Hydrophobic Coatings with Charge Permeability via Plasma Deposition of Long-Chain Perfluorocarbons.

Hydrophobization of nanotextured catalyst materials is a promising route to enhance the yield of N2 and CO2 conversion into green fuels. However, these applications require a hydrophobic coating to not only promote air trapping but also allow charge transfer at the electrode-electrolyte interface. In this work, nano thin films with thicknesses as low as 7 nm were deposited from the plasma phase of perfluorohexene, perfluorodecene, and perfluorooctane (PFO) precursors using a mild vacuum and gentle powers. Atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) characterization reveal that the resulting films are conformal and hydrophobic thanks to a good retention of CF2 and CF3 moieties. The PFO films exhibited the highest water contact angle and achieved superhydrophobic states when deposited on top of re-entrant nano features, an indication of successful air trapping. Electrochemical studies further demonstrated that the plasma-deposited PFO films allow charge transfer but could only sustain repeated cyclic voltammetry cycles without losing their hydrophobicity when deposited under optimal conditions. This result indicates that plasma deposition could become a viable route for the hydrophobization of electrocatalysts required to enhance the yield of poorly soluble gas reduction reactions.

Facile Preparation Method of TiO2/Activated Carbon for Photocatalytic Degradation of Methylene Blue.

The development of nanocomposite photocatalysts with high photocatalytic activity, cost-effectiveness, a simple preparation process, and scalability for practical applications is of great interest. In this study, nanocomposites of TiO2 Degussa P25 nanoparticles/activated carbon (TiO2/AC) were prepared at various mass ratios of (4:1), (3:2), (2:3), and (1:4) by a facile process involving manual mechanical pounding, ultrasonic-assisted mixing in an ethanol solution, paper filtration, and mild thermal annealing. The characterization methods included XRD, SEM-EDS, Raman, FTIR, XPS, and UV-Vis spectroscopies. The effects of TiO2/AC mass ratios on the structural, morphological, and photocatalytic properties were systematically studied in comparison with bare TiO2 and bare AC. TiO2 nanoparticles exhibited dominant anatase and minor rutile phases and a crystallite size of approximately 21 nm, while AC had XRD peaks of graphite and carbon and a crystallite size of 49 nm. The composites exhibited tight decoration of TiO2 nanoparticles on micron-/submicron AC particles, and uniform TiO2/AC composites were obtained, as evidenced by the uniform distribution of Ti, O, and C in an EDS mapping. Moreover, Raman spectra show the typical vibration modes of anatase TiO2 (e.g., E1g(1), B1g(1), Eg(3)) and carbon materials with D and G bands. The TiO2/AC with (4:1), (3:2), and (2:3) possessed higher reaction rate constants (k) in photocatalytic degradation of methylene blue (MB) than that of either TiO2 or AC. Among the investigated materials, TiO2/AC = 4:1 achieved the highest photocatalytic activity with a high k of 55.2 × 10-3 min-1 and an MB removal efficiency of 96.6% after 30 min of treatment under UV-Vis irradiation (120 mW/cm2). The enhanced photocatalytic activity for TiO2/AC is due to the synergistic effect of the high adsorption capability of AC and the high photocatalytic activity of TiO2. Furthermore, TiO2/AC promotes the separation of photoexcited electron/hole (e-/h+) pairs to reduce their recombination rate and thus enhance photocatalytic activity. The optimal TiO2/AC composite with a mass ratio of 4/1 is suggested for treating industrial or household wastewater with organic pollutants.

Correlation Between Vestibular Disorders and Superior Semicircular Dehiscence on High-resolution Computed Tomography at Tam Anh Ho Chi Minh General Hospital.

