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Abstract Bloodstream infection (BSI) poses a global health problem, with diverse organisms and rising antimicrobial resistance (AMR). Here, we characterized trends in BSI prevalence, AMR, and antibiotic use at a Vietnamese infectious diseases hospital from 2010 to 2020. Among 108,303 cultured blood samples, 8.8% were positive, yielding 7995 pathogens. Of 7553 BSI cases, 86.4% were community-acquired. BSI prevalence varied from 17 to 35 cases/1000 admissions/year, highest in HIV/hepatitis wards and patients >60. The in-hospital mortality or hospice discharge outcome was 21.3%. The top three pathogens, E. coli (24%), K. pneumoniae (8.7%) and S. aureus (8.5%) exhibited increasing prevalence and multidrug resistance. Pathogens like Cryptococcus neoformans (8.4%), Talaromyces marneffei (6.7%), and Salmonella enterica (6.5%) declined. E. coli and K. pneumoniae were prevalent in older adults with community-acquired BSIs. Antibiotic use reached 842.6 DOT/1000 PD and significantly reduced after an antibiotic control policy. Enhanced surveillance and antimicrobial stewardship are crucial for managing BSIs in Vietnam.

Abstract Histone deacetylases (HDACs) play a crucial role in transcriptional regulation and are implicated in various diseases, including cancer. They are involved in histone tail deacetylation and canonically linked to transcriptional repression. Previous studies suggested that HDAC recruitment to cell-cycle gene promoters via the retinoblastoma (RB) protein or the DREAM complex through SIN3B is essential for G1/S and G2/M gene repression during cell-cycle arrest and exit. Here we investigate the interplay among DREAM, RB, SIN3 proteins, and HDACs in the context of cell-cycle gene repression. Knockout of SIN3B does not globally derepress cell-cycle genes in non-proliferating HCT116 and C2C12 cells. Loss of SIN3A/B moderately upregulates several cell-cycle genes in HCT116 cells but does so independently of DREAM/RB. HDAC inhibition does not induce general upregulation of RB/DREAM target genes in arrested transformed or non-transformed cells. Our findings suggest that E2F:RB and DREAM complexes can repress cell-cycle genes without relying on HDAC activity.

IntroductionCurrent social issues such as bullying, online violence, and local conflicts are all prominent topics in the field of psychology and linked to dehumanization. However, research on dehumanization from a non-Western background has been rare. As a key factor influencing individual behavior, attachment has not been sufficiently integrated into studies on dehumanization. Therefore, this study provides empirical evidence to explore the relationship between adult attachment (both trait and state) and dehumanization. The sample consisted of college students from China.MethodsIn Study 1 (N = 705) latent profile analysis was employed to exploring the potential categories of trait adult attachment in China, and to investigate how these categories impact dehumanization. Study 2 (N = 281) focused on activating secure attachment and examined the effects of three state attachment types, security, avoidance and anxiety, on dehumanization.ResultsStudy 1 identified four types of adult attachment: preoccupied, secure, fearful, and dismissing, and revealed that these different attachment types have varying impacts on dehumanization. Study 2 showed that both security and avoidance predict dehumanization.DiscussionThis research established a link between adult attachment and dehumanization, offering new insights into the psychological mechanisms underlying dehumanization and suggesting novel strategies for its prevention and intervention.

Three main areas of research revolve around extracellular vesicles (EVs): their use as early detection diagnostics for cancer prevention, engineering of EVs or other enveloped viral-like particles for therapeutic purposes and to understand how EVs impact biological processes. When investigating the biology of EVs, it is important to consider strategies able to track and alter EVs directly in vivo, as they are released by donor cells. This can be achieved by suitable engineering of EV donor cells, either before implantation or directly in vivo. Here, we make a case for the study of native EVs, that is, EVs released by cells living within a tissue. Novel genetic approaches to detect intercellular communications mediated by native EVs and profile recipient cells are discussed. The use of Rab35 dominant negative mutant is proposed for functional in vivo studies on the roles of native EVs. Ultimately, investigations on native EVs will tremendously advance our understanding of EV biology and open novel opportunities for therapy and prevention.

Purpose: Recruiting prospective physicians to radiation oncology can be challenging, because of limited familiarity with the field. The Assistant Clinical Research Coordinator (ACRC) program can help provide trainees early exposure to radiation oncology. Methods and Materials: The ACRC program involves hiring a college graduate to provide administrative and research support for faculty members. The program was developed with our institution's clinical trials office, which provided guidance on regulatory compliance and training. A structured selection process identifies top candidates, and a rigorous onboarding process ensures smooth transitions between ACRCs. We report characteristics and outcomes of ACRC employees and surveyed them to assess their program experience using a Likert scale. Results: From 2005 to 2023, the ACRC program paired 73 ACRCs with faculty. Most faculty (68%) are currently supported by ACRCs. In 2023, 113 applications were received for 4 positions. ACRCs have contributed to research publications (293 as coauthors and 43 as first authors) and taken on leadership roles in the department. Most program alumni have attended medical school (34 of 64 program graduates; 53%). Eight have chosen to specialize in radiation oncology (13%; 2 applying into radiation oncology, 1 in residency, and 5 attendings). Of the 25% of alumni who responded to our survey, 77% responded that the mentorship provided by the ACRC program was very or extremely effective in guiding their academic development. All respondents rated the research opportunities as good or excellent, and 77% rated the clinical experience opportunities as good or excellent. Most (77%) reported that the ACRC program had substantial or significant influence on their choice of career path. Conclusions: The ACRC program provides an opportunity to address recruitment challenges in radiation oncology by offering early exposure to the field, clinical research skills, and mentorship. With the strong interest in our job posting this year, there is potential to expand this program to other institutions.

Objectives: SARS-CoV-2 transmission and epidemic potential is related to the population's immunity levels. As such, assessing different regions’ preexisting immune responses to SARS-CoV-2 is important to understand the transmission potential of emerging SARS-CoV-2 variants. Design: In 975 serum samples from Vietnam (2014 to 2019), anti-SARS-CoV-2 Immunoglobulin G levels were determined by enzyme-linked immunosorbent assay. Plaque reduction neutralization test (PRNT) was performed using Wuhan strain and variants of concern (VOCs). Cross-reactivity was confirmed by analyzing B-cell receptor (BCR) repertoire sequences and identifying BCR repertoire sequences-derived T-cell epitopes. Results: Overall, 20.9% (n = 76/364) and 9.2% (n = 7) demonstrated SARS-CoV-2 neutralizing activity (PRNT50) against the Wuhan and Alpha strain, respectively. Neutralizing activity against Beta, Gamma, and Delta strains was absent (PRNT50

