonly found flavonoid in medicinal plants. The cancer stem cell (CSC) population is a promising target for triple-negative breast cancer (TNBC). In this study, flavonoid screening was performed in the established MDA-MB-231/IR cell line, which is enriched in CSCs. Ampelopsin suppressed the proliferation and colony formation of stem cell-rich MDA-MB-231/IR, while inducing their apoptosis. Importantly, ampelopsin displayed an inhibitory impact on the stemness features of MDA-MB-231/IR cells, demonstrated by decreases in mammosphere formation, the CD44 + /CD24 -/low population, aldehyde dehydrogenase activity, and the levels of stem cell markers (e.g., CD44, MRP1, β-catenin, and KLF4). Ampelopsin also suppressed the epithelial-mesenchymal transition, as evidenced by decreases in migration, invasion capacity, and mesenchymal markers, as well as an increase in the epithelial marker E-cadherin. Moreover, ampelopsin significantly impaired oxidative phosphorylation by reducing the oxygen consumption rate and adenosine triphosphate production in MDA-MB-231/IR cells. Notably, ampelopsin treatment significantly reduced the levels of the phosphorylated forms of IκBα and NF-κB p65, as well as the levels of tumor necrosis factor (TNF)-α-stimulated phosphorylation of IκBα and NF-κB p65. These results demonstrated that ampelopsin prevents the TNF-α/NF-κB signaling axis in breast CSCs.

This work presents a gas-phase approach for the synthesis of Cu 2 O/TiO 2 powder-based photocatalysts using atomic layer deposition (ALD). The process is carried out in a fluidized bed reactor working at atmospheric pressure using (trimethylvinylsilyl)-hexafluoroacetulacetonate copper(I) as the Cu-precursor and H 2 O vapor as the oxidizer. The saturating regime of the chemical reactions and the linear growth of ALD are achieved. In combination with the unsaturated regime, the ALD approach enables the deposition of ultrasmall Cu 2 O clusters with average diameters in the range of 1.3-2.0 nm, narrow particle size distributions and tunable Cu 2 O loadings on P25 TiO 2 nanoparticles. The photocatalytic performance of Cu 2 O/TiO 2 photocatalysts is investigated by the degradation of organic dyes, including Rhodamine B (RhB), methyl orange, and methylene blue; the results demonstrate that the surface modification of TiO 2 nanoparticles by Cu 2 O nanoclusters significantly enhances the photocatalytic activity of TiO 2 . This is attributed to the efficient charge transfer between Cu 2 O and TiO 2 that reduces the charge recombination. The photocatalytic reaction mechanism is further investigated for the degradation of RhB, revealing the dominating role of holes, which contribute to both direct hole oxidation and indirect oxidation (i.e. via the formation of hydroxyl radicals). Our approach provides a fast, scalable and efficient process to deposit ultrasmall Cu 2 O clusters in a controllable fashion for surface engineering and modification., (© 2021 IOP Publishing Ltd.)

Using the laboratory-based fuel consumption models for predicting real-world fuel consumption requires the measurement of data under certain conditions to obtain high accuracy of predicted result. Therefore, it is necessary to develop a logging device for measuring the real-time fuel consumption and speed of vehicle on the road. This article presents a study on developing the on-board data logging device to collect real-world data of fuel consumption and speed for motorcycles with the update rate of 1 Hz. The instantaneous speed of the motorcycle was determined based on the rotational speed of the wheel and the wheel radius. Another module was used to determine the instantaneous fuel consumption rate (FR) though measuring the duration injection pulse. The relationship between the duration injection pulse and the injected amount of fuel was established with high correlation coefficient of 0.997. In addition, a filter was designed to remove noise in the dataset collected using the data logging device. The random errors in the speed and the FR profiles were detected and replaced, the percentage of these errors is 1.8% and 2.4%, respectively. The developed method is a precise one for transient fuel consumption and speed measurement. In chassis dynamometer test, the average deviation between steady speed measured by the chassis and the data logging device is only approximately 0.35%. At transient state, the biggest deviation between these two datasets is less than 3.5%. The average FR at steady speed measured by the developed method is slightly different from the one measured by the carbon balance method. The difference is 0.9%, 2.5%, and 0.25% at the speeds of 30 km/h, 50 km/h, and 70 km/h, respectively. Following the transient test cycle, the fuel consumption measured by the developed method is 4.35% lower than that determined by the carbon balance method. Implications : A robust method for collecting and processing the on-road instantaneous data of fuel consumption and speed was developed for motorcycles. The proposed method can record well the real-world driving data for motorcycles, including the fuel consumption and speed, with the update rate of 1 Hz. The filter was designed to minimize noise while maintaining data integrity of the collected dataset, the percentage of errors in the the speed and the FR profiles is 1.8% and 2.4%, respectively. The proposed method, therefore, can be used as effective tools for future studies relating to the fuel consumption and emission of motorcycles on the road.

The sensitivity of heterogeneous energetic (HE) materials (propellants, explosives, and pyrotechnics) is critically dependent on their microstructure. Initiation of chemical reactions occurs at hot spots due to energy localization at sites of porosities and other defects. Emerging multi-scale predictive models of HE response to loads account for the physics at the meso-scale, i.e. at the scale of statistically representative clusters of particles and other features in the microstructure. Meso-scale physics is infused in machine-learned closure models informed by resolved meso-scale simulations. Since microstructures are stochastic, ensembles of meso-scale simulations are required to quantify hot spot ignition and growth and to develop models for microstructure-dependent energy deposition rates. We propose utilizing generative adversarial networks (GAN) to spawn ensembles of synthetic heterogeneous energetic material microstructures. The method generates qualitatively and quantitatively realistic microstructures by learning from images of HE microstructures. We show that the proposed GAN method also permits the generation of new morphologies, where the porosity distribution can be controlled and spatially manipulated. Such control paves the way for the design of novel microstructures to engineer HE materials for targeted performance in a materials-by-design framework.