Objective: Superior semicircular canal dehiscence (SSCD) is a pathologic condition within the inner ear characterized by various vestibular manifestations. Numerous studies have reported an incidence rate of SSCD ranging from 3.6% to 9% in the general population. The objective of this medical study was to evaluate the prevalence of superior SSCD and investigate its correlation with vestibular symptoms among patients who underwent high-resolution computed tomography (HRCT) scans. To the best of our knowledge, there is limited research and awareness regarding SSCD in Vietnam. In addition, the secondary aim of our investigation is to assess the prevalence of SSCD in Vietnam and compare it with findings from previous studies worldwide. Methods: This retrospective study was conducted at Tam Anh Ho Chi Minh General Hospital from March 2022 to February 2024. Medical records and HRCT scans of the patients were collected. Patients were categorized into two groups: those with and without vestibular disorders. SSCD was defined as the absence of bone overlying the superior semicircular canal facing toward the dura of the middle cranial fossa. Statistical analysis was performed to determine the correlation between vestibular symptoms and the presence of SSCD. Results: A total of 362 patients (including 151 men and 211 women) were recruited. The prevalence of SSCD was 10.2% according to the HRCT scan results. The study found that 18.33% of patients with vestibular disorders had SSCD on HRCT scans, whereas only 6.2% of patients without vestibular disorders exhibited SSCD, indicating a significant association (p-value <0.001). Conclusions: These findings highlight the importance of considering SSCD as a potential etiology in patients presenting with vestibular symptoms and emphasize the diagnostic utility of HRCT.

Outcomes of balloon angioplasty and stent placement for iliac artery lesions classified as TASC II A, B: a single-center study.

Background: Iliac artery stenosis or occlusion is a critical condition that can severely impact a patient's quality of life. The effectiveness of balloon angioplasty and intraluminal stenting for the treatment of iliac artery lesions classified as TASC II A and B was evaluated in this single-center prospective study. Methods: Conducted between October 2016 and September 2020 at Cho Ray Hospital's Vascular Surgery Department, this prospective study involved PAD patients categorized by TASC II A and B classifications who underwent endovascular intervention. Intervention outcomes were assessed peri-procedure and during short-term and mid-term follow-ups. Results: Of the total of 133 patients, 34.6% underwent balloon angioplasty, while 65.4% received stenting. The immediate technical success rate was 97.7%, while the clinical success rate was 62.4%. Complications were minimal, with major limb amputation reported in 1.5% of the cases. There was a significant improvement in Rutherford classification and ABI at short-term follow-up, with a patency rate of 90.2%. The mid-term post-intervention follow-up yielded similar results with an 86.1% patency rate. The mortality rates associated with arterial occlusion were 2.3% during short-term follow-up and 1.7% during mid-term follow-up. Conclusion: Balloon angioplasty and stent placement are effective and safe interventions for TASC II A and B iliac artery occlusions with favorable short and mid-term outcomes. Further, multi-center studies with larger sample sizes are recommended for more comprehensive conclusions, including long-term follow-up assessment.

A 24-year longitudinal study of Klebsiella pneumoniae isolated from patients with bacteraemia and urinary tract infections reveals the association between capsular serotypes, antibiotic resistance, and virulence gene distribution.

Longitudinal studies on the variations of phenotypic and genotypic characteristics of K. pneumoniae across two decades are rare. We aimed to determine the antimicrobial susceptibility and virulence factors for K. pneumoniae isolated from patients with bacteraemia or urinary tract infection (UTI) from 1999 to 2022. A total of 699 and 1,267 K. pneumoniae isolates were isolated from bacteraemia and UTI patients, respectively, and their susceptibility to twenty antibiotics was determined; PCR was used to identify capsular serotypes and virulence-associated genes. K64 and K1 serotypes were most frequently observed in UTI and bacteraemia, respectively, with an increasing frequency of K20, K47, and K64 observed in recent years. entB and wabG predominated across all isolates and serotypes; the least frequent virulence gene was htrA. Most isolates were susceptible to carbapenems, amikacin, tigecycline, and colistin, with the exception of K20, K47, and K64 where resistance was widespread. The highest average number of virulence genes was observed in K1, followed by K2, K20, and K5 isolates, which suggest their contribution to the high virulence of K1. In conclusion, we found that the distribution of antimicrobial susceptibility, virulence gene profiles, and capsular types of K. pneumoniae over two decades were associated with their clinical source.

Effect of Fish Oil and Linseed Oil on Intake, Milk Yield and Milk Fatty Acid Profile in Goats.

