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BIVV003 is a gene-edited autologous cell therapy in clinical development for the potential treatment of sickle cell disease (SCD). Hematopoietic stem cells (HSC) are genetically modified with mRNA encoding zinc finger nucleases (ZFN) that target and disrupt a specific regulatory GATAA motif in the BCL11A erythroid enhancer to reactivate fetal hemoglobin (HbF). We characterized ZFN-edited HSC from healthy donors and donors with SCD. Results of preclinical studies show that ZFN-mediated editing is highly efficient, with enriched biallelic editing and high frequency of on-target indels, producing HSC capable of long-term multilineage engraftment in vivo, and express HbF in erythroid progeny. Interim results from the Phase 1/2 PRECIZN-1 study demonstrated that BIVV003 was well-tolerated in seven participants with SCD, of whom five of the six with more than 3 months of follow-up displayed increased total hemoglobin and HbF, and no severe vaso-occlusive crises. Our data suggest BIVV003 represents a compelling and novel cell therapy for the potential treatment of SCD.

Abstract Post-translational modifications of histone H3 on lysine 9, specifically acetylation (H3K9ac) and tri-methylation (H3K9me3), play a critical role in regulating chromatin accessibility. However, the role of these modifications in lineage segregation in the mammalian blastocyst remains poorly understood. We demonstrate that di- and tri-methylation marks, H3K9me2 and H3K9me3, decrease during cavitation and expansion of the rabbit blastocyst. Notably, H3K9me3 levels are particularly low in inner cell mass cells at the onset of blastocyst formation but increase again just before gastrulation. Conversely, H3K9ac is abundant in early blastocyst stages but decreases during the transition from the inner cell mass to the epiblast. These distinct distribution patterns correlate with high expression levels of methyltransferases (EHMT1, EHMT2, SETDB1) and deacetylases (HDAC1, HDAC2, HDAC5) in expanding blastocysts. Functionally, inhibiting H3K9me2/3 through an EHMT1/2 inhibitor disrupts primitive endoderm segregation, whereas enhancing histone acetylation (including H3K9ac) using a class I HDAC inhibitor promotes epiblast expansion at the expense of the primitive endoderm. These modifications impact the expression of genes associated with pluripotency and lineage determination, underscoring the importance of H3K9 modifications in embryonic cell fate decisions.

Abstract This study investigated Vietnamese people’s behavior and future intention to purchase medicines and functional foods online and their associated factors. From March to May 2023, a Google Form questionnaire was distributed via social networks and online platforms. Convenience and snowballing sampling methods were employed to recruit 1,305 Vietnamese people. In the past year, 50.3% of participants purchased at least one kind of medicine and/or functional foods online (medicines: 27.6%, functional foods: 45.1%). Among 656 buyers, nearly a third bought these products more than three times and only 5.9% felt dissatisfied with their previous experiences. This purchasing behavior was more prevalent among females, those married, having higher education levels, usually shopping online, having longer time of Internet use per day, and seeking health information on the Internet (p

Background Cervical cancer (CC) is preventable through regular screening and vaccination against human papillomavirus (HPV). However, CC remains a significant public health issue in low-income and middle-income countries (LMICs) like Vietnam, where financial constraints hinder the widespread implementation of HPV vaccination and screening programmes. Currently, Vietnam lacks both a national CC screening intervention and an HPV vaccination programme for women and girls. To date, cost-effectiveness studies evaluating CC screening methods in Vietnam remain limited.Objectives To evaluate the cost-effectiveness of two CC screening strategies for Vietnamese women aged 25–55 years: (1) cotesting combining cytology and HPV testing conducted three times at 5 year intervals (intervention) and (2) cytology-based screening conducted five times at 2 year intervals (comparator). The objective is to provide evidence to inform policy and clinical practice in Vietnam.Design Cost-effectiveness analysis using a Markov model with 1 year cycles to simulate the natural progression of CC.Setting The Vietnamese healthcare system, modelled from the provider’s perspective, with parameters adapted to the local context through expert consultations.Participants A simulated cohort of Vietnamese women aged 25–55 years.Interventions The intervention involved cotesting (cytology and HPV testing) three times at 5 year intervals. The comparator was cytology-based screening conducted five times at 2 year intervals.Primary and secondary outcome measures The primary outcome measure was quality-adjusted life years (QALYs). Costs and cost-effectiveness ratios were assessed using Vietnam’s gross domestic product (GDP) per capita as the cost-effectiveness threshold (1–3 times GDP per capita). Sensitivity analyses (one-way deterministic and probabilistic) were conducted to account for uncertainties.Results The cotesting strategy was less effective and more costly than cytology-based screening across all age groups. Cotesting resulted in higher costs and fewer QALYs than the comparator. Probabilistic sensitivity analyses confirmed that cotesting was not cost-effective under current conditions in Vietnam.Conclusions Cytology-based screening conducted five times at 2 year intervals is a more cost-effective option for CC screening in Vietnamese women aged 25–55 years. The cotesting strategy cannot be recommended due to its higher cost and lower effectiveness.