Abstract Background Vietnam is undergoing a rapid epidemiological transition with a considerable burden of non-communicable diseases (NCDs), especially hypertension and diabetes (T2DM). Continuity of care (COC) is widely acknowledged as a benchmark for an efficient health system. This study aimed to determine the COC level for hypertension and T2DM within and across care levels and to investigate its associations with health outcomes and disease control. Methods A cross-sectional study was conducted on 602 people with T2DM and/or hypertension managed in primary care settings. We utilized both the Nijmegen continuity of care questionnaire (NCQ) and the Bice - Boxerman continuity of care index (COCI) to comprehensively measure three domains of COC: interpersonal, informational, and management continuity. ANOVA, paired-sample t-test, and bivariate and multivariable logistic regression analysis were performed to examine the predictors of COC. Results Mean values of COC indices were: NCQ: 3.59 and COCI: 0.77. The proportion of people with low NCQ levels was 68.8%, and that with low COCI levels was 47.3%. Primary care offered higher informational continuity than specialists (p

In this paper, we report a simple yet efficient method for rapid and high-performance SERS substrate fabrication by a combination of cold plasma and laser treatment. Our analysis reveals that cold plasma pre-treatment significantly reduced surface roughness, transforming 200 nm spikes into an almost perfectly uniform surface, while enhancing the substrate’s surface energy by lowering the water contact angle from 59° to 0°, all achieved within just 30 s of 0.9-mW plasma treatment, while 15-min green-laser treatment facilitated more uniform deposition of AuNPs across the entire treated area, effectively creating the SERS substrates. The combined treatments result in enhancement of the Raman intensity (11 times) and consistency over the whole area of the SERS substrates, and their reusability (up to 10 times). The fabricated SERS substrates exhibit a significant enhancement factor of approximately 3 × 10⁸ with R6G, allowing detection down to a concentration of 10−12 M. We demonstrate the application of these SERS substrates by detecting amoxicillin—an antibiotic used worldwide to treat a diversity of bacterial infections—in a dynamic expanded linear range of seven orders (from 10−3 to 10−9 M) with high reliability (R2 = 0.98), and a detection limit of 9 × 10−10 M. Our approach to high-performance SERS substrate fabrication holds potential for further expansion to other metallic NPs like Ag, or magnetic NPs (Fe3O4).

Ischemia and subsequent reperfusion (IR) produces injury to brain, eye and other tissues, contributing to the progression of important clinical pathologies. The response of cells to IR involves activation of several signaling pathways including those activating hypoxia and heat shock responsive transcription factors. However, specific roles of these responses in limiting cell damage and preventing cell death after IR have not been fully elucidated. Here, we have examined the role of heat shock factor 1 (HSF1) in the response of zebrafish embryos to hypoxia and subsequent return to normoxic conditions (HR) as a model for IR. Heat shock preconditioning elevated heat shock protein expression and protected zebrafish embryo eye and brain tissues against HR-induced apoptosis. These effects were inhibited by translational suppression of HSF1 expression. Reduced expression of HSF1 also increased cell death in brain and eye tissues of embryos subjected to hypoxia and reperfusion without prior heat shock. Surprisingly, reduced expression of HSF1 had only a modest effect on hypoxia-induced expression of Hsp70 and no effect on hypoxia-induced expression of Hsp27. These results establish the zebrafish embryo as a model for the study of ischemic injury in the brain and eye and reveal a critical role for HSF1 in the response of these tissues to HR. Our results also uncouple the role of HSF1 expression from that of Hsp27, a well characterized heat shock protein considered essential for cell survival after hypoxia. Alternative roles for HSF1 are considered.

Abstract An HPMC-based nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (nasal antibody spray or NAS) was developed to strengthen COVID-19 management. NAS exhibited potent broadly neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, ancestral, Delta, Omicron BA.1, BA.2, BA.4/5, and BA.2.75. Biocompatibility assessment showed no potential biological risks. Intranasal NAS administration in rats showed no circulatory presence of human IgG1 anti-SARS-CoV-2 antibodies within 120 h. A double-blind, randomized, placebo-controlled trial (NCT05358873) was conducted on 36 healthy volunteers who received either NAS or a normal saline nasal spray. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. NAS was well tolerated, with no significant adverse effects during the 14 days of the study. The SARS-CoV-2 neutralizing antibodies were detected based on the signal inhibition percent (SIP) in nasal fluids pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SIP values in nasal fluids collected immediately or 6 h after NAS application were significantly increased from baseline for all three variants tested, including ancestral, Delta, and Omicron BA.2. In conclusion, NAS was safe for intranasal use in humans to increase neutralizing antibodies in nasal fluids that lasted at least 6 h.

In today's uncertain business setting, the intensity of rivalry amongst service firms requires a high level of quality and adaptability from service staff to fulfill increasing customer needs and wants. Indeed, every individual's ability to adjust to changing demands is vital for management to promote within their companies. The present study proposes and tests a novel self-regulatory adapting mechanism to examine the conditions within which service staff might activate their ambidextrous behavior which can be beneficial for their proactive service performance. Based on Trait Activation theory (TAT), Individual Adaptability Theory, and Job demands-resources theory, we analyze the direct and mediating effects of certain personal characteristics (Proactive Personality) and initiatives (Playful work design and Uncertainty adaptability) to activate the ambidextrous mode of employees toward higher proactive service performance. To test our hypotheses, we collected survey data from 368 frontline banking employees in all three regions of Vietnam. Practically, the results and recommendations from this study will assist in the hands-on management and motivation of service representatives toward better proactive performance.

The engine oil signifies key importance in the automobile industry. The thermal capataince of engine oil is quite necessary to retained the peak performances. The aim of current research is to enhance the thermal mechanism of engine oil base fluid with applications of hybrid-nanofluid. The graphene oxide and molybdenum disulfide nanoparticles are used to justify the thermal mechanism of hybrid nanofluid. The contribution of magnetic force and buoyancy forces are consdeired. The equations of velocity and temperature are transformed into non-dimensional forms with dimensionless parameters. The problem is transformed to fractional form by employing the Atangana-Baleanu fractional approach and generalized Fourier’s law. These equations are solved with the Laplace transform. Disparities in momentum and energy are exposed to several fractional and material parameters. It has been observed that temperature profile increases due to nanoparticles volume fraction and fractional parameter. The increasing impact of Grashof number is observed on velocity field.

In the modern world, research in the field of thermal enhancement is going to increasing due to their diverse applications in the field of chemical industries and engineering domains. In the current study, the hydrodynamic or magnetohydrodynamics (MHD) instability of Hartmann flow in the porous medium is considered. Here, the special nature of magnetic field known as the transverse magnetic field is used in the current analysis. The investigation of hydrodynamic stability of electrically conductive for Hartmann flow in channel along with applied magnetize field is analyzed. The fluid layers are penetrated by a constant magnetize field and flow is considered through porous medium. Reynolds number (Re) is utilized to main system of hydrodynamic stability equations. A Chebyshev collocation technique is applied through numerical method to analyze magnetohydrodynamic instability system. The obtained flow equations represent system of ODEs. The current analysis makes use of a unique type of magnetic field known as the transverse magnetic field. The instabilities of nanofluids that contains nanoparticles with water as based fluid for with physical parameters are compared and discussed for growth rate and neutral graphs. These flow equations are solved numerically by using “Cheybeshev Collocation Method”. The mathematical technique “QZ (Qualitat and Zuverlassigkeit)” is applied to find out eigenvalues from comprehensive Orr-sommerfeld technique by using MATLAB software. Different embedded physical parameters Reynolds number (Re), Hartmann number (Ha) wave number (k) are compared and discussed for growth rate and neutral graphs. The instabilities of Hartmann flow in porous medium different embedded physical parameters are compared and discussed using growth rate and neutral graphs. It predicted that the flow become stable due to the magnetic field, Reynolds number and wave number the fluids transportation. The outcomes of current study are utilized in drug-delivery systems, photodynamic therapy and delivery of antitumor.

