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Soluble epoxide hydrolase (sEH) is essential for converting epoxy fatty acids, such as epoxyeicosatrienoic acids (EETs), into their dihydroxy forms. EETs play a crucial role in regulating blood pressure, mediating anti-inflammatory responses, and modulating pain, making sEH a key target for therapeutic interventions. Current research is increasingly focused on identifying sEH inhibitors from natural sources, particularly marine environments, which are rich in bioactive compounds due to their unique metabolic adaptations. In this study, the sEH inhibitory activities of ten cembranoid diterpenes ( 1 - 10 ) isolated from the soft coral Sinularia maxima were evaluated. Among them, compounds 3 and 9 exhibited considerable sEH inhibition, with IC 50 values of 70.68 μM and 78.83 μM, respectively. Enzyme kinetics analysis revealed that these two active compounds inhibit sEH through a non-competitive mode. Additionally, in silico approaches, including molecular docking and molecular dynamics simulations, confirmed their stability and interactions with sEH, highlighting their potential as natural therapeutic agents for managing cardiovascular and inflammatory diseases.

This study showed that a polylactide (PLA)-based composite filled with nanostructured hydroxyapatite (HAp) and a natural extract from the rhizome of Curcuma longa L. could provide an alternative to commonly used fossil-based plasticsfor food packaging. The incorporation of HAp into the PLA matrix had a positive effect on improving selected properties of the composites; the beneficial effect could be enhanced by introducing a green modifier in the form of an extract. Prior to the fabrication of the composite, the filler was characterized in terms of morphology and composition, and the composite was then fully characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), Raman and Fourier transform infrared spectroscopy (FT-IR), and the mechanical, thermal, thermomechanical, and optical properties were investigated. The proposed material exhibits antioxidant properties against DPPH radicals and antibacterial performance against Escherichia coli ( E. coli ). The results showed that the nanocomposite has the highest antioxidant and antibacterial properties for 10 wt% HAp with an average diameter of rod-shaped structures below 100 nm. In addition, the introduction of turmeric extract had a positive effect on the tensile strength of the nanocomposites containing 1 and 5% HAp. As the resulting material adsorbs light in a specific wavelength range, it can be used in the medical sector, food-packaging, or coatings.

Three titanium alloys with 0.5, 6, and 9 wt.% iron were investigated, and the samples were pre-annealed in three different regions of the Ti-Fe phase diagram, namely β, α+β, and α+FeTi. After annealing, five samples of different phases and structural compositions were studied. They were then subjected to the high-pressure torsion (HPT). The microstructure of the samples before and after HPT treatment was studied using transmission and scanning electron microscopy. The microstructure of the samples obtained during heat treatment before HPT treatment had a fundamental effect on the microstructure after HPT. Grain boundary layers and chains of particles formed during the annealing process made it difficult to mix the material during HPT, which led to the formation of areas with non-uniform mixing of components. Thus, the grain boundary layers of the α-phase formed in the Ti-6wt % Fe alloy after annealing at 670 °C significantly decreased the mixing of the components during HPT. Despite the fact that the microstructure and phase composition of Ti-6wt % Fe alloys pre-annealed in three different regions of the Ti-Fe phase diagram had significant differences, after HPT treatment, the phase compositions of the studied samples were quite similar. Moreover, the measured micro- and nanohardness as well as the Young's modulus of Ti-6wt % Fe alloy had similar values. It was shown that the microhardness of the studied samples increased with the iron content. The values of nanohardness and Young's modulus correlated well with the fractions of β- and ω-phases in the studied alloys.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV; Coronaviridae, Rhinacovirus ) was detected in 2017 in Guangdong Province (China), where it caused high mortality rates in piglets. According to previous studies, SADS-CoV evolved from horseshoe bat reservoirs. Here, we report the first five Rhinacovirus genomes sequenced in horseshoe bats from Vietnam and their comparisons with data published in China. Our phylogenetic analyses provided evidence for four groups: rhinacoviruses from Rhinolphus pusillus bats, including one from Vietnam; bat rhinacoviruses from Hainan; bat rhinacoviruses from Yunnan showing a divergent synonymous nucleotide composition; and SADS-CoV and related bat viruses, including four rhinacoviruses from Vietnam sampled in Rhinolophus affinis and Rhinolophus thomasi . Our phylogeographic analyses showed that bat rhinacoviruses from Dien Bien (Vietnam) share more affinities with those from Yunnan (China) and that the ancestor of SADS-CoVs arose in Rhinolophus affinis circulating in Guangdong. We detected sequencing errors and artificial chimeric genomes in published data. The two SADS-CoV genomes previously identified as recombinant could also be problematic. The reliable data currently available, therefore, suggests that all SADS-CoV strains originate from a single bat source and that the virus has been spreading in pig farms in several provinces of China for at least seven years since the first outbreak in August 2016.

The molecular machines of life, proteins, are made up of twenty kinds of amino acids, each with distinctive side chains. We present a geometrical analysis of the protrusion statistics of side chains in more than 4000 high-resolution protein structures. We employ a coarse-grained representation of the protein backbone viewed as a linear chain of C α atoms and consider just the heavy atoms of the side chains. We study the large variety of behaviors of the amino acids based on both rudimentary structural chemistry as well as geometry. Our geometrical analysis uses a backbone Frenet coordinate system for the common study of all amino acids. Our analysis underscores the richness of the repertoire of amino acids that is available to nature to design protein sequences that fit within the putative native state folds.

Background and Objectives : We aimed to investigate the carriage of colistin-resistant genes among both patients with a history of antibiotic exposure and apparently healthy adults with no recent healthcare contact. Materials and Methods : Stool swabs were collected from healthy people, and specimens were collected at the infection foci from the patients. Eleven primer/probe sets were used to perform the Multiplex Real-Time PCR assay with the QuantiNova Multiplex Probe PCR kit for screening the carriage of colistin-resistant genes ( mcr -1 to mcr -10) and 16S rRNA gene as internal control. Results : In total, 86 patients and 96 healthy residents were included. Twenty two patients (25.9%) were positive with at least one colistin-resistance encoding gene. The mcr -1 gene was the most frequent (16.5%), followed by mcr -9, mcr -6, and mcr -4 genes, where the prevalence was 11.8%, 10.6%, and 9.4%, respectively. No patient was positive with mcr -3, mcr -7, and mcr -8 genes. Eight patients (9.4%) were positive with multiple colistin-encoding genes. Twenty-three healthy people (24.0%) were positive with at least one colistin-resistance encoding gene, and the mcr -10 gene was the most frequent (27.0%), followed by the mcr -1, mcr -8, and mcr -9 genes, where the prevalence was 24.3%, 21.6%, and 13.5%, respectively. No person was positive with the mcr -2 and mcr -5 genes. Conclusions : Our findings underscore the urgent need for enhanced surveillance, infection control measures, and stewardship interventions to mitigate the spread of colistin resistance in Vietnam.

Background and Objectives : Malaria continues to be a significant global health challenge. The efficacy of artemisinin-based combination therapies (ACTs) has declined in many parts of the Greater Mekong Subregion, including Vietnam, due to the spread of resistant malaria strains. This study was conducted to assess the efficacy of the Dihydroartemisinin (DHA)-Piperaquine (PPQ) regimen in treating uncomplicated falciparum malaria and to conduct molecular surveillance of antimalarial drug resistance in Binh Phuoc and Dak Nong provinces. Materials and Methods : The study included 63 uncomplicated malaria falciparum patients from therapeutic efficacy studies (TES) treated following the WHO treatment guidelines (2009). Molecular marker analysis was performed on all 63 patients. Methods encompassed Sanger sequencing for pfK13 mutations and quantitative real-time PCR for the pfpm2 gene. Results : This study found a marked decrease in the efficacy of the DHA-PPQ regimen, with an increased rate of treatment failures at two study sites. Genetic analysis revealed a significant presence of pfK13 mutations and pfpm2 amplifications, indicating emerging resistance to artemisinin and its partner drug. Conclusions : The effectiveness of the standard DHA-PPQ regimen has sharply declined, with rising treatment failure rates. This decline necessitates a review and possible revision of national malaria treatment guidelines. Importantly, molecular monitoring and clinical efficacy assessments together provide a robust framework for understanding and addressing detection drug resistance in malaria.

