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T cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T cell cancer. Mutations in IL7R have been analyzed genetically, but downstream effector functions such as STAT5A and STAT5B hyperactivation are poorly understood. Here, we studied the most frequent and clinically challenging STAT5BN642H driver in T cell development and immature T cell cancer onset and compared it with STAT5A hyperactive variants in transgenic mice. Enhanced STAT5 activity caused disrupted T cell development and promoted an early T cell progenitor-ALL phenotype, with upregulation of genes involved in T cell receptor (TCR) signaling, even in absence of surface TCR. Importantly, TCR pathway genes were overexpressed in human T-ALL and mature T cell cancers and activation of TCR pathway kinases was STAT5 dependent. We confirmed STAT5 binding to these genes using ChIP-Seq analysis in human T-ALL cells, which were sensitive to pharmacologic inhibition by dual STAT3/5 degraders or ZAP70 tyrosine kinase blockers in vitro and in vivo. We provide genetic and biochemical proof that STAT5A and STAT5B hyperactivation can initiate T-ALL through TCR pathway hijacking and suggest similar mechanisms for other T cell cancers. Thus, STAT5 or TCR component blockade are targeted therapy options, particularly in patients with chemoresistant clones carrying STAT5BN642H.

According to a review of numerous publications and scientific reports, the effects of urbanization on urban climate are of greatest concern. This study aims to evaluate the impact of urbanization focusing on population growth on precipitation trends in 11 provinces across Vietnam during the period 2008-2018 by identifying the relationship between population growth and precipitation change. Regression analysis is used to determine the trends of precipitation and population growth. Precipitation maps and graphs show the overall precipitation trends, changes, and patterns in past decades. Overall, population growth tends to correlate with precipitation change trends. Furthermore, the type of region groups (countryside region, small city, or medium city) also plays a crucial role in determining the magnitude of the change in precipitation trends for each region. This further lends credibility to the notion that urbanization contributes to changes in precipitation trends., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Processing with heat treatment has been reported to alter several therapeutic effects of turmeric. In Vietnamese traditional medicine, turmeric has been long used for bacterial infections, and roasting techniques are sometimes applied with this material. However, there have been no studies investigating the effects of these thermal processes on the plant's antibacterial properties. Our study was therefore performed to examine the changes that roasting produced on this material. Slices of dried turmeric were further subjected to light-roasting (80 °C in 20 min) or dark-roasting (160 °C in 20 min) processes. Broth dilution and agar-well diffusion methods were applied to examine and compare the effects of ethanol extracts obtained from non-roasted, light-roasted and dark-roasted samples, on a set of 6 gram-positive and gram-negative bacteria. In both investigations, dark-roasted turmeric was significantly less antibacterial than non-roasted and light-roasted materials, as evident by the higher values of minimum inhibitory concentrations and the smaller diameters of induced inhibitory zones. In addition, dark-roasting was also found to clearly reduce curcumin contents, total polyphenol values and antioxidant activities of the extracts. These results suggest that non-roasting or light-roasting might be more suitable for the processing of turmeric materials that are aimed to be applied for bacterial infections.

Recent blood transcriptomic analysis of rhodesiense sleeping sickness patients has revealed that neutrophil signature genes and activation markers constitute the top indicators of trypanosomiasis-associated inflammation. Here, we show that Trypanosoma brucei infection results in expansion and differentiation of four splenic neutrophil subpopulations, including Mki67 + Birc5 + Gfi1 + Cebpe + proliferation-competent precursors, two intermediate immature subpopulations and Cebpb + Spi1 + Irf7 + Mcl1 + Csf3r + inflammation reprogrammed mature neutrophils. Transcriptomic scRNA-seq profiling identified the largest immature subpopulation by Mmp8/9 positive tertiary granule markers. We confirmed the presence of both metalloproteinases in extracellular spleen homogenates and plasma. During infection, these enzymes digest extracellular matrix components in the absence of sufficient TIMP inhibitory activity, driving remodeling of the spleen follicular architecture. Neutrophil depletion prevents the occurrence of organ damage, resulting in increased plasma cell numbers and prolonged host survival. We conclude that trypanosomiasis-associated neutrophil activation is a major contributor to the destruction of the secondary lymphoid architecture, required for maintaining an efficient adaptive immune response., (© 2023. Springer Nature Limited.)

Objectives: To evaluate the impact of clinical pharmacist-led interventions on the switch from intravenous (IV) to oral (PO) antibiotics among inpatients with infectious diseases., Methods: A before-and-after study was conducted among inpatients aged 18 or older who were diagnosed with infectious diseases and received IV antibiotics for at least 24 h at the Thong Nhat Hospital during the pre-intervention (between January 2021 and June 2021) and intervention (between January 2022 and June 2022) periods. Information on patient characteristics, antibiotic usage, length of hospital stay and treatment outcomes was obtained from medical records. The interventions included introducing IV-to-PO switch guidelines to physicians and clinical pharmacists' feedback on eligible cases. The impact of the pharmacists' interventions was evaluated by comparing primary outcomes (switch rate and appropriateness of switching) and secondary outcomes (duration of IV therapy, length of hospital stay and treatment outcomes) between the two study periods., Results: We included 99 patients in the pre-intervention and 80 patients in the intervention period. The proportion of patients who switched from IV-to-PO antibiotics increased from 44.4% in the pre-intervention period to 67.8% in the intervention period (p = 0.008). The overall rate of appropriate conversion increased significantly from 43.8% to 67.5% (p = 0.043). There were no statistically significant differences between the two periods with respect to the median duration of IV therapy (9 days vs. 8 days), length of hospital stay (10 days vs. 9 days) and treatment outcomes. Logistic regression analysis showed that the interventions resulted in a higher switch rate, whereas age was negatively associated with the switching rate., Conclusions: The implementation of clinical pharmacist-led interventions was effective in promoting IV-to-PO antibiotic conversion., (© 2023 John Wiley & Sons Ltd.)