The study examines the propagation of solitary waves in optical fibers controlled by the Radhakrishnan–Kundu–Lakshmanan model (RKL) equation, which includes a cubic–quintic non-Kerr refractive index. The first step in this study involves utilizing the extended algebraic method to derive solitonic solutions for the given equation. These solutions are subsequently graphically represented for a variety of parameter values. The proposed strategy allows for the discovery of a range of solutions.The controlling model is incorporated into a planar dynamical system via the Galilean transformation, resulting in the transformation of the governing model. The effects of both the quintic nonlinearity and self-phase modulation on the perturbed and unperturbed systems are explored using the effective potential and related phase portrait. The governing model is thus transformed into a planar dynamical system. Furthermore, this study harnessed a variety of numerical techniques. These methods encompassed time series analysis, phase portraits examination, and meticulous sensitivity inspections. Additionally, we employed a Poincaré section to assess the equation’s responsiveness to external perturbations. The outcomes reveal a fascinating observation: the perturbed system’s behavior shifts from a quasi-periodic state to a chaotic one, contingent upon the amplitude and frequency of the external perturbation. Moreover, we conducted multistability analysis for specific sets of physical parameters, uncovering the equation’s tendency to exhibit multistability in such scenarios.

AbstractThe current study aims at examining the impact of earnings management on equity liquidity in the Vietnam stock market when considering the direction of earnings management. We used two proxies of equity liquidity, namely quoted spread and effective spread, and analyzed the data using ordinary least squares (OLS), fixed and random effect models (FEM, REM), and regression with generalized least squares (GLS) to determine the most suitable model. The findings of the study indicate that when downward earnings management increases, the quoted spread also decreases, thus the bid-ask spread is low, meaning that the liquidity is high. This can be explained by the fact that when firms conduct downward earnings management to reduce taxes, investors may expect to buy stocks from these firms at a better price, leading to an increase in trading demand on the market. Whereas upward earnings management has no impact on quoted spread. Our results also showed that there is no evidence to suggest that earnings management has an impact on the effective spread. This means that, in the absence of other factors, an increase in earnings management in either upward or downward directions does not affect the difference between buying and selling prices.

AbstractThis paper aims to research factors that affect corporate social responsibility (CSR) disclosure in the context of listed companies in Vietnam. Our research uses data from listed companies in the Hanoi and Ho Chi Minh City Stock Exchanges from 2015 to 2020. We conduct the quantitative research by analyzing regression models therefore the relation between factors and CSR disclosure is found. We measure CSR disclosure in two ways: by total score and percentage. The result found that in both ways of measuring, the percentage of women on board and company age have a positive impact on CSR disclosure. In contrast to this, board size and board age have a negative effect on CSR disclosure. The other independent variables have no impact on CSR disclosure. Therefore, we have given some practical implications for companies that want to improve their CSR disclosure.

AbstractThis paper contributes to the literature by separately examining the impact of board characteristics and ownership structure on upward and downward earnings management of non-financial firms listed on Hanoi Stock Exchange and Ho Chi Minh Stock Exchange. In our research, we conduct Pooled OLS, Fixed and Random effect models, and Generalized least squares. Then, we run a regression with the System Generalized Method of Moments (System GMM) to find the most appropriate model. Firms with high average board age, high ownership concentration, and high financial leverage tend to manage earnings downward. High managerial ownership tends to reduce downward earnings management. Firms with high state ownership reduce upward earnings management. Stakeholders should be more cautious of firms with high average board age, high ownership concentration, high financial performance, and high financial leverage as they tend to manage earnings. Previous studies combined upward and downward earnings management in one regression model, therefore ignoring the chance to investigate the impact of board characteristics and ownership structure on earnings management in each case. The impact of a factor on upward and downward earnings management may be different, and the combination of them in one regression model can drive the findings of previous studies toward errors of unknown directions. Therefore, assessing the effects of board characteristics and ownership structure on earnings management in each case is necessary. To the best of our knowledge, this paper is the first to do so.

Concerns over the spread of non-native species in aquatic environments have led to the need for effective methods to prevent and control their spread while protecting native species. This study investigated the potential of yeast vacuolar enzymes as a natural hatching inhibitor for controlling aquatic organisms. Hatching experiments with Daphnia magna eggs demonstrated that exposure to yeast vacuole enzymes inhibited hatching in a concentration-dependent manner, suggesting their potential as an effective inhibitor of egg hatching in aquatic organisms. Interestingly, the protease used for comparative purposes did not inhibit hatching, but instead increased the mortality of hatched D. magna. Additionally, chorionic changes were observed in non-hatched D. magna eggs and zebrafish eggs exposed to yeast vacuole enzymes, suggesting that the enzyme can alter the chorion and interfere with hatching. These findings suggest that yeast vacuolar enzymes may be a promising and natural management tool for controlling the spread of harmful aquatic organisms, and further research is warranted to explore their potential for species-specific control.

With impressive thermal outcomes, the nanofluids present multidisciplinary applications in the cooling processes, thermal systems, extrusion processes, heat storage devices and many more. The aim of current research is to inspect thermal impact of Jeffrey fluid with tiny particles under the assumptions of variable thermal conductivity. The problem is supported with applications of chemical reaction, activation energy and magnetic force. For heat and mass transfer phenomenon, Cattaneo-Christov diffusion theories have been implemented. The formulated model is solved by using the homotopy analysis method (HAM) with excellent accuracy. The graphical analysis is performed with specified range of parameters like 0.2⩽H⩽0.8, 0.1⩽ϖ⩽1.7, 0.0⩽N⩽1.5, 0.0⩽Π⩽3.1, 0.3⩽γ⩽0.6, 0.6⩽Ψ⩽3.2, 0.5⩽Ω⩽2.0, 0.0⩽Σ⩽1.5, 0.2⩽Nt⩽1.7, 1.0⩽Pr⩽1.9, 0.5⩽Sc⩽1.4,0.3⩽β⩽1.5, 0.1⩽ε⩽1.0, 0.2⩽Nb⩽1.7. The assessment of flow parameters is graphically evaluated. It is observed that both velocity profiles periodically enhance for Deborah number while temperature, microorganisms and concentration distributions decelerate. The greater estimates of variable thermal conductivity and heat generation improve the temperature distribution while conflicting scenario ensures for thermic relaxation constant.

