Environmental contamination with Clostridioides (Clostridium) difficile in Vietnam.

AIMS: To investigate the prevalence, molecular type, and antimicrobial susceptibility of Clostridioides difficile in the environment in Vietnam, where little is known about C. difficile. METHODS AND RESULTS: Samples of pig faeces, soils from pig farms, potatoes, and the hospital environment were cultured for C. difficile. Isolates were identified and typed by polymerase chain reaction (PCR) ribotyping. The overall prevalence of C. difficile contamination was 24.5% (68/278). Clostridioides difficile was detected mainly in soils from pig farms and hospital soils, with 70%-100% prevalence. Clostridioides difficile was isolated from 3.4% of pig faecal samples and 5% of potato surfaces. The four most prevalent ribotypes (RTs) were RTs 001, 009, 038, and QX574. All isolates were susceptible to metronidazole, fidaxomicin, vancomycin, and amoxicillin/clavulanate, while resistance to erythromycin, tetracycline, and moxifloxacin was common in toxigenic strains. Clostridioides difficile RTs 001A+B+CDT- and 038A-B-CDT- were predominantly multidrug resistant. CONCLUSIONS: Environmental sources of C. difficile are important to consider in the epidemiology of C. difficile infection in Vietnam, however, contaminated soils are likely to be the most important source of C. difficile. This poses additional challenges to controlling infections in healthcare settings.

Clostridioides (Clostridium) difficile in adults with diarrhoea in Vietnam.

BACKGROUND: Clostridioides (Clostridium) difficile causes antimicrobial-associated diarrhoea, however, presentations may range from asymptomatic carriage to severe diarrhoea, life-threatening toxic megacolon and even death. Reports on C. difficile infection (CDI) in Vietnam remain limited. The objectives of this study were to evaluate the epidemiology, molecular characteristics, and antimicrobial susceptibility of C. difficile isolated from adults with diarrhoea in Vietnam. METHODS: Diarrhoeal stool samples from adult patients aged ≥17 years old were collected at Thai Binh General Hospital in northern Vietnam between March 1, 2021 and February 28, 2022. All samples were transported to The University of Western Australia, Perth, Western Australia for C. difficile culture, toxin gene profiling, PCR ribotyping and antimicrobial susceptibility testing. RESULTS: A total of 205 stool samples were collected from patients aged from 17 to 101 years old. The overall prevalence of C. difficile was 15.1% (31/205) with the recovery of toxigenic and non-toxigenic isolates 9.8% (20/205) and 6.3% (13/205), respectively. Thus 33 isolates were recovered comprising 18 known ribotypes (RTs) and one novel RT (two samples contained two different RTs in each sample). The most prevalent strains were RT 012 (five strains) and RTs 014/020, 017 and QX 070 three strains each. All C. difficile were susceptible to amoxicillin/clavulanate, fidaxomicin, metronidazole, moxifloxacin and vancomycin, while resistance to varying degrees was seen to clindamycin, erythromycin, tetracycline and rifaximin, 78.8% (26/33), 51.5% (17/33), 27.3% (9/33) and 6.1% (2/33), respectively. The prevalence of multidrug resistance was 27.3% (9/33) and multidrug resistance was most common in toxigenic RT 012 and non-toxigenic RT 038 strains. CONCLUSION: The prevalence of C. difficile in adults with diarrhoea and multidrug resistance in C. difficile isolates was relatively high. A clinical assessment to differentiate between CDI/disease and colonisation is required.

Unraveling the Function of Metal-Amorphous Support Interactions in Single-Atom Electrocatalytic Hydrogen Evolution.