Objectives: To compare the safety and efficacy of combined laser iridoplasty followed by surgical iridectomy (LI-SI) versus trabeculectomy in the management of medically unresponsive acute primary angle closure (APAC) with minimal cataract., Patients and Methods: This was a randomized controlled trial conducted among patients with medically unresponsive APAC without significant cataract. Study participants were randomized into: LI-SI or unaugmented trabeculectomy. Primary outcome of the study was the rate of post-operative surgical complications in the first 3 months after surgery. Secondary outcome assessed at 1 year was whether treatment was completely successful (IOP < 21 mmHg without IOP lowering drops), or partially successful (IOP < 21 mmHg with IOP lowering drops). Failure was defined as IOP ≥ 21 mmHg with IOP lowering drops., Results: The study included 67 eyes of 67 patients (59 females/8 males = 7.4/1) who were randomized into 2 groups: LI-SI (Group 1, 37 eyes), and trabeculectomy (Group 2, 30 eyes). There was no statistical difference between the two groups at baseline. Overall, there were more post-operative complications in Group 1 versus Group 2 (45.9% versus 33.3% - p = 0.23), although all responded well to medical treatment and resolved without sequelae. Complete success was found in 97.1% (34/35 eyes) in Group 1 and 92.6% in group 2 (p = 0.19, Fisher's exact test)., Conclusions: There was a higher rate of post-operative complications after LI-SI compared to trabeculectomy performed for medically unresponsive APAC with minimal cataract. Both procedures had similar surgical outcomes at 1 year., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objectives: This work aimed to construct a versatile, effective, and food-grade Agrobacterium tumefaciens-mediated transformation (ATMT) system for recombinant expression in the filamentous fungus Penicillium rubens (also known as Pencillium chrysogenum)., Results: In this study, the wild-type P. chrysogenum VTCC 31172 strain was re-classified as P. rubens by a multilocus sequencing analysis. Further, the pyrG gene required for uridine/uracil biosynthesis was successfully deleted in the VTCC 31172 strain by homologous recombination to generate a stable uridine/uracil auxotrophic mutant (ΔpyrG). The growth of the P. rubens ΔpyrG strain could be restored by uridine/uracil supplementation, and a new ATMT system based on the uridine/uracil auxotrophic mechanism was established for this strain. The optimal ATMT efficiency could reach 1750 transformants for 10 6 spores (equivalent to 0.18%). In addition, supplementation of uridine/uracil at the concentrations of 0.005-0.02% during the co-cultivation process significantly promoted transformation efficiency. Especially, we demonstrated that the pyrG marker and the amyB promoter from the koji mold Aspergillus oryzae were fully functional in P. rubens ΔpyrG. Expression of the DsRed reporter gene under the regulation of the A. oryzae amyB promoter lighted up the mycelium of P. rubens with a robust red signal under fluorescence microscopy. Furthermore, genomic integration of multiple copies of the Aspergillus fumigatus phyA gene under the control of the amyB promoter significantly enhanced phytase activity in P. rubens., Conclusions: The ATMT system developed in our work provides a safe genetic platform for producing recombinant products in P. rubens without using drug resistance markers., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Detection of antenatal common mental disorders in low-resource settings like Vietnam is important and requires a reliable, valid and practical screening tool. Currently, there is no such tool validated for use among pregnant women in Vietnam. This study aims to assess the validity of the Vietnamese version of the 20-item Self Reporting Questionnaire (SRQ-20) by evaluating its reliability, factorial structure, and performance in detecting common mental disorder (CMD) symptoms, thereby identifying the optimum cut-off score for CMD screening among pregnant women in Vietnam., Participants and Methods: A total of 210 pregnant women from four rural communes participated in a face-to-face interview using the Vietnamese version of the SRQ-20, followed by a clinical diagnostic interview based on ICD-10 diagnostic criteria of CMDs. The reliability of the SRQ-20 was assessed by calculating the scale's Cronbach's alpha to measure internal consistency. Factor analyses were undertaken to examine the factor structure of the instrument. The Receiver Operating Characteristic (ROC) curve analysis was performed to assess the performance of the SRQ-20 against the clinical diagnosis and to identify the optimum cut-off score., Results: Internal consistency was good, with a Cronbach's alpha of 0.87. Factor analyses resulted in a 4-factor solution. The area under the ROC curve (AUC) for detection of CMDs was 0.90. The optimum cut-off score of the SRQ-20 for detection of CMD symptoms among Vietnamese pregnant women was 5/6., Conclusion: The Vietnamese version of the SRQ-20 has the capacity to detect CMDs among pregnant women effectively and is recommended for use as a screening tool for CMDs in antenatal care settings in Vietnam., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Do et al.)

Background: Invasive gastrointestinal surgery may be performed as an open or endoscopic procedure, such as laparoscopic semi-colon surgery, laparoscopic appendectomy, laparoscopic gastrectomy, and anal surgery, among other such operations. Regardless of the approach, the operative procedure interferes with the patient's gastrointestinal tract, necessitating the rational use of prophylactic antibiotics to improve treatment outcomes and minimize postoperative infections., Objective: To investigate the prophylactic and postoperative antibiotic usage in patients who underwent invasive gastrointestinal surgery, and to identify factors associated with postoperative infection., Design: This descriptive, cross-sectional study included 112 patients who underwent invasive gastrointestinal surgery at the Department of Gastroenterology, Thong Nhat Hospital. We conducted a cross-sectional study in all inpatients aged 18 years and older, who underwent invasive gastrointestinal surgery between January 2020 and December 2020. We recorded patient characteristics, the administration and appropriateness of antibiotics, as well as treatment outcomes. The appropriateness of prophylactic and postoperative antibiotic usage was assessed based on 2015 Vietnamese national guideline for antibiotic use. Multivariable logistic regression analysis was used to determine the factors associated with postoperative infection., Results: Patients' mean age was 59.7 ± 17.2 years. Most surgeries (89.3%) were clean-contaminated procedures. The rates of appropriate types of antibiotics selected, doses, and overall rates of appropriateness of antibiotic prophylaxis were 68.0%, 76.4% and 54.7%, respectively. Of the patients investigated, 34.8% had at least one sign of postoperative infection; the overall appropriate rate of postoperative antibiotic was 38.5%. Old age was associated with postoperative infection and longer length of hospitalization., Conclusion: Implementation of the guidelines recommended for the prophylactic and therapeutic use of antibiotics is essential to improve treatment outcomes., (© 2022. The Author(s).)

Postpartum Depression (PPD) is a burden on women's mental health after delivery, predominantly occurring in the 1st year. PPD poses a threat to the mother's life and affects the quality of childcare. Early detection by family members of depressive symptoms is critical. This study aimed to examine the role of family members in reporting depressive symptoms of PPD among new mothers. A cross-sectional study was conducted, where 56 family members were asked to report depressive symptoms observed in new mothers. At the same time, the new mothers were also screened for PPD using the Edinburgh Postpartum Depression Scale (EPDS). Binary logistic regression was performed. Depressive symptoms of new mothers reported by family members, including emotional and behavioral disturbance, being under stress, high anxiety, isolation, changing lifestyle, and inability to take care of their children, were found as predictors of PPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nguyen, Do, Pham, Hoang, Truong and Nguyen.)

The development of superconcentrated or water-in-salt electrolytes (WISEs) has paved a new way toward realizing environmentally friendly, nonflammable batteries and supercapacitors based on aqueous electrolytes. The development of new electrolytes, such as WISEs, needs to be accompanied by further studies of the charging mechanism. This is essential to guide the choice of the electrode/electrolyte pairs for optimizing the performance of WISE-based supercapacitors. Therefore, to optimize the performance of carbon/carbon supercapacitors when using new, superconcentrated electrolytes, we present a detailed investigation of the carbon/electrolyte interface by combining electrochemical measurements with Raman and NMR spectroscopy and mass spectrometry. In particular, NMR provides crucial information about the local environment of electrolyte ions inside the carbon pores of the electrode. The results show that the structure of the electrolyte strongly depends on the concentration of the electrolyte and affects the mechanism of charge storage at the positive and negative electrodes.