10-gingerol is a major phenolic lipid found in the rhizomes of ginger (Zingiber officinale). Being amphiphilic in nature, phenolic lipids have the ability to incorporate into cell membranes and modulate membrane properties. The purpose of the present study was to evaluate the effects of 10-gingerol on lipid raft/membrane raft modulation in radio-resistant triple negative breast cancer (MDA-MB-231/IR) cells. The effects of 10-gingerol on MDA-MB-231/IR cells' proliferation, clonogenic growth, migration, and invasion were assayed using MTT, colony formation, cell migration, and invasion assays, respectively. Sucrose density gradient centrifugation was used to extract lipid rafts. Western blotting and immunofluorescence were employed to assess the effects of 10-gingerol on lipid raft/membrane raft modulation and lipid rafts-associated PI3K/Akt signaling. Cholesterol measurements were carried out using a commercially available kit. 10-gingerol suppressed the proliferation, migration, invasion, and induced apoptosis through targeting the PI3K/Akt signaling pathway in MDA-MB-231/IR cells. Moreover, 10-gingerol was found to modulate the lipid rafts of MDA-MB-231/IR cells and attenuate the key PI3K/Akt signaling components in lipid rafts. The cholesterol content of the lipid rafts and rafts-resident Akt signaling were also affected by exposure to 10-gingerol. The results of the present study highlight rafts-associated PI3K/Akt signaling as a new target of 10-gingerol in MDA-MB-231/IR cells, thus rationalizing a new rafts-mediated treatment approach for radio-resistant triple negative breast cancer cells., Competing Interests: The authors declare no conflict of interest

Saturated fatty acids possess few health benefits compared to unsaturated fatty acids. However, increasing experimental evidence demonstrates the nutritionally beneficial role of odd-chain saturated fatty acids in human health. In this study, the anti-cancer effects of pentadecanoic acid were evaluated in human breast carcinoma MCF-7/stem-like cells (SC), a cell line with greater mobility, invasiveness, and cancer stem cell properties compared to the parental MCF-7 cells. Pentadecanoic acid exerted selective cytotoxic effects in MCF-7/SC compared to in the parental cells. Moreover, pentadecanoic acid reduced the stemness of MCF-7/SC and suppressed the migratory and invasive ability of MCF-7/SC as evidenced by the results of flow cytometry, a mammosphere formation assay, an aldehyde dehydrogenase activity assay, and Western blot experiments conducted to analyze the expression of cancer stem cell markers-CD44, β-catenin, MDR1, and MRP1-and epithelial-mesenchymal transition (EMT) markers-snail, slug, MMP9, and MMP2. In addition, pentadecanoic acid suppressed interleukin-6 (IL-6)-induced JAK2/STAT3 signaling, induced cell cycle arrest at the sub-G1 phase, and promoted caspase-dependent apoptosis in MCF-7/SC. These findings indicate that pentadecanoic acid can serve as a novel JAK2/STAT3 signaling inhibitor in breast cancer cells and suggest the beneficial effects of pentadecanoic acid-rich food intake during breast cancer treatments.

Resistance to chemotherapy and radiation therapy is considered a major therapeutic barrier in breast cancer. Cancer stem cells (CSCs) play a prominent role in chemo and radiotherapy resistance. The established chemo and radio-resistant triple-negative breast cancer (TNBC) cell line MDA-MB-231/IR displays greater CSC characteristics than the parental MDA-MB-231 cells. Escalating evidence demonstrates that metadherin (MTDH) is associated with a number of cancer signaling pathways as well as breast cancer therapy resistance, making it an attractive therapeutic target. Kaplan-Meier plot analysis revealed a correlation between higher levels of MTDH and shorter lifetimes in breast cancer and TNBC patients. Moreover, there was a positive correlation between the MTDH and CD44 expression levels in The Cancer Genome Atlas breast cancer database. We demonstrate that MTDH plays a pivotal role in the regulation of stemness in MDA-MB-231/IR cells. Knockdown of MTDH in MDA-MB-231/IR cells resulted in a reduction in the CSC population, aldehyde dehydrogenase activity, and major CSC markers, including β-catenin, CD44 + , and Slug. In addition, MTDH knockdown increased reactive oxygen species (ROS) levels in MDA-MB-231/IR cells. We found that phenethyl isothiocyanate (PEITC), a well-known pro-oxidant phytochemical, suppressed stemness in MDA-MB-231/IR cells through ROS modulation via the downregulation of MTDH. Co-treatment of PEITC and N-Acetylcysteine (a ROS scavenger) caused alterations in PEITC induced cell death and CSC markers. Moreover, PEITC regulated MTDH expression at the post-transcriptional level, which was confirmed using cycloheximide, a protein synthesis inhibitor., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The study aims to make an update on the distribution and ecology of sand flies in the Quang Ninh province, Northern Vietnam, where Leishmania cases were reported in 2001. Seventeen sites were chosen in three districts of the province: Ha Long, Cam Pha, and Hoanh Bo. Phlebotomine sand flies were collected using 68 CDC light traps from May 30 to 3 June 2016. Captured specimens were transferred individually into Eppendorf tubes with 90% ethanol. The sand fly heads and genitalia were removed and were mounted in Euparal after successive different baths. Specimen identification was determined based on the morphology of the cibarium, pharynx, and/or male genitalia or female spermathecae. A total of 416 sand flies (125 females, 283 males) belonging to four genera were collected and 10 sand fly species were identified: Sergentomyia silvatica, Se. barraudi, Se. hivernus, Se. bailyi, Phlebotomus mascomai, Ph. stantoni, Ph. yunshengensis, Ph. betisi, Chinius junlianensis, Idiophlebotomus longiforceps. The Sergentomyia genus prevailed (79.7% of the collected sand flies), followed by the Phlebotomus genus (13.7%), the Chinius genus (6.1%), and the Idiophlebotomus genus (0.8%). Besides these well-defined taxa, five specimens, named sp1, showed unknown morphological characteristics, requiring further study. The majority of sand flies were collected in rock caves suggesting the cavernicolous character of the species in the Quang Ninh province. However, specimens were also collected in intra and peridomiciliary sites in which Ph. stantoni and Se. hivernus were found as the main species. It is worth noting that two Ph. stantoni were found in the house of a patient affected by Leishmania., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: It is unclear whether improving feed efficiency by selection for low residual feed intake (RFI) compromises pigs' immunocompetence. Here, we aimed at investigating whether pig lines divergently selected for RFI had different inflammatory responses to lipopolysaccharide (LPS) exposure, regarding to clinical presentations and transcriptomic changes in peripheral blood cells., Results: LPS injection induced acute systemic inflammation in both the low-RFI and high-RFI line (n = 8 per line). At 4 h post injection (hpi), the low-RFI line had a significantly lower (p = 0.0075) mean rectal temperature compared to the high-RFI line. However, no significant differences in complete blood count or levels of several plasma cytokines were detected between the two lines. Profiling blood transcriptomes at 0, 2, 6, and 24 hpi by RNA-sequencing revealed that LPS induced dramatic transcriptional changes, with 6296 genes differentially expressed at at least one time point post injection relative to baseline in at least one line (n = 4 per line) (|log 2 (fold change)| ≥ log 2 (1.2); q < 0.05). Furthermore, applying the same cutoffs, we detected 334 genes differentially expressed between the two lines at at least one time point, including 33 genes differentially expressed between the two lines at baseline. But no significant line-by-time interaction effects were detected. Genes involved in protein translation, defense response, immune response, and signaling were enriched in different co-expression clusters of genes responsive to LPS stimulation. The two lines were largely similar in their peripheral blood transcriptomic responses to LPS stimulation at the pathway level, although the low-RFI line had a slightly lower level of inflammatory response than the high-RFI line from 2 to 6 hpi and a slightly higher level of inflammatory response than the high-RFI line at 24 hpi., Conclusions: The pig lines divergently selected for RFI had a largely similar response to LPS stimulation. However, the low-RFI line had a relatively lower-level, but longer-lasting, inflammatory response compared to the high-RFI line. Our results suggest selection for feed efficient pigs does not significantly compromise a pig's acute systemic inflammatory response to LPS, although slight differences in intensity and duration may occur.