Amorphization of the support in single-atom catalysts is a less researched concept for promoting catalytic kinetics through modulating the metal-support interaction (MSI). We modeled single-atom ruthenium (RuSAs ) supported on amorphous cobalt/nickel (oxy)hydroxide (Ru-a-CoNi) to explore the favorable MSI between RuSAs and the amorphous skeleton for the alkaline hydrogen evolution reaction (HER). Differing from the usual crystal counterpart (Ru-c-CoNi), the electrons on RuSAs are facilitated to exchange among local configurations (Ru-O-Co/Ni) of Ru-a-CoNi since the flexibly amorphous configuration induces the possible d-d electron transfer and medium-to-long range p-π orbital coupling, further intensifying the MSI. This embodies Ru-a-CoNi with enhanced water dissociation, alleviated oxophilicity, and rapid hydrogen migration, which results in superior durability and HER activity of Ru-a-CoNi, wherein only 15 mV can deliver 10 mA cm-2 , significantly lower than the 58 mV required by Ru-c-CoNi.

Revealing well-defined cluster-supported bi-atom catalysts for enhanced CO2 electroreduction: a theoretical investigation.

It remains a great challenge to explore high-performance electrocatalysts for the CO2 reduction reaction (CO2RR) with high activity and selectivity. Herein, we employ first principles calculations to systematically investigate an emerging family of extended surface catalysts, bi-atom catalysts (BACs), in which bimetals anchored on graphitic carbon nitride (g-CN), for the CO2RR; and propose a novel framework to boost the CO2RR via incorporation with well-defined clusters. Among 28 BACs, five candidates (Cr2, CrFe, Mn2, MnFe and Fe2/g-CN) are first selected with efficient CO2 activation and favorability for CO2 reduction over H2 evolution. Fe2@g-CN is then served as a superior electrocatalyst for the CO2RR with low limiting potentials (UL) of -0.58 and -0.54 V towards C1 and C2 products. Intriguingly, the CO2RR performance of pure Fe2@g-CN could be controlled by tunable Fe atomic cluster integration. In particular, the presence of an Fe13 cluster could strengthen the CO2 adsorption, effectively deactivate H, and intriguingly break the adsorbate (CO* and CHO*) scaling relation to achieve the distinguished CO2RR with a lowered UL to -0.45 V for the C1 mechanism, which is attributed to the exceptional charge redistribution of bimetals modulated by Fe13. Our findings might open up possibilities for the rational design of BACs towards the CO2RR and other reactions.

Detection of antibiotics in chicken eggs obtained from supermarkets in Ho Chi Minh City, Vietnam.

The residual levels of antibiotics in Vietnamese eggs were monitored from 2014 to 2015. A total of 111 egg packages, distributed by 11 different companies, were collected from supermarkets in Ho Chi Minh City and the levels of 28 antibiotics were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) screening method. Sixteen samples tested positive for antibiotics; a total of eight compounds (enrofloxacin, ciprofloxacin, norfloxacin, sulfadimethoxine, sulfamethazine, sulfamonomethoxine, tilmicosin and trimethoprim) were detected. Enrofloxacin was detected in eight samples, with two samples exhibiting concentrations exceeding 1,000 µg kg-1. Tilmicosin was detected in three samples at a range of 49-568 µg kg-1. We observed that two of the 11 companies frequently sold antibiotic-contaminated eggs (detection rates of 56 and 60%), suggesting that a number of companies do not regulate the use of antibiotics in egg-laying hens. Our findings indicate that livestock farmers require instruction regarding antibiotic use and that continual antibiotic monitoring is essential in Vietnam.

Multilayer immobilizing of denitrifying Bacillus sp. and TiO2-AgNPs on floating expanded clay carrier for co-treatment of nitrite and pathogens in aquaculture.

