Single-cell RNA sequencing unveils unique transcriptomic signatures of endothelial cells and role of ENO1 in response to disturbed flow.

Flow patterns exert significant effects on vascular endothelial cells (ECs) to lead to the focal nature of atherosclerosis. Using a step flow chamber to investigate the effects of disturbed shear (DS) and pulsatile shear (PS) on ECs in the same flow channel, we conducted single-cell RNA sequencing analyses to explore the distinct transcriptomic profiles regulated by DS vs. PS. Integrated analysis identified eight cell clusters and demonstrated that DS induces EC transition from atheroprotective to proatherogenic phenotypes. Using an automated cell type annotation algorithm (SingleR), we showed that DS promoted endothelial-to-mesenchymal transition (EndMT) by inducing the transcriptional phenotypes for inflammation, hypoxia responses, transforming growth factor-beta (TGF-ß) signaling, glycolysis, and fatty acid synthesis. Enolase 1 (ENO1), a key gene in glycolysis, was one of the top-ranked genes in the DS-induced EndMT cluster. Pseudotime trajectory analysis revealed that the kinetic expression of ENO1 was significantly associated with EndMT and that ENO1 silencing repressed the DS- and TGF-ß-induced EC inflammation and EndMT. Consistent with these findings, ENO1 was highly expressed in ECs at the inner curvature of the mouse aortic arch (which is exposed to DS) and atherosclerotic lesions, suggesting its proatherogenic role in vivo. In summary, we present a comprehensive single-cell atlas of ECs in response to different flow patterns within the same flow channel. Among the DS-regulated genes, ENO1 plays an important role in DS-induced EC inflammation and EndMT. These results provide insights into how hemodynamic forces regulate vascular endothelium in health and disease.

A putative cAMP-binding protein in Trypanosoma brucei cooperates with FLAM3 to promote flagellar connection and cell morphogenesis.

Trypanosoma brucei is a flagellated parasitic protozoan, and within the insect vector the parasite transitions from the trypomastigote form to the epimastigote form by repositioning its mitochondrial genome and relocating the flagellum. The mechanisms underlying such morphology changes are still poorly understood, but several flagellum-localized proteins are involved in this process by modulating the flagellum attachment zone (FAZ) that adheres the flagellum to the cell membrane. We report here a putative cAMP-binding protein named cAMP-BP1, which promotes flagellar connection and morphology transition. cAMP-BP1 contains two cyclic nucleotide-binding domains and five calcium-binding C2 domains and localizes to the flagella connector and the new FAZ tip. Depletion of cAMP-BP1 in the trypomastigote form of T. brucei causes major morphology changes, generating epimastigote-like cells with repositioned kinetoplast and relocated flagellum. At the flagella connector and the new FAZ tip, cAMP-BP1 associates with FLAM3, a regulator of morphology transition, depends on the latter for localization, and is required for FLAM3 localization to the flagella connector. Knockdown of cAMP-BP1 inhibits FAZ elongation and disrupts flagellar connection by impairing flagella connector structural integrity. These results identify a flagella connector- and new FAZ tip-localized protein as a regulator of morphology transition and flagellar connection in trypanosomes and uncover its functional interplay with FLAM3 to promote FAZ elongation for maintaining trypomastigote morphology.

Macacine alphaherpesvirus 1 (B Virus) Infection in Humans, Japan, 2019.

Two human patients with Macacine alphaherpesvirus 1 infection were identified in Japan in 2019. Both patients had worked at the same company, which had a macaque facility. The rhesus-genotype B virus genome was detected in cerebrospinal fluid samples from both patients.

Ethanolic extract from fruiting bodies of Cordyceps militaris HL8 exhibits cytotoxic activities against cancer cells, skin pathogenic yeasts, and postharvest pathogen Penicillium digitatum.