This study aimed to evaluate the effect of incorporating linseed oil and fish oil in the diet on intake, ruminal fermentation, milk yield, and milk fatty acid profiles in dairy goats. Four crossbred Saanen lactating goats in mid-lactation and milking 1.30 ± 0.28 g/day were used in a 4 × 4 Latin square design. The basal diet contained concentrate and Para grass (C:F 40:60). Treatments included a basal diet without oil supplementation (Ctrl) or with 2.5% linseed oil (LO2.5), 2.5% linseed oil and fish oil (3:2, w/w, LFO2.5), and 4.16% linseed oil and fish oil (3:2, w/w, LFO4.16). Diets had no effect on intake, milk yield, milk composition, or ruminal fermentation (p > 0.05). Compared with Ctrl, lower (p < 0.05) proportions of C10:0-C14:0 in milk fat were observed with LFO4.16. Compared with the Ctrl and linseed oil added alone, feeding LFO4.16 led to a greater (p < 0.01) concentration of C18:1 t11. Compared with both the Ctrl and LO2.5 diets, milk c9,t11 CLA was 4.53 and 2.94 times greater with the LFO4.16 diet. Compared with Ctrl and LO2.5 diets (0.06% and 0.08%), goats fed LFO2.5, and LFO4.16 had greater (p < 0.001) concentrations of C22:6n-3 (0.63% and 0.87%). Overall, the combined data suggested that including 4.16% linseed oil and fish oil in the diet of dairy goats was effective in improving the concentrations of health-promoting fatty acids in milk without affecting milk production.

Genome-based characterization of conjugative IncHI1B plasmid carrying carbapenemase genes blaVIM-1, blaIMP-23, and truncated blaOXA-256in Klebsiella pneumoniae NTU107224.

The wide dissemination of plasmids carrying antibiotic resistance determinants among bacteria is a severe threat to global public health. Here, we characterized an extensively drug-resistant (XDR) Klebsiella pneumoniae NTU107224 by whole genome sequencing (WGS) in combination with phenotypic tests. Broth dilution method was used to determine the minimal inhibitory concentrations (MICs) of NTU107224 to 24 antibiotics. The whole genome sequence of NTU107224 was determined by Nanopore/Illumina hybrid genome sequencing. Conjugation assay was performed to determine the transferability of plasmids in NTU107224 to recipient K. pneumoniae 1706. Larvae infection model was used to determine the effect(s) of conjugative plasmid pNTU107224-1 on bacterial virulence. Among the 24 antibiotics tested, XDR K. pneumoniae NTU107224 had low MICs only for amikacin (≤1 µg/mL), polymyxin B (0.25 µg/mL), colistin (0.25 µg/mL), eravacycline (0.25 µg/mL), cefepime/zidebactam (1 µg/mL), omadacycline (4 µg/mL), and tigecycline (0.5 µg/mL). Whole genome sequencing showed that the closed NTU107224 genome comprises a 5,076,795-bp chromosome, a 301,404-bp plasmid named pNTU107224-1, and a 78,479-bp plasmid named pNTU107224-2. IncHI1B plasmid pNTU107224-1 contained three class 1 integrons accumulated various antimicrobial resistance genes (including carbapenemase genes blaVIM-1, blaIMP-23, and truncated blaOXA-256) and the blast results suggested the dissemination of IncHI1B plasmids in China. By day 7 after infection, larvae infected with K. pneumoniae 1706 and transconjugant had 70% and 15% survival rates, respectively. We found that the conjugative plasmid pNTU107224-1 is closely related to IncHI1B plasmids disseminated in China and contributes to the virulence and antibiotic resistance of pathogens.

Targeting Olokizumab-Interleukin 6 interaction interface to discover novel IL-6 inhibitors.

The IL-6/IL-6R or IL-6/GP130 protein-protein interactions play a significant role in controlling the development of chronic inflammatory diseases, such as rheumatoid arthritis, Castleman disease, psoriasis, and, most recently, COVID-19. Modulating or antagonizing protein-protein interactions of IL6 binding to its receptors by oral drugs promises similar efficacy to biological therapy in patients, namely monoclonal antibodies. In this study, we used a crystal structure of the Fab part of olokizumab in a complex with IL-6 (PDB ID: 4CNI) to uncover starting points for small molecule IL-6 antagonist discovery. Firstly, a structure­based pharmacophore model of the protein active site cavity was generated to identify possible candidates, followed by virtual screening with a significant database Drugbank. After the docking protocol validation, a virtual screening by molecular docking was carried out and a total of 11 top hits were reported. Detailed analysis of the best scoring molecules was performed with ADME/T analysis and molecular dynamics simulation. Furthermore, the Molecular Mechanics-Generalized Born Surface Area (MM/GBSA) technique has been utilized to evaluate the free binding energy. Based on the finding, one newly obtained compound in this study, namely DB15187, may serve as a lead compound for the discovery of IL-6 inhibitors.Communicated by Ramaswamy H. Sarma.