Nitrite contamination and the spread of pathogens can seriously degrade water quality. To simultaneously control these factors, an innovative approach of fabricating a remediation agent that contained denitrifying bacteria and TiO2-AgNPs co-immobilized on floating expanded clay (EC) was proposed in this study. The EC was fabricated from a mixture of clay and rice husk through pyrolysis at a high temperature of 1200 °C, followed by a rapid cooling step to create a porous structure for the material. TiO2NPs were modified with Ag to shift the absorbance threshold of TiO2-AgNPs into the visible region of 700-800 nm. The experimental results showed that the stirring speed of 250 rpm was suitable for immobilizing TiO2-AgNPs on EC and achieved the highest Ti and Ag content of 639.38 ± 3.04 and 200.51 ± 3.71 ppm, respectively. Coating TiO2-Ag/EC with chitosan (0.5%) significantly reduced the detachment level of immobilized TiO2-AgNPs compared to that of the material with no coating. In particular, this functionalized material inhibited 99.93 ± 0.1% of Vibrio parahaemolyticus pathogen but did not adversely affect the denitrifying bacteria after 2 h of visible light irradiation. Based on the electrostatic bond between oppositely charged polymers, the denitrifying bacteria, Bacillus sp., in alginate solution was successfully immobilized on the chitosan-coated TiO2-Ag/EC with a bacteria density of (76.67 ± 9.43) × 107 CFU g-1, retaining its nitrite removal efficiency at 99.0 ± 0.27% through six treatment cycles. These findings provide solid evidence for further investigating the combination of biodegradation and photodegradation in wastewater treatment.

The Roles of NOTCH3 p.R544C and Thrombophilia Genes in Vietnamese Patients With Ischemic Stroke: Study Involving a Hierarchical Cluster Analysis.

BACKGROUND: The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary disease that causes stroke and other neurological symptoms. OBJECTIVE: We aimed to identify the variants of NOTCH3 and thrombophilia genes, and their complex interactions with other factors. METHODS: We conducted a hierarchical cluster analysis (HCA) on the data of 100 patients diagnosed with ischemic stroke. The variants of NOTCH3 and thrombophilia genes were identified by polymerase chain reaction with confronting 2-pair primers and real-time polymerase chain reaction. The overall preclinical characteristics, cumulative cutpoint values, and factors associated with these somatic mutations were analyzed in unidimensional and multidimensional scaling models. RESULTS: We identified the following optimal cutpoints: creatinine, 83.67 (SD 9.19) µmol/L; age, 54 (SD 5) years; prothrombin (PT) time, 13.25 (SD 0.17) seconds; and international normalized ratio (INR), 1.02 (SD 0.03). Using the Nagelkerke method, cutpoint 50% values of the Glasgow Coma Scale score; modified Rankin scale score; and National Institutes of Health Stroke Scale scores at admission, after 24 hours, and at discharge were 12.77, 2.86 (SD 1.21), 9.83 (SD 2.85), 7.29 (SD 2.04), and 6.85 (SD 2.90), respectively. CONCLUSIONS: The variants of MTHFR (C677T and A1298C) and NOTCH3 p.R544C may influence the stroke severity under specific conditions of PT, creatinine, INR, and BMI, with risk ratios of 4.8 (95% CI 1.53-15.04) and 3.13 (95% CI 1.60-6.11), respectively (Pfisher<.05). It is interesting that although there are many genes linked to increased atrial fibrillation risk, not all of them are associated with ischemic stroke risk. With the detection of stroke risk loci, more information can be gained on their impacts and interconnections, especially in young patients.

Quality assessment of LNP-RNA therapeutics with orthogonal analytical techniques.

The availability of analytical methods for the characterization of lipid nanoparticles (LNPs) for in-vivo intracellular delivery of nucleic acids is critical for the fast development of innovative RNA therapies. In this study, analytical protocols to measure (i) chemical composition, (ii) drug loading, (iii) particle size, concentration, and stability as well as (iv) structure and morphology were evaluated and compared based on a comprehensive characterization strategy linking key physical and chemical properties to in-vitro efficacy and toxicity. Furthermore, the measurement protocols were assessed either by testing the reproducibility and robustness of the same technique in different laboratories, or by a correlative approach, comparing measurement results of the same attribute with orthogonal techniques. The characterization strategy and the analytical measurements described here will have an important role during formulation development and in determining robust quality attributes ultimately supporting the quality assessment of these innovative RNA therapeutics.