Cordyceps militaris is a well-known medicinal mushroom in Asian countries. This edible fungus has been widely exploited for traditional medicine and functional food production. C. militaris is a heterothallic fungus that requires both the mating-type loci, MAT1-1 and MAT1-2, for fruiting body formation. However, recent studies also indicated two groups of C. militaris, including monokaryotic strains carrying only MAT1-1 in their genomes and heterokaryotic strains harboring both MAT1-1 and MAT1-2. These strain groups are able to produce fruiting bodies under suitable cultivating conditions. In previous work, we showed that monokaryotic strains are more stable than heterokaryotic strains in fruiting body formation through successive culturing generations. In this study, we report a high cordycepin-producing monokaryotic C. militaris strain (HL8) collected in Vietnam. This strain could form normal fruiting bodies with high biological efficiency and contain a cordycepin content of 14.43 mg/g lyophilized fruiting body biomass. The ethanol extraction of the HL8 fruiting bodies resulted in a crude extract with a cordycepin content of 69.15 mg/g. Assays of cytotoxic activity on six human cancer cell lines showed that the extract inhibited the growth of all these cell lines with the IC50 values of 6.41-11.51 µg/mL. Notably, the extract significantly reduced cell proliferation and promoted apoptosis of breast cancer cells. Furthermore, the extract also exhibited strong antifungal activity against Malassezia skin yeasts and the citrus postharvest pathogen Penicillium digitatum. Our work provides a promising monokaryotic C. militaris strain as a bioresource for medicine, cosmetics, and fruit preservation.

Rhizosphere bacterial exopolysaccharides: composition, biosynthesis, and their potential applications.

Bacterial exopolysaccharides (EPS) are biopolymers of carbohydrates, often released from cells into the extracellular environment. Due to their distinctive physicochemical properties, biocompatibility, biodegradability, and non-toxicity, EPS finds applications in various industrial sectors. However, the need for alternative EPS has grown over the past few decades as lactic acid bacteria's (LAB) low-yield EPS is unable to meet the demand. In this case, rhizosphere bacteria with the diverse communities in soil leading to variations in composition and structure, are recognized as a potential source of EPS applicable in various industries. In addition, media components and cultivation conditions have an impact on EPS production, which ultimately affects the quantity, structure, and biological functions of the EPS. Therefore, scientists are currently working on manipulating bacterial EPS by developing cultures and applying abiotic and biotic stresses, so that better production of exopolysaccharides can be attained. This review highlights the composition, biosynthesis, and effects of environmental factors on EPS production along with the potential applications in different fields of industry. Ultimately, an overview of potential future paths and tactics for improving EPS implementation and commercialization is pointed out.

Development and validation of multiplex real-time PCR for simultaneous detection of six bacterial pathogens causing lower respiratory tract infections and antimicrobial resistance genes.

BACKGROUND: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumoniae and Staphylococcus aureus are major bacterial causes of lower respiratory tract infections (LRTIs) globally, leading to substantial morbidity and mortality. The rapid increase of antimicrobial resistance (AMR) in these pathogens poses significant challenges for their effective antibiotic therapy. In low-resourced settings, patients with LRTIs are prescribed antibiotics empirically while awaiting several days for culture results. Rapid pathogen and AMR gene detection could prompt optimal antibiotic use and improve outcomes. METHODS: Here, we developed multiplex quantitative real-time PCR using EvaGreen dye and melting curve analysis to rapidly identify six major pathogens and fourteen AMR genes directly from respiratory samples. The reproducibility, linearity, limit of detection (LOD) of real-time PCR assays for pathogen detection were evaluated using DNA control mixes and spiked tracheal aspirate. The performance of RT-PCR assays was subsequently compared with the gold standard, conventional culture on 50 tracheal aspirate and sputum specimens of ICU patients. RESULTS: The sensitivity of RT-PCR assays was 100% for K. pneumoniae, A. baumannii, P. aeruginosa, E. coli and 63.6% for S. aureus and the specificity ranged from 87.5% to 97.6%. The kappa correlation values of all pathogens between the two methods varied from 0.63 to 0.95. The limit of detection of target bacteria was 1600 CFU/ml. The quantitative results from the PCR assays demonstrated 100% concordance with quantitative culture of tracheal aspirates. Compared to culture, PCR assays exhibited higher sensitivity in detecting mixed infections and S. pneumoniae. There was a high level of concordance between the detection of AMR gene and AMR phenotype in single infections. CONCLUSIONS: Our multiplex quantitative RT-PCR assays are fast and simple, but sensitive and specific in detecting six bacterial pathogens of LRTIs and their antimicrobial resistance genes and should be further evaluated for clinical utility.