Bioassay-guided fractionation of the 80% ethanol extract of Gynostemma compressum X. X. Chen & D. R. Liang (Cucurbitaceae) resulted in the isolation and identification of eight undescribed triterpenoids, gycomol VN1, gycomol VN2, and gycomosides VN1-6 from the bioactive n-butanol fraction. The structures of these compounds were elucidated by one- and two-dimensional nuclear magnetic resonance spectroscopy, high-resolution electrospray ionisation mass spectrometry, and chemical methods. All isolated compounds were evaluated for their 5'-adenosine monophosphate-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) activation effects on 3T3-L1 cells. Importantly, gycomol VN2, gycomoside VN1, and gycomosides VN3-5 activated the phosphorylation of AMPK and its downstream substrate ACC in 3T3-L1 cells at a dose of 10 μM. These effects imply that the activation of AMPK and ACC by active compounds from G. compressum has considerable potential for the prevention of obesity and its related disorders by activating AMPK signaling pathways., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The strategic design of the cathode is a critical feature for high-performance and long-lasting reversibility of an energy storage system. In particular, the round-trip efficiency and cycling performance of nonaqueous lithium-oxygen batteries are governed by minimizing the discharge products, such as Li 2 O and Li 2 O 2 . Recently, a metal-organic framework has been directly pyrolyzed into a carbon frame with controllable pore volume and size. Furthermore, selective metallic catalysts can also be obtained by adjusting metal ions for outstanding electrochemical reactions. In this study, various bimetallic zeolitic imidazolate framework (ZIF)-derived carbons were designed by varying the ratio of Zn to Co ions. Moreover, carbon nanotubes (CNTs) are added to improve the electrical conductivity further, ultimately leading to better electrochemical stability in the cathode. As a result, the optimized bimetallic ZIF-carbon/CNT composite exhibits a high discharge capacity of 16,000 mAh·g -1 , with a stable cycling performance of up to 137 cycles. This feature is also beneficial for lowering the overpotential of the cathode during cycling, even at the high current density of 2,000 mA·g -1 ., (Copyright © 2022, Pham et al.)

Over the past decade, the extent and magnitude of acid rain in Vietnam and other Asian countries have become more apparent. In this study, the effect of simulated acid rain (pH 5.0, 4.0, and 3.0) and control treatment (pH 6.0) are observed for three species Brassica integrifolia, Brassica rapa, and Brassica juncea in Hanoi. The pot experiment was conducted for 42 days and arranged according to a randomized complete block design (RCBD), replicated 3 times with acid rain exposure being supplied every 4 days. The results show that acid rain causes direct damage to leaves. Observations reveal white spots on leaves; leaves getting discolored and gradually turning yellow, curling leaf marginals, and turning dark blue, with the most severe symptoms being necrotic leaves. Parameters of the shoot and root length, leaf area, biomass, and chlorophyll content all decrease as pH drops. However, the accumulation of proline content in leaves tends to increase with greater acidity. In conclusion, Brassica rara has the highest resistance capability to acid rain compared with Brassica integrifolia and Brassica juncea, especially its proline content is the highest at pH 3.0 in three Brassicaceae species., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant., Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients., Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group., Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses., Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC., Competing Interests: TPN, HK, TML, TTNT, TTD, TVV, TTTV, QBPN, VTP, VTT, MTNT, TTTN, PTH, HTH, KDN, CCD, TTU, SMD are employees of Nanogen Pharmaceutical Biotechnology JSC. MTNT, and SMD are authors of a pending patent for Nanocovax., (© 2022 The Author(s).)

Objectives: We investigated the characteristics of prophylactic antimicrobial use in clean and clean-contaminated surgical procedures and assessed the efficacy of a prophylactic antimicrobial stewardship intervention at Thong Nhat Hospital, Ho Chi Minh City, Vietnam., Methods: A cross-sectional study was conducted on 354 patients who underwent either clean or clean-contaminated surgical procedures at Thong Nhat Hospital. Eligible patients were classified with respect to three periods of intervention from 2017 to 2020. Data collection included surgical procedures, patient characteristics, and prophylactic antimicrobial usage. We determined the efficacy of antimicrobial stewardship intervention based on comparisons among the primary outcome (the appropriateness of prophylactic antimicrobials) and secondary outcomes (postoperative antimicrobial prophylaxis (AP) prolongation, length of postoperative hospital stay, and cost of antimicrobials)., Results: The mean age of patients in periods 1, 2, and 3 was 54.5 ± 16.6, 50.2 ± 16.5, and 52.8 ± 17.3 years, respectively, with an overall male/female ratio of 1.1/1. No significant differences were detected in basic patient characteristics during the three periods. Majority of the surgical procedures were clean (56%-59%) and scheduled (85%-86%). Prophylactic antimicrobial stewardship intervention enhanced AP appropriateness (by 12.7%, 12.7%, and 39.0% in periods 1, 2, and 3, respectively, p < 0.001), decreased postoperative prophylactic antimicrobial duration [3.0 (0-6), 1.5 (0-5), and 0.0 (0-1) days, respectively, p < 0.001], and reduced average antimicrobial expenses (p < 0.001)., Conclusions: The prophylactic antimicrobial stewardship interventions introduced at Thong Nhat Hospital had several positive impacts on the appropriateness of prophylactic antimicrobial use and treatment costs., (© 2022 John Wiley & Sons Ltd.)

The occurrence of nonenzymaticbrowning in fruit juices during storage is a major quality defect. It negatively affects consumer acceptance and consumption behavior and determines the shelf-life of these products. Although nonenzymatic browning of fruit juices has been the subject of research for a long time, the exact mechanism of the nonenzymatic browning reactions is not yet completely understood. This review paper aims to give an overview of the compounds and reactions playing a key role in nonenzymatic browning during the storage of fruit juices. The chemistry of the plausible reactions and their relative importance will be discussed. To better understand nonenzymatic browning, factors affecting these reactions will be reviewed and several strategies and methods to evaluate color changes and browning will be discussed. Nonenzymatic browning involves three main reactions: ascorbic acid degradation, acid-catalyzed sugar degradation, and Maillard-associated reactions. The most important NEB pathway depends on the matrix. Nonenzymatic browning is affected by many factors, such as the juice composition, the pH, the oxygen availability (packaging material), and the storage conditions. Nonenzymatic browning can thus be considered as a complex problem. To characterize color changes and browning and obtain insight into the browning mechanism of fruit juices, food scientists applied several approaches and strategies. These included the use of model systems with/without the addition of labeled compound and real systems as well as advanced analytical methods., (© 2021 Institute of Food Technologists®.)

Genome-wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID-19) cases and outbreaks. We performed whole-genome sequencing of 27 SARS-CoV-2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (<25) in real-time reverse-transcription polymerase chain reaction diagnostic tests than the original D614 (prevalence ratio = 2.75; 95% confidence interval, 1.19-6.38). The integration of sequencing and epidemiological data suggests that SARS-CoV-2 transmission in both quarantine areas and in the community in Vietnam occur at the beginning of the epidemic although the country implemented strict quarantine quite early, with strict contact tracing, and testing. These findings provide insights into the nature of the epidemic, as well as shape strategies for COVID-19 prevention and control in Vietnam., (© 2021 Wiley Periodicals LLC.)