Abstract Loss of estrogen as a result of aging, pelvic cancer therapy, genetics, or eating disorders affects numerous body systems including the reproductive tract. Specifically, a chronic hypoestrogenic state fosters debilitating vaginal symptoms like atrophy, dryness, and dyspareunia. Current treatment options, including vaginal estrogen and hyaluronan (HA), anecdotally improve symptoms, but rectifying mechanisms are largely understudied. In order to study the hypoestrogenic vaginal environment, in particular the extracellular matrix (ECM), as well as understand the mechanisms behind current treatments and develop new therapies, we characterized a reliable and reproducible animal model. Bilateral ovariectomies (OVX) were performed on 9‐week‐old CD1 mice. After 1 month of estrogen loss due to ovarian removal, a phenotype that is similar to human vaginal tissue in an estrogen reduced state was noted in mice compared to sham‐operated controls. The uterine to body weight ratio decreased by 80% and vaginal epithelium was significantly thinner in OVX compared to sham mice. Estrogen signaling was altered in OVX, but submucosal ERα localization did not reach statistical differences. HA localization in the submucosal area was altered and CD44 expression decreased in OVX mice. Collagen turn‐over was altered following OVX. The inflammation profile was also disrupted, and submucosal vaginal CD45+ and F4/80+ cell populations were significantly reduced in the OVX mice. These results show altered cellular and molecular changes due to reduced estrogen levels. Developing new treatments for hypoestrogenic vaginal symptoms rely on better understanding of not only the cellular changes, but also the altered vaginal ECM environment. Further studies using this mouse model has the potential to advance women's vaginal health treatments and aid in understanding the interplay between organ systems in both healthy, aged, and diseased states.

Background and Aim: Mosaicism – the presence of both wild-type and mutant alleles – is a serious problem for zygotic gene modification through gene editing using the Clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR/ Cas9) system. Different delivery methods, such as microinjection (MI), electroporation (EP), and transfection (TF), can be used to transfer CRISPR/Cas9 components into porcine zygotes. This study aimed to develop a method that combines MI, EP, and TF to improve mutation efficiency mediated through the CRISPR/Cas9 system for a triple-gene knockout in pigs. Materials and Methods: The study consisted of three groups: The MI group with three simultaneously microinjected guide RNAs (gRNAs) targeting α-1,3-galactosyltransferase (GGTA1), cytidine 32 monophosphate-N-acetylneuraminic acid hydroxylase (CMAH), and β-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2); the MI + EP group with two gRNAs targeting GGTA1 and B4GALNT2 genes delivered into zygotes through MI, followed by EP of gRNA targeting the CMAH 1 h later; and the MI + EP + TF group with MI of gRNA targeting GGTA1 gene into zygotes, followed by EP of gRNA targeting CMAH 1 h later, and then TF of gRNA targeting the B4GALNT2 gene into zona-free zygotes after another hour. Results: The rate of blastocysts carrying mutations in one or two gene(s) was significantly higher in the MI + EP + TF group than in the MI group. However, the blastocyst formation rate of zygotes in the MI + EP + TF group was lower than that of the zygotes in the other treatment groups. Conclusion: The combination of CRISPR/Cas9 delivery methods may improve the mutation efficiency of triple-gene edited porcine blastocysts.

Abstract Background Epstein-Barr Virus (EBV)-associated nasopharyngeal carcinoma (NPC) exhibits unusual geographic restriction despite ubiquitous lifelong infection. Screening programs can detect most NPC cases at an early stage, but existing EBV diagnostics are limited by false positives and low positive predictive value (PPV), leading to excess screening endoscopies, MRIs, and repeated testing. Recent EBV genome-wide association studies (GWAS) suggest that EBV BALF2 variants account for more than 80% of attributable NPC risk. We therefore hypothesized that high-risk BALF2 variants could be readily detected in plasma for once-lifetime screening triage. Methods We designed and validated a multiplex genotyping assay to detect EBV BALF2 polymorphisms in human plasma. Targeted next-generation sequencing was used to validate this assay, conduct association studies with clinical phenotype, and longitudinally genotype plasma to assess within-host haplotype stability. We examined the association between NPC and BALF2 haplotypes in a large non-endemic population and three prior EBV GWAS. Finally, we estimated NPC mortality reduction, resource utilization, and cost-effectiveness of BALF2 variant-informed screening using a previously-validated cohort model. Results Following analytical validation, the BALF2 genotyping assay had 99.3% concordance with sequencing in a cohort of 24 NPC cases and 155 non-NPC controls. BALF2 haplotype was highly associated with NPC in this non-endemic population (I613V: odds ratio [OR] 7.9; V317M: OR 178.8). No other candidate BALF2 polymorphisms were significantly associated with NPC or hematologic disorders. Longitudinal genotyping revealed 97.8% within-host haplotype concordance, indicative of lifelong latent infection. In a meta-analysis of 755 NPC cases and 981 non-NPC controls, BALF2 I613V and V317M were significantly associated with NPC in both endemic and non-endemic populations. Modeled variant-informed screening strategies achieved a 46% relative increase in PPV with 7% decrease in effective screening sensitivity, thereby averting nearly half of screening endoscopies/MRIs among endemic populations in east/southeast Asia. Conclusions EBV BALF2 haplotypes are temporally stable within hosts and can be readily detected in plasma via an inexpensive multiplex genotyping assay that offers near-perfect sequencing concordance. In endemic and non-endemic populations, I613V and V317M were highly associated with NPC and could be leveraged to develop variant-informed screening programs that mitigate false positives with small reductions in screening sensitivity.

Abstract Canine mesenchymal stem cells (cMSCs) have potential applications for regenerative therapy, including the generation of insulin-producing cells (IPCs) for studying and treating diabetes. In this study, we established a useful protocol for generating IPCs from canine adipose mesenchymal stem cells (cAD-MSCs). Subsequently, in vitro preservation of pluronic F127-coated alginate (ALGPA)-encapsulated cAD-MSC-derived IPCs was performed to verify ready-to-use IPCs. IPCs were induced from cAD-MSCs with the modulated three-stepwise protocol. The first step of definitive endoderm (DE) induction showed that the cooperation of Chir99021 and Activin A created the effective production of Sox17-expressed DE cells. The second step for pancreatic endocrine (PE) progenitor induction from DE indicated that the treatment with taurine, retinoic acid, FGF2, EGF, TGFβ inhibitor, dorsomorphin, nicotinamide, and DAPT showed the significant upregulation of the pancreatic endocrine precursor markers Pdx1 and Ngn3. The last step of IPC production, the combination of taurine, nicotinamide, Glp-1, forskolin, PI3K inhibitor, and TGFβ inhibitor, yielded efficiently functional IPCs from PE precursors. Afterward, the maintenance of ALGPA-encapsulated cAD-MSC-derived IPCs with VSCBIC-1, a specialized medium, enhanced IPC properties. Conclusion, the modulated three-stepwise protocol generates the functional IPCs. Together, the encapsulation of cAD-MSC-derived IPCs and the cultivation with VSCBIC-1 enrich the maturation of generated IPCs.