As solids pyrolyse during combustion, they lose chemical and structural integrity by gradually degrading into residual char and forming defects such as voids, fissures and cracks. The material degradation process, which is coupled to the crack formation process, is described using a theoretical model and is numerically simulated using the finite-element method for a generic, charring, rubber-like material. In this model, a slab of material is subjected to an external, localized heat flux and, as the material degrades, cracks form when the local principal stress exceeds a defined cracking threshold. The magnitude of the cracking threshold σ c is systematically varied in order to examine its influences on crack initiation, evolution, distribution and behaviour over time. When σ c exceeds the maximum principal stress for the entire process, σ m , then no cracks are generated. We quantify how the average crack spacing, total crack length and crack initiation time depend upon the ratio σ c / σ m . Two characteristic domains of crack formation behaviour are identified from the crack initiation behaviour. Correlations are produced for the crack length evolution and final crack length values as functions of σ c / σ m . Crack intersection patterns and behaviour are described and characterized., Competing Interests: We declare we have no competing interests., (© 2019 The Author(s).)

This paper develops the specific emission factors for buses in the real-world traffic conditions in the inner city of Hanoi, Vietnam. An engine stationary cycle consisting of 14 modes was developed based on the typical driving cycle of Hanoi buses which had been constructed with the application of Markov chain theory. This is the first engine stationary emissions test cycle constructed for heavy-duty engine in Vietnam. Based on this cycle, the country-specific emission factors (CSEFs) of air pollutants including CO, HC, NO x , CO 2 , and PM for buses in Hanoi have been developed using the emission measurements on the engine test bed. It is found that almost all developed emission factors are higher than those derived from the emission measurements to the ECE R49 on the same engine. These emission factors, therefore, can be used to improve the quality of the emission inventory of buses in Hanoi.

dsDNA breaks (DSBs) are resected in a 5'→3' direction, generating single-stranded DNA (ssDNA). This promotes DNA repair by homologous recombination and also assembly of signaling complexes that activate the DNA damage checkpoint effector kinase Chk1. In fission yeast ( Schizosaccharomyces pombe ), genetic screens have previously uncovered a family of three xeroderma pigmentosum G (XPG)-related nucleases (XRNs), known as Ast1, Exo1, and Rad2. Collectively, these XRNs are recruited to a euchromatic DSB and are required for ssDNA production and end resection across the genome. Here, we studied why there are three related but distinct XRN enzymes that are all conserved across a range of species, including humans, whereas all other DSB response proteins are present as single species. Using S. pombe as a model, ChIP and DSB resection analysis assays, and highly efficient I-PpoI-induced DSBs in the 28S rDNA gene, we observed a hierarchy of recruitment for each XRN, with a progressive compensatory recruitment of the other XRNs as the responding enzymes are deleted. Importantly, we found that this hierarchy reflects the requirement for different XRNs to effect efficient DSB resection in the rDNA, demonstrating that the presence of three XRN enzymes is not a simple division of labor. Furthermore, we uncovered a specificity of XRN function with regard to the direction of transcription. We conclude that the DSB-resection machinery is complex, is nonuniform across the genome, and has built-in fail-safe mechanisms, features that are in keeping with the highly pathological nature of DSB lesions., (© 2019 Barnum et al.)

This paper develops a typical driving cycle for buses in Hanoi that does not require the deconstruction of the natural driving patterns. Real velocity-time data were collected along 15 routes in the inner city. The raw velocity-time series were preprocessed to remove errors, and smooth and denoise the data. These data, then, were tested for stationary behavior before being used in the construction of the driving cycle based on Markov chain theory. The 14 representative parameters of the driving cycle, including vehicle-specific power, which were extracted from 33 driving cycle parameters using the hierarchical agglomerative clustering method, were used to integrate the features of realistic driving patterns into the typical driving cycle. The conformity of the developed driving cycle with the real-world driving data was evaluated by the speed-acceleration frequency distribution (SAFD). A typical driving cycle for buses in Hanoi with a SAFD of 13.2% was developed. This is the first driving cycle developed for buses in Vietnam. Implications: A typical driving cycle was developed for the first time for buses in Hanoi. With the deviation in speed-acceleration frequency distribution (SAFD) reaching to 13.2%, the developed driving cycle reflects well the overall real-world driving data in the city. This driving cycle, therefore, can be applied for the development of the country-specific emission factors and emission inventories for buses which are a very good tool as well as useful information for integrated air quality management in Hanoi.