Objective: This study aimed to estimate the effectiveness of a standard clinical training program for new graduate nurses in Vietnam., Methods: A quasi-experimental longitudinal study with a difference-in-differences design was conducted. A total of 280 new graduate nurses completed a self-administered questionnaire. The intervention group consisted of 206 respondents (those having participated in standard clinical training) and the control group (those that did not receive training) of 74. Differences in mean increases in competency scores between the intervention and control groups were estimated. The effect size of the intervention was estimated by calculating Cohen's d. A generalized linear model was employed to identify the factors associated with mean increases., Results: The mean increase in total competency scores (range: 0-6 points) in the intervention group was 0.73 points greater than in the control group with an intermediate effect size (Cohen's d = 0.53; 95% CI 0.26 to 0.80). A greater reduction in standard deviation of total competency scores in the intervention group was confirmed. Participation in standard clinical training produced a positive association with a mean increase in total competency score without significance (β = 0.04, P = 0.321). Provincial hospitals as clinical training venues had a significantly positive association (β = 0.11, P = 0.007) with the mean increase in total competency scores. Competency at pre-clinical training was negatively (β = -0.75, P < 0.001) associated with the mean increase., Conclusion: Findings implied that the standard clinical training program could contribute to both increasing and standardizing new graduate nurses' competencies in Vietnam. Further studies are needed to more precisely examine the attribution of standard clinical training to better increase new graduate nurses' competencies., Competing Interests: The authors have declared that no competing interests exist.

Background: Clinical training for new graduate nurses has a positive impact on their clinical competence; however, there is limited evidence on the impact of this training at the organizational level and on the processes that mediate these impacts., Objectives: To identify the individual and organizational impacts of a clinical training system and the mechanism that produces them by exploring nurses' perceptions of the changes in health facilities after the introduction of a standardized clinical training system in Vietnam., Design: Qualitative research using an ethnographic approach; photovoice was used to obtain insights into nurses' perceptions., Setting: Health facilities of four provinces and one city in Vietnam participated in the Project for Strengthening of the Clinical Training System for New Graduate Nurses., Participants: New graduate nurses, preceptors, and managers who engaged in the clinical training program., Methods: Qualitative data, including photographs, were collected through photovoice sessions and inductively analyzed using thematic analysis., Results: Sixteen photovoice sessions were conducted with 94 nurses from 22 hospitals. Three themes emerged: "acquiring competency" as an individual change, "fostering mutual learning culture" as an organizational change, and "improved quality of care and nurse empowerment" as the impact. The clinical training system was found to enhance diverse competencies of new graduate nurses, preceptors, and nurse managers, while facilitating collaboration among different professions, departments, and organizations and cultivating a better learning environment. Organizational changes were initiated with the hospital director's support. These changes were interactively related and produced the impact., Conclusions: The novel clinical training system for new graduate nurses could strengthen nurses' competencies and facilitate organizational changes to actualize a positive impact on nursing care and nurses' status. These findings could facilitate the design of an effective training program to stimulate organizational learning to produce better health outcome., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In 2016-2017, 68 women in Southern Vietnam had RT-PCR confirmed Zika virus (ZIKV) infection during pregnancy. We report here the outcomes of the pregnancies and the virological analyses related to this outbreak., Methods: We collected clinical and epidemiological information from the women who were enrolled in the study. Medical records related to the pregnancy in 2016-2017 were retrieved for those who were not able to be enrolled in the study. Children born to women with ZIKV infection during pregnancy were also enrolled. Serum samples were evaluated for presence of ZIKV antibodies. Phylogenetic analyses were performed on Zika virus genomes sequenced from the 2016-2017 serum samples., Findings: Of the 68 pregnancies, 58 were livebirths and 10 were medically terminated. Four of the medical records from cases of fetal demise were able to be retrieved, of which one was consistent with congenital ZIKV infection. Of the 58 women with a livebirth, 21 participated in the follow-up investigation. All but two women had serologic evidence of ZIKV infection. Of the 21 children included in the study (mean age: 30.3 months), 3 had microcephaly at birth. No other clinical abnormalities were reported and no differences in neurodevelopment were observed compared to a control group. Phylogenetic analysis revealed a clade within the ZIKV Asian lineage and branch at the root of samples from the 2013-2014 French Polynesian outbreak. The prM S139N mutation was not observed., Interpretation: We have been able to demonstrate a clade within the ZIKV Asian lineage implicated in adverse pregnancy outcomes in Southern Vietnam., Funding: INCEPTION project (PIA/ANR-16-CONV-0005) and a grant received from BNP Paribas Simplidon., Competing Interests: All authors declare no competing interests., (© 2021 The Author(s). Published by Elsevier Ltd.)

Ethnopharmacological Relevance: G. pentaphyllum, also known as Jiao-Gu-Lan, has been used traditionally as folk remedies for many diseases, including diabetes mellitus, metabolic syndrome, aging, and neurodegenerative diseases in China and some countries in East and Southeast Asia. It is considered as an "immortality herb" in Guizhou Province, because it was consumed regularly by the elderly native inhabitants. Other species of the same genus Gynostemma such as G. longipes and G. laxum have been used as alternatives to G. pentaphyllum in ethno-medicine in Vietnam and other Asian countries., Aim of the Review: The review aims to summarize up-to-date study results on Gynostemma species, including traditional usage, phytochemical profile, pharmacological activities, and toxicological studies, in order to suggest future research orientation and therapeutic applications on acute and chronic diseases., Materials and Methods: The relevant literature on the genus Gynostemma was gathered from secondary databases (Web of Science and PubMed), books, and official websites. The latest literature cited in this review was published in February 2020., Results: The genus Gynostemma has been widely used in traditional medicine, mainly for treatment of diabetes, hypertension, obesity, and hepatosteatosis. To date, 328 dammarane-type saponins were isolated and structurally elucidated from Gynostemma species. Crude extracts, saponin-rich fractions (gypenosides), and pure compounds were reported to show a wide range of pharmacological activities in both in vitro and in vivo experiments. The most notable pharmacological effects were anti-cancer, cardioprotective, hepatoprotective, neuroprotective, anti-diabetic, anti-obesity, and anti-inflammatory activities. Toxicological studies were conducted only on G. pentaphyllum, showing that the plant extracts were relatively safe in both acute and long-term toxicity experiments at the given dosage while no toxicological studies were reported for the other species., Conclusions: The review summarizes current studies on traditional uses, phytochemistry, biological properties, and toxicology of medicinal Gynostemma species. Till now, the majority of publications still focused only on G. pentaphyllum. However, the promising preliminary data of other Gynostemma species indicated the research potential of this genus, both in phytochemical and pharmacological aspects. Furthermore, clinical data are required to evaluate the efficacy and undesired effects of crude extracts, standard saponin fractions, and pure compounds prepared from Gynostemma medicinal plants., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Vietnam, a high tuberculosis (TB) burden country, conducted national TB prevalence surveys in 2007 and 2017. In both surveys participants were screened by using a questionnaire and chest radiograph; sputum samples were then collected to test for Mycobacterium tuberculosis by smear microscopy and Löwenstein-Jensen culture. Culture-positive, smear-positive, and smear-negative TB cases were defined by laboratory results, and the prevalence of tuberculosis was compared between the 2 surveys. The results showed prevalence of culture-positive TB decreased by 37% (95% CI 11.5%-55.4%), from 199 (95% CI 160-248) cases/100,000 adults in 2007 to 125 (95% CI 98-159) cases/100,000 adults in 2017. Prevalence of smear-positive TB dropped by 53% (95% CI 27.0%-69.7%), from 99 (95% CI 78-125) cases/100,000 adults to 46 (95% CI 32-68) cases/100,000 adults; smear-negative TB showed no substantial decrease. Replacing microscopy with molecular methods for primary diagnostics might enhance diagnosis of pulmonary TB cases and further lower TB burden.