Multidimensional Machine Learning for Assessing Parameters Associated With COVID-19 in Vietnam: Validation Study.

BACKGROUND: Machine learning (ML) is a type of artificial intelligence strategy. Its algorithms are used on big data sets to see patterns, learn from their results, and perform tasks autonomously without being instructed on how to address problems. New diseases like COVID-19 provide important data for ML. Therefore, all relevant parameters should be explicitly quantified and modeled. OBJECTIVE: The purpose of this study was to determine (1) the overall preclinical characteristics, (2) the cumulative cutoff values and risk ratios (RRs), and (3) the factors associated with COVID-19 severity in unidimensional and multidimensional analyses involving 2173 SARS-CoV-2 patients. METHODS: The study population consisted of 2173 patients (1587 mild status [mild group] and asymptomatic patients, 377 moderate status patients [moderate group], and 209 severe status patients [severe group]). The status of the patients was recorded from September 2021 to March 2022. Two correlation tests, relative risk, and RR were used to eliminate unbalanced parameters and select the most remarkable parameters. The independent methods of hierarchical cluster analysis and k-means were used to classify parameters according to their r values. Finally, network analysis provided a 3-dimensional view of the results. RESULTS: COVID-19 severity was significantly correlated with age (mild-moderate group: RR 4.19, 95% CI 3.58-4.95; P<.001), scoring index of chest x-ray (mild-moderate group: RR 3.29, 95% CI 2.76-3.92; P<.001; moderate-severe group: RR 3.03, 95% CI 2.4023-3.8314; P<.001), percentage of neutrophils (mild-moderate group: RR 3.18, 95% CI 2.73-3.70; P<.001; moderate-severe group: RR 3.32, 95% CI 2.6480-4.1529; P<.001), quantity of neutrophils (moderate-severe group: RR 3.15, 95% CI 2.6153-3.8025; P<.001), albumin (moderate-severe group: RR 0.46, 95% CI 0.3650-0.5752; P<.001), C-reactive protein (mild-moderate group: RR 3.4, 95% CI 2.91-3.97; P<.001), and ratio of lymphocytes (moderate-severe group: RR 0.34, 95% CI 0.2743-0.4210; P<.001). Significant inversion of correlations among the severity groups is important. Alanine transaminase and leucocytes showed a significant negative correlation (r=-1; P<.001) in the mild group and a significant positive correlation in the moderate group (r=1; P<.001). Transferrin and anion Cl showed a significant positive correlation (r=1; P<.001) in the mild group and a significant negative correlation in the moderate group (r=-0.59; P<.001). The clustering and network analysis showed that in the mild-moderate group, the closest neighbors of COVID-19 severity were ferritin and age. C-reactive protein, scoring index of chest x-ray, albumin, and lactate dehydrogenase were the next closest neighbors of these 3 factors. In the moderate-severe group, the closest neighbors of COVID-19 severity were ferritin, fibrinogen, albumin, quantity of lymphocytes, scoring index of chest x-ray, white blood cell count, lactate dehydrogenase, and quantity of neutrophils. CONCLUSIONS: This multidimensional study in Vietnam showed possible correlations between several elements and COVID-19 severity to provide clinical reference markers for surveillance and diagnostic management.

Association of ADH1B rs1229984, ADH1C rs698, and ALDH2 rs671 with Alcohol abuse and Alcoholic Cirrhosis in People Living in Northeast Vietnam.

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.

Comorbidity Burden and Treatment Patterns of Psoriasis in Vietnam: Real-World Data from the EXPAND Study.