Background and Objectives: Drug resistant epilepsy (DRE) is a major hurdle in epilepsy, which hinders clinical care, patients' management and treatment outcomes. DRE may partially result from genetic variants that alter proteins responsible for drug targets and drug transporters in the brain. We aimed to examine the relationship between SCN1A , GABRA1 and ABCB1 polymorphism and drug response in epilepsy children in Vietnam. Materials and Methods : In total, 213 children diagnosed with epilepsy were recruited in this study (101 were drug responsive and 112 were drug resistant). Sanger sequencing had been performed in order to detect six single nucleotide polymorphisms (SNPs) belonging to SCN1A (rs2298771, rs3812718, rs10188577), GABRA1 (rs2279020) and ABCB1 (rs1128503, rs1045642) in study group. The link between SNPs and drug response status was examined by the Chi-squared test or the Fisher's exact test. Results : Among six investigated SNPs, two SNPs showed significant difference between the responsive and the resistant group. Among those, heterozygous genotype of SCN1A rs2298771 (AG) were at higher frequency in the resistant patients compared with responsive patients, playing as risk factor of refractory epilepsy. Conversely, the heterozygous genotype of SCN1A rs3812718 (CT) was significantly lower in the resistant compared with the responsive group. No significant association was found between the remaining four SNPs and drug response. Conclusions : Our study demonstrated a significant association between the SCN1A genetic polymorphism which increased risk of drug-resistant epilepsy in Vietnamese epileptic children. This important finding further supports the underlying molecular mechanisms of SCN1A genetic variants in the pathogenesis of drug-resistant epilepsy in children.

This first study investigated the presence of dioxins and furans in river sediments around a craft village in Vietnam, focusing on Secondary Steel Recycling. Sediment samples were collected from various locations along the riverbed near the Da Hoi Secondary Steel Recycling village in Bac Ninh province. The analysis was conducted using a HRGC/HRMS-DFS device, detecting a total of 17 dioxin/furan isomers in all samples, with an average total concentration of 288.86 ng/kg d.w. The concentrations of dioxin/furan congeners showed minimal variation among sediment samples, ranging from 253.9 to 344.2 ng/kg d.w. The predominant compounds in the dioxin group were OCDD, while in the furan group, they were 1,2,3,4,6,7,8-HpCDF and OCDF. The chlorine content in the molecule appeared to be closely related to the concentration of dioxins and their percentage distribution. However, the levels of furan isomers did not vary significantly. The distribution of these compounds was not dependent on the flow direction, as they were mainly found in solid waste and are not water-soluble. Although the hepta and octa congeners had high concentrations, when converted to TEQ values, the tetra and penta groups (for dioxins) and the penta and hexa groups (for furans) contributed more to toxicity. Furthermore, the source of dioxins in sediments at Da Hoi does not only originate from steel recycling production activities but also from other combustion sites. The average total toxicity was 10.92 ng TEQ/kg d.w, ranging from 4.99 to 17.88 ng TEQ/kg d.w, which did not exceed the threshold specified in QCVN 43:2017/BTNMT, the National Technical Regulation on Sediment Quality. Nonetheless, these levels are still concerning. The presence of these toxic substances not only impacts aquatic organisms in the sampled water environment but also poses potential health risks to residents living nearby.

Infectious bronchitis virus (IBV) causes a highly contagious respiratory disease in chickens, leading to significant economic losses in the poultry industry worldwide. IBV exhibits a high mutation rate, resulting in the continuous emergence of new variants and strains. A complete genome analysis of IBV is crucial for understanding its characteristics. However, it is challenging to obtain whole-genome sequences from IBV-infected clinical samples due to the low abundance of IBV relative to the host genome. Here, we present a novel approach employing next-generation sequencing (NGS) to directly sequence the complete genome of IBV. Through in silico analysis, six primer pairs were designed to match various genotypes, including the GI-19 lineage of IBV. The primer sets successfully amplified six overlapping fragments by long-range PCR and the size of the amplicons ranged from 3.7 to 6.4 kb, resulting in full coverage of the IBV genome. Furthermore, utilizing Illumina sequencing, we obtained the complete genome sequences of two strains belonging to the GI-19 lineage (QX genotype) from clinical samples, with 100% coverage rates, over 1000 × mean depth coverage, and a high percentage of mapped reads to the reference genomes (96.63% and 97.66%). The reported method significantly improves the whole-genome sequencing of IBVs from clinical samples; thus, it can improve understanding of the epidemiology and evolution of IBVs.

The Streptomyces strain G222, isolated from a Vietnamese marine sediment, was confidently identified by 16 S rRNA gene sequencing. Its AcOEt crude extract was successfully analyzed using non-targeted LC-MS/MS analysis, and molecular networking, leading to a putative annotation of its chemical diversity thanks to spectral libraries from GNPS and in silico metabolite structure prediction obtained from SIRIUS combined with the bioinformatics tool conCISE (Consensus Annotation Propagation of in silico Elucidations). This dereplication strategy allowed the identification of an interesting cluster of a series of putative cyclic and linear lipopeptides of the lichenysin and surfactin families. Lichenysins ( 3 - 7 ) were isolated from the sub-fraction, which showed significant anti-biofilm activity against Pseudomonas aeruginosa MUC-N1. Their structures were confirmed by detailed 1D and 2D NMR spectroscopy (COSY, HSQC, HMBC, TOCSY, ROESY) recorded in CD 3 OH, and their absolute configurations were determined using the modified Marfey's method. The isolated lichenysins showed anti-biofilm activity at a minimum concentration of 100 µM. When evaluated for antibacterial activity against a panel of Gram-positive and Gram-negative strains, two isolated lichenysins exhibited selective activity against the MRSA strain without affecting its growth curve and without membranotropic activity. This study highlights the power of the MS/MS spectral similarity strategy using computational methods to obtain a cross-validation of the annotated molecules from the complex metabolic profile of a marine sediment-derived Streptomyces extract. This work provides the first report from a Streptomyces strain of combined cyclic and linear lichenysins and surfactins, known to be characteristic compounds of the genus Bacillus .

Prodigiosin, a red pigment produced by numerous bacterial species, exerts various antibiotic effects on prokaryotic and eukaryotic organisms. For instance, human carcinoma cell lines appear to suffer from endoplasmic reticulum (ER) stress in the presence of prodigiosin. Here, we demonstrated that prodigiosin also triggers the unfolded-protein response (UPR), which is a cytoprotective response against ER stress, in yeast Saccharomyces cerevisiae . An S. cerevisiae mutant carrying a UPR-deficient mutation was hypersensitive to prodigiosin. Our observations cumulatively indicate that protein folding in the ER is impaired by prodigiosin, illustrating a new mode of action.

Background: Cells are sensitive to changes in gravity, especially the cytoskeletal structures that determine cell morphology. The aim of this study was to assess the effects of simulated microgravity (SMG) on 3T3 cell morphology, as demonstrated by a characterization of the morphology of cells and nuclei, alterations of microfilaments and microtubules, and changes in cycle progression., Methods: 3T3 cells underwent induced SMG for 72 h with Gravite ® , while the control group was under 1G. Fluorescent staining was applied to estimate the morphology of cells and nuclei and the cytoskeleton distribution of 3T3 cells. Cell cycle progression was assessed by using the cell cycle app of the Cytell microscope, and Western blot was conducted to determine the expression of the major structural proteins and main cell cycle regulators., Results: The results show that SMG led to decreased nuclear intensity, nuclear area, and nuclear shape and increased cell diameter in 3T3 cells. The 3T3 cells in the SMG group appeared to have a flat form and diminished microvillus formation, while cells in the control group displayed an apical shape and abundant microvilli. The 3T3 cells under SMG exhibited microtubule distribution surrounding the nucleus, compared to the perinuclear accumulation in control cells. Irregular forms of the contractile ring and polar spindle were observed in 3T3 cells under SMG. The changes in cytoskeleton structure were caused by alterations in the expression of major cytoskeletal proteins, including β-actin and α-tubulin 3. Moreover, SMG induced 3T3 cells into the arrest phase by reducing main cell cycle related genes, which also affected the formation of cytoskeleton structures such as microfilaments and microtubules., Conclusions: These results reveal that SMG generated morphological changes in 3T3 cells by remodeling the cytoskeleton structure and downregulating major structural proteins and cell cycle regulators.