For the first time, a model system approach was combined with 1 H NMR fingerprinting in studying non-enzymatic browning (NEB) of pasteurized shelf-stable orange juice during storage. Various NEB precursors were used individually or in combinations to formulate simple or complex model systems, respectively, in citric acid buffer. Based on orange juice composition, ascorbic acid, sugars (sucrose, glucose and fructose) and amino acids (proline, arginine, asparagine, aspartic acid, serine and glutamic acid) were selected as the precursors for the model systems. After pasteurization and during subsequent accelerated storage (42 °C, 16 weeks) the model systems displayed a three-phase browning development. The initial browning phase was mainly the result of ascorbic acid degradation especially in the presence of amino acids and sugars. In the later phases, the contribution of reactions of sugars and amino acids to browning became apparent. The application of 1 H NMR fingerprinting on a simple model system containing ascorbic acid revealed that its degradation pathway to intermediates such as xylonic acid, acetic acid and erythrulose was responsible for the major changes during storage. When this model system was complexed by inclusion of sugars and amino acids, the hydrolysis of sucrose to glucose and fructose was identified as the main reaction leading to differences in the samples throughout storage. These three sugars dominated the NMR spectra of the samples, overshadowing several important compounds for NEB such as ascorbic acid and its degradation products. Other more advanced NMR experiments such as two-dimensional NMR analyses should be applied in future research to identify unknown compounds from NEB reactions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Metastatic melanoma is hallmarked by its ability of phenotype switching to more slowly proliferating, but highly invasive cells. Here, we tested the impact of signal transducer and activator of transcription 3 (STAT3) on melanoma progression in association with melanocyte inducing transcription factor (MITF) expression levels. We established a mouse melanoma model for deleting Stat3 in melanocytes with specific expression of human hyperactive NRAS Q61K in an Ink4a-deficient background, two frequent driver mutations in human melanoma. Mice devoid of Stat3 showed early disease onset with higher proliferation in primary tumors, but displayed significantly diminished lung, brain, and liver metastases. Whole-genome expression profiling of tumor-derived cells also showed a reduced invasion phenotype, which was further corroborated by 3D melanoma model analysis. Notably, loss or knockdown of STAT3 in mouse or human cells resulted in the upregulation of MITF and induction of cell proliferation. Mechanistically we show that STAT3-induced CAAT Box Enhancer Binding Protein (CEBP) expression was sufficient to suppress MITF transcription. Epigenetic analysis by ATAC-seq confirmed that CEBPa/b binding to the MITF enhancer region silenced the MITF locus. Finally, by classification of patient-derived melanoma samples, we show that STAT3 and MITF act antagonistically and hence contribute differentially to melanoma progression. We conclude that STAT3 is a driver of the metastatic process in melanoma and able to antagonize MITF via direct induction of CEBP family member transcription.

In this study, we propose a versatile design for metal-organic framework cathodes with the aim of improving the reversibility of Li-O 2 and Li-O 2 /CO 2 batteries. The porous nanoarchitecture of Co 3 O 4 -incorporated carbon wrapped with carbon nanotubes is beneficial for facilitating the reversible electrochemical reactions with O 2 and CO 2 , ensuring long-term cycling performance.

In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS-CoV-2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human-to-human transmission of SARS-CoV-2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi-morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies., (© 2020 Wiley Periodicals LLC.)

Fusion proteins involving Nucleoporin 98 (NUP98) are recurrently found in acute myeloid leukemia (AML) and are associated with poor prognosis. Lack of mechanistic insight into NUP98-fusion-dependent oncogenic transformation has so far precluded the development of rational targeted therapies. We reasoned that different NUP98-fusion proteins deregulate a common set of transcriptional targets that might be exploitable for therapy. To decipher transcriptional programs controlled by diverse NUP98-fusion proteins, we developed mouse models for regulatable expression of NUP98/NSD1, NUP98/JARID1A, and NUP98/DDX10. By integrating chromatin occupancy profiles of NUP98-fusion proteins with transcriptome profiling upon acute fusion protein inactivation in vivo, we defined the core set of direct transcriptional targets of NUP98-fusion proteins. Among those, CDK6 was highly expressed in murine and human AML samples. Loss of CDK6 severely attenuated NUP98-fusion-driven leukemogenesis, and NUP98-fusion AML was sensitive to pharmacologic CDK6 inhibition in vitro and in vivo. These findings identify CDK6 as a conserved, critical direct target of NUP98-fusion proteins, proposing CDK4/CDK6 inhibitors as a new rational treatment option for AML patients with NUP98-fusions., (© 2020 by The American Society of Hematology.)

[This corrects the article DOI: 10.1371/journal.pone.0232142.].

Background: Non-enzymatic browning (NEB) is the main quality defect in shelf-stable orange juice and other fruit juices during storage. Previous studies on NEB focused solely on the soluble fraction of orange juice, regardless of the fact that both soluble and insoluble fractions turn brown during extended storage. Clear evidence of the relative contribution of both fractions to NEB is currently lacking in the literature. This study investigated the contribution of the soluble and insoluble fractions of orange juice, which were obtained by centrifugation and ethanol precipitation, to NEB during storage. Changes in different NEB-related attributes, such as ascorbic acid (AA) degradation, and the browning index (BI), were quantified and kinetically modeled., Results: Evaluation of color during storage showed that the orange juice and the soluble compound-containing fractions turned brown whereas the insoluble fractions did not. The soluble compound-containing fractions showed exactly the same browning behavior with storage as the plain orange juice. Based on the kinetic parameters obtained, the degradation of AA, the hydrolysis of sucrose, the increase in the glucose and fructose content, and the formation of furfural and 5-hydroxymethylfurfural during storage were similar for the plain orange juice and the soluble compound-containing fractions., Conclusion: This work provided evidence that the soluble fraction of orange juice plays the major role in NEB, unlike the insoluble fraction, which seems to make no contribution. Results from this work also demonstrate the potential use of the soluble fraction as an orange-juice-based model system of reduced complexity that can be used for the further investigation of NEB processes. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

Aims: We investigated the potential cooperative effects of carotenoid-producing Bacillus aquimaris SH6 and nonpigmented Bacillus subtilis SH23 on white-leg shrimp growth and health., Methods and Results: SH6, SH23 and a combination of both spores (1 × 10 6  CFU per g pellet) were administered in shrimp. The growth rate (2·36% day -1 ), red-colour score (25) and astaxanthin concentration (3·5 µg g -1 shrimp) were maximum in two-spore-administered shrimp. Immune-related Rho mRNA expression level and phenoloxidase and superoxidase dismutase activities were higher in two-spore-administered shrimp than in control shrimp, with Rho mRNA expression level being 55-fold higher in two-spore-administered shrimp than in SH6-administered shrimp and phenoloxidase activity being 1·2-fold higher in two-spore-administered shrimp than in SH23-administered shrimp. Although live SH6 count was 2·7-fold lower, SH6 germination level was 3·5-fold higher in the combination group than in SH6 group., Conclusions: When both SH6 and SH23 spores were administered, SH6 spore germination was enhanced and cooperative improvement was seen in growth, astaxanthin level and red-colour score of white-leg shrimp; however, immune-related parameters were induced in a noncooperative manner., Significance and Impact of the Study: This is the first report showing the cooperative probiotic activities of Bacillus strains and their possible mechanisms in a shrimp model., (© 2020 The Society for Applied Microbiology.)