Abstract Objective To investigate Vietnamese people’s knowledge, attitudes, and experience in purchasing medicines and functional foods online. Methods Via an online survey, the data of 1,070 participants were collected, including their general characteristics, Internet use, previous experience, knowledge, and attitudes towards purchasing medicines/functional foods online. Factors associated with their knowledge and attitudes were identified via multivariate linear regression models. Results During 2022–2023, about 97.2% of participants used the Internet to seek health information (self-diagnosis: 65.0%, self-medication: 72.6%). Roughly 52.8% bought medicines and/or functional foods online. Among 565 buyers, 41.8% felt satisfied. Only 19.9% understood that selling medicines online was illegal in Vietnam. The main benefits of purchasing medicines/functional foods online that many people agreed on included convenience (87.1%), freedom from location (84.8%), and being able to order/buy products after opening hours (84.7%). Many people felt worried about the ability to buy counterfeit or substandard products (87.7%), inaccurate product information (85.0%), the lack of supervision of the authorities (83.7%), and increasing risks of drug abuse, self-medication, and treatment non-adherence (82.5%). Roughly 84.3% found distinguishing between legal and illegal online pharmacies difficult. Participants’ average knowledge and attitude scores were 6.514 ± 2.461 (range: 0–16) and 89.330 ± 13.720 (range: 23–115), respectively. The main factors associated with people’s knowledge and attitudes towards purchasing these products online included their frequency of Internet use, seeking health information online for self-medication, feeling satisfied with previous experience, and having at least one chronic disease. Conclusions Many Vietnamese people’s knowledge about purchasing medicines/functional foods online was limited. With the increasing need for online shopping, enhancing their knowledge is paramount. In the forthcoming years, when the Ministry of Health and relevant authorities publish legal documents and enact laws involving online pharmacies and trading medicines on the Internet, ways to recognize licensed online pharmacies must be widely propagated and disseminated in the community.

In the modern online society, where social networks are increasingly developed, the authenticity of information is one of the essential needs. There are many problems with detecting fake information, such as fake news detection, fake review detection, etc. Fake job description (FJD) detection is an interesting problem many groups have studied recently. However, current studies still need improvement in predictability. Therefore, this study develops a new method named NLP2FJD that utilizes deep learning-based NLP techniques for improving FJD detection. Firstly, we utilize the pre-trained Word2Vec to extract features from textual information from the dataset. Next, combining textual information and meta-information in the experimental dataset to improve the performance of FJD detection. The above two improvements will help the recommender system significantly improve the predictive ability of the proposed model. Finally, the empirical experiments are conducted to confirm the effectiveness of the proposed method on the experimental dataset compared with cutting-edge methods. The experimental results demonstrate that the NLP2FJD framework transcends other experimental methods for FJD detection on the experimental dataset. Besides, this study also conducts ROC curve analysis to show how to determine the optimal threshold for distinguishing the fake or real job description on the experimental dataset.