Linear chain molecules play a central role in polymer physics with innumerable industrial applications. They are also ubiquitous constituents of living cells. Here, we highlight the similarities and differences between two distinct ways of viewing a linear chain. We do this, on the one hand, through the lens of simulations for a standard polymer chain of tethered spheres at low and high temperatures and, on the other hand, through published experimental data on an important class of biopolymers, proteins. We present detailed analyses of their local and non-local structures as well as the maps of their closest contacts. We seek to reconcile the startlingly different behaviors of the two types of chains based on symmetry considerations.

Tuberculosis is one of the most common infectious diseases in the world, caused by Mycobacterium tuberculosis . The outbreak of multiple drug-resistant tuberculosis has become a major challenge to prevent this disease worldwide. ClpC1 is a Clp ATPase protein of Mycobacterium tuberculosis , functioning as a chaperon when combined with the Clp complex. ClpC1 has emerged as a new target to discover anti-tuberculosis drugs. This study aimed to explore the ClpC1 inhibitors from actinomycetes, which have been known to provide abundant sources of antibiotics. Two cyclic peptides, including nocardamin ( 1 ), halolitoralin A ( 3 ), and a lactone pleurone ( 2 ), were isolated from the culture of Streptomyces aureus (VTCC43181). The structures of these compounds were determined based on the detailed analysis of their spectral data and comparison with references. This is the first time these compounds have been isolated from S. aureus. Compounds 1 - 3 were evaluated for their affection of ATPase activity of the recombinant ClpC1 protein. Of these compounds, halolitoralin A ( 1 ), a macrocyclic peptide, was effective for the ATPase hydrolysis of the ClpC1 protein.

Thickener, also known as a gelling agent, is a critical component of lubricating greases. The most critical property of thickener, temperature resistance, is determined by the molecular structure of the compounds. Currently, all high-temperature-resistant thickeners are based on 12-hydroxystearic acid, which is exclusively produced from castor oil. Since castor oil is also an important reagent for other processes, finding a sustainable alternative to 12-hydroxystearic acid has significant economic implications. This study synthesises an alternative thickener from abundant agricultural waste, cashew nut shell liquor (CNSL). The synthesis and separation procedure contains three steps: (i) forming and separating calcium anacardate by precipitation, (ii) forming and separating anacardic acid (iii) forming lithium anacardate. The obtained lithium anacardate can be used as a thickener for lubricating grease. It was found that the recovery of anacardic acid was around 80%. The optimal reaction temperature and time conditions for lithium anacardate were 100 °C and 1 h, respectively. The method provides an economical alternative to castor and other vegetable oils. The procedure presents a simple pathway to produce the precursor for the lubricating grease from agricultural waste. The first reaction step can be combined with the existing distillation of cashew nut shell processing. An effective application can promote CNSL to a sustainable feedstock for green chemistry. The process can also be combined with recycled lithium from the spent batteries to improve the sustainability of the battery industry.

The essential oils of five Vietnamese Syzygium species ( Syzygium levinei , S. acuminatissimum , S. vestitum , S. cumini , and S. buxifolium ) were first hydro-distilled and analyzed using GC-FID/MS (gas chromatography-flame ionization detection/mass spectrometry). Monoterpene hydrocarbons, sesquiterpene hydrocarbons, and oxygenated sesquiterpenoids were the main chemical classes in these oils. All these essential oils showed good-excellent antimicrobial activities against Gram-positive bacteria Enterococcus faecalis , Staphylococcus aureus , and Bacillus cereus , and the yeast Candida albicans. S. levinei leaf essential oil, rich in bicyclogermacrene (25.3%), ( E )- β -elemene (12.2%), ( E )-caryophyllene (8.2%), and β -selinene (7.4%), as well as S. acuminatissimum fruit essential oil containing ( E )-caryophyllene (14.2%), α -pinene (12.1%), caryophyllene oxide (10.9%), β -selinene (10.8%), α -selinene (8.0%), and α -humulene (5.7%), established the same MIC value of 8 µg/mL against E. faecalis and B. cereus , which were much better than the positive control streptomycin (MIC 128-256 µg/mL). The studied essential oils showed the potential to defend against mosquitoes since they caused the 24 and 48 h LC 50 values of less than 50 µg/mL against the growth of Culex quinquefasciatus and Aedes aegypti larvae. Especially, S. buxifolium leaf essential oil strongly inhibited Ae. aegypti larvae with 24 and 48 h LC 50 values of 6.73 and 6.73 µg/mL, respectively, and 24 and 48 h LC 90 values of 13.37 and 10.83 µg/mL, respectively. These findings imply that Vietnamese Syzygium essential oils might have potential for use as supplemental antibacterial agents or as "green" alternatives for the control of mosquitoes.

Ulvan, a sulfated heteropolysaccharide with structural and functional properties of interest for various uses, was extracted from the green seaweed Ulva papenfussii . U. papenfussii is an unexplored Ulva species found in the South China Sea along the central coast of Vietnam. Based on dry weight, the ulvan yield was ~15% ( w / w ) and the ulvan had a sulfate content of 13.4 wt%. The compositional constitution encompassed L-Rhamnose (Rha p ), D-Xylose (Xyl p ), D-Glucuronic acid (GlcA p ), L-Iduronic acid (IdoA p ), D-Galactose (Gal p ), and D-Glucose (Glc p ) with a molar ratio of 1:0.19:0.35:0.52:0.05:0.11, respectively. The structure of ulvan was determined using High-Performance Liquid Chromatography (HPLC), Fourier Transform Infrared Spectroscopy (FT-IR), and Nuclear Magnetic Resonance spectroscopy (NMR) methods. The results showed that the extracted ulvan comprised a mixture of two different structural forms, namely ("A3s") with the repeating disaccharide [→4)-β-D-GlcA p -(1→4)-α-L-Rha p 3S-(1→]n, and ("B3s") with the repeating disaccharide [→4)-α-L-IdoA p -(1→4)-α-L-Rha p 3S(1→]n. The relative abundance of A3s, and B3s was 1:1.5, respectively. The potential anticarcinogenic attributes of ulvan were evaluated against a trilogy of human cancer cell lineages. Concomitantly, Quantitative Structure-Activity Relationship (QSAR) modeling was also conducted to predict potential adverse reactions stemming from pharmacological interactions. The ulvan showed significant antitumor growth activity against hepatocellular carcinoma (IC 50 ≈ 90 µg/mL), human breast cancer cells (IC 50 ≈ 85 µg/mL), and cervical cancer cells (IC 50 ≈ 67 µg/mL). The QSAR models demonstrated acceptable predictive power, and seven toxicity indications confirmed the safety of ulvan, warranting its candidacy for further in vivo testing and applications as a biologically active pharmaceutical source for human disease treatment.

The results of in silico screening of the 50 isolated compounds from Millettia dielsiana against the target proteins PDE4 (PDE4A, PDE4B, and PDE4D) showed binding affinity ranges from -5.81 to -11.56, -5.27 to -13.01, and -5.80 to -12.12 kcal mol -1 , respectively, with median values of -8.83, -8.84, and -8.645 kcal mol -1 , respectively. Among these compounds, Millesianin F was identified as the most promising PDE4A inhibitor due to its strongest binding affinity with the target protein PDE4A. (-11.56 kcal mol -1 ). This was followed by the compound 5,7,4'-trihydroxyisoflavone 7- O-β -d-apiofuranosyl-(1→6)-β-d-glucopyranoside (D50) with the binding affinity value of -11.35 kcal mol -1 . For the target protein PDE4B, compound D50 exhibited the strongest binding affinity value of -13.01 kcal mol -1 , while showing poorer inhibition ability for PDE4D. The 100 ns MD simulation examination (radius of gyration, Solvent Accessible Surface Area (SASA), Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), and hydrogen bonding) was carried out to examine the overall stability and binding efficiency of the protein-ligand complex between compounds (Millesianin F, Millesianin G, Claclrastin-7- O-β -d-glucopyranoside, 7-hydroxy-4',6 dimethoxyisoflavone-7- O-β -d-apiofuranosyl-(1→6)- β -d-glucopyranoside, 7-hydroxy-4',8-dimethoxyisoflavone 7- O-β -d-apiofuranosyl-(1→6)-β-d-glucopyranoside, Odoratin-7- O-β -d-glucopyranoside, and 5,7,4'-trihydroxyisoflavone 7- O-β -d-apiofuranosyl-(1→6)- β -d-glucopyranoside) and PDE4 (A, B) subtype proteins. Compound D50 has shown strong anti -inflammatory activity, as evidenced by experimental results. It effectively inhibits PDE4B and PDE4D, with IC 50 values of 6.56 ± 0.7 µM and 11.74 ± 1.3 µM, respectively. Additionally, it reduces NO production, with an IC 50 value of 5.40 ± 0.9 µM. Based on these findings, it is promising and considered a potential novel anti -inflammatory drug for future development.