In silico approach to identify novel allosteric intracellular antagonist for blocking the interleukin-8/CXCR2 receptor signaling pathway.

The role of interleukin-8 (IL-8) and its receptor CXCR2 in inflammatory responses and tumor development and progression has been well documented. Our study aims to discover novel compounds as CXCR2 antagonists to block the IL-8 signaling pathway using an in silico drug design. Herein, a structure-based pharmacophore model was developed based on the crystal structure of inactive CXCR2 in a complex with an allosteric inhibitor. This model was validated and refined, followed by virtual screening with the ZINC15 database. Subsequent molecular docking allows for predicting the best pose of a ligand inside a receptor binding site. We found that the 35 top-ranked hits exhibited docking scores from -30.81 to -25.28 kJ/mol and better interaction potential comparing the reference inhibitor. Analysis of ADME and toxicity properties revealed the efficacy and safety of the selected seven compounds. To validate the stability of the protein-ligand complex structure MD simulations approach has also been performed and confirmed via the critical parameters. The MD results explained that the CXCR2 receptor bound with two best-proposed molecules, including ZINC77105530 and ZINC93176465, was quite stable states as observed from low RMSD, RMSF, Rg, SASA values, and high occupancy of the interaction types. Finally, our data identified that these compounds play as potential inhibitors of IL-8 signaling pathways with the MM/GBSA binding free energies of -41.77 ± 6.45 kcal/mol and -38.84 ± 6.16 kcal/mol, respectively.Communicated by Ramaswamy H. Sarma.

Identification of small molecules as potential inhibitors of interleukin 6: a multi-computational investigation.

IL(interleukin)-6 is a multifunctional cytokine crucial for immunological, hematopoiesis, inflammation, and bone metabolism. Strikingly, IL-6 has been shown to significantly contribute to the initiation of cytokine storm-an acute systemic inflammatory syndrome in Covid-19 patients. Recent study has showed that blocking the IL-6 signaling pathway with an anti-IL-6 receptor monoclonal antibody (mAb) can reduce the severity of COVID-19 symptoms and enhance patient survival. However, the mAb has several drawbacks, such as high cost, potential immunogenicity, and invasive administration due to the large-molecule protein product. Instead, these issues could be mitigated using small molecule IL-6 inhibitors, but none are currently available. This study aimed to discover IL-6 inhibitors based on the PPI with a novel camelid Fab fragment, namely 68F2, in a crystal protein complex structure (PDB ID: 4ZS7). The pharmacophore models and molecular docking were used to screen compounds from DrugBank databases. The oral bioavailability of the top 24 ligands from the screening was predicted by the SwissAMDE tool. Subsequently, the selected molecules from docking and MD simulation illustrated a promising binding affinity in the formation of stable complexes at the active binding pocket of IL-6. Binding energies using the MM-PBSA technique were applied to the top 4 hit compounds. The result indicated that DB08402 and DB12903 could form strong interactions and build stable protein-ligand complexes with IL-6. These potential compounds may serve as a basis for further developing small molecule IL-6 inhibitors in the future.

Mortality benefits of reduction fine particulate matter in Vietnam, 2019.