Huntington disease (HD) is a progressive neurodegenerative disease that initially affects the striatum and leads to changes in behavior and loss of motor coordination. It is caused by an expansion in the polyglutamine repeat at the N terminus of huntingtin (HTT) that leads to aggregation of mutant HTT. The loss of wild-type function, in combination with the toxic gain of function mutation, initiates various cell death pathways. Wild-type and mutant HTT are regulated by different posttranslational modifications that can positively or negatively regulate their function or toxicity. In particular, we have previously shown that caspase cleavage of mutant HTT at amino acid position aspartate 586 (D586) by caspase-6 is critical for the pathogenesis of the disease in an HD mouse model. Herein, we describe the identification of a new caspase cleavage site at position D572 that is mediated by caspase-1. Inhibition of caspase-1 also appeared to decrease proteolysis at D586, likely by blocking the downstream activation of caspase-6 through caspase-1. Inhibition of caspase cleavage at D572 significantly decreased mutant HTT aggregation and significantly increased the turnover of soluble mutant HTT. This suggests that caspase-1 may be a viable target to inhibit caspase cleavage of mutant HTT at both D572 and D586 to promote mutant HTT clearance.-Martin, D. D. O., Schmidt, M. E., Nguyen, Y. T., Lazic, N., Hayden, M. R. Identification of a novel caspase cleavage site in huntingtin that regulates mutant huntingtin clearance.

Post-translational modifications (PTMs) are key modulators of protein function. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the huntingtin (HTT) gene. A spectrum of PTMs have been shown to modify the normal functions of HTT, including proteolysis, phosphorylation and lipidation, but the full contribution of these PTMs to the molecular pathogenesis of HD remains unclear. In this study, we examine all commonly occurring missense mutations in HTT to identify potential human modifiers of HTT PTMs relevant to HD biology. We reveal a SNP that modifies post-translational myristoylation of HTT, resulting in downstream alterations to toxic HTT proteolysis in human cells. This is the first SNP shown to functionally modify a PTM in HD and the first validated genetic modifier of post-translational myristoylation. This SNP is a high-priority candidate modifier of HD phenotypes and may illuminate HD biology in human studies.

This study evaluated the capacity to remove lead by an indigenous consortium of five sulfate-reducing bacteria (SRB): Desulfobacterium autotrophicum, Desulfomicrobium salsugmis, Desulfomicrobium escambiense, Desulfovibrio vulgaris, and Desulfovibrio carbinolicus, using continuous moving bed biofilm reactor systems. Four continuous moving bed biofilm reactors (referred as R1-R4) were run in parallel for 40 days at lead loading rates of 0, 20, 30 and 40 mg l -1 day -1 , respectively. The impact of lead on community structure of the SRB consortium was investigated by dsrB gene-based denaturing gradient gel electrophoresis (dsrB-based DGGE), fluorescence in situ hybridization (FISH) and chemical analysis. These results indicated that D. escambiense and D. carbinolicus were dominant in all analyzed samples and played a key role in lead removal in R2 (20 mg l -1 day -1 ) and R3 (30 mg l -1 day - 1 ). However, in R4 (40 mg l -1 day -1 ), these two strains were barely detected by FISH and dsrB-based DGGE. As a result, SRB activity was severely affected by lead toxicity. High lead removal efficiencies of lead (99-100%) were observed in R2 and R3 throughout the operation, whereas that in R4 was significantly decreased (91%) after 40 days of operation. This data strongly implied that the investigated SRB consortium might have potential application for lead removal. Moreover, to improve the efficiency of the lead treatment process, the lead loading rates below the inhibitory level to SRB activity should be selected.

Background: Improving feed efficiency (FE) of pigs by genetic selection is of economic and environmental significance. An increasingly accepted measure of feed efficiency is residual feed intake (RFI). Currently, the molecular mechanisms underlying RFI are largely unknown. Additionally, to incorporate RFI into animal breeding programs, feed intake must be recorded on individual pigs, which is costly and time-consuming. Thus, convenient and predictive biomarkers for RFI that can be measured at an early age are greatly desired. In this study, we aimed to explore whether differences exist in the global gene expression profiles of peripheral blood of 35 to 42 day-old pigs with extremely low (more efficient) and high RFI (less efficient) values from two lines that were divergently selected for RFI during the grow-finish phase, to use such information to explore the potential molecular basis of RFI differences, and to initiate development of predictive biomarkers for RFI., Results: We identified 1972 differentially expressed genes (DEGs) (q ≤ 0.15) between the low (n = 15) and high (n = 16) RFI groups of animals by using RNA sequencing technology. We validated 24 of 37 selected DEGs by reverse transcription-quantitative PCR (RT-qPCR) in a joint analysis of 24 (12 per line) of the 31 samples already used for RNA-seq plus 24 (12 per line) novel samples from the same contemporary group of pigs. Using an analysis of the 24 novel samples alone, only nine of the 37 selected DEGs were validated. Genes involved in small molecule biosynthetic process, antigen processing and presentation of peptide antigen via major histocompatibility complex (MHC) class I, and steroid biosynthetic process were overrepresented among DEGs that had higher expression in the low versus high RFI animals. Genes known to function in the proteasome complex or mitochondrion were also significantly enriched among genes with higher expression in the low versus high RFI animals. Alternatively, genes involved in signal transduction, bone mineralization and regulation of phosphorylation were overrepresented among DEGs with lower expression in the low versus high RFI animals. The DEGs significantly overlapped with genes associated with disease, including hyperphagia, eating disorders and mitochondrial diseases (q < 1E-05). A weighted gene co-expression network analysis (WGCNA) identified four co-expression modules that were differentially expressed between the low and high RFI groups. Genes involved in lipid metabolism, regulation of bone mineralization, cellular immunity and response to stimulus were overrepresented within the two modules that were most significantly differentially expressed between the low and high RFI groups. We also found five of the DEGs and one of the co-expression modules were significantly associated with the RFI phenotype of individual animals (q < 0.05)., Conclusions: The post-weaning blood transcriptome was clearly different between the low and high RFI groups. The identified DEGs suggested potential differences in mitochondrial and proteasomal activities, small molecule biosynthetic process, and signal transduction between the two RFI groups and provided potential new insights into the molecular basis of RFI in pigs, although the observed relationship between the post-weaning blood gene expression and RFI phenotype measured during the grow-finish phase was not strong. DEGs and representative genes in co-expression modules that were associated with RFI phenotype provide a preliminary list for developing predictive biomarkers for RFI in pigs.