METTL3-dependent N6-methyladenosine RNA modification mediates the atherogenic inflammatory cascades in vascular endothelium.

Atherosclerosis is characterized by the plaque formation that restricts intraarterial blood flow. The disturbed blood flow with the associated oscillatory stress (OS) at the arterial curvatures and branch points can trigger endothelial activation and is one of the risk factors of atherosclerosis. Many studies reported the mechanotransduction related to OS and atherogenesis; however, the transcriptional and posttranscriptional regulatory mechanisms of atherosclerosis remain unclear. Herein, we investigated the role of N6-methyladenosine (m6A) RNA methylation in mechanotransduction in endothelial cells (ECs) because of its important role in epitranscriptome regulation. We have identified m6A methyltransferase METTL3 as a responsive hub to hemodynamic forces and atherogenic stimuli in ECs. OS led to an up-regulation of METTL3 expression, accompanied by m6A RNA hypermethylation, increased NF-κB p65 Ser536 phosphorylation, and enhanced monocyte adhesion. Knockdown of METTL3 abrogated this OS-induced m6A RNA hypermethylation and other manifestations, while METTL3 overexpression led to changes resembling the OS effects. RNA-sequencing and m6A-enhanced cross-linking and immunoprecipitation (eCLIP) experiments revealed NLRP1 and KLF4 as two hemodynamics-related downstream targets of METTL3-mediated hypermethylation. The METTL3-mediated RNA hypermethylation up-regulated NLRP1 transcript and down-regulated KLF4 transcript through YTHDF1 and YTHDF2 m6A reader proteins, respectively. In the in vivo atherosclerosis model, partial ligation of the carotid artery led to plaque formation and up-regulation of METTL3 and NLRP1, with down-regulation of KLF4; knockdown of METTL3 via repetitive shRNA administration prevented the atherogenic process, NLRP3 up-regulation, and KLF4 down-regulation. Collectively, we have demonstrated that METTL3 serves a central role in the atherogenesis induced by OS and disturbed blood flow.

Inhibitory Activity of Compounds Isolated from Ligustrum robustum (Roxb.) Against HepG2 Liver Cancer Cells: Isocubein and 4-(2-Acetoxyethyl)phenol as Potential Candidates.

Many herbal species in the genus Ligustrum have been shown to contain compounds with anti-cancer biological activity. This study aimed to isolate some compounds from the leaves of Ligustrum robustum (Roxb.) Blume (L. robustum) and evaluate their effects against liver cancer cells. As a result, seven previously reported compounds (1-7) were isolated, including four lignans (1-4) and three phenolic derivatives (5-7). The structures of these compounds were determined using spectroscopic methods and comparison with reported data. All isolates were assessed for their inhibitory effects on HepG2 liver cancer cells. Screening results revealed that two compounds, isocubein (3) and 4-(2-acetoxyethyl)phenol (7), exhibited strong inhibitory activity against cell proliferation, with IC50 values of 3.1±0.9 and 4.5±14 µM, respectively. Further analyses demonstrated that both compounds could suppress the formation and development of 3D tumorspheres in terms of quantity and size. Additionally, isocubein (3) and 4-(2-acetoxyethyl)phenol (7) exhibited the ability to inhibit the migration of HepG2 cells. This study represents the first report on the inhibitory activity against HepG2 liver cancer cells of extracts and isolated compounds from L. robustum, providing valuable information for future research aiming to develop products for liver cancer treatment.

Anti-cancer activity of green synthesized silver nanoparticles using Ardisia gigantifolia leaf extract against gastric cancer cells.