INTRODUCTION: Psoriasis is a multi-faceted, immune-mediated inflammatory disease associated with a wide range of comorbidities. Real-world data on treatment patterns, comorbidities, and economic burden in patients with psoriasis are needed for comprehensive patient care in Vietnam. METHODS: A retrospective chart review study was conducted using secondary data extracted from patients' medical records of two hospitals in Vietnam, with the aim of identifying adult patients with a confirmed diagnosis of psoriasis. The index date was defined as the date of first diagnosis between 1 January 2020 and 31 October 2021. Sociodemographic factors, disease characteristics, comorbidities, medication usage, drug survival, and medication costs were analyzed. RESULTS: A total of 661 patients were identified (mean ± standard deviation [SD] age 43.5 ± 14.8 years). The most prevalent comorbidity was dyslipidemia (49.6% of patients), followed by hypertension (23.4%), and psoriatic arthritis (10.4%). In total, 44% of patients received biologic therapies. Overall, 66.7% and 54.3% of patients receiving biologic and non-biologic therapies, respectively, had ≥ 1 comorbidity. Only 23.2% of patients with psoriasis-related comorbidities stopped therapy with biologics. Biologics had a longer retention time (17.0 months) than non-biologics (6.0 months) in patients with comorbidities. Patients with comorbidities had significantly higher total annual healthcare costs than those without comorbidities (in US dollars: USD901 vs. USD304; p < 0.001), mainly due to the relatively higher costs associated with the use of biologics. CONCLUSION: Patients with psoriasis in Vietnam experience a high disease and economic burden due to comorbidities. Evidence from this real-world study supports the need for routine monitoring of and an appropriate treatment course for psoriasis-related comorbidities.

Depression, anxiety and stress among healthcare workers in the context of the COVID-19 pandemic: a cross-sectional study in a tertiary hospital in Northern Vietnam.

Introduction: The outbreak of coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) had significant effects on the mental well-being in general, particularly for healthcare professionals. This study examined the prevalence of depression, anxiety, and stress, and identified the associated risk factors amongst healthcare workers during the COVID-19 outbreak in a tertiary hospital located in Vietnam. Methods: We conducted a cross-sectional study at a tertiary-level hospital, where the Depression Anxiety and Stress Scale 21 (DASS-21) web-based questionnaire was employed. We analyzed the determinant factors by employing multivariate logistic models. Results: The prevalence of depression, anxiety, and stress symptoms were 19.2%, 24.7%, and 13.9%, respectively. Factors such as engaging in shift work during the pandemic, taking care of patients with COVID-19, and staff's health status were associated with mental health issues among health professionals. In addition, having alternate rest periods was likely to reduce the risk of stress. Conclusion: The prevalence of mental health problems in healthcare workers during the COVID-19 pandemic was relatively high. Having resting periods could potentially mitigate the development of stress among health professionals. Our findings could be taken into account for improving mental health of the health professional population.

SWEET Gene Family in Sugar Beet (Beta vulgaris): Genome-Wide Survey, Phylogeny and Expression Analysis.

<b>Background and Objective:</b> The SWEET (Sugars Will Eventually be Exported Transporter) proteins play important roles in modulating the growth and development processes in plants. However, little information is available on the SWEET family in sugar beet (<i>Beta vulgaris</i>). The objectives of this present study were to genome-wide identify and characterize the BvSWEET family in sugar beet. <b>Materials and Methods:</b> Based on the available genome, proteome and transcriptome databases of sugar beet, various computational tools have been used to analyze the nucleotide and full-length protein sequences of members of the BvSWEET family. <b>Results:</b> A total of 16 members of the BvSWEET family has been identified in sugar beet at the genome-wide scale. Structural analysis indicated that the BvSWEET family exhibited variable characteristics. Furthermore, the BvSWEET family in sugar beet could be categorized into four distinct groups like in other plant species. Of our interest, we found that some <i>BvSWEET</i> genes exhibited strongly preferential expression in major organs/tissues under adverse environmental stimuli. <b>Conclusion:</b> The results provided a comprehensive foundation for further functional characterization of the <i>BvSWEET </i>gene family.