Chikungunya fever is an acute febrile illness caused by the chikungunya virus (CHIKV), which is transmitted by Aedes mosquitoes. Since 1965, only a few studies with limited scope have been conducted on CHIKV in Vietnam. Thus, this study aimed to determine the seroprevalence and molecular epidemiology of CHIKV infection among febrile patients in Vietnam from 2017 to 2019. A total of 1063 serum samples from 31 provinces were collected and tested for anti-CHIKV IgM and IgG ELISA. The 50% focus reduction neutralization test (FRNT50) was used to confirm CHIKV-neutralizing antibodies. Quantitative real-time RT–PCR (RT–qPCR) was performed to confirm the presence of the CHIKV genome. The results showed that 15.9% (169/1063) of the patients had anti-CHIKV IgM antibodies, 20.1% (214/1063) had anti-CHIKV IgG antibodies, 10.4% (111/1063) had CHIKV-neutralizing antibodies, and 27.7% (130/469) of the samples were positive in RT–qPCR analysis. The E1 CHIKV genome sequences were detected among the positive RT–qPCR samples. Our identified sequences belonged to the East/Central/South/African (ECSA) genotype, which has been prevalent in Vietnam previously, suggesting CHIKV has been maintained and is endemic in Vietnam. This study demonstrates a high prevalence of CHIKV infection in Vietnam and calls for an annual surveillance program to understand its impact.

Background and Aim: We previously developed the gene-editing by electroporation (EP) of Cas9 protein method, in which the CRISPR/Cas9 system was introduced into porcine in vitro fertilized (IVF) zygotes through EP to disrupt a target gene. This method should be further developed, and a combination of EP and MI methods should be evaluated in pigs. This study aimed to determine that a combination of microinjection (MI) and EP of CRISPR/Cas9 system could increase the rates of biallelic mutation for triple-gene knockout in porcine blastocysts. We targeted the pancreatic and duodenal homeobox1 (PDX1) gene using cytoplasmic MI 1 h before or after EP, which was used to edit alpha-1,3-galactosyltransferase (GGTA1) and cytidine 32 monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) genes in porcine zygotes. Materials and Methods: We introduced guide RNAs targeting PDX1, GGTA1, and CMAH with the Cas9 protein into IVF zygotes (one-cell stage) through EP 10 h after the start of IVF (IVF; EP group) or in combination with MI (1 h before, MI-EP group, or after EP treatment EP-MI group) and evaluated the blastocyst formation rate and efficiency of target mutations in the resulting blastocysts. Results: Our results revealed a significant reduction in the rate of blastocyst formation in the two groups that underwent MI before and after EP (MI-EP and EP-MI group), compared with that in the groups treated with EP alone (EP group) (p=0.0224 and p

Abstract Background Dengue virus (DENV) is a member of insect vector-borne viruses, and it causes dengue fever. Southeast Asia is the epi-center of dengue fever in the world. The characterization of the virus is essential to identify the transmission and evolution of DENV. Objectives In 2017, there was an outbreak of Dengue virus type 1 (DENV1) in northern Vietnam and the neighboring countries. To identify the genetic character of the outbreak virus in the area, we conducted whole-genome sequencing analysis on the samples positive for the DENV1 along with real-time PCR. Study design In total, 1026 blood samples were collected from patients with suspected dengue fever in Ha Nam and Hai Duong province, nearby areas of the capital of Vietnam. After screening by real-time PCR, 40 of DENV1 positive samples were subjected to whole-genome sequencing, and 28 complete coding sequences were obtained. Results All 28 sequences were genotype I of DENV1, which is dominant in the southeast and East Asian countries. The phylogenetic analysis of the E region showed that they fell into a single cluster with the reported sequences from Vietnam between 2009 and 2016, in which the isolates from other countries are very rare. Our results suggested that the 2017 outbreak in the area was caused by locally circulating viruses.

Abstract Background Increasing the permeability of the zona pellucida (ZP) of oocytes before CRISPR/Cas9 electroporation may improve the efficiency of gene editing; however, the effects of this approach on subsequent developmental processes are unclear. In this study, the effects of ZP treatment before electroporation on embryonic development and gene editing in porcine embryos were evaluated. Methods The ZP of zygotes was weakened or removed by exposure to 0.5% actinase E, followed by electroporation of the Cas9 protein with guide RNA targeting GGTA1. Results The blastocyst formation rate of ZP‐free zygotes after electroporation was significantly lower (p

ObjectivesA phase II = design is used to evaluate the efficacy and feasibility of full dose docetaxel, platinum, and 5-fluorouracil (TPF) in a sequential chemoradiation treatment locally advanced (LA) or oligometastatic (OM) NPC patients.Materials and methodsTwenty patients with LANPC (M0 cohort) and six patients with OMNPC (M1 cohort) received induction standard dose T (75 mg/m2) P (75 mg/m2) F (750 mg/m2 IVCI x 5days) x 3 followed by weekly cisplatin (40 mg/m2) or carboplatin (AUC 1.5) x 6 concurrent with radiation therapy of 70 Gy over 6.5-7 weeks. The first five patients received bevacizumab as part of an exploratory objective of hypoxia modification using correlative fluoromisonidasole (18F-MISO) PET CT scanning.ResultsThe 18F-MISO imaging failed to reveal adequate levels of baseline hypoxia necessary to evaluate for changes with chemotherapy and bevacizumab. Ninety percent of M0 patients and 83% of M1 patients received the full-intended TPF and radiation dose. Eighty-five percent of M0 patients and all M1 patients received at least 60% of the full-intended concurrent platinum dose. The 2-year progression free survival (PFS) rate for the M0 cohort was 90% (95% CI: 77.8%- 100%), and was sustained at 5 years. The 2-year PFS rate for the M1 cohort was 66.7% (95% CI: 37.9%- 100%). The 2-year overall survival (OS) rates for the M0 and M1 cohorts were 100% and 83.3% (95% CI: 58.3%- 100%), respectively. At five years, OS was 94.4% for the M0 cohort.ConclusionAdministration of standard-dose TPF as induction chemotherapy in this NPC patient population is both feasible and effective when coupled with definitive concurrent chemoradiation.Clinicaltrials.gov identifierNCT00896181.

