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Abstract Background To investigate the aetiology of acute undifferentiated fever (AUF) among children under the age of five in Vietnam. Methods This prospective study was conducted in the Thai Binh paediatric hospital, between July 2020 and July 2021 among children with AUF at admission. Real-time PCR testing 18 microbial pathogens were done on blood samples. Results 286 children were included, with median age of 16 months. 64.7% were male. 53.9% were positive for at least one pathogen by PCR. Enterovirus, human herpesvirus 6, adenovirus, and varicella zoster virus PCR were positive for 31.1, 12.6, 1.4, and 1.0% patients, respectively. Other pathogens tested negative by PCR. During the hospital stay, based on clinical criteria 47.2% children secondarily presented with signs of respiratory tract infections, 18.9% had hand, foot and mouth disease, 4.6% had chickenpox. 4.2% presented signs of central nervous system infections, 1.0% had dengue (antigenic test) and 1.0% had signs of gastrointestinal infection. Finally, 23.1% patients presented a fever with or without a rash and no other symptoms and ultimately received a diagnosis of AUF. Conclusion Real-time PCR of blood is useful for detecting pathogens and diagnosing infectious causes of AUF. Further prospective studies with blood and urine culture testing and PCR investigation of not only blood but also cerebrospinal fluid, throat, and skin samples according to symptoms would be of interest to confirm the predominance of viral infections in children with AUF and to guide therapeutic options.

From July to October 2020, 99 cases of central nervous system (CNS) infections were identified in Thai Binh Pediatric Hospital, Viet Nam, representing a five-fold increase compared to the baseline incidence during the previous five years. Clinical data were retrospectively collected. Cerebrospinal fluid specimens (CSF) were secondarily tested for pathogens using viral culture and PCR assays. Patient median age was 5 years (0–12 years); 58.6% were male. Of these children, 83.8% had CSF white blood culture (WBC) counts of ≥ 10 cells/µL, including 58 of 99 (58.6%) with a WBC count ≥ 100 cells/µL. Overall, 72 (72.7%) patients had confirmed infections with a pathogen identified in the CSF, the majority of which (66) were enterovirus. Sequencing results suggested that the rise of incidence observed in 2020 was due to Echovirus 4 (n = 45), Echovirus 30 (n = 8), and Echovirus 6 (n = 1) circulation. A confirmed CNS infection was significantly associated with older age (≥5 years, OR = 3.64, p = 0.03) and with an increased WBC count in the CSF (OR = 6.38, p-value = 0.01 for WBCs from 10 to

This study aimed to develop the eco-friendly production of bioactive 1-hydroxyphenazine (HP) through fermentation using an industrial processing by-product of cassava as the main carbon/nitrogen source. Cassava starch processing by-product (CSPB) was screened as a suitable substrate for fermentation to produce HP with a high yield. Mixing CSPB with a minor amount of tryptic soy broth (TSB) at a ratio of 8/2 and with 0.05% K2HPO4 and 0.05% FeSO4 was effective in HP production by Pseudomonas aeruginosa TUN03. HP was also further scaled up through production on a bioreactor system, which achieved a higher level yield (36.5 µg/mL) in a shorter fermentation time (10 h) compared to its production in the flask (20.23 µg/mL after 3 days). In anti-fungal activity tests against various Fusarium phytopathogens, HP exhibited the most significant effect on Fusarium oxysporum F10. It could inhibit the mycelial growth of this fungus, with an inhibition rate of 68.7% and anti-spore germination activity of up to 98.4%. The results of the docking study indicate that HP effectively interacted with the protein 1TRY targeting anti-F. oxysporum, with all obtained docking parameters in the accepted range. This study supports the novel use of CSPB as the carbon/nitrogen source for P. aeruginosa fermentation to produce HP, a F. oxysporum anti-fungal agent reported here for the first time.