Single Nucleotide Polymorphisms of ADH1B, ADH1C and ALDH2 Genes in 235 People Living in Thai Nguyen Province of Vietnam.

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.

Granulocyte-colony stimulating factor GCSF mobilizes hematopoietic stem cells in Kasai patients with biliary atresia in a phase 1 study and improves short term outcome.

AIMS: In RCT of adults with decompensated cirrhosis, GCSF mobilizes hematopoietic stem cells HSC and improves short-term outcome. An FDA-IND for sequential Kasai-GCSF treatment in biliary atresia BA was approved. This phase 1 study examines GCSF safety in Kasai subjects. Preliminary short-term outcome was evaluated. METHODS: GCSF (Neupogen) at 5 or 10 µg/kg (n = 3/group) was given in 3 daily doses starting on day 3 of Kasai surgery (NCT03395028). Serum CD34+ HSC cell counts, and 1-month of GCSF-related adverse events were monitored. The 6-months Phase 1 clinical outcome was compared against 10 subsequent post Phase 1 Kasai patients who did not receive GCSF. RESULTS: With GCSF, WBC and platelet count transiently increased, LFT and serum creatinine remained stable. Reversible splenic enlargement (by 8.5-20%) occurred in 5/6 subjects. HSC count increased 12-fold and 17.5-fold for the 5 µg/kg and10 ug/kg dose respectively; with respective median total bilirubin levels for GCSF vs no-GCSF groups of 55 vs 91 µM at 1 month, p = 0.05; 15 vs 37 µM at 3 months, p = 0.24); and the 6-months cholangitis frequency of 40% vs 90%, p = 0.077. CONCLUSIONS: GCSF safely mobilizes HSC in Kasai infants and may improve short-term biliary drainage and cholangitis. Phase 2 efficacy outcome of GCSF adjunct therapy for sequential Kasai and GCSF is pending.

Moving beyond bimetallic-alloy to single-atom dimer atomic-interface for all-pH hydrogen evolution.

Single-atom-catalysts (SACs) afford a fascinating activity with respect to other nanomaterials for hydrogen evolution reaction (HER), yet the simplicity of single-atom center limits its further modification and utilization. Obtaining bimetallic single-atom-dimer (SAD) structures can reform the electronic structure of SACs with added atomic-level synergistic effect, further improving HER kinetics beyond SACs. However, the synthesis and identification of such SAD structure remains conceptually challenging. Herein, systematic first-principle screening reveals that the synergistic interaction at the NiCo-SAD atomic interface can upshift the d-band center, thereby, facilitate rapid water-dissociation and optimal proton adsorption, accelerating alkaline/acidic HER kinetics. Inspired by theoretical predictions, we develop a facile strategy to obtain NiCo-SAD on N-doped carbon (NiCo-SAD-NC) via in-situ trapping of metal ions followed by pyrolysis with precisely controlled N-moieties. X-ray absorption spectroscopy indicates the emergence of Ni-Co coordination at the atomic-level. The obtained NiCo-SAD-NC exhibits exceptional pH-universal HER-activity, demanding only 54.7 and 61 mV overpotentials at -10 mA cm-2 in acidic and alkaline media, respectively. This work provides a facile synthetic strategy for SAD catalysts and sheds light on the fundamentals of structure-activity relationships for future applications.

Effect of electrostatic interaction between fluoxetine and lipid membranes on the partitioning of fluoxetine investigated using second derivative spectrophotometry and FTIR.