Dengue encephalitis is considered as a severe but unusual clinical presentation of dengue infection. Limited molecular information is available on the neurotropism of dengue virus (DENV), highlighting the need for further research. During a dengue outbreak in Vietnam in 2013, two DENV-3 strains were isolated, in which one was isolated from cerebrospinal fluid (CSF) samples from a dengue encephalitis patient and another strain was isolated from a patient with classical dengue fever in Hai Phong, Vietnam. DENV serotype-3 (DENV-3) isolated from these samples belonged to genotype III, marking the first report of this genotype in the country at that time. Genetic variation between both strains was elucidated by using a full genome sequencing by next-generation sequencing (NGS). The infectivity of the isolated DENV-3 strains was further characterized using human and mouse neuronal cell lines. Phylogenetic analysis of the isolates demonstrated high homogeneity between the CSF-derived and serum-derived DENV-3, in which the full genome sequences of the CSF-derived DENV-3 presented a Thr-1339-Ile mutation in the nonstructural 2A (NS2A) protein. The CSF-derived DENV-3 isolate grew preferentially in human neuronal cells, with a significant proportion of cells that were positive for nonstructural 1 (NS1), nonstructural 4B (NS4B), and nonstructural 5 (NS5) antigens. These results suggest that NS2A may be a crucial region in the neuropathogenesis of DENV-3 and its growth in human neuronal cells. Taken together, our results demonstrate that a CSF-derived DENV-3 has unique infectivity characteristics for human neuronal cells, which might play a crucial role in the neuropathogenesis of DENV infection.

Abstract The specificity and efficiency of CRISPR/Cas9 gene-editing systems are determined by several factors, including the mode of delivery, when applied to mammalian embryos. Given the limited time window for delivery, faster and more reliable methods to introduce Cas9-gRNA ribonucleoprotein complexes (RNPs) into target embryos are needed. In pigs, somatic cell nuclear transfer using gene-modified somatic cells and the direct introduction of gene editors into the cytoplasm of zygotes/embryos by microinjection or electroporation have been used to generate gene-edited embryos; however, these strategies require expensive equipment and sophisticated techniques. In this study, we developed a novel lipofection-mediated RNP transfection technique that does not require specialized equipment for the generation of gene-edited pigs and produced no detectable off-target events. In particular, we determined the concentration of lipofection reagent for efficient RNP delivery into embryos and successfully generated MSTN gene-edited pigs (with mutations in 7 of 9 piglets) after blastocyst transfer to a recipient gilt. This newly established lipofection-based technique is still in its early stages and requires improvements, particularly in terms of editing efficiency. Nonetheless, this practical method for rapid and large-scale lipofection-mediated gene editing in pigs has important agricultural and biomedical applications.

Abstract Objective Lipofection-mediated introduction of the CRISPR/Cas9 system in porcine zygotes provides a simple method for gene editing, without requiring micromanipulation. However, the gene editing efficiency is inadequate. The aim of this study was to improve the lipofection-mediated gene editing efficiency by optimizing the timing and duration of lipofection. Results Zona pellucida (ZP)-free zygotes collected at 5, 10, and 15 h from the start of in vitro fertilization (IVF) were incubated with lipofection reagent, guide RNA (gRNA) targeting GGTA1, and Cas9 for 5 h. Lipofection of zygotes collected at 10 and 15 h from the start of IVF yielded mutant blastocysts. Next, ZP-free zygotes collected at 10 h from the start of IVF were incubated with lipofection reagent, gRNA, and Cas9 for 2.5, 5, 10, or 20 h. The blastocyst formation rate of zygotes treated for 20 h was significantly lower (p

Purpose: An evolutionary action scoring algorithm (EAp53) based on phylogenetic sequence variations stratifies patients with head and neck squamous cell carcinoma (HNSCC) bearing TP53 missense mutations as high-risk, associated with poor outcomes, or low-risk, with similar outcomes as TP53 wild-type, and has been validated as a reliable prognostic marker. We performed this study to further validate prior findings demonstrating that EAp53 is a prognostic marker for patients with locally advanced HNSCC and explored its predictive value for treatment outcomes to adjuvant bio-chemoradiotherapy. Methods and Materials: Eighty-one resection samples from patients treated surgically for stage III or IV human papillomavirus-negative HNSCC with high-risk pathologic features, who received either radiation therapy + cetuximab + cisplatin (cisplatin) or radiation therapy + cetuximab + docetaxel (docetaxel) as adjuvant treatment in a phase 2 study were subjected to TP53 targeted sequencing and EAp53 scoring to correlate with clinical outcomes. Due to the limited sample size, patients were combined into 2 EAp53 groups: (1) wild-type or low-risk; and (2) high-risk or other. Results: At a median follow-up of 9.8 years, there was a significant interaction between EAp53 group and treatment for overall survival (P = .008), disease-free survival (P = .05), and distant metastasis (DM; P = .004). In wild-type or low-risk group, the docetaxel arm showed significantly better overall survival (hazard ratio [HR] 0.11, [0.03-0.36]), disease-free survival (HR 0.24, [0.09-0.61]), and less DM (HR 0.04, [0.01-0.31]) than the cisplatin arm. In high-risk or other group, differences between treatments were not statistically significant. Conclusions: The docetaxel arm was associated with better survival than the cisplatin arm for patients with wild-type or low-risk EAp53. These benefits appear to be largely driven by a reduction in DM.

In this work, we aimed to prepare chromium substituted cobalt ferrite Co(CrxFe1–x)2O4 powders by a simple coprecipitationannealing method with different Cr contents to create novel magnetic adsorbents for the removal of phosphate ions from water. The effects of Cr substitution on the crystal structure, phase composition, morphology, surface atomic composition, surface area and magnetic properties of our adsorbents were investigated by X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, Brunauer-Emmett-Teller nitrogen adsorption-desorption and vibrating sample magnetometry. According to the results, all our Co(CrxFe1–x)2O4 samples exhibited higher phosphate adsorption than CoFe2O4 powder but their magnetic properties were reduced for increasing Cr substitution. Among them, the Co(Cr0.25Fe0.75)2O4 sample was found to be the most promising material since its magnetic properties are still high to allow it to be easily separated from the solution and its maximum P adsorption capacity (according to the Langmuir model) was estimated to be 4.84 times higher than CoFe2O4, which can be attributed to the presence of Cr3+ ions on the surface and the enhanced surface specific area of this substituted sample. Moreover, the adsorption data of Co(Cr0.25Fe0.75)2O4 sample also fitted well to the pseudo second order kinetic model, revealing the adsorption rate constant of 0.87 mgP–1s–1, two times superior to CoFe2O4.

Abstract Nasopharyngeal carcinoma (NPC) is a squamous carcinoma with apparent geographical and racial distribution, mostly prevalent in East and Southeast Asia, particularly concentrated in southern China. The epidemiological trend over the past decades has suggested a substantial reduction in the incidence rate and mortality rate due to NPC. These results may reflect changes in lifestyle and environment, and more importantly, a deeper comprehension of the pathogenic mechanism of NPC, leading to much progress in the preventing, screening, and treating for this cancer. Herein, we present the recent advances on the key signal pathways involved in pathogenesis of NPC, the mechanism of Epstein‐Barr virus (EBV) entry into the cell, and the progress of EBV vaccine and screening biomarkers. We will also discuss in depth the development of various therapeutic approaches including radiotherapy, chemotherapy, surgery, targeted therapy, and immunotherapy. These research advancements have led to a new era of precision medicine in NPC.

Here, the authors report bi-functional, wide tropic macrocycles that bind the influenza viral envelope protein hemagglutinin and inhibit virus infection by blocking adsorption and fusion and show efficacy in preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models.