Using extracts from herbs for silver nanoparticle synthesis is attracting attention for its anticancer activity. Ardisia gigantifolia is a herb used in traditional Chinese medicine for treating stomach ailments, and some compounds isolated from this plant exhibit the inhibitory activity against different cancer cells. However, the synthesis of silver nanoparticle using extract of Ardisia gigantiflia leaves and their anti-cancer activity was not reported. In this report, the green synthesized silver nanoparticles using Ardisia gigantiflia extract (Arg-AgNPs) has average diameter of 6 nm with functional groups including O-H, C-H, and CO founded on the surface of these nanoparticles. The viability assays results revealed Arg-AgNPs reduced gastric cancer cell proliferation in a dose-dependent manner, with IC50 values of 1.37 and 0.65 µg/mL for AGS cells and 1.03 and 0.96 µg/mL for MKN45 cells. Arg-AgNPs caused cell cycle arrest at the G0/G1 phase and suppressed cell migration. Additionally, Arg-AgNPs significantly increased the percentage of senescent cells and promoted overproduction of reactive oxygen species (ROS) compared to the control. Thus, this study indicates that Arg-AgNPs can be considered as a promising candidate against human gastric cancer cells.

Fragmented understanding: exploring the practice and meaning of informed consent in clinical trials in Ho Chi Minh City, Vietnam.

BACKGROUND: The informed consent process in clinical trials has been extensively studied to inform the development processes which protect research participants and encourage their autonomy. However, ensuring a meaningful informed consent process is still of great concern in many research settings due to its complexity in practice and interwined socio-cultural factors. OBJECTIVES: This study explored the practices and meaning of the informed consent process in two clinial trials conducted by Oxford University Clinical Research Unit in collaboration with the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. METHODS: We used multiple data collection methods including direct observervations, in-depth interviews with study physicians and trial participants, review of informed consent documents from 2009 to 2018, and participant observation with patients' family members. We recruited seven physicians and twenty-five trial participants into the study, of whom five physicians and thirteen trial participants completed in-depth interviews, and we held twenty-two direct observation sessions. RESULTS: We use the concept "fragmented understanding" to describe the nuances of understanding about the consent process and unpack underlying reasons for differing understandings. CONCLUSIONS: Our findings show how practices of informed consent and different understanding of the trial information are shaped by trial participants' characteristics and the socio-cultural context in which the trials take place.

Effectiveness of Continuous Endotracheal Cuff Pressure Control for the Prevention of Ventilator-Associated Respiratory Infections: An Open-Label Randomized, Controlled Trial.

BACKGROUND: An endotracheal tube cuff pressure between 20 and 30 cmH2O is recommended to prevent ventilator-associated respiratory infection (VARI). We aimed to evaluate whether continuous cuff pressure control (CPC) was associated with reduced VARI incidence compared with intermittent CPC. METHODS: We conducted a multicenter open-label randomized controlled trial in intensive care unit (ICU) patients within 24 hours of intubation in Vietnam. Patients were randomly assigned 1:1 to receive either continuous CPC using an automated electronic device or intermittent CPC using a manually hand-held manometer. The primary endpoint was the occurrence of VARI, evaluated by an independent reviewer blinded to the CPC allocation. RESULTS: We randomized 600 patients; 597 received the intervention or control and were included in the intention to treat analysis. Compared with intermittent CPC, continuous CPC did not reduce the proportion of patients with at least one episode of VARI (74/296 [25%] vs 69/301 [23%]; odds ratio [OR] 1.13; 95% confidence interval [CI] .77-1.67]. There were no significant differences between continuous and intermittent CPC concerning the proportion of microbiologically confirmed VARI (OR 1.40; 95% CI .94-2.10), the proportion of intubated days without antimicrobials (relative proportion [RP] 0.99; 95% CI .87-1.12), rate of ICU discharge (cause-specific hazard ratio [HR] 0.95; 95% CI .78-1.16), cost of ICU stay (difference in transformed mean [DTM] 0.02; 95% CI -.05 to .08], cost of ICU antimicrobials (DTM 0.02; 95% CI -.25 to .28), cost of hospital stay (DTM 0.02; 95% CI -.04 to .08), and ICU mortality risk (OR 0.96; 95% CI .67-1.38). CONCLUSIONS: Maintaining CPC through an automated electronic device did not reduce VARI incidence. CLINICAL TRIAL REGISTRATION: NCT02966392.