We studied the winter activity of Aedes albopictus (Skuse) from November 2008 to April 2009 in Bat Trang village of Hanoi, Vietnam. We selected 12 houses and collected: 1) adults with BG sentinel traps, 2) pupae from household water containers, and 3) eggs with ovitraps. Aedes albopictus adults, pupae, and eggs were not collected from early January to early February. Though the egg hatching probability tended to be initially high at longer day length, the maximum probability gradually shifted to shorter day length, as the observation period elapsed. When females were reared under long day length and their eggs were immersed 1 or 5 wk after oviposition, >50% of eggs hatched within 20 days. However, when females were reared under short day length and their eggs were immersed after 1 wk, hatching was suppressed for 60 days. When females were reared under short day length, the median hatching day occurred earlier in eggs kept dry for 5 and 10 wk after oviposition than in those dried for only 1 wk. This indicates that the extended dry periods accelerate egg hatching. Our results showed that hatchability gradually changed with day length, suggesting that selection for overwintering is not as strong relative to Ae. albopictus living in the temperate zone, where winter conditions are less favorable than in tropical and subtropical areas., (© The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Improving the ability to predict livestock performance using biomarkers will provide a benefit for livestock genetic evaluation and improvement. The most practical biological sample to screen for development of biomarkers is serum due to the ease of collection. However, protein profiles in serum are complex and dynamic. Strategies are needed to manage variation in serum proteins used for biomarker identification. Albumin is the most abundant protein in serum, comprising over 50% of the overall protein content, and has historically been depleted from serum before biomarker identification. The objective of this study was to investigate the use of gel-based proteomic techniques to evaluate the need for porcine albumin depletion in biomarker identification. Albumin is known to bind many proteins in the blood, thus potential biomarkers could be removed during albumin depletion. Using two-dimensional difference in gel electrophoresis (2D-DIGE), we show whole serum can be used for biomarker discovery. The data obtained show that albumin removal methods are effective for porcine sera. Over 85% of the protein spots resolved on at least half of the gels were changed in abundance between whole and albumin depleted sera. Of the 204 protein spots significantly altered in abundance, 59 were changed over 400%. However, albumin removal also altered the serum proteome in an unpredictable manner; in the depleted sera, 86 protein spots were increased in abundance and 118 were decreased. Furthermore, the abundance of 59.4% of the protein spots in the albumin depleted samples had a larger standard error than whole sera. However, the resolution of albumin in 2D-DIGE analysis of whole sera permitted the detection and quantification of substantial numbers of proteins. Thus, it is proposed that whole serum can be used in a gel-based proteomics system for the identification of porcine biomarkers.

Species of the Culex vishnui subgroup, Cx. fuscocephala and Cx. gelidus, which are known Japanese encephalitis (JE) vectors, are distributed in rice agroecosystems in Asian countries. Hence, although ecological studies of rice agroecosystems in northern Vietnam are necessary, very few integrated studies of breeding habitats of mosquitoes, including JE vectors, have been conducted. We carried out a field study and investigated the mosquito fauna in six rice production areas in northern Vietnam during the rainy and dry seasons of 2009. Mosquitoes and potential mosquito predators were collected from aquatic habitats by using larval dippers. We collected 1780 Culex individuals (including 254 Cx. tritaeniorhynchus; 113 Cx. vishnui, 58 Cx. vishnui complex, consisting of Cx. vishnui and Cx. pseudovishnui; 12 Cx. gelidus; 1 Cx. bitaeniorhynchus; and 1 Cx. fuscocephala), 148 Anopheles individuals (including 5 An. vagus), 1 Mansonia annulifera, and 1 Mimomyia chamberlaini during the rainy season. During the dry season, we collected 176 Culex individuals (including 33 Cx. vishnui, 24 Cx. tritaeniorhynchus, 8 Cx. vishnui complex, and 1 Cx. gelidus) and 186 Anopheles individuals (including 9 An. tessellatus, 2 An. kochi, and 2 An. barbumbrosus). We found mosquitoes in all aquatic habitats, namely, rice fields, ditches, ponds, wetlands, irrigation canals, and rice nurseries, and Cx. tritaeniorhynchus and Cx. vishnui complex were found in all the above six areas. Heteroptera such as Micronecta, Veliidae, and Pleidae were abundant and widely distributed in both the seasons. The abundance of mosquito larvae was higher in the rice fields, ditches, and ponds during the rainy season than during the dry season. Cx. tritaeniorhynchus, Cx. vishnui complex, Cx. fuscocephala, and Cx. gelidus were abundant in rice agroecosystems (rice fields, ditches, ponds, and wetlands) in northern Vietnam, and their abundance was high during the rainy season. These findings deepen our understanding of mosquito ecology and strengthen mosquito control strategies to be applied in rice ecosystems Vietnam in the future., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Previous studies showed that the common UV filter substances benzophenone-3 (BP-3), butyl methoxydibenzoylmethane (BM-DBM), octocrylene (OCR), ethylhexyl methoxycinnamate (EHMC), ethylhexyl salicylate (EHS) and ethylhexyl triazone (EHT) were able to react with amino side chains of different proteins in vitro. To transfer the results to mammalian skin conditions, sunscreen products were applied on both prepared fresh porcine skin and glass plates, followed by UV irradiation and the determination of depletion of the respective UV filters. Significantly lower recoveries of the UV filters extracted from skin samples than from glass plates indicated the additional reaction of the UV filters with skin constituents, when proteins will be the most important reactants. Among the products tested, BP-3 showed the greatest differences in recoveries between glass and skin samples of about 13% and 24% after 2 and 4 h of irradiation, respectively, followed by EHS > BM-DBM > OCR > EHMC > EHT. The obtained results raise the question, whether the common in vitro evaluations of sunscreens, using inert substrate materials like roughened quartz or polymethyl methacrylate (PMMA) plates are really suitable to fully replace in vivo methods, as they cannot include skin-typical reactions., (© 2014 The American Society of Photobiology.)