Landslides are one of the most frequent natural disasters that cause significant damage to property in Vietnam, which is characterized by mountainous terrain covering three-quarters of the territory. In 17 northern mountainous provinces of the country, over 500 communes are at a high to very high landslide hazard. The main goal of this study was to establish landslide hazard maps and conduct a comparative evaluation of the efficiency of the methods employed in Tinh Tuc town, Cao Bang province. The landslide hazard assessment was carried out in this study using the combined Fractal-frequency ratio (FFR) and the Frequency ratio (FR) methods. The FR method is based on the actualist principle, which assumes that future landslides may be caused by the same factors that contributed to slope failure in the past and present. The FFR method is based on the determination of the fractal dimension, which serves as a measure of the landslide filling density in the study area. Eight landslide-related factors were considered and presented in cartographic format: elevation, distance to roads, slope, geology, distance to faults, land use, slope aspect, and distance to drainage. Determining the area under the receiver operating characteristic curve (ROC-AUC) and verification index (LRclass) was performed to assess the performance of prediction models and the accuracy of the obtained maps. As a result, five zones were identified for the study area, characterized by very low, low, moderate, high, and very high landslide hazards. The analysis of the reliability of the obtained landslide hazard maps using the AUC and LRclass indices revealed that the FFR model has a higher degree of reliability (AUC = 86 %, LRclass = 86 %) compared to the FR model (AUC = 72 %, LRclass = 73 %); therefore, its use is more effective.

Since its public introduction in 2009, Bitcoin has grown to be the most well-known cryptocurrency worldwide. There is still debate as to whether Bitcoin may be used as a hedge against other assets. The purpose of this study is to investigate the correlation between Bitcoin and conventional commodity markets such as gold, crude oil, stock markets, and investor interest (quantified via Google Trends). In addition, the paper also tests Bitcoin’s safe haven role compared to other commodity markets. The Vector Autoregression model using daily database collected during the period 2013–2021 is employed to investigate the relationship between Bitcoin and traditional commodity markets. The impulse response function is used to analyze Bitcoin price movements against economic shocks from gold, oil prices, and the Dow Jones Industrial Average. In addition, the value-at-risk (VaR) model is used to test Bitcoin’s safe-haven property compared to other conventional commodity markets. The research results show that Bitcoin has negative impacts on gold, crude oil prices, and the stock market. Besides, Bitcoin responds negatively to a sharp decline in investor interest. Furthermore, the results of the VaR model show that Bitcoin is the second most volatile and risky asset, only after the crude oil market, and much riskier than gold. This result proves that Bitcoin cannot yet be considered a safe-haven instrument. These findings have several implications for investors and policymakers to minimize the risks associated with this cryptocurrency. AcknowledgmentThe authors would like to send their sincere thanks to the Reviewers and Editorial Board of the Journal. Their valuable comments and helpful support helped improve the paper’s quality. No funding was granted for this study.

Over the past decade, the textile-reinforced concrete (TRC) composite was gradually used to replace the fibre-reinforced polymer in the strengthening or repairing of existing reinforced-concrete structures, thanks to many criteria of sustainable development. The reinforcement ratio of textiles within TRC composites emerges as a crucial factor significantly impacting their reinforcement effectiveness, altering the material’s mechanical behaviour and properties. This study presents both experimental and numerical findings concerning the tensile behaviour of carbon TRC composites, exploring reinforcement ratios ranging from 0.5 to 1.5%. As experimental results, the carbon TRC specimens exhibited a strain-hardening behaviour with the cracking phase. The ultimate strength improved by 95 and 146% compared to that of non-reinforced specimens, respectively, with the reinforcement ratio of 0.92 and 1.32%. As numerical results, the model reached the strain-hardening curve with three distinct phases when the reinforcement ratio was higher than a critical value (0.7%). The effect of reinforcement ratio ranging from 0.5 to 1.5% on the mechanical behaviour and properties of carbon TRC was also highlighted and analysed.