Introduction and objectives: Studies assessing the health benefits of air pollution reduction in Vietnam are scarce. This study quantified the annual mortality burden due to PM2.5 pollution in Vietnam above the World Health Organization recommendation for community health (AQG: 5 µg/m3) and the proposed National Technical Regulation on Ambient Air Quality (proposed QCVN: 15 µg/m3). Methodology: This study applied a health impact assessment methodology with the hazard risk function for non-communicable diseases (NCDs) and lower respiratory infections (LRIs) in the Global Exposure Mortality Model (GEMM) to calculate attributable deaths, Years of Life lost, and Loss of Life expectancy at birth due to air pollution in the Vietnamese population above 25 years of age in 11 provinces. We obtained annual average PM2.5 concentrations for Vietnam in 2019 at a 3x3 km grid modeled using Mixed Linear regression and multi-data sources. Population and baseline mortality data were obtained from administrative data system in Vietnam. We reported the findings at both the provincial and smaller district levels. Results: Annual PM2.5 concentrations in all studied provinces exceeded both the AQG and the proposed QCVN. The maximum annual number of attributable deaths in the studied provinces if they had complied with WHO air quality guidelines was in Ha Noi City, with 5,090 (95%CI: 4,253-5,888) attributable deaths. At the district level, the highest annual rate of attributable deaths if the WHO recommendation for community health had been met was 104.6 (95%CI: 87.0-121.5) attributable deaths per 100,000 population in Ly Nhan (Ha Nam province). Conclusion: A much larger number of premature deaths in Vietnam could potentially be avoided by lowering the recommended air quality standard. These results highlight the need for effective clean air action plans by local authorities to reduce air pollution and improve community health.

Severe chronic cough relating to post-COVID-19 interstitial lung disease: a case report.

Cough is a common symptom occurring in patients with acute coronavirus disease 2019 (COVID-19) infection as well as during the post-COVID-19 period. The post-COVID-19 cough can improve over time and the incidence of sustained post-COVID-19 chronic cough is low. Approaching post-COVID-19 cough is challenging to clinicians including pulmonologists and allergists due to a diverse set of etiologies and the lack of published guidance on effective treatments. A 60-year-old male ex-smoker presented to the outpatient long COVID-19 clinic because of a prolonged cough for 4 months after a severe COVID-19 infection. His cough was so violent that he had suffered a spontaneous pneumothorax on 2 occasions. In addition, he also complained of exertional breathlessness. Due to concerns over ongoing systemic inflammation from COVID-19 or thromboembolism, a serum C-reactive protein and d-dimer where checked and were normal. Chest computed tomography (CT) images revealed diffuse ground glass opacities combined with scattered emphysema in the bilateral upper lobes and several small bullae located close to the pleura. His diagnosis was post-COVID-19 interstitial lung disease (ILD) and he was treated with methylprednisolone 32 mg/day. After 2 weeks of treatment, he showed improvement with near cessation of cough and a significant decline in dyspnea. The follow-up chest CT also showed improvement in the ground glass opacities. Severe chronic cough could be a manifestation of post-COVID-19 ILD. This case demonstrates the use of systemic corticosteroid to improve both post-COVID-19 ILD and its associated chronic cough.

Bringing Sectors Together in Da Nang, Vietnam: Participatory Systems Mapping.

The USAID-funded Building Healthy Cities (BHC) work in Da Nang, Vietnam, engaged 108 multi-sector stakeholders to gather qualitative data across two workshops and three citizen town halls from 2019 to 2021. These data were synthesized with the results from BHC's seven other activities in Da Nang to build systems maps. Contextual findings showed that multi-sector, multi-level participation and collaboration have been the key to moving the city toward their smart and livable city goals. Currently, citizen, nongovernmental organization, and private sector collaboration are low for many government sectors, which results in policy and programs that are mismatched to actual needs and therefore have less powerful impacts. When these policies and programs are implemented, they struggle to demonstrate strong benefits to these stakeholder groups, further decreasing participation. This is central to the systems map that BHC developed, and is expanded upon through additional patterns that fall within four main areas: management quality; vision and leadership; workforce capacity; and community engagement. Stakeholders found four key leverage points within this context that, if included in every action, could help overcome barriers. These leverage opportunities are: (1) investing at all levels; (2) improving function and innovation of information technology; (3) increasing participation and feedback; and (4) creating more responsive policy. As BHC concludes activities in Da Nang, local university students will be trained on systems mapping techniques to embed systems thinking skills into the next generation of workforce, and a set of recommendations will be developed to share with the government to act on these findings.

PRMT1 suppresses doxorubicin-induced cardiotoxicity by inhibiting endoplasmic reticulum stress.