Activation of caspase-6 in the striatum of both presymptomatic and affected persons with Huntington's disease (HD) is an early event in the disease pathogenesis. However, little is known about the role of caspase-6 outside the central nervous system (CNS) and whether caspase activation might play a role in the peripheral phenotypes, such as muscle wasting observed in HD. We assessed skeletal muscle tissue from HD patients and well-characterized mouse models of HD. Cleavage of the caspase-6 specific substrate lamin A is significantly increased in skeletal muscle obtained from HD patients as well as in muscle tissues from two different HD mouse models. p53, a transcriptional activator of caspase-6, is upregulated in neuronal cells and tissues expressing mutant huntingtin. Activation of p53 leads to a dramatic increase in levels of caspase-6 mRNA, caspase-6 activity and cleavage of lamin A. Using mouse embryonic fibroblasts (MEFs) from YAC128 mice, we show that this increase in caspase-6 activity can be mitigated by pifithrin-α (pifα), an inhibitor of p53 transcriptional activity, but not through the inhibition of p53's mitochondrial pro-apoptotic function. Remarkably, the p53-mediated increase in caspase-6 expression and activation is exacerbated in cells and tissues of both neuronal and peripheral origin expressing mutant huntingtin (Htt). These findings suggest that the presence of the mutant Htt protein enhances p53 activity and lowers the apoptotic threshold, which activates caspase-6. Furthermore, these results suggest that this pathway is activated both within and outside the CNS in HD and may contribute to both loss of CNS neurons and muscle atrophy.

Influenza virus infections result in considerable morbidity and mortality both in the temperate and tropical world. Influenza surveillance over multiple years is important to determine the impact and epidemiology of influenza and to develop a national vaccine policy, especially in countries developing influenza vaccine manufacturing capacity, such as Vietnam. We conducted surveillance of influenza and influenza-like illness in Vietnam through the National Influenza Surveillance System during 2006-2010. At 15 sentinel sites, the first two patients presenting each weekday with influenza-like illness (ILI), defined as fever and cough and/or sore throat with illness onset within 3 days, were enrolled and throat specimens were collected and tested for influenza virus type and influenza A subtype by RT-PCR. De-identified demographic and provider reported subsequent hospitalization information was collected on each patient. Each site also collected information on the total number of patients with influenza-like illness evaluated per week. Of 29,804 enrolled patients presenting with influenza-like illness, 6516 (22%) were influenza positive. Of enrolled patients, 2737 (9.3%) were reported as subsequently hospitalized; of the 2737, 527 (19%) were influenza positive. Across all age groups with ILI, school-aged children had the highest percent of influenza infection (29%) and the highest percent of subsequent hospitalizations associated with influenza infection (28%). Influenza viruses co-circulated throughout most years in Vietnam during 2006-2010 and often reached peak levels multiple times during a year, when >20% of tests were influenza positive. Influenza is an important cause of all influenza-like illness and provider reported subsequent hospitalization among outpatients in Vietnam, especially among school-aged children. These findings may have important implications for influenza vaccine policy in Vietnam., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We did a prospective study in southern Vietnam where new water infrastructure was added. New 1,200-L tanks may present potential breeding grounds for Aedes aegypti, particularly when sealed lids were not always supplied. Some householders in these communes received a piped water supply, however there was no reduction in water storage practices. The prevalence of Aedes aegypti immatures in tank and tap households reached 73%, but were non-significantly different from each other and from control households that received no infrastructure. In all three communes, standard jars comprised from 48% to 71% of containers but were associated with > 90% of III-IV instars and pupae on occasions. In contrast, project tanks contributed from 0-21% of the total population. Non-functional or no lids were apparent 4 months after installation in 45-76% of new tanks, but there was no difference between communes with lids and without lids.

Cancer gene therapy involves the replacement of missing or altered genes with healthy ones. In this paper, we have proposed tumor suppressor gene-carrying superparamagnetic iron oxide nanoparticles (SPIONs) for anti-cancer gene therapy. Thermally crosslinked SPIONs (TCL-SPIONs) were conjugated with branched polyethylenimine (PEI 1800 Da) by EDC-NHS chemistry for p53 plasmid DNA delivery. The morphology of the bPEI conjugated TCL-SPIONs (bPEI-TCL-SPION) and pDNA-loaded bPEI-TCL-SPION nanoparticles was measured using transmission electron microscopy (TEM). The particle sizes of the pDNA-loaded bPEI-TCL-SPION nanoparticles were also confirmed by dynamic light scattering, and ranged from 100 to 130 nm, depending on the molar charge ratio. The fluorescently labeled pDNA was complexed with bPEI-TCL-SPION and its intracellular internalization was investigated using confocal microscopy. The p53 plasmid-loaded bPEI-TCL-SPION nanoparticles achieved significantly higher p53 tumor suppressor gene expression and cellular viability compared to positive controls. The expressed wild-type p53 protein suppressed tumor cell proliferation as compared to the mutant control. When transgene expression of the p53 tumor suppressor gene was evaluated at the mRNA level and quantified using real-time PCR, the results were highly dependent on the molar charge ratio (N/P) as well as the cancer cell type. SPIONs internalized within cancer cells were tracked by magnetic resonance (MR) imaging. It was concluded that bPEI-TCL-SPION could be used as efficient gene delivery carriers that can be tracked by MR imaging.