In this article, the authors apply the relative air pollution index (RAPI) proposed by Pham Ngoc Ho for aggregate assessment of daily air pollution level (RAPI d ) using data from 3 daily standards (1, 8, and 24 h) of each country's standard, including Vietnam Technical Regulation QCVN 05:2013/MONRE. By using the automated data of ambient air at 3 monitoring stations in Cam Pha coal mining area, Quang Ninh province in 2018, results of the frequency of pollution by month (f%) have shown that overall, the air quality in dry season (October-March) is worse than that in rainy season (April-September). Results of pollution frequency by month in a year f% also indicate that air pollution in 2018 at 3 stations is mostly at level I (no pollution) with f% ranged from 10 to 58.3%, but pollution level II-IV (light pollution-very heavy pollution) also happened as f% fluctuated from 20 to 42% in some months. Comparing with air quality assessment in 2011-2015 at this area by periodic monitoring equipment of Quang Ninh Center for Environmental Monitoring, results in 2018 have shown that individual index of RAPI is consistent with the current status of air quality with high accuracy. To compare with RAPI d , we used VN&#95;AQI d index of the Vietnam Environment Administration (VEA). Comparison results show that both indices do not encounter eclipsing effect. However, ambiguous effect occurred in the case of VN&#95;AQI d index (warning not suitable for reality in some cases). In addition, advantages and limitations of these two methods have been analyzed and explained in detail.

Nonenzymatic browning during storage of pasteurized shelf-stable orange juice causes a major color deterioration, which negatively affects consumer acceptance of the juice. This study, for the first time, investigated on a kinetic basis the effect of pH and suspected nonenzymatic browning reaction precursors such as ascorbic acid, fructose, and arginine on nonenzymatic browning during accelerated storage (42 °C) using an orange-juice-based model system. The results showed that lowering the pH of the model juice system from 3.8 to 1.5 significantly increased the rate of ascorbic acid degradation, the rate changes (increases and decreases) in different sugars, and the rates of furfural and 5-hydroxymethylfurfural formation. These changes coincided with a higher browning intensity, which became more pronounced toward the end of storage of the juice model system. Similarly, adding more ascorbic acid and fructose largely increased the formation of furfural and 5-hydroxymethylfurfural, respectively, and resulted in a higher browning intensity. In conclusion, lowering the pH of the orange juice or addition of ascorbic acid or fructose will enhance its browning during prolonged storage.

During an effort to find insulin mimetic compounds, the leaves of Gymnema inodorum were shown to have a stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation on a 70% ethanol extract of G. inodorum was applied to yield two new ( 1 and 2 ) and two known ( 8 and 9 ) oleanane triterpenoids with a methyl anthranilate moiety together with five further new oleanane triterpenoids ( 3 - 7 ). The chemical structures of all isolates were determined based on their spectroscopic data, including IR, UV, NMR, and mass spectrometric analysis. The isolated compounds ( 1 - 9 ) were determined for their stimulatory activities on glucose uptake in differentiated 3T3-L1 adipocyte cells using 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-d-glucose (2-NBDG) as a fluorescent-tagged glucose probe. Three compounds ( 3 , 5 , and 9 ) showed stimulatory effects on the uptake of 2-NBDG in 3T3-L1 adipocyte cells. Chemicals with a methyl anthranilate moiety have been considered as crucial contributors of flavor odor in foods, and quantitative analysis showed the content of compound 8 to be 0.90 ± 0.01 mg/g of the total extract. These results suggest that the leaves of G. inodorum have the potential to be used as an antidiabetic functional food or tea.

Introduction: Tuberculosis (TB) remains a significant cause of morbidity and mortality in Vietnam. The current TB burden is unknown as not all individuals with TB are diagnosed, recorded and notified. The second national TB prevalence survey was conducted in 2017-2018 to assess the current burden of TB disease in the country., Method: Eighty-two clusters were selected using a multistage cluster sampling design. Adult (≥15 years of age) residents having lived for 2 weeks or more in the households of the selected clusters were invited to participate in the survey. The survey participants were screened for TB by a questionnaire and digital chest X-ray after providing written informed consent. Individuals with a positive symptom screen and/or chest X-ray suggestive of TB were asked to provide sputum samples to test for Mycobacterium tuberculosis by Ziehl-Neelsen direct light microscopy, Xpert MTB/RIF G4, BACTEC MGIT960 liquid culture and Löwenstein-Jensen solid culture. Bacteriologically confirmed TB cases were defined by an expert panel following a standard decision tree., Result: Of 87,207 eligible residents, 61,763 (70.8%) participated, and 4,738 (7.7%) screened positive for TB. Among these, 221 participants were defined as bacteriologically confirmed TB cases. The estimated prevalence of bacteriologically confirmed adult pulmonary TB was 322 (95% CI: 260-399) per 100,000, and the male-to-female ratio was 4.0 (2.8-5.8, p<0.001). In-depth interviews with the participants with TB disease showed that only 57.9% (95% CI: 51.3-64.3%) reported cough for 2 weeks or more and 32.1% (26.3-38.6%) did not report any symptom consistent with TB, while their chest X-ray results showed that 97.7% (95% CI: 94.6-99.1) had abnormal chest X-ray images suggesting TB., Conclusion: With highly sensitive diagnostics applied, this survey showed that the TB burden in Vietnam remains high. Half of the TB cases were not picked up by general symptom-based screening and were identified by chest X-ray only. Our results indicate that improving TB diagnostic capacity and access to care, along with reducing TB stigma, need to be top priorities for TB control and elimination in Vietnam., Competing Interests: The authors have declared that no competing interests exist.