Prostate cancer (PC) is the second most common cancer in men worldwide. Despite recent advances in diagnosis and treatment, castration-resistant prostate cancer (CRPC) remains a significant medical challenge. Prostate cancer cells can develop mechanisms to resist androgen deprivation therapy, such as AR overexpression, AR mutations, alterations in AR coregulators, increased steroidogenic signaling pathways, outlaw pathways, and bypass pathways. Various treatment options for CRPC exist, including androgen deprivation therapy, chemotherapy, immunotherapy, localized or systemic therapeutic radiation, and PARP inhibitors. However, more research is needed to combat CRPC effectively. Further investigation into the underlying mechanisms of the disease and the development of new therapeutic strategies will be crucial in improving patient outcomes. The present work summarizes the current knowledge regarding the underlying mechanisms that promote CRPC, including both AR-dependent and independent pathways. Additionally, we provide an overview of the currently approved therapeutic options for CRPC, with special emphasis on chemotherapy, radiation therapy, immunotherapy, PARP inhibitors, and potential combination strategies.

Background and Objectives : Psoriasis is an immune-mediated chronic inflammatory skin disorder and commonly associated with highly noticeable erythematous, thickened and scaly plaques. Deubiquitinase genes, such as tumor necrosis factor-alpha protein 3 (TNFAIP3, A20), the cylindromatosis (CYLD) and Cezanne, function as negative regulators of inflammatory response through the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. In this study, polymorphisms and expressions of A20, CYLD and Cezanne genes as well as immunophenotype in psoriatic patients were determined. Materials and Methods : In total, 82 patients with psoriasis and 147 healthy individuals with well-characterized clinical profiles were enrolled. Gene polymorphisms were determined by direct DNA sequencing, gene expression profile by quantitative real time-polymerase chain reaction (PCR), immunophenotype by flow cytometry, and the secretion of cytokines and cancer antigen (CA) 125 by enzyme-linked Immunosorbent assay (ELISA). Results : The inactivation of A20, CYLD and Cezanne and increased levels of TNF-α, IFN-γ and CA 125 was observed in psoriatic patients. Importantly, patients with low A20 expression had significant elevations of triglyceride and total cholesterol concentrations and higher numbers of CD13 + CD117 - and CD19 + CD23 + (activated B) cells than those with high A20 expression. Genetic analysis indicated that all rs4495487 SNPs in the JAK2 gene, rs200878487 SNPs in the A20 gene and four SNPs (c.1584-375, c.1584-374, rs1230581026 and p.W433R) in the Cezanne gene were associated with significant risks, while the rs10974947 variant in the JAK2 gene was at reduced risk of psoriasis. Moreover, in the Cezanne gene, p.W433R was predicted to be probably damaging by the Polyphen-2 prediction tool and an AA/CC haplotype was associated with a high risk of psoriasis. In addition, patients with higher CA 125 levels than the clinical cutoff 35 U/mL showed increased levels of IFN-γ than those with normal CA 125 levels. Conclusions : A20 expression was associated with lipid metabolism and the recruitment of CD13 + CD117 - and activated B cells into circulation in psoriatic patients. Besides this, the deleterious effect of the p.W433R variant in the Cezanne gene may contribute to the risk of psoriasis.

Bats are a major reservoir of zoonotic viruses, including coronaviruses. Since the emergence of SARS-CoV in 2002/2003 in Asia, important efforts have been made to describe the diversity of Coronaviridae circulating in bats worldwide, leading to the discovery of the precursors of epidemic and pandemic sarbecoviruses in horseshoe bats. We investigated the viral communities infecting horseshoe bats living in Northern Vietnam, and report here the first identification of sarbecoviruses in Rhinolophus thomasi and Rhinolophus siamensis bats. Phylogenetic characterization of seven strains of Vietnamese sarbecoviruses identified at least three clusters of viruses. Recombination and cross-species transmission between bats seemed to constitute major drivers of virus evolution. Vietnamese sarbecoviruses were mainly enteric, therefore constituting a risk of spillover for guano collectors or people visiting caves. To evaluate the zoonotic potential of these viruses, we analyzed in silico and in vitro the ability of their RBDs to bind to mammalian ACE2s and concluded that these viruses are likely restricted to their bat hosts. The workflow applied here to characterize the spillover potential of novel sarbecoviruses is of major interest for each time a new virus is discovered, in order to concentrate surveillance efforts on high-risk interfaces.

Little is known about the chemical and biological profiles of Dicranopteris linearis and Psychotria adenophylla . No previous studies have investigated alpha-glucosidase inhibition using extracts from D. linearis and P. adenophylla . In this paper, bioactive-guided isolation procedures were applied to the plants D. linearis and P. adenophylla based on alpha-glucosidase inhibition. From the most active fractions, 20 compounds ( DL1 - DL13 and PA1 - PA7 ) were isolated. The chemical structures were elucidated using spectroscopic data and compared with those available in the literature. These compounds were evaluated for alpha-glucosidase inhibition, while a molecular docking study was performed to elucidate the mechanisms involved. Consequently, D. linearis and P. adenophylla might serve as a good potential for developing new antidiabetic preparations.

Microbial fuel cells are one of the alternative methods that generate green, renewable sources of energy from wastewater. In this study, a new bio-electrochemical system called the sulfide-oxidizing fuel cell (SOFC) is developed for the simultaneous removal of sulfide/sulfide and electricity generation. To improve the application capacity of the SOFC, a system combining sulfate-reducing and sulfide-oxidizing processes for sulfate/sulfide removal and electricity generation was designed. Key factors influencing the sulfide-removal efficiency and electricity-generation capacity of the SOFC are the anolytes and catholytes. The sulfide produced from the sulfate-reducing process is thought to play the key role of an electron mediator (anolyte), which transfers electrons to the electrode to produce electricity. Sulfide can be removed in the anodic chamber of the SOFC when it is oxidized to the element sulfur (S°) through the biochemical reaction at the anode. The performance of wastewater treatment for sulfate/sulfide removal and electricity generation was evaluated by using different catholytes (dissolved oxygen in deionized water, a phosphate buffer, and ferricyanide). The results showed that the sulfate-removal efficiency is 92 ± 1.2% during a 95-day operation. A high sulfide-removal efficiency of 93.5 ± 1.2 and 83.7 ± 2% and power density of 18.5 ± 1.1 and 15.2 ± 1.2 mW/m 2 were obtained with ferricyanide and phosphate buffers as the catholyte, respectively, which is about 2.6 and 2.1 times higher than dissolved oxygen being used as a catholyte, respectively. These results indicated that cathode electron acceptors have a direct effect on the performance of the treatment system. The sulfide-removal efficiency and power density of the phosphate buffer SOFC were only slightly less than the ferricyanide SOFC. Therefore, a phosphate buffer could serve as a low-cost and effective pH buffer for practical applications, especially for wastewater treatment. The results presented in this study clearly revealed that the integrated treatment system can be effectively applied for sulfate/sulfide removal and electricity generation simultaneously.

A wastewater treatment system has been established based on sulfate-reducing and sulfide-oxidizing processes for treating organic wastewater containing high sulfate/sulfide. The influence of COD/SO 4 ratio and hydraulic retention time (HRT) on removal efficiencies of sulfate, COD, sulfide and electricity generation was investigated. The continuous operation of the treatment system was carried out for 63 days with the optimum COD/SO 2- ratio and HRT. The result showed that the COD and sulfate removal efficiencies were stable, reaching 94.8 ± 0.6 and 93.0 ± 1.3% during the operation. A power density level of 18.0 ± 1.6 mW/m 4 was obtained with a sulfide removal efficiency of 93.0 ± 1.2%. However, the sulfide removal efficiency and power density decreased gradually after 45 days. The results from scanning electron microscopy (SEM) with an energy dispersive X-ray (EDX) show that sulfur accumulated on the anode, which could explain the decline in sulfide oxidation and electricity generation. This study provides a promising treatment system to scale up for its actual applications in this type of wastewater.2- ratio and HRT. The result showed that the COD and sulfate removal efficiencies were stable, reaching 94.8 ± 0.6 and 93.0 ± 1.3% during the operation. A power density level of 18.0 ± 1.6 mW/m 2 was obtained with a sulfide removal efficiency of 93.0 ± 1.2%. However, the sulfide removal efficiency and power density decreased gradually after 45 days. The results from scanning electron microscopy (SEM) with an energy dispersive X-ray (EDX) show that sulfur accumulated on the anode, which could explain the decline in sulfide oxidation and electricity generation. This study provides a promising treatment system to scale up for its actual applications in this type of wastewater.