We examined changes in the abundance of immature Aedes aegypti at the household and water storage container level during the dry-season (June-July, 2008) in Tri Nguyen village, central Vietnam. We conducted quantitative immature mosquito surveys of 171 containers in the same 41 households, with replacement of samples, every two days during a 29-day period. We developed multi-level mixed effects regression models to investigate container and household variability in pupal abundance. The percentage of houses that were positive for I/II instars, III/IV instars and pupae during any one survey ranged from 19.5-43.9%, 48.8-75.6% and 17.1-53.7%, respectively. The mean numbers of Ae. aegypti pupae per house ranged between 1.9-12.6 over the study period. Estimates of absolute pupal abundance were highly variable over the 29-day period despite relatively stable weather conditions. Most variability in pupal abundance occurred at the container rather than the household level. A key determinant of Ae. aegypti production was the frequent filling of the containers with water, which caused asynchronous hatching of Ae. aegypti eggs and development of cohorts of immatures. We calculated the probability of the water volume of a large container (>500 L) increasing or decreasing by ≥20% to be 0.05 and 0.07 per day, respectively, and for small containers (<500 L) to be 0.11 and 0.13 per day, respectively. These human water-management behaviors are important determinants of Ae. aegypti production during the dry season. This has implications for choosing a suitable Wolbachia strain for release as it appears that prolonged egg desiccation does not occur in this village.

Aberrant activation of caspase-6 has recently emerged as a major contributor to the pathogeneses of neurodegenerative disorders such as Alzheimer's and Huntington disease. Commercially available assays to measure caspase-6 activity commonly use the VEID peptide as a substrate. However these methods are not well suited to specifically assess caspase-6 activity in the presence of other, confounding protease activities, as often encountered in cell and tissue samples. Here we report the development of a method that overcomes this limitation by using a protein substrate, lamin A, which is highly specific for caspase-6 cleavage at amino acid 230. Using a neo-epitope antibody against cleaved lamin A, we developed an electrochemiluminescence-based ELISA assay that is suitable to specifically detect and quantify caspase-6 activity in highly apoptotic cell extracts. The method is more sensitive than VEID-based assays and can be adapted to a high-content imaging platform for high-throughput screening. This method should be useful to screen for and characterize caspase-6 inhibitor compounds and other interventions to decrease intracellular caspase-6 activity for applications in neurodegenerative disorders.

Although quantitative surveillance data for immature stages of Aedes aegypti are often used to prioritize containers or specific types of containers for control, the relationship between immature and emergent adult populations under field conditions is largely unknown. We examined the relationships between abundance of III/IV instars and pupae, and emerging adult population for a series of water storage containers in southern Vietnam. A large proportion of III/IV instars failed to progress to adulthood, and the relationships between III/IV instars and adults were poor. Collected IV instars appeared to be nutritionally deprived, although their size and nutrient levels were not reliable indicators of emergence success. Conversely, pupal abundance was a good indicator of emerging adult populations, especially over the ensuing 48-h period. Although there were clear advantages of pupal surveillance over surveillance of III/IV instars for the estimation of adult mosquito productivity, there were practical limitations associated with the enumeration of pupae, and their comparatively low densities may preclude the identification of potentially productive containers.

Community-based perceptions and behaviour around water source preference, household water storage patterns and water use, and householders' knowledge and behaviour with respect to dengue etiology and transmission, were examined in three communes located in the Mekong Delta area in southern Vietnam. Through focus group discussions, most participants identified poorly screened or uncovered water containers (including household water storage containers and other types of artificial containers) as habitats for mosquitoes that transmit dengue viruses, and thereby demonstrated a clear understanding of the links between household water storage practices and the threat of dengue. Our qualitative analyses also revealed broader community-based concerns about the limited availability of water and strong preferences for storage of rainwater based upon perceptions of cost, quality and security of supply. These perceptions are central to shaping householders' responses to water infrastructure projects. The limited availability of water during the dry season and insufficient numbers of water storage containers are over-riding community concerns which provide an important context to understanding community behaviours and responses to public health interventions against dengue. Such concerns are important precursors to selecting the type of intervention.

Nucleic acids can be complexed with cationic polymer to form DNA nanoparticles (polyplex) which are then immobilized on the surface coated extracellular matrix protein (ECM), the process termed as reverse transfection. ECM-containing proteins provide a surface for cell attachment and sustain the release of polyplexes from their surface, thereby inducing transgene expression for prolonged period of time. Consequently, long-term expression of the desired protein can be achieved with the smaller amount of required DNA, as compared to bolus delivery. First of all, we investigated the different ECM components as a coating material and the range of optimal coating density in different ECM was examined for enhanced transfection to neighboring cells. Reporter genes such as luciferase (luc) and enhanced green fluorescent protein (eGFP) were initially used to quantitate transfection efficiencies from polyplex from the coated ECMs of Collagen type I (Col I), fetal bovine serum protein (FBS), bovine serum albumin (BSA). DNA was complexed with positively charged polyethyleneimine (PEI) at N/P ratio 9. Our initial work exhibited that, in the case of both NIH/3T3 cell line and bone marrow stromal (D1) cell line, Col I facilitated the greatest cell adhesion compared to the other coating proteins and 0.5 microg/cm2 of Col I coating density resulted in highest transfection efficiency. On the other hand, comparison of reverse delivery system with atelocollagen-I have shown that reverse delivery system to yield ten times higher transfection efficiency than atelocollagen-PEI/DNA delivery system and one hundred times higher than atelocollagen-naked plasmid delivery system. Moreover, the amount of DNA used for reverse delivery system was much lower than the other systems. This methodology would be applied to induce cellular differentiation in 3-dimensional scaffold after coating scaffolds with genes inducing the differentiation in the nanoparticle formulation. Our final goal is to search for the optimal conditions for the differentiation of stem cells to specific cell types.