Doxorubicin (Dox) is a widely used anti-cancer drug that has a significant limitation, which is cardiotoxicity. Its cardiotoxic side effect is dose dependent and occurs through any age. Dox has been known to exert its toxic effect through oxidative stress, but an emerging mechanism is endoplasmic reticulum (ER) stress that activates proapoptotic pathway involving PERK/ATF4/CHOP axis. These stresses lead to dysfunction of myocardium associated with cell death. Although accumulating evidence support their involvement to Dox-induced cardiotoxicity, the mechanism is not well elucidated. Protein arginine methyltransferases 1 (PRMT1) has been known to play a role in cardiomyocyte cell survival through modulation of ER response. In this study, we demonstrate an important role of PRMT1 in Dox-induced cardiotoxicity via ER stress. Depletion of PRMT1 in H9c2 cardiomyocytes enhanced Dox-stimulated cell death, and increased reactive oxygen species (ROS) production and DNA damage by enhancing the levels of proapoptotic cleaved Caspase-3 and γH2AX in response to Dox. Consistently, overexpression of PRMT1 attenuated the apoptotic effect of Dox. In addition, the acute treatment of Dox induced a substantial increase in PRMT1 activity and the translocation of PRMT1 to ER. Overexpression of PRMT1 in cardiomyocyte diminished Dox-induced ER stress, and ATF4 methylation by PRMT1 was involved in the suppression of ER stress. Taken together, our data suggest that PRMT1 is a novel target molecule for protection from Dox-induced cardiotoxicity.

Allele and Haplotype Frequencies of HLA-A, -B, -C, and -DRB1 Genes in 3,750 Cord Blood Units From a Kinh Vietnamese Population.

The frequencies and diversities of human leukocyte antigen (HLA) alleles and haplotypes are representative of ethnicities. Matching HLA alleles is essential for many clinical applications, including blood transfusion, stem cell transplantation, and tissue/organ transplantation. To date, the information about the frequencies and distributions of HLA alleles and haplotypes among the Kinh Vietnamese population is limited because of the small sample size. In this study, more than 3,750 cord blood units from individuals belonging to the Kinh Vietnamese population were genotyped using PCR sequence-specific oligonucleotide (PCR-SSO) for HLA testing. The results of the study demonstrated that the most frequently occurring HLA-A, -B, -C, and -DRB1 alleles were A*11:01 (25%), A*24:02 (12.3%), A*02:01 (11.2); A*03:03 (8.95%), A*02:03 (7.81%), A*29:01 (7.03%); B*15:02 (15.1%), B*46:01 (10.7%), B*58:01 (7.65%), B*38:02 (7.29%); C*08:01 (17.2), C*07:02 (16.2%), C*01:02 (15.2), C*03:02 (8.3%), C*15:05 (6.13); DRB1*12:02 (31.0%), DRB1*09:01 (10.47%), DRB1*15:02 (7.54%); DRB1*07:01 (6.68%), DRB1*10:01 (6.63%), respectively, with the highest allele diversity level observed in locus B (93 alleles). The most frequent haplotypes of two-locus combinations of HLA-A-B, HLA-A-C, HLA-A-DRB1, HLA-B-C, HLA-B-DRB1, and HLA-C-DRB1 haplotypes were A*11:01-B*15:02 (7.63%), A*11:01-C*08:01 (7.98%), A*11:01-DRB1*12:02 (10.56%), B*15:02-C*08:01 (14.0%), B*15:02-DRB1*12:02 (10.47%), and C*08:01-DRB1*12:02 (11.38%), respectively. In addition, the most frequent haplotypes of three- and four-locus sets of HLA-A-B-C, HLA-A-B-DRB1, HLA-A-C-DRB1, HLA-B-C-DRB1, and HLA-A-B-C-DRB1 were A*11:01-B*15:02-C*08:01 (7.57%), A*11:01-B*15:02-DRB1*12:02 (5.39%), A*11:01-C*08:01-DRB1*12:02 (5.54%), B*15:02-C*08:01-DRB1*12:02 (10.21%), and A*11:01-B*15:02-C*08:01-DRB1*12:02 (5.45%), respectively. This study provides critical information on the frequencies and distributions of HLA alleles and haplotypes in the Kinh Vietnamese population, accounting for more than 85% of Vietnamese citizens. It paves the way to establish an umbilical cord blood bank for cord blood transplantation programs in Vietnam.

Synthesis and characterization of some novel polythiophene derivatives containing pyrazoline.