This study aimed to assess the effects of hexavalent chromium on zebrafish ( Danio rerio ) embryo development. The zebrafish embryos were treated with solutions containing chromium at different concentrations (0.1, 1, 3.125, 6.25, 12.5, 50, and 100 µg/mL). The development of zebrafish embryos was estimated by the determination of survival rate, heart rate, and the measurement of larvae body length. Real time RT-PCR and Western blot were performed to assess the expression of apoptosis- and antioxidant-related genes. The results showed that the reduced survival rate of zebrafish embryos and larvae was associated with an increase in chromium concentration. The exposure of higher concentrations resulted in a decrease in body length of zebrafish larvae. In addition, a marked increase in heart rate was observed in the zebrafish larvae under chromium treatment, especially at high concentrations. The real-time RT-PCR analysis showed that the transcript expressions for cell-cycle-related genes ( cdk4 and cdk6 ) and antioxidant-related genes ( sod1 and sod2 ) were downregulated in the zebrafish embryos treated with chromium. Western blot analysis revealed the upregulation of Caspase 3 and Bax, while a downregulation was observed in Bcl2. These results indicated that hexavalent chromium induced changes in zebrafish embryo development by altering apoptosis- and antioxidant-related genes.

A superior heterojunction of HC-ZnBi-LDO was synthesized in two steps, namely hydrothermal carbonization, followed by co-precipitation. The 2% HC-ZnBi-LDO heterojunction photocatalysts could degrade over 90.8% of 30 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) using 1.0 g/L of the catalyst after 135 min of visible light exposure at pH 4. The activity of 2% HC-ZnO-LDO was remarkably stable. Approximately 86.4-90.8% of 30 mg/L 2,4-D was degraded, and more than 79-86.4% of TOC was mineralized by 2% HC-ZnBi-LDO at pH 4 after 135 min of visible light exposure during four consecutive cycles. The rapid separation and migration of charge carriers at the interfaces between HC and ZnBi-LDO were achieved within 2% HC-ZnBi-LDO. Moreover, the electron acceptor characteristic of HC in 2% HC-ZnBi-LDO caused the recombination of charge carriers to decrease significantly, thus generating more reactive radicals, such as hydroxyl radicals (OH ● ) and superoxide radicals (O 2 ). These results demonstrate that the novel 2% HC-ZnBi-LDO is a superior photocatalyst for the remediation of hazardous organic pollutants.●- ). These results demonstrate that the novel 2% HC-ZnBi-LDO is a superior photocatalyst for the remediation of hazardous organic pollutants.

Induced by the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 pandemic underlined the clear need for antivirals against coronaviruses. In an effort to identify new inhibitors of SARS-CoV-2, a screening of 824 extracts prepared from various parts of 400 plant species belonging to the Rutaceae and Annonaceae families was conducted using a cell-based HCoV-229E inhibition assay. Due to its significant activity, the ethyl acetate extract of the leaves of Clausena harmandiana was selected for further chemical and biological investigations. Mass spectrometry-guided fractionation afforded three undescribed phenolic lipids ( 1 - 3 ), whose structures were determined via spectroscopic analysis. The absolute configurations of 1 and 2 were determined by analyzing Mosher ester derivatives. The antiviral activity against SARS-CoV-2 was subsequently shown, with IC 50 values of 0.20 and 0.05 µM for 2 and 3 , respectively. The mechanism of action was further assessed, showing that both 2 and 3 are inhibitors of coronavirus entry by acting directly on the viral particle. Phenolic lipids from Clausena harmandiana might be a source of new antiviral agents against human coronaviruses.

This study applied a molecular-based method to detect parainfluenza virus 5 (PIV5) collected from 2016 to 2018 in nine provinces of Republic of Korea. We demonstrated that PIV5 was detectable in both serum and pooled organs at an average positive rate of 1.78% (99/5566). Among these, the complete genome sequence of 15,246 nucleotides was obtained for 12 field strains. Three out of the 12 strains had the lowest genetic identity (96.20-96.68%) among the 21 porcine PIV5 genomes collected in Germany, China, India, and Republic of Korea from 1998 to 2017. By analyzing a large collection of complete genome sequences of the structural protein-coding F and HN genes, this study proposed a classification of PIV5 into two lineages, 1 and 2, and identified that group 2.2.2 within sub-lineage 2.2 was substantially divergent. The evolution of two structural protein-coding genes was largely under purifying selection. A few codons (6/9 for the F gene, 7/8 for the HN gene) had elevated dN/dS values, which were loaded on internal branches and were predicted to be related to beneficial trait(s) of the virus.

Panax vietnamensis var. vietnamensis (PVV) and Panax vietnamensis var. fuscidiscus (PVF) both belong to Panax vietnamensis species and are chemically and morphologically similar, making it hard to distinguish for the consumer. Herein, 42 PVF and 12 PVV samples were collected in Quang Nam and Lai Chau Province, respectively, and subsequently characterized by ITSr-DNA sequence data to verify their origins. Next, untargeted metabolomics combined with multivariate statistical analysis was developed to differentiate PVV and PVF. The metabolic profiles of PVV and PVF were found to be distinct and classified well using Partial Least-Squares Discriminant Analysis (PLS-DA) in the training set. Among them, seven ginsenosides were of high abundance in PVV, while six were of high abundance in PVF. Next, the test set was used to validate 13 putative differential markers found in the training set, illustrating a complete match with the expression patterns of these ginsenosides in the training set. Finally, PLS-DA and linear Support Vector Machine models both indicated distinct ginsenoside profiles of PVV and PVF without misclassification in the test set. Conclusively, the developed untargeted metabolomics approach might serve as a powerful tool for the authentication of PVV and PVF at the metabolome level.

Cancer is among the leading causes of death worldwide, with no effective and safe treatment to date. This study is the first to co-conjugate the natural compound cinchonain Ia, which has promising anti-inflammatory activity, and L-asparaginase (ASNase), which has anticancer potential, to manufacture nanoliposomal particles (CALs). The CAL nanoliposomal complex had a mean size of approximately 118.7 nm, a zeta potential of -47.00 mV, and a polydispersity index (PDI) of 0.120. ASNase and cinchonain Ia were encapsulated into liposomes with approximately 93.75% and 98.53% efficiency, respectively. The CAL complex presented strong synergistic anticancer potency, with a combination index (CI) < 0.32 in two-dimensional culture and 0.44 in a three-dimensional model, as tested on NTERA-2 cancer stem cells. Importantly, the CAL nanoparticles demonstrated outstanding antiproliferative efficiency on cell growth in NTERA-2 cell spheroids, with greater than 30- and 2.5-fold increases in cytotoxic activity compared to either cinchonain Ia or ASNase liposomes, respectively. CALs also presented extremely enhanced antitumor effects, reaching approximately 62.49% tumor growth inhibition. Tumorized mice under CALs treatment showed a survival rate of 100%, compared to 31.2% in the untreated control group ( p < 0.01), after 28 days of the experiment. Thus, CALs may represent an effective material for anticancer drug development.