Gymnema sylvestre (Retz.) R. Br. ex Schult. has a long history to be used as an antidiabetic herbal medicine. Various varieties of G. sylvestre, have been studied intensively on their 3β-hydroxy oleanane triterpenoid composition for hypoglycemic effects. It is also well-known that most species belonging to the same genus have similar chemical composition and biological activity. Thus, an extract of the Gymnema latifolium Wall. ex Wight, which showed considerable protein tyrosine phosphatase 1B (PTP1B) inhibitory activity (>70% inhibition at 30 μg/mL), was studied intensively. Extensive chemical investigation on the 70% EtOH of G. latifolium led to the isolation of four previously undescribed oleanane hemiacetal glycosides, gymlatinosides GL1-GL4, three previously undescribed oleanane glycosides, gymlatinosides GL5-GL7, and two known 3β-hydroxy oleanane analogs. The structures of the previously undescribed compounds were elucidated using diverse spectroscopic methods. The hemiacetal structure of the glycoside portion was further elaborated precisely by HMBC and J resolved proton NMR. Gymlatinosides GL2 and GL3 showed considerable PTP1B inhibitory effect., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Recurrent gain-of-function mutations in the transcription factors STAT5A and much more in STAT5B were found in hematopoietic malignancies with the highest proportion in mature T- and natural killer-cell neoplasms (peripheral T-cell lymphoma, PTCL). No targeted therapy exists for these heterogeneous and often aggressive diseases. Given the shortage of models for PTCL, we mimicked graded STAT5A or STAT5B activity by expressing hyperactive Stat5a or STAT5B variants at low or high levels in the hematopoietic system of transgenic mice. Only mice with high activity levels developed a lethal disease resembling human PTCL. Neoplasia displayed massive expansion of CD8 + T cells and destructive organ infiltration. T cells were cytokine-hypersensitive with activated memory CD8 + T-lymphocyte characteristics. Histopathology and mRNA expression profiles revealed close correlation with distinct subtypes of PTCL. Pronounced STAT5 expression and activity in samples from patients with different subsets underline the relevance of JAK/STAT as a therapeutic target. JAK inhibitors or a selective STAT5 SH 2 domain inhibitor induced cell death and ruxolitinib blocked T-cell neoplasia in vivo We conclude that enhanced STAT5A or STAT5B action both drive PTCL development, defining both STAT5 molecules as targets for therapeutic intervention., (Copyright© 2020 Ferrata Storti Foundation.)

For the first time in literature, this study revealed the participation of polymeric components of orange juice cloud and pulp (such as proteins, arabinogalactan proteins, or protein-pectin complexes) during nonenzymatic browning. In a quest to better understand the nonenzymatic browning of shelf-stable orange juice during storage, the juice was fractionated into different fractions depending on the solubility in water/ethanol and the obtained fractions were characterized. The results showed that brown compounds that were formed during storage of orange juice were distributed over water insoluble (pulp), ethanol insoluble (cloud), and ethanol soluble (serum) fractions. In the ethanol insoluble fraction, the brown compounds are hypothesized to be associated with proteins, arabinogalactan proteins, and/or protein-pectin complexes of this fraction without significantly changing their molecular weight distributions, monosaccharide compositions, and protein contents. The changes in the ethanol soluble fraction including ascorbic acid degradation, acid-catalyzed hydrolysis of sucrose, and formation of furfural and 5-hydroxymethylfurfural were highly correlated to the browning development of the juice during storage.

Melicope pteleifolia has long been consumed as a popular vegetable and tea in Southeast Asian countries, including Malaysia and southern mainland China, and is effective in the treatment of colds and inflammation. In the search for active metabolites that can explain its traditional use as an antipyretic, six new phloroacetophenone derivatives ( 3 - 8 ) along with seven known compounds ( 1 , 2 , and 9 - 13 ) were isolated from the leaves of M. pteleifolia . Their chemical structures were confirmed by extensive spectroscopic analysis including NMR, IR, ECD, and HRMS. All compounds isolated from the leaves of M. pteleifolia ( 1 - 13 ) have a phloroacetophenone skeleton. Notably, the new compound 8 contains an additional cyclobutane moiety in its structure. The bioactivities of the isolated compounds were evaluated, and compounds 1 , 6 , and 7 inhibited tumor necrosis factor-α-induced prostaglandin E 2 . Moreover, the major constituent, 3,5-di- C -β-d-glucopyranosyl phloroacetophenone ( 1 ), was found to be responsible for the antipyretic activity of M. pteleifolia based on in vivo experiments.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Hyper-activated STAT5B variants are high value oncology targets for pharmacologic intervention. STAT5B N642H , a frequently-occurring oncogenic driver mutation, promotes aggressive T-cell leukemia/lymphoma in patient carriers, although the molecular origins remain unclear. Herein, we emphasize the aggressive nature of STAT5B N642H in driving T-cell neoplasia upon hematopoietic expression in transgenic mice, revealing evidence of multiple T-cell subset organ infiltration. Notably, we demonstrate STAT5B N642H -driven transformation of γδ T-cells in in vivo syngeneic transplant models, comparable to STAT5B N642H patient γδ T-cell entities. Importantly, we present human STAT5B and STAT5B N642H crystal structures, which propose alternative mutation-mediated SH2 domain conformations. Our biophysical data suggests STAT5B N642H can adopt a hyper-activated and hyper-inactivated state with resistance to dephosphorylation. MD simulations support sustained interchain cross-domain interactions in STAT5B N642H , conferring kinetic stability to the mutant anti-parallel dimer. This study provides a molecular explanation for the STAT5B N642H activating potential, and insights into pre-clinical models for targeted intervention of hyper-activated STAT5B.

Herein, we report a functionalized alginate(Alg)-based terpolymeric semi-interpenetrating (semi-IPN) hydrogel, synthesized via free radical polymerization for the delivery of bovine albumin serum (BSA) and 5-amino salicylic acid (5-ASA). To improve mechanical properties, and to modulate surface morphology of Alg, 2-hydroxyethyl acrylate (HEA) was grafted on alginate and then crosslinked using poly(ethylene glycol) diacrylate (PEGDA). The probable structure and compositions of the synthesized semi-IPN terpolymer were identified by FTIR, 1 H-HR-MAS NMR, and TGA analyses. Achievement of equilibrium swelling state (ESS) and higher elastic modulus values confirmed terpolymer gel formation in aqueous media. Differences in the ESS of the prepared gel at pH 2.5 and 7.4 signify its stimuli-responsive behaviour. The influence of PEGDA on swelling, mechanical properties, surface morphology, cell viability and proliferation, and BSA and 5-ASA delivery were characterized. SEM images show that higher % PEGDA resulted in smaller sized pores in the gel network. Texture analyses demonstrate that hardness, adhesiveness and chewiness of the gel were enhanced at higher PEGDA concentrations. Increases in PEGDA concentration also induced increases in osteoblastic cell viability and higher rates of cell proliferation compared with gels containing lower concentrations of PEGDA. The release results indicate that the gels containing higher concentrations of PEGDA more sustainably release BSA and 5-ASA at 5 days and 30 h, respectively. The experimental data revealed that the synthesized terpolymeric semi-IPN hydrogel may have useful biomedical applications, especially as a carrier of protein (BSA), or 5-ASA (a therapeutic option for conditions of the colon such as Crohn's Disease and Ulcerative Colitis)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Sialylated oligosaccharides contribute 12.6-21.9% of total free oligosaccharides in human milk ( hMOS). These acidic hMOS possess prebiotic properties and display antiadhesive effects against pathogenic bacteria. Only limited amounts of sialylated hMOS are currently available. The aim of our work is to enzymatically synthesize sialylated oligosaccharides mimicking hMOS functionality. In this study, we tested mixtures of glucosylated-lactose (GL34), galactosylated-lactulose (LGOS), and galacto-oligosaccharide (Vivinal GOS) molecules, as trans-sialylation acceptor substrates. The recombinant trans-sialidase enzyme from Trypanosoma cruzi (TcTS) was used for enzymatic decoration, transferring (α2→3)-linked sialic acid from donor substrates to nonreducing terminal β-galactopyranosyl units of these acceptor substrates. The GL34 F2 2-Glc-Lac compound with an accessible terminal galactosyl residue was sialylated efficiently (conversion degree of 47.6%). TcTS sialylated at least 5 LGOS structures and 11 Vivinal GOS DP3-4 compounds. The newly synthesized sialylated oligosaccharides are interesting as potential hMOS mimics for applications in biomedical and functional-food products.

