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Tiantian Xuan,1 Zhanmei Wang,1 Sibo Meng,1 Jiaxin Li,1 Jisheng Li,2 Fangli Cao,1,* Linli Qu1,* 1Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangli Cao; Linli Qu, Department of Medical Oncology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, 758 Hefei Road, Qingdao, Shandong, 266035, People’s Republic of China, Tel +86-18561811936 ; +86-18561811457, Email caofangliqilu@163.com; qulinli2021@163.comPurpose: Cetuximab (CET) combined with chemotherapy significantly improved the survival in RAS and RAF wild-type metastatic colorectal cancer (mCRC) patients, while clinical evidence was lacking on the use of maintenance therapy (MT). The study aimed to explore the role of maintenance therapy following Cetuximab + chemotherapy and the optimal Cetuximab-based maintenance therapy regimen.Patients and Methods: We retrospectively reviewed data on the efficacy and safety of CET-based MT in patients with mCRC who achieved disease control after induction therapy.Results: Eighty-one patients with mCRC who achieved disease control after CET + chemotherapy induction were enrolled. Overall median progression-free survival (PFS) was 10.5 (95% CI = 8.8– 12.2) months and median maintenance/observation PFS (mnPFS) was 6.0 (95% CI = 5.0– 7.0) months. Among these 81 patients, 61 patients were prescribed MT (CET alone for 21 patients and CET + chemotherapy for 40 patients). Median PFS and mnPFS in the MT group were significantly longer than those for the non-MT group. Different MT regimens did not affect PFS and mnPFS significantly. Univariate and multivariate analysis demonstrated MT, complete response/partial response during induction therapy, and absence of peritoneal metastasis to be positively associated with longer PFS and mnPFS. Treatment-related adverse events (AEs) were tolerable during MT, and AE-related deaths were not observed.Conclusion: MT with CET or CET + chemotherapy was an appropriate option following initial induction chemotherapy for patients with RAS and RAF wild-type mCRC. This strategy endowed survival benefits and a tolerable safety profile.Keywords: colorectal cancer, maintenance therapy, cetuximab, RAS and RAF wild-type, targeted therapy

Abstract Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.

Striped catfish is one of the most important farmed fish species in Vietnam but often susceptible to hemorrhagic septicemia caused by Aeromonas hydrophila. Phage therapy is a promising solution alternative to antibiotic usage due to the bacterial antibiotic resistance. In this study, five individual factors including molasses concentration, KH2PO4 concentration, yeast extract concentration, bacterial culture time and phage collection time were investigated for their effects on the producion of phage TG25P. Plackett-Burman design revealed that the bacterial culture time, phage collection time and molasses concentration were the most significant factors affecting the phage production. Application of response surface methodology for optimization of phage production showed that optimal values for these variables were 1.76 h, 2.22 h and 2.03 g/L, respectively. In the optimized medium, the phage production of (1.44 ( 0.2) ( 109 PFU/mL was obtained, which agreed well with the predicted value of 1.37 ( 109 PFU/mL. The findings really help us produce phage TG25P under the optimal condition at a low cost.

Abstract The novel Coronavirus-2019 (COVID-19) was declared a pandemic by the World Health Organization (WHO) in March 2020, impacting the lifestyles, economy, physical and mental health of individuals globally. This study aimed to test the model triggered by physical symptoms resembling COVID-19 infection, in which the need for health information and perceived impact of the pandemic mediated the path sequentially, leading to adverse mental health outcomes. A cross-sectional research design with chain mediation model involving 4612 participants from participating 8 countries selected via a respondent-driven sampling strategy was used. Participants completed online questionnaires on physical symptoms, the need for health information, the Impact of Event Scale-Revised (IES-R) questionnaire and Depression, Anxiety and Stress Scale (DASS-21). The results showed that Poland and the Philippines were the two countries with the highest levels of anxiety, depression and stress; conversely, Vietnam had the lowest mean scores in these areas. Chain mediation model showed the need for health information, and the perceived impact of the pandemic were sequential mediators between physical symptoms resembling COVID-19 infection (predictor) and consequent mental health status (outcome). Excessive and contradictory health information might increase the perceived impact of the pandemic. Rapid COVID-19 testing should be implemented to minimize the psychological burden associated with physical symptoms, whilst public mental health interventions could target adverse mental outcomes associated with the pandemic.