Thiobencarb is an herbicide component extensively applied for weed control. In this study, the mixed culture of Pseudomonas sp. Th1 and Cupriavidus oxalaticus Th2 was determined for degradability towards thiobencarb at several conditions. The degradation of thiobencarb at 50 µM by the mixture of these strains in the medium without any co-substrate was 48.5±5.5% for 24 hours, increased to 78.0% with the addition of 0.5 mg/L ammonium sulfate and 0.5 mg/L succinate in to the medium. Moreover, the mixed culture could degrade the compound at quite ranges of NaCl concentrations, pH and temperatures. To increase the degradation of the compound in a commercial herbicide, bacteria were immobilized in a matrix consisting of polyvinyl alcohol and sodium alginate. The average degradation of thiobencarb in an herbicide named Satunil 60E by immobilized bacteria was 25.8% higher than that of non-immobilized bacteria at a cell density of 1.0×107 CFUs/mL.

Nghiên cứu được thực hiện nhằm tuyển chọn một số dòng nấm men có khả năng lên men ethanol và chịu được nhiệt độ cao. Trong nghiên cứu này, tổng cộng có 27 dòng nấm men được phân lập từ các nguồn nguyên liệu như trái cây chín, mùn cưa, bã mía, rỉ đường, hoa cây ăn quả và mật ong. Tuyển chọn được 14 dòng nấm men có khả năng lên men tốt trong dung dịch đường glucose (2,0% w/v). Trong thử nghiệm lên men ethanol từ dung dịch đường glucose (18,5% w/v), ba dòng MC1, MC2 và BM1 có khả năng lên men mạnh với nồng độ ethanol cao nhất đạt 11,0% (v/v). Trong đó, 2 dòng MC1 và BM1 có thể phát triển ở 40oC và có khả năng lên men glucose, sucrose và galactose. Dựa vào đặc điểm hình thái, đặc tính sinh lý, sinh hóa và giải trình tự vùng D1/D2 trên 26S rDNA, dòng nấm men MC1 và BM1 được tuyển chọn định danh với kết quả là Saccharomyces cerevisiae và Torulaspora globosa.

The authors would like to make the following corrections to the paper published [...]

This study utilized the WRF model to investigate the track evolution and rapid intensification (RI) of Typhoon Doksuri (2023) as it moved across the Luzon Strait and through the South China Sea (SCS). The simulation results indicate that Doksuri has a smaller track sensitivity to the use of different physics schemes, while having a greater intensity sensitivity. Sensitivity numerical experiments with different physics schemes can well capture its northwestward movement in the first two days, but they predict less westward track deflection as the typhoon moves across the Luzon Strait and through the SCS. Moreover, all the experiments successfully simulated Doksuri’s RI, albeit with quite different rates and a time lag of 12 h. Among different combinations of physics schemes, there exists an optimal set of cumulus parameterization and cloud microphysics schemes for track and intensity predictions. Doksuri’s track changes as the typhoon moved across the Luzon Strait and through the SCS were influenced by the topographic effects of the terrain of the Philippines and Taiwan, to different extents. The track changes of Doksuri are explained by the wavenumber-one potential vorticity (PV) tendency budget from different physical processes, highlighting that the horizontal PV advection dominates the PV tendency throughout most of the simulation time due to the offset of vertical PV advection and differential diabatic heating. In addition, this study applies the extended Sawyer–Eliassen (SE) equation to compare the transverse circulations of the typhoon induced by various forcing sources. The SE solution indicates that radial inflow was largely driven in the lower-tropospheric vortex by strong diabatic heating, while being significantly enhanced in the lower boundary layer due to turbulent friction. All other physical forcing terms were relatively insignificant for the induced transverse circulation. The coordinated radial inflow at low levels may have led to the eyewall development in unbalanced dynamics. Intense diabatic heating thus was vital to the severe RI of Doksuri under a weak vertical wind shear.