(1) Background: Magnetite (Fe 3 O 4 ) nanoparticles have great potential for biomedical applications, including hyperthermia and magnetic resonance imaging. In this study, we aimed to identify the biological activity of nanoconjugates composed of superparamagnetic Fe 3 O 4 nanoparticles coated with alginate and curcumin (Fe 3 O 4 /Cur@ALG) in cancer cells. (2) Methods: The nanoparticles were evaluated for the biocompatibility and toxicity on mice. The MRI enhancement and hyperthermia capacities of Fe 3 O 4 /Cur@ALG were determined in both in vitro and in vivo sarcoma models. (3) Results: The results show that the magnetite nanoparticles exhibit high biocompatibility and low toxicity in mice at Fe 3 O 4 concentrations up to 120 mg/kg when administered via intravenous injection. The Fe 3 O 4 /Cur@ALG nanoparticles enhance the magnetic resonance imaging contrast in cell cultures and tumor-bearing Swiss mice. The autofluorescence of curcumin also allowed us to observe the penetration of the nanoparticles into sarcoma 180 cells. In particular, the nanoconjugates synergistically inhibit the growth of sarcoma 180 tumors via magnetic heating and the anticancer effects of curcumin, both in vitro and in vivo. (4) Conclusions: Our study reveals that Fe 3 O 4 /Cur@ALG has a high potential for medicinal applications and should be further developed for cancer diagnosis and treatment.

Polymer-based micro-optical components are very important for applications in optical communication. In this study, we theoretically investigated the coupling of polymeric waveguide and microring structures and experimentally demonstrated an efficient fabrication method to realize these structures on demand. First, the structures were designed and simulated using the FDTD method. The optical mode and loss in the coupling structures were calculated, thereby giving the optimal distance for optical mode coupling between two rib waveguide structures or for optical mode coupling in a microring resonance structure. Simulations results then guided us in the fabrication of the desired ring resonance microstructures using a robust and flexible direct laser writing technique. The entire optical system was thus designed and manufactured on a flat base plate so that it could be easily integrated in optical circuits.

Solvent extraction has been ubiquitously used to recover valuable metals from wastes such as spent batteries and electrical boards. With increasing demands for energy transition, there is a critical need to improve the recycling rate of critical metals, including copper. Therefore, the sustainability of reagents is critical for the overall sustainability of the process. Yet, the recycling process relies on functional organic compounds based on the hydroxyoxime group. To date, hydroxyoxime extractants have been produced from petrol-based chemical feedstocks. Recently, natural-based cardanol has been used to produce an alternative hydroxyoxime. The natural-based oxime has been employed to recover valuable metals (Ga, Ni, Co) via a liquid/liquid extraction process. The natural compound has a distinctive structure with 15 carbons in the alkyl tail. In contrast, petrol-based hydroxyoximes have only 12 or fewer carbons. However, the molecular advantages of this natural-based compound over the current petrol-based ones remain unclear. In this study, molecular dynamics simulation was employed to investigate the effect of extractant hydrocarbon chains on the extraction of copper ions. Two hydroxyoxime extractants with 12 and 15 carbons in the alkyl chain were found to have similar interactions with Cu 2+ ions. Yet, a slight molecular binding increase was observed when the carbon chain was increased. In addition, lengthening the carbon chain made the extracting stage easier and the stripping stage harder. The binding would result in a lower pH in the extraction step and a lower pH in the stripping step. The insights from this molecular study would help design the extraction circuit using natural-based hydroxyoxime extractants. A successful application of cashew-based cardanol will improve the environmental benefits of the recycling process. With cashew-producing regions in developing countries, the application also improves these regions' social and economic sustainability.

The metabolic profile of the Aspergillus sp. 1901NT-1.2.2 sponge-associated fungal strain was investigated using the HPLC MS technique, and more than 23 peaks in the HPLC MS chromatogram were detected. Only two minor peaks were identified as endocrocin and terpene derivative MS data from the GNPS database. The main compound was isolated and identified as known anthraquinone derivative vismione E. The absolute stereochemistry of vismione E was established for the first time using ECD and quantum chemical methods. Vismione E showed high cytotoxic activity against human breast cancer MCF-7 cells, with an IC 50 of 9.0 µM, in comparison with low toxicity for normal human breast MCF-10A cells, with an IC 50 of 65.3 µM. It was found that vismione E inhibits MCF-7 cell proliferation and arrests the cell cycle in the G1 phase. Moreover, the negative influence of vismione E on MCF-7 cell migration was detected. Molecular docking of vismione E suggested the IMPDH2 enzyme as one of the molecular targets for this anthraquinone derivative.

Lactoferrin (Lf)-a glycoprotein of the transferrin family-has been investigated as a promising molecule with diverse applications, including infection inhibition, anti-inflammation, antioxidant properties and immune modulation. Along with that, Lf was found to inhibit the growth of cancerous tumors. Owing to unique properties such as iron-binding and positive charge, Lf could interrupt the cancer cell membrane or influence the apoptosis pathway. In addition, being a common mammalian excretion, Lf offers is promising in terms of targeting delivery or the diagnosis of cancer. Recently, nanotechnology significantly enhanced the therapeutic index of natural glycoproteins such as Lf. Therefore, in the context of this review, the understanding of Lf is summarized and followed by different strategies of nano-preparation, including inorganic nanoparticles, lipid-based nanoparticles and polymer-based nanoparticles in cancer management. At the end of the study, the potential future applications are discussed to pave the way for translating Lf into actual usage.

Sea urchins ( Tripneustes gratilla ) are among the most highly prized seafood products in Vietnam because of their nutritional value and medicinal properties. In this research, lipid classes and the phospholipid (PL) molecular species compositions from the body and eggs of T. gratilla collected in Hon Tam, Nha Trang, Khanh Hoa, Vietnam, were investigated. Hydrocarbon and wax (HW), triacylglycerol (TG), mono- and diacylglycerol (MDAG), free fatty acid (FFA), sterol (ST), polar lipid (PoL), and monoalkyl-diacylglycerol are the major lipid classes. In PL, five main glycerophospholipid classes have been identified, in which 137 PL molecular species were detected in the body and eggs of T. gratilla , including 20 inositol glycerophospholipids (PI), 11 serine glycerophospholipids (PS), 22 ethanolamine glycerophospholipids (PE), 11 phosphatidic acids (PA), and 73 choline glycerophospholipids (PC). PI 18:0/20:4, PS 20:1/20:1, PE 18:1e/20:4, PA 20:1/20:1, and PC 18:0e/20:4 are the most abundant species with the highest content values of 38.65-48.19%, 42.48-44.41%, 41.21-40.03%, 52.42-52.60%, and 7.77-7.18% in each class of the body-eggs, respectively. Interestingly, PL molecules predominant in the body sample were also found in the egg sample. The molecular species with the highest content account for more than 40% of the total species in each molecular class. However, in the PC class containing 73 molecular species, the highest content species amounted to only 7.77%. For both the body and egg TL samples of the sea urchin T. gratilla , a substantial portion of C20:4n polyunsaturated fatty acid was found in PI, PE, and PC, but C16, C18, C20, and C22 saturated fatty acids were reported at low levels. The most dominant polyunsaturated fatty acid in PI, PE, and PC was tetracosapolyenoic C20, while unsaturated fatty acid C20:1 was the most dominant in PS and PA. To our knowledge, this is the first time that the chemical properties of TL and phospholipid molecular species of the PoL of Vietnamese sea urchin ( T. gratilla ) have been studied.

Synthetic peptides are promising structural and functional components of bioactive and tissue-engineering scaffolds. Here, we demonstrate the design of self-assembling nanofiber scaffolds based on peptide amphiphile (PA) molecules containing multi-functional histidine residues with trace metal (TM) coordination ability. The self-assembly of PAs and characteristics of PA nanofiber scaffolds along with their interaction with Zn, Cu, and Mn essential microelements were studied. The effects of TM-activated PA scaffolds on mammalian cell behavior, reactive oxygen species (ROS), and glutathione levels were shown. The study reveals the ability of these scaffolds to modulate adhesion, proliferation, and morphological differentiation of neuronal PC-12 cells, suggesting a particular role of Mn(II) in cell-matrix interaction and neuritogenesis. The results provide a proof-of-concept for the development of histidine-functionalized peptide nanofiber scaffolds activated with ROS- and cell-modulating TMs to induce regenerative responses.