Abstract Breast cancer cells release a large quantity of biocargo‐bearing extracellular vesicles (EVs), which mediate intercellular communication within the tumour microenvironment and promote metastasis. To identify EV‐bound proteins related to metastasis, we used mass spectrometry to profile EVs from highly and poorly metastatic breast cancer lines of human and mouse origins. Comparative mass spectrometry indicated that integrins, including αv and β1 subunits, are preferentially enriched in EVs of highly metastatic origin over those of poorly metastatic origin. These results are consistent with our histopathological findings, which show that integrin αv is associated with disease progression in breast cancer patients. Integrin αv colocalizes with the multivesicular‐body marker CD63 at a higher frequency in the tumour and is enriched in circulating EVs of breast cancer patients at late stages when compared with circulating EVs from early‐stage patients. With a magnetic bead‐based flow cytometry assay, we confirmed that integrins αv and β1 are enriched in the CD63+ subsets of EVs from both human and mouse highly metastatic cells. By analysing the level of integrin αv on circulating EVs, this assay could predict the metastatic potential of a xenografted mouse model. To explore the export mechanism of integrins into EVs, we performed immunoprecipitation mass spectrometry and identified members of the galectin family as potential shuttlers of integrin αvβ1 into EVs. In particular, knockdown of galectin‐3, but not galectin‐1, causes a reduction in the levels of cell surface integrins β1 and αv, and decreases the colocalization of these integrins with CD63. Importantly, knockdown of galectin‐3 leads to a decrease of integrin αvβ1 export into the EVs concomitant with a decrease in the metastatic potential of breast cancer cells. Moreover, inhibition of the integrin αvβ1 complex leads to a reduction in the binding of EVs to fibronectin, suggesting that integrin αvβ1 is important for EV retention in the extracellular matrix. EVs retained in the extracellular matrix are taken up by fibroblasts, which differentiate into cancer associated fibroblasts. In summary, our data indicate an important link between EV‐bound integrin αvβ1 with breast cancer metastasis and provide additional insights into the export of integrin αvβ1 into EVs in the context of metastasis.

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

Abstract Background Extracorporeal membrane oxygenation (ECMO) support can be life-saving in critically ill COVID-19 patients. However, there are many complications associated with this procedure, including Heparin-induced thrombocytopenia (HIT.) Despite its rarity in ECMO cases, HIT can lead to devastating consequences and is difficult to manage. Case presentation In this report, we present a case of a COVID-19 patient on ECMO support who was diagnosed with HIT and required intensive treatment. Initially, HIT was only suspected due to newly-developed thrombocytopenia and oxygenator dysfunction, with thrombi observed later. Regarding his treatment, since there was no recommended replacement to heparin available to us at the time of diagnosis, we decided to use rivaroxaban temporarily. No adverse events were recorded during that period. The patient was able to make a full recovery. Conclusion HIT may jeopardize patient’s care during ECMO. As COVID-19 may bring about a surge in the number of patients requiring ECMO support, we need consented guidance to optimize treatment in this specific situation.