COVID-19 has disconnected humanity, reduced social interaction in physical urban areas, and led to the new normal, which describes the anticipated changes in human life and professionals due to the impact of the pandemic. In addition, as part of digital transformation, the post-pandemic New Normal includes accelerating digital solutions and new standards for virtual urban exploration and planning. This study applies the concept of digital twin and serious game design and uses Minecraft, a game-based platform that inspires creative, inclusive learning through play, for virtual urban exploration and the development of social interaction among participants. Dadaocheng, a historical area of Taipei city, is then studied as a case study with the Geoboxers application to develop the prototype for a co-creation experiment in Minecraft. The prototype development and the results of the experiment are then used in the Analytic Hierarchical Process (AHP) method to evaluate a set of influential criteria proposed in this study through pairwise comparisons by expert panelists. The results of the AHP analysis reveal users' simultaneous preferences for urban planning and social interaction with urban characteristics (22.14%), urban exploration (12.29%), and 3D models (11.97%). Subsequently, the research results showed a need to promote the integration of digital twins and serious game applications as digital tools for urban exploration and social interaction, increasing post-pandemic virtual urban planning and applying new urban design techniques. This study also contributes to the acceleration of digital transformation in urban planning and management.

Nasopharyngeal carcinoma (NPC) is the most common cancer among head and neck cancers in Vietnam. We aimed to identify the rate of a 30 bp deletion mutation of the LMP1-EBV gene in nasopharyngeal biopsy tissue samples, the HLA genotypes of NPC patients, and the relationship between these two targets. Patients with NPC at Can Tho Oncology Hospital from September 2014 to December 2018 were selected. A length of 30 bp of the del-LMP1-EBV gene was analyzed using a PCR technique, and the HLA genotypes in patients’ blood samples were analyzed with PCR-SSO technology. HLA-B*15 gene carriers had the highest risk of 30 bp LMP1-EBV gene deletion mutation, which was found in 51 out of 70 patients (72.9%). Carriers of the HLA-B*15 allele had a 4.6-fold increased risk of a 30 bp del-LMP1-EBV gene compared with non-carriers of this allele. The initial identification of NPC was related to the 30 bp del-LMP1-EBV gene and high frequencies of the -A*02, -B*15, -DRB1*12, -DQB1*03, and -DQA1*01 HLA alleles. Our study results suggest an association of the 30 bp del-LMP1-EBV gene and the HLA-B*15 allele with NPC susceptibility.

Summary: This protocol describes the use of silicon photonic microring resonator sensors for detection of Ebola virus (EBOV) and Sudan virus (SUDV) soluble glycoprotein (sGP). This protocol encompasses biosensor functionalization of silicon microring resonator chips, detection of protein biomarkers in sera, preparing calibration standards for analytical validation, and quantification of the results from these experiments. This protocol is readily adaptable toward other analytes, including cytokines, chemokines, nucleic acids, and viruses.For complete details on the use and execution of this protocol, please refer to Qavi et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Recommender systems are challenged with providing accurate recommendations that meet the diverse preferences of users. The main information sources for these systems are the utility matrix and textual sources, such as item descriptions, users’ reviews, and users’ profiles. Incorporating diverse sources of information is a reasonable approach to improving recommendation accuracy. However, most studies primarily use the utility matrix, and when they use textual sources they do not integrate them with the utility matrix. This is due to the risk of combined information causing noise and reducing the effectiveness of good sources. To overcome this challenge, in this study we propose a novel method that utilizes the Transformer Model, a deep learning model that efficiently integrates textual and utility matrix information. The study suggests feature extraction techniques suitable for each information source and an effective integration method in the Transformer model. The experimental results indicate that the proposed model significantly improves recommendation accuracy compared to the baseline model (MLP) for the Mean Absolute Error (MAE) metric, with a reduction range of 10.79% to 31.03% for the Amazon sub-datasets. Furthermore, when compared to SVD, which is known as one of the most efficient models for recommender systems, the proposed model shows a decrease in the MAE metric by a range of 34.82% to 56.17% for the Amazon sub-datasets. Our proposed model also outperforms the graph-based model with an increase of up to 108% in Precision, a decrease of up to 65.37% in MAE, and a decrease of up to 59.24% in RMSE. Additionally, experimental results on the Movielens and Amazon datasets also demonstrate that our proposed model, which combines information from the utility matrix and textual sources, yields better results compared to using only information from the utility matrix.