Multi-drug resistance to antibiotics represents a growing challenge in treating infectious diseases. Outside the hospital, bacteria with the multi-drug resistance (MDR) phenotype have an increased prevalence in anthropized environments, thus implying that chemical stresses, such as metals, hydrocarbons, organic compounds, etc., are the source of such resistance. There is a developing hypothesis regarding the role of metal contamination in terrestrial and aquatic environments as a selective agent in the proliferation of antibiotic resistance caused by the co-selection of antibiotic and metal resistance genes carried by transmissible plasmids and/or associated with transposons. Efflux pumps are also known to be involved in either antibiotic or metal resistance. In order to deal with these situations, microorganisms use an effective strategy that includes a range of expressions based on biochemical and genetic mechanisms. The data from numerous studies suggest that heavy metal contamination could affect the dissemination of antibiotic-resistant genes. Environmental pollution caused by anthropogenic activities could lead to mutagenesis based on the synergy between antibiotic efficacy and the acquired resistance mechanism under stressors. Moreover, the acquired resistance includes plasmid-encoded specific efflux pumps. Soil microbiomes have been reported as reservoirs of resistance genes that are available for exchange with pathogenic bacteria. Importantly, metal-contaminated soil is a selective agent that proliferates antibiotic resistance through efflux pumps. Thus, the use of multi-drug efflux pump inhibitors (EPIs) originating from natural plants or synthetic compounds is a promising approach for restoring the efficacy of existing antibiotics, even though they face a lot of challenges.

The essential oils (EOs) of the aerial parts of four Asarum species ( A. geophilum , A. yentunensis , A. splendens and A. cordifolium) were isolated by steam distillation and analyzed by the GC/MS method. The A. cordifolium EO contains 33 constituents with the main component being elemicine (77.20%). The A. geophilum EO was contains 49 constituents with the main components being determined as 9- epi -( E )-caryophyllene (18.43%), eudesm-7(11)-en-4-ol (13.41%), β -caryophyllene (8.05%) and phytol (7.23%). The A. yentunensis EO contains 26 constituents with the main components being safrole (64.74%) and sesquicineole (15.34%). The EO of A. splendens contains 41 constituents with the main components being 9- epi -(E)-caryophyllene (15.76%), eudesm-7(11)-en-4-ol (14.21%), β -caryophyllene (9.52%) and trans -bicyclogermacrene (7.50%). For antimicrobial activity, the A. yentunensis EO exhibited the highest inhibition activity against Staphylococcus aureus and the A. cordifolium EO against Bacillus subtillis (MIC values of 100 μg/mL). For antioxidant activity, the A. geophilum EO showed the highest potential with an SC (%) value of 63.34 ± 1.0%, corresponding to an SC 50 value of 28.57 µg/mL. For anti-inflammatory activity, the A. splendens EO exhibited the highest potential with an IC 50 value of 21.68 µg/mL, corresponding to an inhibition rate of NO production of 69.58 ± 1.3% and the percentage of cell life was 81.85 ± 0.9%.

Using essential oils to control vectors, intermediate hosts, and disease-causing microorganisms is a promising approach. The genus Croton in the family Euphorbiaceae is a large genus, with many species containing large amounts of essential oils, however, essential oil studies are limited in terms of the number of Croton species investigated. In this work, the aerial parts of C. hirtus growing wild in Vietnam were collected and analyzed by gas chromatography/mass spectrometry (GC/MS). A total of 141 compounds were identified in C. hirtus essential oil, in which sesquiterpenoids dominated, comprising 95.4%, including the main components β-caryophyllene (32.8%), germacrene D (11.6%), β-elemene (9.1%), α-humulene (8.5%), and caryophyllene oxide (5.0%). The essential oil of C. hirtus showed very strong biological activities against the larvae of four mosquito species with 24 h LC 50 values in the range of 15.38-78.27 μg/mL, against Physella acuta adults with a 48 h LC 50 value of 10.09 μg/mL, and against ATCC microorganisms with MIC values in the range of 8-16 μg/mL. In order to provide a comparison with previous works, a literature survey on the chemical composition, mosquito larvicidal, molluscicidal, antiparasitic, and antimicrobial activities of essential oils of Croton species was conducted. Seventy-two references (seventy articles and one book) out of a total of two hundred and forty-four references related to the chemical composition and bioactivity of essential oils of Croton species were used for this paper. The essential oils of some Croton species were characterized by their phenylpropanoid compounds. The experimental results of this research and the survey of the literature showed that Croton essential oils have the potential to be used to control mosquito-borne and mollusk-borne diseases, as well as microbial infections. Research on unstudied Croton species is needed to search for species with high essential oil contents and excellent biological activities.

In traditional herbal medicine, the Polyscias fruticosa has been frequently used for the treatment of ischemia and inflammation. Oxidative stress mediated by elevated glutamate levels cause neuronal cell death in ischemia and various neurodegenerative diseases. However, so far, the neuroprotective effects of this plant extract against glutamate-mediated cell death have not been investigated in cell models. The current study investigates the neuroprotective effects of ethanol extracts of Polyscias fruticosa (EEPF) and elucidates the underlying molecular mechanisms of EEPFs relevant to neuroprotection against glutamate-mediated cell death. The oxidative stress-mediated cell death was induced by 5 mM glutamate treatment in HT22 cells. The cell viability was measured by a tetrazolium-based EZ-Cytox reagent and Calcein-AM fluorescent dye. Intracellular Ca 2+ and ROS levels were measured by fluorescent dyes, fluo-3 AM and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA), respectively. Protein expressions of p-AKT, BDNF, p-CREB, Bax, Bcl-2, and apoptosis-inducing factor (AIF) were determined by western blot analysis. The apoptotic cell death was measured by flow cytometry. The in vivo efficacy of EEPF was evaluated using the Mongolian gerbil mouse by surgery-induced brain ischemia. EEPF treatment showed a neuroprotective effect against glutamate-induced cell death. The EEPF co-treatment reduced the intracellular Ca 2+ and ROS and apoptotic cell death. Furthermore, it recovered the p-AKT, p-CREB, BDNF, and Bcl-2 levels decreased by glutamate. The EEPF co-treatment suppressed the activation of apoptotic Bax, the nuclear translocation of AIF, and mitogen-activated protein kinase (MAPK) pathway proteins (ERK1/2, p38, JNK). Further, EEPF treatment significantly rescued the degenerative neurons in the ischemia-induced Mongolian gerbil in vivo model. EEPF exhibited neuroprotective properties that suppress glutamate-mediated neurotoxicity. The underlying mechanism of EEPF is increasing the level of p-AKT, p-CREB, BDNF, and Bcl-2 associated with cell survival. It has therapeutic potential for the treatment of glutamate-mediated neuropathology.

Spinal cord injury (SCI) causes inflammation and neuronal degeneration, resulting in functional movement loss. Since the availability of SCI treatments is still limited, stem cell therapy is an alternative clinical treatment for SCI and neurodegenerative disorders. Human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) are an excellent option for cell therapy. This study aimed to induce hWJ-MSCs into neural stem/progenitor cells in sphere formation (neurospheres) by using neurogenesis-enhancing small molecules (P7C3 and Isx9) and transplant to recover an SCI in a rat model. Inducted neurospheres were characterized by immunocytochemistry (ICC) and gene expression analysis. The best condition group was selected for transplantation. The results showed that the neurospheres induced by 10 µM Isx9 for 7 days produced neural stem/progenitor cell markers such as Nestin and β-tubulin 3 through the Wnt3A signaling pathway regulation markers ( β-catenin and NeuroD1 gene expression). The neurospheres from the 7-day Isx9 group were selected to be transplanted into 9-day-old SCI rats. Eight weeks after transplantation, rats transplanted with the neurospheres could move normally, as shown by behavioral tests. MSCs and neurosphere cells were detected in the injured spinal cord tissue and produced neurotransmitter activity. Neurosphere-transplanted rats showed the lowest cavity size of the SCI tissue resulting from the injury recovery mechanism. In conclusion, hWJ-MSCs could differentiate into neurospheres using 10 µM Isx9 media through the Wnt3A signaling pathway. The locomotion and tissue recovery of the SCI rats with neurosphere transplantation were better than those without transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Over time, the proportion of resistant bacteria will increase. This is a major concern. Therefore, effective and biocompatible therapeutic strategies against these bacteria are urgently needed. Non-thermal plasma has been exhaustively characterized for its antibacterial activity. This study aims to investigate the inactivation efficiency and mechanisms of plasma-generated nitric oxide water (PG-NOW) on pathogenic water, air, soil, and foodborne Gram-negative and Gram-positive bacteria. Using a colony-forming unit assay, we found that PG-NOW treatment effectively inhibited the growth of bacteria. Moreover, the intracellular nitric oxide (NO) accumulation was evaluated by 4-amino-5-methylamino-2',7'-dichlorofluorescein diacetate (DAF-FM DA) staining. The reduction of viable cells unambiguously indicates the anti-microbial effect of PG-NOW. The soxR and soxS genes are associated with nitrosative stress, and oxyR regulation corresponds to oxidative stress in bacterial cells. To support the nitrosative effect mediated by PG-NOW, we have further assessed the soxRS and oxyR gene expressions after treatment. Accordingly, soxRS expression was enhanced, whereas the oxyR expression was decreased following PG-NOW treatment. The disruption of cell morphology was observed using scanning electron microscopy (SEM) analysis. In conclusion, our findings furnish evidence of an initiation point for the further progress and development of PG-NOW-based antibacterial treatments.