Soybean Glicine max. (L.) Merr. is one of the most major food crops. In some areas, its responses to different climates have not been well studied, particularly in tropical countries where other crops are more dominant. Accordingly, we adopted the SIMPLE crop model to investigate the responses of soybeans to the climate. We conducted two experiments on crop growth in the Summer–Autumn season of 2020, and Winter–Spring 2021 in the Hoa Binh Commune, in the Mekong Delta, Vietnam, which is an area that is vulnerable to climate change impacts, to obtain data for our model input and assessment. The assessment was concerned with the effects of climate variables (temperature and CO2) on soybean biomass and yield. The results indicated that the SIMPLE model performed well in simulating soybean yields, with an RRMSE of 9–10% overall. The drought stress results showed a negative impact on the growth and development of soybeans, although drought stress due to less rainfall seemed more serious in Spring–Winter 2021 than in Summer–Autumn 2020. This study figured out the trend that higher temperatures can shorten biomass development and lead to yield reduction. In addition, soybeans grown under high CO2 concentrations of 600 ppm gave a higher biomass and a greater yield than in the case with 350 ppm. In conclusion, climate variance can affect the soybean yield, which can be well investigated using the SIMPLE model.

The coronavirus disease (COVID-19) pandemic has impacted the economy, livelihood, and physical and mental well-being of people worldwide. This study aimed to compare the mental health status during the pandemic in the general population of seven middle income countries (MICs) in Asia (China, Iran, Malaysia, Pakistan, Philippines, Thailand, and Vietnam). All the countries used the Impact of Event Scale-Revised (IES-R) and Depression, Anxiety and Stress Scale (DASS-21) to measure mental health. There were 4479 Asians completed the questionnaire with demographic characteristics, physical symptoms and health service utilization, contact history, knowledge and concern, precautionary measure, and rated their mental health with the IES-R and DASS-21. Descriptive statistics, One-Way analysis of variance (ANOVA), and linear regression were used to identify protective and risk factors associated with mental health parameters. There were significant differences in IES-R and DASS-21 scores between 7 MICs (p

Gac is valued for the nutritious aril surrounding its seed. When pollinators are limited or when flower sex expression is female-biased, hand pollination is necessary. Here, female flowers were hand pollinated with male flowers or pollen stored for up to 84 days at 4 or −20 °C, and fruit set and some qualities of mature fruit were evaluated. Cool storage reduced pollen viability (germinability and pollen tube length) and compromised fruit set (10–87%) compared with fresh pollen (97%). Fruit weight was also reduced at least by 8%, and oil concentration in aril by 40%. However, the lycopene and β-carotene concentrations in aril were largely uncompromised, and some fruits were of a marketable weight (>1.2 kg) and quality. Cool storage is a low-cost method for the short-term storage of Gac pollen. However, methods for drying pollen to an inactive state need investigation for a storage protocol, and for improvements in fruit set and fruit physicochemical qualities using hand pollination.

Despite the recent advances in drug development, the majority of novel therapeutics have not been successfully translated into clinical applications. One of the major factors hindering their clinical translation is the lack of a safe, non-immunogenic delivery system with high target specificity upon systemic administration. In this respect, extracellular vesicles (EVs), as natural carriers of bioactive cargo, have emerged as a promising solution and can be further modified to improve their therapeutic efficacy. In this review, we provide an overview of the biogenesis pathways, biochemical features, and isolation methods of EVs with an emphasis on their many intrinsic properties that make them desirable as drug carriers. We then describe in detail the current advances in EV therapeutics, focusing on how EVs can be engineered to achieve improved target specificity, better circulation kinetics, and efficient encapsulation of therapeutic payloads. We also identify the challenges and obstacles ahead for clinical translation and provide an outlook on the future perspective of EV-based therapeutics.

Bacterial pathogens like Salmonella and Legionella establish intracellular niches in host cells known as bacteria-containing vacuoles. In these vacuoles, bacteria can survive and replicate. Ubiquitin-dependent selective autophagy is a host defense mechanism to counteract infection by invading pathogens. The Legionella effector protein RavZ interferes with autophagy by irreversibly deconjugating LC3, an autophagy-related ubiquitin-like protein, from a phosphoglycolipid phosphatidylethanolamine. Using a co-infection system with Salmonella, we show here that Legionella RavZ interferes with ubiquitin recruitment to the Salmonella-containing vacuoles. The inhibitory activity is dependent on the same catalytic residue of RavZ that is involved in LC3 deconjugation. In semi-permeabilized cells infected with Salmonella, external addition of purified RavZ protein, but not of its catalytic mutant, induced removal of ubiquitin associated with Salmonella-containing vacuoles. The RavZ-mediated restriction of ubiquitin recruitment to Salmonella-containing vacuoles took place in the absence of the host system required for LC3 conjugation. These observations suggest the possibility that the targets of RavZ deconjugation activity include not only LC3, but also ubiquitin.