The interaction between a drug molecule and lipid bilayers is highly important regarding the pharmaceutical activity of the drug. In this study, the interaction of fluoxetine, a well-known selective serotonin reuptake inhibitor antidepressant and lipid bilayers composed of 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was studied from the aspect of electrostatics using second derivative spectrophotometry and Fourier transform infrared spectroscopy (FTIR) in order to provide insights into the drug behavior. Changing pH from 7.4 to 9.5 to increases the neutral state of fluoxetine, the partitioning of fluoxetine into the zwitterionic DPPC large unilamellar vesicles (LUVs) was increased whereas it was reduced into the negatively charged DPPG LUVs. Fluoxetine was found to exhibit a disordering effect on the acyl chains of DPPC and DPPG bilayers upon its partitioning. In addition, increasing concentration of NaCl lessened the binding of fluoxetine into DPPG bilayers due to the reduction in electrostatic attraction between positively charged fluoxetine and negatively charged DPPG LUVs. In addition, the FTIR study revealed that increasing the NaCl concentration could trigger the shift to higher frequency of the CH2 stretching as well as the notable blue shift in the PO2- regions of DPPG, indicating that fluoxetine had deeper penetration into DPPG LUVs. The differences in the NaCl concentration showed a negligible effect on the incorporation of fluoxetine into the zwitterionic DPPC LUVs. In summary, the electrostatic interaction plays an important role on the partitioning of a cationic amphiphilic SSIR drug into the lipid bilayers and the drug partitioning induces the lipids' conformational change. These imply a possible influence on the drug pharmacology.

Antibiotic residue monitoring results for pork, chicken, and beef samples in Vietnam in 2012-2013.

A monitoring plan of residual antibiotics in food of animal origin was conducted in Vietnam from 2012 to 2013. Meat samples were collected from slaughterhouses and retail stores in Ho Chi Minh City and Nha Trang. A total of 28 antibiotics were analyzed using a LC-MS/MS screening method. Sulfonamides, fluoroquinolones, and tilmicosin were detected in some of the samples. Sulfaclozine and fluoroquinolones were mainly detected in chicken samples, and sulfamethazine was mainly detected in pork samples. High levels of sulfonamide residues, ranging between 2500 and 2700 µg/kg sulfaclozine and between 1300 and 3600 µg/kg sulfamethazine, were present in two chicken and three pork samples, respectively. Tilmicosin was detected at ranges of 150-450 µg/kg in 10 chicken samples. Positive percentages were 17.3, 8.8, and 7.4% for chicken, pork, and beef, respectively, for an average of 11.9%. The results suggest an appropriate withdrawal period after drug administration had not been observed in some livestock.

Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.

Sitaxsentan (1) (Wu et al. J. Med. Chem. 1997, 40, 1690) is our first endothelin antagonist being evaluated in clinical trials. It has demonstrated biological effects in an acute hemodynamic study in CHF (Givertz et al. Circulation 2000, 101, 2922), an open-label 20-patient pulmonary hypertension trial (Barst et al. Chest 2002, 121, 1860-1868), and a 31-patient trial in essential hypertension (Calhoun et al. AHA Scientific Sessions 2000). In a phase 2b/3 pulmonary arterial hypertension trial, once a day treatment of 100 mg of sitaxsentan statistically significantly improved 6-min walk distance and NYHA class at 12 weeks (Barst et al. Am. J. Respir. Crit. Care Med. 2004, 169, 441). We have since reported on our efforts in generating follow-up compounds (Wu et al. J. Med. Chem. 1999, 42, 4485) and recently communicated that an ortho acyl group on the anilino ring enhanced oral absorption in this category of compounds (Wu et al. J. Med. Chem. 2001, 44, 1211). Here we report an expansion of this work by substituting a variety of electron-withdrawing groups at the ortho position and evaluating their effects on oral bioavailability as well as structure-activity relationships. As a result, TBC3711 (7z) was identified as our second endothelin antagonist to enter the clinic due to its good oral bioavailability (approximately 100%) in rats, high potency (ET(A) IC(50) = 0.08 nM), and optimal ET(A)/ET(B) selectivity (441 000-fold). Compound 7z has completed phase-I clinical development and was well tolerated with desirable pharmacokinetics in humans (t(1/2) = 6-7 h, oral availability > 80%).