Background: Screening with anti-Epstein-Barr virus (EBV) serology and endoscopy decreased nasopharyngeal carcinoma (NPC) mortality in Guangdong in a randomized trial. We conducted a secondary analysis of this trial using local incidence and cost data to optimize screening programs, hypothesizing that screening could be cost-effective in southern China. Methods: Screening costs and life-years after NPC diagnosis were obtained from the Guangdong trial's intent-to-screen population (men and women aged 30-69). Seropositive subjects were rescreened annually for 5 years. Thereafter, we evaluated 12 screening strategies in Guangdong and Guangxi using a validated model. Strategies used combinations of serology, nasopharyngeal swab PCR (NP PCR), endoscopy, and MRI from trial subcohorts. Incidence data and costs were obtained from local cancer registries and the provincial healthcare system. Results: In the intent-to-screen population, screening with serology and endoscopy was cost-effective (¥42,366/life-year, 0.52 GDP per capita). Screening for 5 to 15 years between ages 35 and 59 years met a willingness-to-pay threshold of 1.5 GDP/quality-adjusted life-years in all modeled populations. Despite doubling costs, adding MRI could be cost-effective via improved sensitivity. NP PCR triage reduced endoscopy/MRI referrals by 37%. One-lifetime screen could reduce NPC mortality by approximately 20%. Conclusions: EBV-based serologic screening for NPC is likely to be cost-effective in southern China. Among seropositive subjects, the preferred strategies use endoscopy alone or selective endoscopy triaged by MRI with or without NP PCR. These data may aid the design of screening programs in this region. Impact: These findings support population-based screening in southern China by defining the target population, cost-effectiveness, and optimized screening approach. [ABSTRACT FROM AUTHOR]

Abstract Upon endoplasmic-reticulum (ER) stress, the ER-located transmembrane protein, Ire1, is autophosphorylated and acts as an endoribonuclease to trigger the unfolded protein response (UPR). Previous biochemical studies have shown that Ire1 exhibits strong endoribonuclease activity when its cytosolic kinase region captures ADP. Here, we asked how this event contributes to the regulation of Ire1 activity. At the beginning of this study, we obtained a luminal-domain mutant of Saccharomyces cerevisiae Ire1, deltaIdeltaIIIdeltaV/Y225H Ire1, which is deduced to be controlled by none of the luminal-side regulatory events. ER-stress responsiveness of deltaIdeltaIIIdeltaV/Y225H Ire1 was largely compromised by a further mutation on the kinase region, D797N/K799N, which allows Ire1 to be activated without capturing ADP. Therefore, in addition to the ER-luminal domain of Ire1, which monitors ER conditions, the kinase region is directly involved in the ER-stress responsiveness of Ire1. We propose that potent ER stress harms cells’ “vividness”, increasing the cytosolic ADP/ATP ratio, and eventually strongly activates Ire1. This mechanism seems to contribute to the suppression of inappropriately potent UPR under weak ER-stress conditions.

Abstract Objective Cytoplasmic microinjection and electroporation of the CRISPR/Cas9 system into zygotes are used for generating genetically modified pigs. However, these methods create mosaic mutations in embryos. In this study, we evaluated whether the gene editing method and embryonic stage for gene editing affect the gene editing efficiency of porcine embryos. Results First, we designed five guide RNAs (gRNAs) targeting the B4GALNT2 gene and evaluated mutation efficiency by introducing each gRNA with Cas9 protein into zygotes by electroporation. Next, the optimized gRNA with Cas9 protein was introduced into 1-cell and 2-cell stage embryos by either microinjection or electroporation. The sequence of gRNA affected the bi-allelic mutation rate and mutation efficiency of blastocysts derived from electroporated embryos. Microinjection significantly decreased the cleavage rates in each embryonic stage and blastocyst formation rates in 2-cell stage embryos compared with electroporation (p

Nasopharyngeal carcinoma (NPC) lacks effective diagnostic and therapeutic strategies, in particular at advanced stages. Here, the authors show that expression of the somatostatin receptor 2 is induced by Epstein-Barr virus in NPC and has a key role in the diagnosis, imaging, targeted therapies and prognosis of NPC.

In this study, we aimed to test whether embryonic development of blastocysts following injection of mouse induced pluripotent stem (iPS) cells can be improved by the supplementation of antioxidants during in vitro maturation. For this, we evaluated the effects of chlorogenic acid (CGA) and insulin–transferrin–selenium (ITS) supplementation either alone or in combination during oocyte in vitro maturation on the quality of porcine blastocysts and the embryonic development after injection of mouse iPS cells. Our results demonstrate that, prior to injection of mouse iPS cells, CGA or ITS supplementation either alone or in combination had no effects on the rates of oocyte maturation, oocyte DNA fragmentation, fertilization, and blastocyst formation. However, the combination of CGA and ITS significantly increased the total cell number in blastocysts compared with the control group (P

This paper was conducted to examine the relationship between dividend policy and share price volatility of companies listed on Hochiminh Stock Exchange (HOSE) in Vietnam. Data set used in this research was compiled from financial statements of 260 listed firms on HOSE from 2009 to 2018. Three statistical approaches employed to address econometrics issues as well as to improve the accuracy of the regression coefficients like fixed effects model (FEM), random effects model (REM) and general method of movement (GMM). Based on the results from GMM, the association between share price volatility and dividend yield, dividend payout ratio has been explored. The findings show a positive relationship between dividend yield and stock price volatilities and a negative relationship between dividend payout ratio and stock price volatility. In addition, it is found that a firm’s growth rate, leverage and earnings volatility had positive influences on share price volatility while firm’s size had negative effect on share price volatility.

Trong công trình này, màng tổ hợp của vật liệu graphene (Gr) – ống nano cácbon hai tường (DWCNT) và hạt nano kim loại vàng (AuNPs) (DWCNT-AuNPs-Gr) đã được chế tạo bằng phương pháp lắng đọng pha hơi nhiệt hóa học (CVD). Hình thái học bề mặt và các tính chất điện, điện hóa của vật liệu tổ hợp đã được khảo sát thông qua kính hiển vi điện tử quét phát xạ trường, phổ Raman, điện trở bốn mũi dò và kỹ thuật quét thế vòng (CV). Với nồng độ DWCNTs 0,3 g/L và tốc độ quay phủ 4000 vòng/phút, vật liệu DWCNTs-AuNPs-Gr có điện trở bề mặt giảm 2,3 lần so với màng Gr và đạt khoảng 549 W/sq; dòng đỉnh đáp ứng trong dung dịch 2 mM K3[Fe(CN)6]/K4[Fe(CN)6] trong 0,1 M PBS đạt 15,79 µA tại 50 mV/s, cao gấp 1,48 lần so với điện cực biến tính màng Gr và gấp 2,57 lần so với điện cực trần. Vật liệu DWCNTs-AuNPs-Gr có tiềm năng ứng dụng trong cảm biến điện hóa để phát hiện các phần tử sinh học khác nhau.