Eight polythiophene derivatives containing pyrazoline side groups were synthesized by a chemical oxidative coupling polymerization using FeCl3. The crystal structures of four monomers were determined which confirm the almost perpendicular orientation of the thiophene and pyrazoline rings, while the other substituents are more coplanar. Analyses of IR, 1H-NMR, Raman and UV-Vis spectra demonstrated that the suggested polymerization was successful to generate the synthesized polythiophenes with the expected structures. The morphology of the synthesized polythiophenes was studied by SEM. The different substituents attached to the 1- and 3-positions of the pyrazoline side chain led to differences in optical properties, electrical conductivity, and thermal stability of the synthesized polythiophenes. By adding a pyrazoline side chain to polythiophenes, some polymers achieve good solubility, electrical conductivity of about 1.3 × 10-6 S/cm, high fluorescence intensity (above 40,000 a.u.) at 505-550 nm and thermal stability up to 590°C in the air.

Whole-genome-sequence-based characterization of an NDM-5-producing uropathogenic Escherichia coli EC1390.

BACKGROUND: Urinary tract infection (UTI) is one of the most common outpatient bacterial infections. In this study, we isolated and characterized an extensively-drug resistant (XDR) NDM-5-producing Escherichia coli EC1390 from a UTI patient by using whole-genome sequencing (WGS) in combination with phenotypic assays. METHODS: Antimicrobial susceptibility to 23 drugs was determined by disk diffusion method. The genome sequence of EC1390 was determined by Nanopore MinION MK1C platform. Conjugation assays were performed to test the transferability of EC1390 plasmids to E. coli recipient C600. Phenotypic assays, including growth curve, biofilm formation, iron acquisition ability, and cell adhesion, were performed to characterize the function of EC1390 plasmids. RESULTS: Our results showed that EC1390 was only susceptible to tigecycline and colistin, and thus was classified as XDR E. coli. A de novo genome assembly was generated using Nanopore 73,050 reads with an N50 value of 20,936 bp and an N90 value of 7,624 bp. WGS analysis showed that EC1390 belonged to the O101-H10 serotype and phylogenetic group A E. coli. Moreover, EC1390 contained 2 conjugative plasmids with a replicon IncFIA (pEC1390-1 with 156,286 bp) and IncFII (pEC1390-2 with 71,840 bp), respectively. No significant difference was observed in the bacterial growth rate in LB broth and iron acquisition ability between C600, C600 containing pEC1390-1, C600 containing pEC1390-2, and C600 containing pEC1390-1 and pEC1390-2. However, the bacterial growth rate in nutrition-limited M9 broth was increased in C600 containing pEC1390-2, and the cell adhesion ability was increased in C600 containing both pEC1390-1 and pEC1390-2. Moreover, these plasmids modulated the biofilm formation under different conditions. CONCLUSIONS: In summary, we characterized the genome of XDR-E. coli EC1390 and identified two plasmids contributing to the antimicrobial resistance, growth of bacteria in a nutrition-limited medium, biofilm formation, and cell adhesion.

A Longitudinal Nine-Year Study of the Molecular Epidemiology of Carbapenemase-Producing Enterobacterales Isolated From a Regional Hospital in Taiwan: Predominance of Carbapenemase KPC-2 and OXA-48.

Enterobacterales clinical isolates are now being resistant to clinically achievable concentrations of most commonly used antibiotics that makes treatment of hospitalized patients very challenging. We hereby determine the molecular characteristics of carbapenemase genes in carbapenem-resistant Enterobacterales (CRE) isolates in Taiwan. A total of 455 CRE isolates were identified between August 2011 to July 2020. Minimum inhibitory concentrations for selected carbapenems were tested using Vitek 2, and carbapenemase genes were determined using polymerase chain reaction in combination with sequencing. Phenotypic detection of carbapenemase was determined by modified carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM) to validate our PCR screening results. Pulsed-field gel electrophoresis (PFGE) was used to determine the clonality of carbapenemase-producing Enterobacterales (CPE) isolates, and the transferability of carbapenemase-carrying plasmids was determined by conjugation assays. A slight increase in carbapenem-resistant E. coli (CREC) was observed, however, the prevalence of carbapenem-resistant K. pneumoniae (CRKP) was steady, during 2011-2020. The dominant species among our CRE was K. pneumoniae (270/455, 59.3%), followed by E. coli (81/455, 17.8%), Morganella morganii (32/455, 7.0%), and Enterobacter cloacae (25/455, 5.5%). From 2011 to 2020, the total percentage of CPE increased steadily, accounting for 61.0% of CRE in 2020. Moreover, 122 of 455 CRE isolates (26.8%) were CPE. Among the CPE isolates, the dominant carbapenemase gene was bla OXA-48-like (54/122, 44.3%), and the second most common carbapenemase gene was bla KPC-2 (47/122, 38.5%). The sensitivity and specificity for mCIM to detect carbapenemase in the 455 isolates were both 100% in this study. The PFGE results showed that 39 carbapenemase-producing E. coli and 69 carbapenemase-producing K. pneumoniae isolates carrying bla KPC-2 and/or bla NDM-5 could be classified into 5 and 12 clusters, respectively. In conclusion, our results showed an increase in CPE isolates in Taiwan. Moreover, the distribution of carbapenemase and antimicrobial susceptibility in CPE were associated with PFGE typing.

