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Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, is resistant to anticancer drugs. Angiogenesis is a major cause of tumor resistance to chemotherapy, and vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis. The purpose of this study is to investigate the impact of small-interfering RNA targeting VEGF gene (VEGF-siRNA) on chemosensitivity of HCC cells in vitro. In this experimental study, transfection was performed on Hep3B cells. After transfection with siRNAs, VEGF mRNA and protein levels were examined. Cell proliferation, apoptosis and anti-apoptotic gene expression were also analyzed after treatment with VEGF-siRNA in combination with doxorubicin in Hep3B cells. Transfection of VEGF-siRNA into Hep3B cells significantly reduced the expression of VEGF at both mRNA and protein levels. Combination therapy with VEGF-siRNA and doxorubicin more effectively suppressed cell proliferation and induced apoptosis than the respective monotherapies. This could be explained by the significant downregulation of B-cell lymphoma 2 (BCL-2) and SURVIVIN. VEGF-siRNA enhanced the chemosensitivity of doxorubicin in Hep3B cells at least in part by suppressing the expression of anti-apoptotic genes. Therefore, the downregulation of VEGF by siRNA combined with doxorubicin treatment has been shown to yield promising results for eradicating HCC cells.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health concern. The development of vaccines with high immunogenicity and safety is crucial for controlling the global COVID-19 pandemic and preventing further illness and fatalities. Here, we report the development of a SARS-CoV-2 vaccine candidate, Nanocovax, based on recombinant protein production of the extracellular (soluble) portion of the spike (S) protein of SARS-CoV-2. The results showed that Nanocovax induced high levels of S protein-specific IgG and neutralizing antibodies in three animal models: BALB/c mouse, Syrian hamster, and a non-human primate ( Macaca leonina ). In addition, a viral challenge study using the hamster model showed that Nanocovax protected the upper respiratory tract from SARS-CoV-2 infection. Nanocovax did not induce any adverse effects in mice ( Mus musculus var. albino) and rats ( Rattus norvegicus ). These preclinical results indicate that Nanocovax is safe and effective.

Stem cell therapy for the treatment of vascular-related diseases through functional revascularization is one of the most important research areas in tissue engineering. The aim of this study was to investigate the in vitro differentiation of umbilical CL-MSC into endothelial lineage cells. In this study, isolated cells were characterized for expression of MSC-specific markers and osteogenic and adipogenic differentiation. They were induced to differentiate into endothelial-like cells and then examined for expression of the endothelial-specific markers, karyotype, and functional behavior of cells. Isolated cells expressed MSC-specific markers and differentiated into adipocytes and osteoblasts. After endothelial differentiation, they expressed CD31, vWF, VE-cadherin, VEGFR1, and VEGFR2 at both mRNA and protein level, but their morphological changes were not apparent when compared with those of undifferentiated cells. There were no significant changes in karyotype of differentiated cells. Furthermore, angiogenesis assay and LDL uptake assay showed that differentiated cells were able to form the capillary-like structures and uptake LDL, respectively. The results indicated that umbilical CL-MSC could differentiate into functional endothelial-like cells. Also, they are suitable for basic and clinical studies to cure several vascular-related diseases.

Kinesin spindle protein (KSP) plays a critical role in mitosis. Inhibition of KSP function leads to cell cycle arrest at mitosis and ultimately to cell death. The aim of this study was to suppress KSP expression by specific small-interfering RNA (siRNA) in Hep3B cells and evaluate its anti-tumor activity. Three siRNA targeting KSP (KSP-siRNA #1-3) and one mismatched-siRNA (Cont-siRNA) were transfected into cells. Subsequently, KSP mRNA and protein levels, cell proliferation, and apoptosis were examined in both Hep3B cells and THLE-3 cells. In addition, the chemosensitivity of KSP-siRNA-treated Hep3B cells with doxorubicin was also investigated using cell proliferation and clonogenic survival assays. The expression of endogenous KSP at both mRNA and protein levels in Hep3B cells was higher than in THLE-3 cells. In Hep3B cells, KSP-siRNA #2 showed a further downregulation of KSP as compared to KSP-siRNA #1 or KSP-siRNA #3. It also exhibited greater suppression of cell proliferation and induction of apoptosis than KSP-siRNA #1 or KSP-siRNA #3; this could be explained by the significant downregulation of cyclin D1, Bcl-2, and survivin. In contrast, KSP-siRNAs had no or lower effects on KSP expression, cell proliferation and apoptosis in THLE-3 cells. We also noticed that KSP-siRNA transfection could increase chemosensitivity to doxorubicin in Hep3B cells, even at low doses compared to control. Reducing the expression level of KSP, combined with drug treatment, yields promising results for eradicating hepatocellular carcinoma (HCC) cells in vitro. This study opens a new direction for liver cancer treatment.