Diphallia is an extremely rare congenital anomaly. Bifid phallus is a type of diphallia and is rarely recorded in published studies. According to the degree of separation of the penises at the base of the shaft or just at the glans, bifid phallus is further classified into complete or partial forms. Bifid phallus is often associated with hypospadias or part of the exstrophy–epispadias complex. We are really lucky to have successfully treated a 2-year-old patient with penoscrotal hypospadias combined with partial bifid phallus in the shaft. After the surgery, the patient had no issues with penile function.

Data play an essential role in the optimal control of smart buildings’ operation, especially in building energy-management for the target of nearly zero buildings. The building monitoring system is in charge of collecting and managing building data. However, device imperfections and failures of the monitoring system are likely to produce low-quality data, such as data loss and inconsistent data, which then seriously affect the control quality of the buildings. This paper proposes a new approach based on Gaussian process regression for data-quality monitoring and sensor network data compensation in smart buildings. The proposed method is proven to effectively detect and compensate for low-quality data thanks to the application of data analysis to the energy management monitoring system of a building model in Viet Nam. The research results provide a good opportunity to improve the efficiency of building energy-management systems and support the development of low-cost smart buildings.

Buildings with solar rooftops have become vital objects in the energy transition in Vietnam. In this context, the demand for research on energy management solutions to use energy efficiently and increase PV energy absorption capacity is rising. In this paper, we present a practical route to developing a low-cost monitoring platform to meet the building energy management in the country. First, our project built a monitoring architecture with high-density wireless sensors in an office building in Vietnam. Next, we discussed the influence of significant obstacles such as technical issues, users, and cost on the resilience and reliability of the monitoring system. Then, we proposed essential solutions for data quality improvement by testing sensors, detecting wireless sensor network errors, and compensating for data losses by embedding machine learning. We found the platform’s potential in developing a rich database of building characteristics and occupants. Finally, we proposed plans exploiting the data to reduce wasted energy in equipment operation, change user behaviors, and increase auto-consumption PV power. The effectiveness of the monitoring platform was an approximate 62% energy reduction in the first year. The results are a cornerstone for implementing advanced research as modeling and real-time optimal control toward nearly zero-energy buildings.

Current experimental monoclonal antibodies (mAbs) for Ebola virus (EBOV) post-exposure immunotherapy are ineffective against Sudan (SUDV) or Marburg virus (MARV). Here, authors develop cocktails of mAbs that protect nonhuman primates against EBOV, SUDV, and MARV infection when given four days post infection.

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The Khmer ethnic is one of 54 ethnic groups in Vietnam, they live mainly in the Mekong Delta, most concentrated in Tra Vinh and Sóc Trang provinces. The Southern Khmer in Tra Vinh province has a life of folk belief that is vibrant and diverse. The diversity and richness in folk belief life have created a philosophy of life that is very different from other ethnic groups in Tra Vinh province. The purpose of this study is to find out the characteristics of folk beliefs, the basic content of the philosophy of life in folk beliefs and the influences of the philosophy of life on the life of the Southern Khmer in Tra Vinh province. Using qualitative and quantitative research methods, and semi-structured interviews with 15 people from 20 to 70 years old, this study shows that the diversity in the philosophy of life of the Southern Khmer originates from ethnic factors, natural conditions, socio-economic conditions and the impacts of changes in current sóciety. With the obtained results, this study contributes to clarifying the values of the philosophy of life in the folk beliefs of the Khmer people, thereby having impacts to promote good values, fostering the positive aspects of the philosophy of life in the folk beliefs of the Southern Khmer people in Tra Vinh province. [ABSTRACT FROM AUTHOR]

Bacterial leaf blight of rice (BLB), caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive diseases in Asian rice fields. A high-quality rice variety, LT2, was used as the recipient parent. IRBB21, which carries the Xa21 gene, was used as the donor parent. The resistance gene Xa21 was introduced into LT2 by marker-assisted backcrossing. Three Xoo races were used to inoculate the improved lines following the clipping method. Eleven BC3F3 lines carrying Xa21 were obtained based on molecular markers and agronomic performance. The 11 lines were then inoculated with the three Xoo races. All the 11 improved lines showed better resistance to BLB than the recipient parent LT2. Based on the level of resistance to BLB and their agronomic performance, five lines (BC3F3 5.1.5.1, BC3F3 5.1.5.12, BC3F3 8.5.6.44, BC3F3 9.5.4.1 and BC3F3 9.5.4.23) were selected as the most promising for commercial release. These improved lines could contribute to rice production in terms of food security.