Japanese encephalitis virus (JEV) is classified into 5 genotypes (GI, GII, GIII, GIV, and GV), and the GI and GIII strains are the most widely distributed in JE endemic areas. In recent years, GV JEV has been detected in China and Korea, suggesting that GV JEV may invade other JE endemic areas, including Vietnam, and that more attention should be paid to the JEV strains circulating in these areas. In this study, we investigated the neutralization ability of the sera collected from 22 Vietnamese patients with JE who lived in northern Vietnam against the GI and GV JEV strains. In most cases, the ratios of the titer against GV to that against GI (GV:GI) were equal to or less than 1:4. However, the titer against GV JEV was equivalent (1:1) to that against GI JEV in only a few cases, and no serum had a ratio higher than 1:1. Thus, our results did not show convincing evidence that GV JEV was emerging in northern Vietnam in 2014.

Ecklonia cava is edible seaweed that is found in Asian countries, such as Japan and Korea; and, its major components include fucoidan and phlorotannins. Phlorotannins that are isolated from E. cava are well-known to have an antioxidant effect and strong antiviral activity against porcine epidemic diarrhea virus (PEDV), which has a high mortality rate in piglets. In this study, the bioactive components were determined based on two different approaches: (i) bio-guided isolation using the antiviral activity against the H1N1 viral strain, which is a representative influenza virus that originates from swine and (ii) high-resolution mass spectrometry-based dereplication, including relative mass defects (RMDs) and HPLC-qTOFMS fragmentation analysis. The EC70 fraction showed the strongest antiviral activity and contained thirteen phlorotannins, which were predicted by dereplication. Ten compounds were directly isolated from E. cava extract and then identified. Moreover, the dereplication method allowed for the discovery of two new phlorotannins. The structures of these two isolated compounds were elucidated using NMR techniques and HPLC-qTOFMS fragmentation analysis. In addition, molecular modelling was applied to determine the absolute configurations of the two new compounds. The antiviral activities of seven major phlorotannins in active fraction were evaluated against two influenza A viral strains (H1N1 and H9N2). Six of the compounds showed moderate to strong effects on both of the viruses and phlorofucofuroeckol A ( 12 ), which showed an EC 50 value of 13.48 ± 1.93 μM, is a potential active antiviral component of E. cava .

As part of an ongoing study of new insulin mimetic agents from medicinal plants, the 70% EtOH extract of Symplocos cochinchinensis was found to have a stimulatory effect on glucose uptake in 3T3-L1 adipocyte cells. The intensive targeted isolation of this active extract resulted in ten new hydroxyoleoside-type compounds conjugated with a phenolic acid and monoterpene (1-6 and 8-11), as well as four known compounds (7 and 12-14). The chemical structures of the new compounds were determined based on spectroscopic data analysis ( 1 H and 13 C NMR, HSQC, HMBC, NOESY and MS). The absolute configurations of the isolated compounds were determined by electronic circular dichroism (ECD) analysis of derivatives obtained after a series of reactions, such as those with dirhodium (ІІ) tetrakis (trifluoroacetate) and dimolybdenum (ІІ) tetraacetate. In vitro, compounds 3, 7 and 8 moderately increased the 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) uptake level in differentiated 3T3-L1 adipocytes. For further studies, we evaluated their effects on the expression of glucose transporter-4 (GLUT4), its translocation, protein tyrosine phosphatase 1B (PTP1B) inhibition and expression of phosphorylated Akt. Our results strongly suggest that the traditional uses of this plant can be described as active constituents by hydroxyoleoside-type compounds.

The aging population is growing rapidly around the world and there is also an increase in sarcopenia, which is characterized by decreased muscle mass, strength and function in the elderly population. AMP-activated protein kinase (AMPK) is an essential sensor and regulator of glucose, lipid and energy metabolism throughout the body. Previous studies have shown that AMPK pathway activation by regular exercise and appropriate dietary control have beneficial effects on skeletal muscle. In the process of searching for new AMPK activators from medicinal plants, we isolated and characterized eight new 12,23-dione dammarane triterpenoids (1-3 and 5-9), as well as one known gypentonoside A from Gynostemma longipes. When all isolates were tested for their AMPK activation activities, seven compounds (1 and 3-8) were significantly activated AMPK phosphorylation in mouse C2C12 skeletal muscle cell lines. Since G. longipes contained a significant amount of active compound 1 (over 2.08% per dried raw plant), it suggested the potential of this plant to be developed as a functional food or botanical drug that enhances muscle proliferation by activating AMPK signaling pathways.

Previously we structurally characterized five glucosylated lactose derivatives (F1-F5) with a degree of polymerization (DP) of 3-4 (GL34), products of Lactobacillus reuteri glucansucrases, with lactose and sucrose as substrates. Here, we show that these GL34 compounds are largely resistant to the hydrolytic activities of common carbohydrate-degrading enzymes. Also, the ability of single strains of gut bacteria, bifidobacteria, lactobacilli, and commensal bacteria, to ferment the GL34 compounds was studied. Bifidobacteria clearly grew better on the GL34 mixture than lactobacilli and commensal bacteria. Lactobacilli and the commensal bacteria Escherichia coli Nissle and Bacteroides thetaiotaomicron only degraded the F2 compound α-D-Glcp-(1 → 2)-[β-D-Galp-(1 → 4)-]D-Glcp, constituting around 30% w/w of GL34. Bifidobacteria digested more than one compound from the GL34 mixture, varying with the specific strain tested. Bifidobacterium adolescentis was most effective, completely degrading four of the five GL34 compounds, leaving only one minor constituent. GL34 thus represents a novel oligosaccharide mixture with (potential) synbiotic properties towards B. adolescentis, synthesized from cheap and abundantly available lactose and sucrose.

A library of extracted natural materials (Korea Bioactive Natural Material Bank) have been screened to discover candidates for the treatment of non-alcoholic liver disease (NAFLD), and the 70% ethanol extract of Sicyos angulatus was found to inhibit hepatic lipid accumulation. Bioassay-guided fractionation of this bioactive extract yielded five previously undescribed flavonoid glycosides and one previously undescribed flavonolignan glycoside along with seven known flavonoid glycosides. The chemical structures of these compounds were elucidated by a combination of extensive spectroscopic analysis, including MS, NMR and UV techniques. Eight compounds of all isolated compounds showed inhibitory effects on the lipid accumulation induced by high concentrations of palmitic acid and glucose in HepG2 cells. Four selected compounds were tested for lipid content in a dose-dependent manner (10, 20 and 40 μM), and among those compounds, kaempferol 3-O-β-d-glucopyranosyl-7-O-α-l-rhamnopyranoside showed the strongest inhibition of hepatic lipid production in HepG2 cells. In an oil-red O staining assay, five compounds were shown to reduce hepatic lipid accumulation better than what was observed in the vehicle control group. The present study suggests a new class of chemical entities for developing bioactive agents for the treatment of diseases caused by fat accumulation in the liver., (Copyright © 2018 Elsevier Ltd. All rights reserved.)