An ancient truncated duplication of the anti-Müllerian hormone receptor type 2 gene is a potential conserved master sex determinant in the Pangasiidae catfish family.

The evolution of sex determination (SD) in teleosts is amazingly dynamic, as reflected by the variety of different master sex-determining genes identified. Pangasiids are economically important catfishes in South Asian countries, but little is known about their SD system. Here, we generated novel genomic resources for 12 Pangasiids and characterized their SD system. Based on a Pangasianodon hypophthalmus chromosome-scale genome assembly, we identified an anti-Müllerian hormone receptor type Ⅱ gene (amhr2) duplication, which was further characterized as being sex-linked in males and expressed only in testes. These results point to a Y chromosome male-specific duplication (amhr2by) of the autosomal amhr2a. Sequence annotation revealed that the P. hypophthalmus Amhr2by is truncated in its N-terminal domain, lacking the cysteine-rich extracellular part of the receptor that is crucial for ligand binding, suggesting a potential route for its neofunctionalization. Reference-guided assembly of 11 additional Pangasiids, along with sex-linkage studies, revealed that this truncated amhr2by duplication is a male-specific conserved gene in Pangasiids. Reconstructions of the amhr2 phylogeny suggested that amhr2by arose from an ancient duplication/insertion event at the root of the Siluroidei radiation that is dated to ~100 million years ago. Together these results bring multiple lines of evidence supporting that amhr2by is an ancient and conserved master sex-determining gene in Pangasiids, a finding that highlights the recurrent use of the transforming growth factor ß pathway, which is often used for the recruitment of teleost master SD genes, and provides another empirical case towards firther understanding of dynamics of SD systems.

Structure-based 3D-Pharmacophore modeling to discover novel interleukin 6 inhibitors: An in silico screening, molecular dynamics simulations and binding free energy calculations.

Interleukin 6 (IL-6) is a cytokine with various biological functions in immune regulation, hematopoiesis, and inflammation. Elevated IL-6 levels have been identified in several severe disorders such as sepsis, acute respiratory distress syndrome (ARDS), and most recently, COVID-19. The biological activity of IL-6 relies on interactions with its specific receptor, IL-6Rα, including the membrane-bound IL-6 receptor (mIL-6R) and the soluble IL-6 receptor (sIL-6R). Thus, inhibition of the interaction between these two proteins would be a potential treatment for IL-6 related diseases. To date, no orally available small-molecule drug has been approved. This study focuses on finding potential small molecules that can inhibit protein-protein interactions between IL-6 and its receptor IL-6Rα using its crystal structure (PDB ID: 5FUC). First, two pharmacophore models were constructed based on the interactions between key residues of IL-6 (Phe74, Phe78, Leu178, Arg179, Arg182) and IL-6Rα (Phe229, Tyr230, Glu277, Glu278, Phe279). A database of approximately 22 million compounds was screened using 3D-pharmacophore models, molecular docking models, and ADMET properties. By analyzing the interactive capability of successfully docked compounds with important amino acids, 12 potential ligands were selected for further analysis via molecular dynamics simulations. Based on the stability of the complexes, the high interactions rate of each ligand with the key residues of IL-6/IL-6Rα, and the low binding free energy calculation, two compounds ZINC83804241 and ZINC02997430, were identified as the most potential IL-6 inhibitor candidates. These results will pave the way for the design and optimization of more specific compounds to combat cytokine storm in severe coronavirus patients.