Summary: Drug combinations are synergistic when their combined efficacy exceeds the sum of the individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several “enabling pairs” of neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a non-neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC50 >1 μM) to exhibit potent neutralization (IC50 1–10 nM). While FVM09 or m8C4 alone failed to protect Ebola-virus-infected mice, a combination of the two antibodies provided 100% protection. Furthermore, non-neutralizers FVM09 and FVM02 exponentially enhanced the potency of two neutralizing antibodies against both Ebola and Sudan viruses. We identified a hotspot for the binding of these enabling antibody pairs near the interface of the glycan cap and GP2. Enabling cooperativity may be an underappreciated phenomenon for viruses, with implications for the design and development of immunotherapeutics and vaccines. : Howell et al. describe the phenomenon of “enabling, cooperative neutralization” where weakly neutralizing and/or non-neutralizing ebolavirus monoclonal antibodies exhibit potent neutralization when combined. The previously identified antibodies m8C4 and FVM09, which are non-protective alone, offer 100% protection against Ebola and Sudan virus challenge in mice when combined. Keywords: Ebola virus, vaccine, filovirus, monoclonal antibody, antibody therapeutics, antibody synergy, cooperative neutralization, synergistic neutralization

Summary: Previous efforts to identify cross-neutralizing antibodies to the receptor-binding site (RBS) of ebolavirus glycoproteins have been unsuccessful, largely because the RBS is occluded on the viral surface. We report a monoclonal antibody (FVM04) that targets a uniquely exposed epitope within the RBS; cross-neutralizes Ebola (EBOV), Sudan (SUDV), and, to a lesser extent, Bundibugyo viruses; and shows protection against EBOV and SUDV in mice and guinea pigs. The antibody cocktail ZMapp™ is remarkably effective against EBOV (Zaire) but does not cross-neutralize other ebolaviruses. By replacing one of the ZMapp™ components with FVM04, we retained the anti-EBOV efficacy while extending the breadth of protection to SUDV, thereby generating a cross-protective antibody cocktail. In addition, we report several mutations at the base of the ebolavirus glycoprotein that enhance the binding of FVM04 and other cross-reactive antibodies. These findings have important implications for pan-ebolavirus vaccine development and defining broadly protective antibody cocktails. : Howell et al. examine a mAb, FVM04, that binds the ebolavirus receptor-binding site and find that FVM04 protects against EBOV and SUDV. When combined with two ZMapp™ components, the antibody cocktail retains EBOV protection similar to that of ZMapp™ and extends protection against SUDV. Specific glycoprotein mutations that enhance the exposure of cross-neutralizing epitopes are described.

The aim of this study was to evaluate the oil and bioactive contents of grape waste by both conventional and microwave-assisted extraction (MAE) methods. Other controlled factors included the segment solvent used (n- hexane-methanol, n-hexane-ethanol), the solid/solvent ratios (1 : 5, 1 : 10, 1 : 20 g/mL) and in MAE, the microwave powers (40 W, 240 W and 440 W). The extracts were analysed for the contents of fatty oil, lipid hydroperoxide content (LP), total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity. The optimal conditions for the grape oil recovery were at 240 W, using n-hexane-ethanol solvent, and the ratio of 1 : 10 by using the MAE method. At the same ratio conditions, the highest contents of LP and TPC were 0.032 mM (at 440 W) and 43.657 mg gallic acid (AG)/dry weight (at 240 W). At 440 W and ratio of 1: 10, TFC peaked the highest point at 37.862 mg quercetin/g dry weight. The results indicated that grape waste is a valuable input for a wide range of applications in nutraceutical and food industries, offering an additional economic by-product for the grape processing.