In this paper, the luminescent complex Eu(3-thenoyltrifluoroacetonate) 3 was integrated with Fe 3 O 4 and gold (Au) nanoparticles to form a multifunctional nanocomposite, Fe 3 O 4 /Au/Eu(TTA) 3 (FOASET NC), for dual magnetic-photothermal therapy and biomedical imaging. Upon functionalization with amine-NH 2 , the FOASET NC exhibits a small size of 60-70 nm and strong, sharp emission at λ max = 614 nm, enhanced by surface plasmon resonance (SPR) of Au nanoparticles that provided an effective label for HT29 colorectal cancer cells by fluorescence microscopy imaging. In addition, a hyperthermia temperature (42-46 °C) was completely achieved by using these FOASET NCs in an aqueous solution with three heating modes for (i) Magnetic therapy (MT), (ii) Photothermal therapy (PT), and (iii) Dual magnetic-photothermal therapy (MPT). The heating efficiency was improved in the dual magnetic-photothermal heating mode.

Recent reviews have reinforced sponge-associated bacteria as a valuable source of structurally diverse secondary metabolites with potent biological properties, which makes these microbial communities promising sources of new drug candidates. However, the overall diversity of secondary metabolite biosynthetic potential present in bacteria is difficult to access due to the fact that the majority of bacteria are not readily cultured in the laboratory. Thus, use of cultivation-independent approaches may allow accessing "silent" and "cryptic" secondary metabolite biosynthetic gene clusters present in bacteria that cannot yet be cultured. In the present study, we investigated the diversity of secondary metabolite biosynthetic gene clusters (BGCs) in metagenomes of bacterial communities associated with three sponge species: Clathria reinwardti , Rhabdastrella globostellata , and Spheciospongia sp. The results reveal that the three metagenomes contain a high number of predicted BGCs, ranging from 282 to 463 BGCs per metagenome. The types of BGCs were diverse and represented 12 different cluster types. Clusters predicted to encode fatty acid synthases and polyketide synthases (PKS) were the most dominant BGC types, followed by clusters encoding synthesis of terpenes and bacteriocins. Based on BGC sequence similarity analysis, 363 gene cluster families (GCFs) were identified. Interestingly, no GCFs were assigned to pathways responsible for the production of known compounds, implying that the clusters detected might be responsible for production of several novel compounds. The KS gene sequences from PKS clusters were used to predict the taxonomic origin of the clusters involved. The KS sequences were related to 12 bacterial phyla with Actinobacteria , Proteobacteria , and Firmicutes as the most predominant. At the genus level, the KSs were most related to those found in the genera Mycolicibacterium , Mycobacterium , Burkholderia , and Streptomyces . Phylogenetic analysis of KS sequences resulted in detection of two known 'sponge-specific' BGCs, i.e., SupA and SwfA, as well as a new 'sponge-specific' cluster related to fatty acid synthesis in the phylum Candidatus Poribacteria and composed only by KS sequences of the three sponge-associated bacterial communities assessed here.

We present a visual tool and facile method to detect MCF-7 breast cancer cells by using YVO 4 :Eu 3+ @silica-NH-GDA-IgG bio-nanocomplexes. To obtain these complexes, YVO 4 :Eu 3+ nanoparticles with a uniform size of 10-25 nm have been prepared firstly by the hydrothermal process, followed by surface functionalization to be bio-compatible and conjugated with cancer cells. The YVO 4 :Eu 3+ @silica-NH-GDA-IgG nanoparticles exhibited an enhanced red emission at 618 nm under an excitation wavelength of 355 nm and were strongly coupled with MCF-7 breast cancer cells via biological conjugation. These bio-nanocomplexes showed a superior sensitiveness for MCF-7 cancer cell labelling with a detection percentage as high as 82%, while no HEK-293A healthy cells were probed under the same conditions of in vitro experiments. In addition, the detection percentage of MCF-7 breast cancer cells increased significantly via the functionalization and conjugation of YVO 4 :Eu 3+ nanoparticles. The experimental results demonstrated that the YVO 4 :Eu 3+ @silica-NH-GDA-IgG bio-nanocomplexes can be used as a promising labelling agent for biomedical imaging and diagnostics.

In silico docking studies of 50 selected compounds from Millettia dielsiana Harms ex Diels (family Leguminosae) were docked into the binding pocket of the PI3K/mTOR protein. In there, compounds trans -3- O-p -hydroxycinnamoyl ursolic acid ( 1 ) and 5,7,4'-trihydroxyisoflavone 7- O - β -D-apiofuranosyl-(1→6)- β -D-glucopyranoside ( 2 ) are predicted to be very promising inhibitors against PI3K/mTOR. They direct their cytotoxic activity against Hepatocellular carcinoma with binding affinity (BA) values, the pulling work spent to the co-crystallized ligand from the binding site of PI3K/mTOR (W and F max ), and the non-equilibrium binding free energy (∆G neq ) as BA values = -9.237 and -9.083 kcal/mol, W = 83.5 ± 10.6 kcal/mol with F Jar = 336.2 ± 45.3 pN and 126.6 ± 21.7 kcal/mol with F max = 430.3 ± 84.0 pN, and ∆G max = -69.86074 and -101.2317 kcal/mol, respectively. In molecular dynamic simulation, the RMSD value of the PI3K/mTOR complex with compounds ( neq and Jar ) was in the range of 0.3 nm to the end of the simulation. Therefore, the compounds ( 1 and 2 ) are predicted to be very promising inhibitors against PI3K/mTOR. The crude extract, ethyl acetate fraction and compounds ( 1 and 2 ) are predicted to be very promising inhibitors against PI3K/mTOR. The crude extract, ethyl acetate fraction and compounds ( 1 and 2 ) from Millettia dielsiana values of 81.2 µg/mL, 60.4 µg/mL, 23.1 μM, and 16.3 μM, respectively, and showed relatively potent to potent in vitro antioxidant activity on mouse hepatocytes with ED Hepatocellular carcinoma values of 24.4 µg/mL, 19.3 µg/mL, 30.7 μM, and 20.5 μM, respectively. In conclusion, 50 and compounds ( 50 and Millettia dielsiana and compounds ( 1 and have a hepatoprotective effect.2 ) are predicted to have very promising cytotoxic activity against Hepatocellular carcinoma and have a hepatoprotective effect.

Aurantiochytrium is a heterotrophic marine microalga that has potential industrial applications. The main objectives of this study were to isolate an Aurantiochytrium strain from Sand Cay (Son Ca) Island, Vietnam, optimize its culture conditions, determine its nutritional composition, extract polyunsaturated fatty acids (PUFAs) in the free (FFA) and the alkyl ester (FAAE) forms, and evaluate the antioxidation and neuroprotection properties of the PUFAs. Aurantiochytrium sp. SC145 can be grown stably under laboratory conditions. Its culture conditions were optimized for a dry cell weight (DCW) of 31.18 g/L, with total lipids comprising 25.29%, proteins 7.93%, carbohydrates 15.21%, and carotenoid at 143.67 µg/L of DCW. The FAAEs and FFAs extracted from Aurantiochytrium sp. SC145 were rich in omega 3-6-9 fatty acids (40.73% and 44.00% of total fatty acids, respectively). No acute or subchronic oral toxicity was determined in mice fed with the PUFAs in FFA or FAAE forms at different doses over 90 days. Furthermore, the PUFAs in the FFA or FAAE forms and their main constituents of EPA, DHA, and ALA showed antioxidant and AChE inhibitory properties and neuroprotective activities against damage caused by H 2 O 2 - and amyloid-ß protein fragment 25-35 (Aβ 25-35 )-induced C6 cells. These data suggest that PUFAs extracted from Aurantiochytrium sp. SC145 may be a potential therapeutic target for the treatment of neurodegenerative disorders.