Human papilloma virus (HPV) vaccine for adolescents was recommended as an effective prevention strategy of HPV-related cancers. In Vietnam, HPV vaccination has not been introduced to male adolescent. This study was conducted to examine the acceptance of having boys vaccinated against HPV and its underlying reasoning, and to identify their parent's willingness to pay (WTP) for HPV vaccination in central Vietnam. 785 parents of boys were directly interviewed based on a structured questionnaire. Parent's acceptability of HPV vaccine for their sons was identified by one question with response on 3-point scale (agree, don't know, and disagree). Multivariate logistic regression model was used to determine contributing factors to participant's acceptance. Bidding game method was applied to elicit WTP values for HPV vaccination with initial bid of 161.2 USD. The results showed that 49.2% of parents agreed to have their sons vaccinated against HPV. Factors that influenced parent's acceptance including son's age older than 12 years (OR = 1.5; 95% CI: 1.08–1.98); being eldest son (OR = 1.6; 95% CI: 1.13–2.19), being mother (OR = 1.4; 95% CI: 1.01–1.91), parents with high educational level (OR = 1.7; 95% CI: 1.11–2.47) and their knowledge of HPV and HPV vaccine (OR = 1.8; 95% CI: 1.23–2.65). Average WTP value for full doses of HPV vaccine was 137.5 USD, ranging between 9 USD and 188.3 USD. Parents' knowledge of HPV and HPV vaccine was the only factor affecting WTP value (Rho: 0.11; p-value: 0.030). The findings suggest a strategy be introduced for HPV vaccination to male adolescents in Vietnam.

Phosphatidylcholine (PC) is produced via two distinct pathways in both hepatocytes and yeast, Saccharomyces cerevisiae. One of these pathways involves the sequential methylation of phosphatidylethanolamine (PE). In yeast cells, the methyltransferase, Cho2, converts PE to phosphatidylmonomethylethanolamine (PMME), which is further modified to PC by another methyltransferase, Opi3. On the other hand, free choline is utilized for PC production via the Kennedy pathway. The blockage of PC production is well known to cause endoplasmic reticulum (ER) stress and activate the ER-stress sensor, Ire1, to induce unfolded protein response (UPR). Here, we demonstrate that even when free choline is sufficiently supplied, the opi3Δ mutation, but not the cho2 Δ mutation, induces the UPR. The UPR was also found to be induced by CHO2 overexpression. Further, monomethylethanolamine, which is converted to PMME probably through the Kennedy pathway, caused or potentiated ER stress in both mammalian and yeast cells. We thus deduce that PMME per se is an ER-stressing molecule. Interestingly, spontaneously accumulated PMME seemed to aggravate ER stress in yeast cells. Collectively, our findings demonstrate the multiple detrimental effects of the low-abundance phospholipid species, PMME.

This study investigated the effects of plasma duration and different reactive species ratios of cold atmospheric-pressure plasma treatment on both physical and endogenous hormone changes in enhancing the germination and growth of mung bean seeds. Seed germination and sprout stem length were significantly enhanced after plasma treatment. The germination rate increased eleven times after 12 h, while the radicles’ length increased ~3 times after 96 h with optimal plasma treatment parameters. SEM images showed that the plasmas directly induced gradual changes in the seed coating, including deformed and shrunken epidermis, and cracks with sizes varying from 0.2 to 1.5 µm after 4 min of plasma treatment. Water contact angle was reduced from 73° with untreated seed to almost 0° with 4 min treated seed. These effects could lead to better water absorption on the surface of treated seeds. We found that a plasma energy dosage of 0.08 Wh per seed and NO concentration between 20–95 ppm were the optimal enhancement conditions. We also showed that, for the first time, through delicate extraction, separation, and quantification processes, NO-induced upregulation of the natural growth hormone gibberellic acid could be the dominant phytochemistry pathway responsible for the enhancement effect.

The evolution of influenza viruses is fundamentally shaped by within-host processes. However, the within-host evolutionary dynamics of influenza viruses remain incompletely understood, in part because most studies have focused on infections in healthy adults based on single timepoint data. Here, we analyzed the within-host evolution of 82 longitudinally sampled individuals, mostly young children, infected with A/H1N1pdm09 or A/H3N2 viruses between 2007 and 2009. For A/H1N1pdm09 infections during the 2009 pandemic, nonsynonymous minority variants were more prevalent than synonymous ones. For A/H3N2 viruses in young children, early infection was dominated by purifying selection. As these infections progressed, nonsynonymous variants typically increased in frequency even when within-host virus titers decreased. Unlike the short-lived infections of adults where de novo within-host variants are rare, longer infections in young children allow for the maintenance of virus diversity via mutation-selection balance creating potentially important opportunities for within-host virus evolution.

The introduction of exogenous molecules into embryos is required for analyses of molecular dynamics and specific gene functions during early embryonic development. Electroporation is an effective method to transport exogenous molecules into cells, but is rarely used in bovine embryos. First, we evaluated the viability of in vivo-derived bovine blastocysts after electroporation with fluorescein (FAM) labeled-oligonucleotides with varying pulse numbers (3, 5, 7, and 10), while keeping the pulse duration at 1 msec and the electric field of 20 V/mm. Next, we examined the effects of zona pellucida status on blastocyst quality after electroporation, by comparing the average diameter of blastocysts before and after electroporation using blastocysts with intact zona pellucida and hatching/hatched blastocysts. Electroporation successfully introduced exogenous molecules into in vivo-derived bovine blastocysts without loss of viability. Moreover, the status of the zona pellucida may be associated with the quality of blastocysts after electroporation.

Cytoplasmic microinjection (CI) of the CRISPR/Cas9 system enabled the induction of site-specific mutations in porcine zygotes and resulting pigs. However, mosaicism is a serious problem for genetically modified pigs. In the present study, we investigated suitable timing and concentration of CRISPR/Cas9 components for introduction into oocytes/zygotes by CI, to reduce mosaicism in the resulting blastocysts. First, we introduced 20 ng/μl of Cas9 protein and guide RNA (gRNA), targeting the α-1,3-galactosyltransferase (GalT) gene in oocytes before in vitro fertilization (IVF), in zygotes after IVF, or in oocytes/zygotes before and after IVF, twice. CI treatment had no detrimental effects on blastocyst formation rates. The highest value of the rate of mutant blastocysts was observed in zygotes injected after IVF. Next, we injected Cas9 protein and gRNA into zygotes after IVF at a concentration of 20 ng/μl each (20 ng/μl group) or 100 ng/μl each (100 ng/μl group). The ratio of the number of blastocysts that carried mutations to the total number of blastocysts examined in the 100 ng/μl group was significantly higher (P < 0.05) than that in the 20 ng/μl group. Although no blastocysts from the 20 ng/μl group carried a biallelic mutation, 16.7% of blastocysts from the 100 ng/μl group carried a biallelic mutation. In conclusion, increasing the concentration of Cas9 protein and gRNA is effective in generating biallelic mutant blastocysts. To reduce mosaicism, however, further optimization of the timing of CI, and the concentration of CRISPR/Cas9 components, is needed.