Allergic airway inflammation induces upregulation of the expression of IL-23R by macrophages and not in CD3 + T cells and CD11c+F4/80- dendritic cells of the lung.

Interleukin 23 and the interleukin 23 receptor (IL-23-IL23R) are described as the major enhancing factors for Interleukin 17 (IL-17) in allergic airway inflammation. IL-17 is considered to induce neutrophilic inflammation in the lung, which is often observed in severe, steroid-resistant asthma-phenotypes. For that reason, understanding of IL-23 and IL-17 axis is very important for future therapy strategies, targeting neutrophil pathway of bronchial asthma.This study aimed to investigate the distribution and expression of IL-23R under physiological and inflammatory conditions. Therefore, a house dust mite (HDM) model of allergic airway inflammation was performed by treating mice with HDM intranasally. Immunofluorescence staining with panel of antibodies was performed in lung tissues to examine the macrophage, dendritic cell, and T cell subpopulations. The allergic airway inflammation was quantified by histopathological analysis, ELISA measurements, and airway function.HDM-treated mice exhibited a significant allergic airway inflammation including higher amounts of NE+ cells in lung parenchyma. We found only a small amount of IL-23R positives, out of total CD3+T cells, and no upregulation in HDM-treated animals. In contrast, the populations of F4/80+ macrophages and CD11c+F4/80- dendritic cells (DCs) with IL-23R expression were found to be higher. But HDM treatment leads to a significant increase of IL-23R+ macrophages, only. IL-23R was expressed by every examined macrophage subpopulation, whereas only Mϕ1 and hybrids between Mϕ1 and Mϕ2 phenotype and not Mϕ2 were found to upregulate IL-23R. Co-localization of IL-23R and IL-17 was only observed in F4/80+ macrophages, suggesting F4/80+ macrophages express IL-23R along with IL-17 in lung tissue.The study revealed that macrophages involving the IL-23 and IL-17 pathway may provide a potential interesting therapeutic target in neutrophilic bronchial asthma.

Efficacy of the incorporation between self-encapsulation and cryoprotectants on improving the freeze-dried survival of probiotic bacteria.

AIMS: This study aimed to improve the viability of probiotic bacteria during freeze-drying by the combination of self-encapsulation and cryoprotectants. METHODS AND RESULTS: Lactiplantibacillus plantarum VAL6 and Lactobacillus acidophilus VAR1 were exposed to environmental stresses including temperature, pH and increased CO2 concentration before performing freeze-drying with the addition of cryoprotectants. The results proved that tested stresses can stimulate the bacteria to synthesize more extracellular polymeric substances to form self-encapsulation that increases their freeze-dried viability. In combination with cryoprotectants to form double-layered microencapsulation, L. plantarum VAL6 stressed at pH 3.5 in combination with whey protein isolate could achieve the highest Improving Cell Viability of 4361-fold, while L. acidophilus VAR1 stressed at 25o C in combination with alginate gave a maximum Improving Cell Viability of 73.33-fold. CONCLUSIONS: The combination of self-encapsulation and cryoprotectants significantly improves the freeze-dried viability of probiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report that uses environmental stress to stimulate extracellular polymeric substance synthesis for self-encapsulation formation combined with the addition of cryoprotectants to enhance the freeze-dried survival of probiotics. This could be a novel approach in improving the viability of probiotic strains for various applications.

Correlation Between the Amount of Extracellular Polymeric Substances and the Survival Rate to Freeze-Drying of Probiotics.