The Coronavirus disease-2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), has become a dire global health concern. The development of vaccines with high immunogenicity and safety is crucial for control of the global COVID-19 pandemic and prevention of further illness and fatalities. Here, we report development of SARS-CoV-2 vaccine candidate, Nanocovax, based on recombinant protein production of the extracellular (soluble) portion of the S protein of SARS-CoV-2. The results showed that Nanocovax induced high levels of S protein-specific IgG, as well neutralizing antibody in three animal models including Balb/C mice, Syrian hamsters, and non-human primate (Macaca leonina). In addition, the viral challenge study using the hamster model showed that Nanocovax protected the upper respiratory tract from SARS-CoV-2 infection. No adverse effects were induced by Nanocovax in swiss mice (Musmusculus var. Albino), Rats (Rattus norvegicus), and New Zealand rabbits. These pre-clinical results indicated that Nanocovax is safe and effective Competing Interest Statement The authors have declared no competing interest.

Information about macromolecular structure of protein complexes and related cellular and molecular mechanisms can assist the search for vaccines and drug development processes. To obtain such structural information, we present DeepTracer, a fully automated deep learning-based method for fast de novo multichain protein complex structure determination from high-resolution cryoelectron microscopy (cryo-EM) maps. We applied DeepTracer on a previously published set of 476 raw experimental cryo-EM maps and compared the results with a current state of the art method. The residue coverage increased by over 30% using Deep-Tracer, and the rmsd value improved from 1.29 Å to 1.18 Å. Additionally, we applied DeepTracer on a set of 62 coronavirus-related cryo-EM maps, among them 10 with no deposited structure available in EMDataResource. We observed an average residue match of 84% with the deposited structures and an average rmsd of 0.93 Å. Additional tests with related methods further exemplify DeepTracer’s competitive accuracy and efficiency of structure modeling. DeepTracer allows for exceptionally fast computations, making it possible to trace around 60,000 residues in 350 chains within only 2 h. The web service is globally accessible at https://deeptracer.uw.edu.

Background Non-invasive multi-cancer early detection (MCED) tests have shown promise in enhancing early cancer detection. However, their clinical utility across diverse populations remains underexplored, limiting their routine implementation. This study aims to validate the clinical utility of a multimodal non-invasive circulating tumor DNA (ctDNA)-based MCED test, SPOT-MAS (Screening for the Presence Of Tumor by DNA Methylation And Size). Methods We conducted a multicenter prospective study, K-DETEK (ClinicalTrials.gov identifier: NCT05227261), involving 9057 asymptomatic individuals aged 40 years or older across 75 major hospitals and one research institute in Vietnam. Participants were followed for 12 months. Results Of the 9024 eligible participants, 43 (0.48%) tested positive for ctDNA. Among these, 17 were confirmed with malignant lesions in various primary organs through standard-of-care (SOC) imaging and biopsy, with 9 cases matching our tissue of origin (TOO) predictions. This resulted in a positive predictive value of 39.53% (95%CI 26.37–54.42) and a TOO accuracy of 52.94% (95%CI 30.96–73.83). Among the 8981 participants (99.52%) who tested negative, 8974 were confirmed cancer-free during a 12-month period after testing, yielding a negative predictive value of 99.92% (95% CI 99.84–99.96). The test demonstrated an overall sensitivity of 70.83% (95%CI 50.83–85.09) and a specificity of 99.71% (95% CI 99.58–99.80) for detecting various cancer types, including those without SOC screening options. Conclusions This study presents a prospective validation of a multi-cancer early detection (MCED) test conducted in a lower middle-income country, demonstrating the potential of SPOT-MAS for early cancer detection. Our findings indicate that MCED tests could be valuable additions to national cancer screening programs, particularly in regions where such initiatives are currently limited. Trial registration ClinicalTrials.gov ID: NCT05227261. Date of registration: 07/02/2022.