In this study, subsidence patterns in the Historical Centre of Hanoi, Vietnam are mapped using the Interferometric Synthetic Aperture Radar (InSAR) technique, with particular emphasis on the stability of ancient monuments, historical buildings and archaeological sectors. Due to the small and scattered characteristics of these structures, not only is a comprehensive coverage of radar targets needed, but also the details of a single building or monument. We took advantage of the high-resolution TerraSAR-X imagery with the aid of oversampling implementation on the Small Baseline (SB) InSAR approach to reveal the subsidence patterns. A total of 6.29 million radar targets were obtained, maintaining the average density of 217,012 points/km2. Our results suggest that image oversampling not only increased the number of measurement points 4.4 times more than the standard processing chain, but also removed some of the noisiest points. The observed subsidence patterns are mostly related to adjacent groundwater extraction and construction activities, with maximum subsiding rate reaching −18.1 mm/year for the study period April 2012 to November 2013. Generally, heritage assets and monuments in the Citadel, the Old Quarter and French Quarter remain in a steady state, whereas those located along the Red River and in southern Hanoi are subject to subsidence.

Neoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of large‐scale EV production hinder their therapeutic applications in clinical settings. Here, we develop an antigen delivery platform for cancer vaccines from red blood cell‐derived EVs (RBCEVs) targeting splenic DEC‐205+ dendritic cells (DCs) to boost the antitumor effect. By loading ovalbumin (OVA) protein onto RBCEVs and delivering the protein to DCs, we were able to stimulate and present antigenic OVA peptide onto major histocompatibility complex (MHC) class I, subsequently priming activated antigen‐reactive T cells. Importantly, targeted delivery of OVA using RBCEVs engineered with anti‐DEC‐205 antibody robustly enhanced antigen presentation of DCs and T cell activation. This platform is potentially useful for producing personalised cancer vaccines in clinical settings. [ABSTRACT FROM AUTHOR]

The present work represents the first effort to evaluate the effect of an in vitro simulated human digestion model on the α-amylase and α-glucosidase inhibitory activities of Callerya speciosa root extracts. Through bioguided fractionation, a series of fractions were obtained from hexane (CSH) and ethyl acetate (CSE) extracts. Initial screening identified active fractions (CSH2, CSH3, CSE2, CSE3, and CSE4) for further in vitro digestion evaluation. The results showed a decrease in antioxidant activity across all samples after digestion, while a simultaneous increase in α-amylase and α-glucosidase inhibitory activities was observed during the small intestinal phase. Notably, compared with the undigested fraction, CSE3 demonstrated a 1.7-fold increase in α-amylase inhibition (IC50 = 0.86 mg/mL). Moreover, the α-glucosidase inhibitory activities of CSH3, CSE3, and CSE4 were significantly greater after digestion, with IC50 values of 0.18, 0.05, and 0.02 mg/mL, respectively. Impressively, during the small intestinal phase, the α-glucosidase inhibitory activities of CSH3, CSE3, and CSE4 were substantially greater than those of acarbose by 13.2-, 47.6-, and 119.0-fold, respectively, and greater than those of palmitic acid by 1.7-, 6.0-, and 15.0-fold, respectively. GC-MS and LC-ESI-MS/MS analyses identified isoflavonoids, fatty acids, and triterpenoids as key bioactive compounds in these fractions. The present work provided foundational insights for the future exploration of C. speciosa root extracts for diabetes management. [ABSTRACT FROM AUTHOR]