To demonstrate that the amount of extracellular polymeric substances (EPS) and the freeze-dried viability of probiotics are correlated. Three strains of probiotics including Lactiplantibacillus plantarum, Lactobacillus acidophilus, and Bifidobacterium bifidum were subjected to environmental challenges, such as temperature, pH, and carbon dioxide. The results indicated that the challenges could stimulate the EPS synthesis of the probiotics. The experimental correlation between the amount of synthesized EPS and the freeze-dried survival rate was also analyzed, and the viability of each of the three strains was represented by the following functions in which the equation of L. plantarum is y = - 0.0336x2 + 2.7059x - 14.849 with R2 = 0.9699, the B. bifidum's equation is y = - 0.0554x2 + 2.6243x - 13.654 with R2 = 0.9554, and the L. acidophilus's one was y = 0.0346x2 + 0.5862x - 9.1339 with R2 = 0.9733. This could be a new approach to determining the freeze-dried viability of probiotic strains based on the measured EPS content.

Design, Synthesis and Cytotoxicity Evalufation of Substituted Benzimidazole Conjugated 1,3,4-Oxadiazoles.

Two series of 2-substituted benzimidazole conjugated 1,3,4-oxadiazole derivatives were designed, synthesized and evaluated for their cytotoxic activities against the three human cancer cell lines (cervical cancer (HeLa), breast cancer (MCF-7) and lung cancer (A549)). As the results 14 compounds demonstrated consistent to stronger cytotoxicities compared to the control 5-fluorouracil (5-FU) towards the tested cell lines including 4c (HeLa); 4b, 4e, 4h, 7i-j, 7m-n, 7s (MCF-7); 7b (MCF-7, A549); 7h (HeLa, MCF-7); and 4d, 4i, 7c (HeLa, MCF-7, A549), with the IC50 ranging from 2.7 to 38 µM. Notably, compound 4b illustrated almost 5-fold activity against the MCF-7 while 4d, 4i were 9- and 8-fold (HeLa), 4.5- and 13-fold (MCF-7), 4.7- and 4-fold (A549) increase in activity compared to 5-FU, respectively, and were found as lead compounds. These findings suggest that compounds 4b, 4d and 4i merit further characterization and can serve as promising scaffolds in the discovery of new potent anticancer agents.

Evaluation of Full-Duplex SWIPT Cooperative NOMA-Based IoT Relay Networks over Nakagami-m Fading Channels.

In this paper, we investigate the performance of non-orthogonal multiple access (NOMA)-based full-duplex Internet-of-Things (IoT) relay systems with simultaneous wireless information and power transfer (SWIPT) over Nakagami-m fading channels to improve the performance of a cell-edge user under perfect and imperfect successive interference cancellation (SIC). Two scenarios, i.e., direct and non-direct links, between the source node and cell-edge user are examined. The exact closed-form analytical and approximate expressions for the outage probability, system throughput, energy efficiency, and ergodic capacities are derived and validated via Monte Carlo simulations to characterize the proposed system performance. To further improve the system performance, we also provide a low-complexity algorithm to maximize the system throughput over-optimizing the time-switching factor. The results show that our proposed NOMA system can achieve superior performance compared to its orthogonal multiple access (OMA) counterpart under perfect SIC and with a low-to-medium signal-to-noise ratio under imperfect SIC, according to the level of residual self-interference and the quality of links.

Antifungal Susceptibility Does Not Correlate With Fungal Clearance or Survival in AIDS-Associated Cryptococcal Meningitis.

We investigated the value of susceptibility testing in predicting response in AIDS-associated cryptococcal meningitis using clinical isolates from a randomized controlled trial of antifungal treatment (amphotericin monotherapy, amphotericin with flucytosine, or amphotericin with fluconazole). We found no correlation between antifungal susceptibility and either early or late survival, or fungal clearance.

Expression of genes involved in exopolysaccharide synthesis in Lactiplantibacillus plantarum VAL6 under environmental stresses.