Concentrations of seven polybrominated diphenyl ethers (PBDEs) congeners were determined in surface sediments collected from several rivers and lakes in Hanoi, the capital city of Vietnam, to understand the status of background contamination, accumulation pattern, sources, and toxic implications for benthic organisms. Total PBDE concentrations in all sediment samples ranged from 0.03 to 17.5 ng/g dry weight (mean 1.33 ng/g dry wt). The most predominant congeners were BDE-47 and BDE-99, which comprised 30 and 25 % of total PBDE concentrations, respectively. Results from statistical analysis indicated that the potential sources of PBDEs of sediments in Hanoi may come from penta-BDE and octa-BDE mixtures. Risk quotients of PBDEs in sediments were also calculated for a benthic species, ranged from 2.12 × 10 −6  − 1.60 × 10 −2 , and were markedly lower than threshold value for occurrence of any ecotoxicological risk. This study provides some of the most comprehensive data on the occurrence of PBDEs in sediments from lake and river systems in Vietnam.

Gallium oxide (Ga 2 O 3 ), a wide bandgap semiconductor of the fourth generation, shows great potential for advanced optoelectronic applications. While β- Ga 2 O 3 -based photodetectors (PDs) have been extensively studied, research on α- Ga 2 O 3 -based PDs remains scarce. This work investigates the structural, electronic, and performance characteristics of α- Ga 2 O 3 -based metal-semiconductor–metal (MSM) PDs. Using first-principles calculations within the GGA+U framework, it was found that Al(111) and Ni(111) electrodes interfacing with α- Ga 2 O 3 (0001) experience tensile and compressive strain, respectively. The bandgaps of bulk α- Ga 2 O 3 were calculated as 5.30 eV (direct) and 5.17 eV (indirect), with negligible metal-induced gap states (MIGS) beyond the sixth Ga layer. The electron affinity of α- Ga 2 O 3 is 4.31 eV, and the Schottky barrier heights for Ga 2 O 3 /Al and Ga 2 O 3 /Ni interfaces are 0.046 eV and 0.650 eV, respectively. Experimentally, symmetric MSM PDs were fabricated using mist-CVD for the epitaxial α- Ga 2 O 3 layer and thermal evaporation for Al and Ni electrodes. The epitaxial layer demonstrated an optical bandgap of 5.247 eV. The PDs exhibited low dark current, with Al-electrode devices achieving a higher photo-to-dark current ratio compared to Ni-electrode devices. Peak photoresponse was observed around 230 nm, with smaller finger gaps and more electrode gaps enhancing performance. This study provides valuable insights into the interfacial properties and design optimization of α- Ga 2 O 3 -based PDs, demonstrating their potential for deep-ultraviolet optoelectronic applications.

This paper examines the synergistic integration of uplink Device-to-Device (D2D), backscatter, and short-packet communication paradigms, highlighting their collective potential to revolutionize next-generation wireless systems. By enhancing spectral efficiency and supporting massive connectivity through diverse receiver techniques, this approach is undeniably transformative. Then, we analyze the approximation forms of average block error ratio (BLER) across three scenarios: selective combining - random selection (SC-RAN), selective combining - maximal ratio combining (SC-MRC), and full-maximal ratio combining (Full-MRC). Results indicate that the full-MRC scheme consistently outperforms the others in reducing BLER, particularly in low-latency scenarios. The findings serve as a foundation for making strategic design decisions about the system’s core operational parameters. Our numerical results strongly validate our analytical findings, clearly demonstrating that the full-MRC technique significantly outperforms others in improving BLER.