There is a high incidence of pediatric asthma in Vietnam, but little lung function data are available. The aim of the study was to compare respiratory resistance (Rrs), reactance (Xrs), and responses to salbutamol between asthmatic and healthy primary school children in Hanoi. Because respiratory mechanics vary along the breathing cycle, measurements were assessed separately in inspiration (Rrsi, Xrsi) and expiration (Rrse, Xrse).Inpatients with doctor-diagnosed asthma were measured 2-3 days following admission using the forced oscillation technique (FOT) at a single frequency (8 Hz). Z-scores and responses to salbutamol were compared between 102 asthmatics and 98 controls, and accuracy of group classification by FOT parameters was assessed by Youden index, an indicator to the proportion of subjects correctly classified in each group.In asthmatics versus controls, Rrsi-but not Rrse-was significantly larger and both Xrsi and Xrse were significantly more negative (P < 0.01). Both Rrs and Xrs responses to salbutamol were significantly larger in asthmatics than controls (P < 0.001). Youden indexes indicated response to salbutamol generally had better diagnostic values than Z-scores and was best discriminative first with Rrsi, then with Xrse.It is concluded that different FOT characteristics may be described in asthmatic and healthy Vietnamese children. The diagnostic value of each parameter depends upon the breathing cycle. Most useful in practice probably is the response to salbutamol measured by Rrsi.

In 2006, national influenza surveillance was implemented in Vietnam. Epidemiologic and demographic data and a throat swab for influenza testing were collected from a subset of outpatients with influenza-like illness (ILI). During January 1, 2006 through December 31, 2007, of 184,521 ILI cases identified at surveillance sites, 11,082 were tested and 2112 (19%) were positive for influenza by reverse transcription polymerase chain reaction. Influenza viruses were detected year-round, and similar peaks in influenza activity were observed in all surveillance regions, coinciding with cooler and rainy periods. Studies are needed to ascertain the disease burden and impact of influenza in Vietnam.

Pyrethroid resistance is envisioned to be a major problem for the vector control program since, at present, there are no suitable chemical substitutes for pyrethroids. Cross-resistance to knockdown agents, which are mainly used in mosquito coils and related products as spatial repellents, is the most serious concern. Since cross-resistance is a global phenomenon, we have started to monitor the distribution of mosquito resistance to pyrethroids. The first pilot study was carried out in Vietnam. We periodically drove along the national road from the north end to the Mekong Delta in Vietnam and collected mosquito larvae from used tires. Simplified susceptibility tests were performed using the fourth instar larvae of Aedes aegypti, Aedes albopictus, and Culex quinquefasciatus. Compared with the other species, Ae. aegypti demonstrated the most prominent reduction in susceptibility. For Ae. aegypti, significant increases in the susceptibility indices with a decrease in the latitude of collection points were observed, indicating that the susceptibility of Ae. aegypti against d-allethrin was lower in the southern part, including mountainous areas, as compared to that in the northern part of Vietnam. There was a significant correlation between the susceptibility indices in Ae. aegypti and the sum of annual pyrethroid use for malaria control (1998-2002). This might explain that the use of pyrethroids as residual treatment inside houses and pyrethroid-impregnated bed nets for malaria control is attributable to low pyrethroid susceptibility in Ae. aegypti. Such insecticide treatment appeared to have been intensively administered in the interior and along the periphery of human habitation areas where, incidentally, the breeding and resting sites of Ae. aegypti are located. This might account for the strong selection pressure toward Ae. aegypti and not Ae. albopictus.

A high incidence of childhood asthma has been reported in Ha Noi, Viet Nam, indicating a need to document lung function in these children. The degree of airway obstruction and reversibility may be evaluated from the forced oscillation assessment of respiratory resistance to reactance (Rrs, Xrs). Appropriate controls are necessary for a proper interpretation of patients. The aim of the study was to provide reference values on Rrs and Xrs and response to salbutamol in healthy Vietnamese children. One hundred seventy-five children aged 6-11 year recruited from one public school in Ha Noi were studied. Measurements were obtained at baseline and after 200 microg inhaled salbutamol. Significant correlations were disclosed between Rrs or Xrs and standing height (P < 0.0001). Salbutamol significantly decreased Rrs (from 7.1 +/- 1.9 hPa.sec/L to 6.2 +/- 1.8 hPa sec/L, P < 0.0001) and increased Xrs (from -1.22 +/- 0.64 to -0.91 +/- 0.61 hPa.sec/L, P < 0.0001). Rrs response to salbutamol lower limit of 95% confidence interval was -38% from baseline Rrs and, Xrs upper limit was +16% from baseline impedance. It is concluded that reference values for respiratory impedance (Zrs) and thresholds for clinically relevant response to bronchodilator are provided in primary school Vietnamese children. A smaller slope for the observed Rrs-body height relationship is suggested with reference to relevant studies in healthy Caucasians., ((c) 2008 Wiley-Liss, Inc.)

Changes in lung function after exercise in healthy primary school children have mostly been described in field studies. More complete description and insight into relevant mechanisms may be provided in lung function laboratory. The aim was to describe airway caliber and response to deep inhalation (DI) after exercise in healthy primary school children. Respiratory resistance (Rrs) by the forced oscillation technique and spirometry were measured before and after exercise in 50 healthy primary school children. The Rrs response to DI was assessed in 31 subjects, assuming a significantly larger decrease in Rrs after exercise would attest relief of exercise-induced airway smooth muscle contraction. Measurements were taken before, 5 min (E5) and 15 min (E15) after exercise. Significantly larger Rrs and lower forced expiratory volume in 0.5 s were observed at E5 versus baseline or E15 (p < 0.05). DI induced significant decrease in Rrs (p = 0.01) that was not different between E5 and baseline. Healthy primary school children exhibit changes in Rrs and spirometry after exercise indicating small but significant airway narrowing. The response to DI similar at baseline and E5 suggests airway narrowing from hyperemia in the bronchial wall rather than airway smooth muscle constriction.