Environmental factors can alter exopolysaccharide biosynthesis in lactic acid bacteria (LAB). To further clarify this potential relationship, the mRNA expression of genes involved in exopolysaccharide synthesis such as glmU, pgmB1, cps4E, cps4F, cps4J, and cps4H in Lactiplantibacillus plantarum VAL6 under different conditions including temperature, pH, sodium chloride (NaCl), and carbon dioxide (CO2) intensification culture was studied. The transcriptomic data revealed that the exposure of L. plantarum VAL6 at pH 3 increased the expression level of cps4H but decreased the expression levels of pgmB1 and cps4E. Under pH 8, cps4F and cps4E were significantly upregulated, whereas pgmB1 was downregulated. Similarly, the expression levels of cps4F, cps4E, and cps4J increased sharply under stresses at 42 or 47 °C. In the case of NaCl stress, glmU, pgmB1, cps4J, and cps4H were downregulated in exposure to NaCl at 7 and 10% concentrations while cps4E and cps4F were upregulated at 1 h of 10%-NaCl treatment and at 5 h of 4%-NaCl treatment. Remarkably, CO2 intensification culture stimulated the expression of all tested genes. In addition, simultaneous changes in expression of cps4E and cps4F under environmental challenges may elicit the possibility of an association between the two genes. These findings indicated that the expression level of eps genes is responsible for changes in the yield and monosaccharide composition of exopolysaccharides under environmental stresses.

Predictors of treatment failures of plasmodium falciparum malaria in Vietnam: a 4-year single-centre retrospective study.

BACKGROUND: Drug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. METHODS: Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. RESULTS: More than half (59.8%, 265/443, CI 55.1-64.4%) of patients acquired Plasmodium falciparum infection of whom 21.9% (58/265, CI 17.1-27.4%) had severe malaria, while 7.2% (19/265, CI 4.6-10.9%) and 19.2% (51/265, CI 14.7-24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. Among 58 patients with severe malaria, 14 (24.1%) acquired infection in regions where artemisinin resistance has been documented including Binh Phuoc (11 patients), Dak Nong (2 patients) and Gia Lai (1 patient). Under treatment with intravenous artesunate, the median (IQR) parasite half-life of 11 patients coming from Binh Phuoc was 3 h (2.3 to 8.3 h), two patients coming from Dak Nong was 2.8 and 5.7 h, and a patient coming from Gia Lai was 6.5 h. Most patients (98.5%, 261/265) recovered completely. Four patients with severe malaria died. Severe malaria was statistically associated with receiving treatment at previous hospitals (P < 0.001), hepatomegaly (P < 0.001) and number of inpatient days (P < 0.001). Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55-19.02, P < 0.001). No predictor of LTF was identified. CONCLUSIONS: Plasmodium falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam, which are known as non-endemic areas of anti-malarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

Unusual Melting Trend in an Alkali Asymmetric Sulfonamide Salt Series: Single-Crystal Analysis and Modeling.

Developing low-melting alkali salts is of interest for both battery electrolytes and inorganic ionic liquids. In this study, we report a series of asymmetric alkali-metal sulfonamide salts based upon the (3-methoxypropyl)((trifluoromethyl)sulfonyl)amide (MPSA) anion. This family of salts features an unusual melting point trend, where the melting point of the salts decreases as the cation increases in size from Li to K but then the melting point increases as the cation further increases in size from K to Cs. Analyses of single crystals reveal that the unusual higher melting points of RbMPSA and CsMPSA in comparison to KMPSA can be attributed to the greater cation-cation distances as well as the increased rigidity of anion-cation coordination due to an increase in cyclic structures in comparison to KMPSA. Exceptionally, KMPSA features a very low melting point of only 50.79 ± 0.31 °C. This low melting point can be attributed to a relatively high degree of disorder, an unusual uncoordinated ether moiety, and a very short K-K distance of only 3.4348(7) Å among other factors, which is supported by the low cohesive energy and small elastic moduli among the rest according to density functional theory (DFT) calculations. The low melting point of KMPSA makes it interesting for low-temperature ionic liquids.