Eclipta prostrata L. (EPL), a medicinal plant, is widely utilized in the central highlands of Vietnam. This study aims to assess the chemical profile and potential medical effects of an EPL extract rich in flavonoids. A total of 36 secondary metabolites were identified from the EPL extract through GC-MS and UHPLC-UV analysis. Among them, 15 volatile compounds and several phenolic and flavonoid chemicals, including salicylic acid, epicatechin gallate, isovitexin, and apigetrin, were reported in EPL extract for the first time. This herbal extract demonstrated moderate inhibition against α-amylase and α-glucosidase, and high anti-oxidant and anti-acetylcholinesterase activities (IC50 = 76.8 ± 0.8 μg/mL). These promising attributes can be likely attributed to the high levels of major compounds, including wedelolactone (1), chlorogenic acid (3), epicatechin gallate (6), salicylic acid (8), isovitexin (9), apigetrin (11), and myricetin (12). These findings align with the traditional use of EPL for enhancing memory and cognitive function, as well as its potential benefits in diabetes management. The results of the molecular docking study reveal that the major identified compounds (1, 6, 9, and 11) showed a more effective acetylcholinesterase inhibitory effect than berberine chloride, with good binding energy (DS values, −12.3 to −14.3 kcal/mol) and acceptable values of RMSD (1.02–1.67 Å). Additionally, almost all the identified major compounds exhibited good ADMET properties within the required limits.

This report aims to characterize and reuse fish head powder (FHP) as a potential carbon/nitrogen source for microbial fermentation to produce prodigiosin (PG), and to evaluate its novel anti-fungal effect via an experimental and docking study. FHP has high protein (30.25%) and lipid (5.12%) content and a diversity of elements, which suggests that FHP is a potential substrate for microbial fermentation. Serratia marcescens TNU01 was screened as the most effective strain to produce PG from FHP. Further experiments indicated that the combination of FHP and crude chitin at the ratio of 9/1 and used at 1.5% as a C/N source for fermentation significantly enhanced PG production. Supplementing a minor amount of 0.05% Ca3(PO4)2, 0.03% K2SO4 also positively affects PG yield production. The fermentation using a bioreactor system (type of 14 L) achieved the highest PG yield production (6.4 mg/mL) in a short cultivation time (10 h) in comparison with the highest PG yield (5.8 mg/mL) obtained after 36 h of fermentation in a flask. In the anti-fungal evaluation of various plant pathogen fungal strains, PG demonstrated efficacy against Fusarium solani F04. The molecular docking results also showed that PG effectively interacted with targeting protein 3QPC of F. solani with good binding energy (DS—9.2 kcal/mol) and an acceptable RMSD value (0.94 Å). In this study, we provide a novel application of FHP for the eco-friendly production of PG, which can potentially used for the management of Fusarium solani.

Alzheimer’s disease (AD) is the most common form of dementia, which is recorded as a global health issue. Natural acetylcholinesterase inhibitors (AChEIs) are considered a helpful therapy for the management of symptoms of patients with mild-to-moderate AD. This work aimed to investigate and characterize Euonymus laxiflorus Champ. (ELC) as a natural source of AChEIs compounds via in vitro and virtual studies. The screening parts used, including the leaves, heartwood, and trunk bark of ELC, revealed that the trunk bark extract possessed the highest activity, phenolics and flavonoid content. The in vitro anti-Alzheimer activity of ELC trunk bark was notably reclaimed for the first time with comparable effect (IC50 = 0.332 mg/mL) as that of a commercial AChEI, berberine chloride (IC50 = 0.314 mg/mL). Among various solvents, methanol was the most suitable to extract ELC trunk bark with the highest activity. Twenty-one secondary metabolites (1–21) were identified from ELC trunk bark extract, based on GCMS and UHPLC analyses. Of these, 10 volatile compounds were identified from this herbal extract for the first time. One phenolic (11) and seven flavonoid compounds (15–21) were also newly found in this herbal extract. Of the identified compounds, chlorogenic acid (11), epigallocatechin gallate (12), epicatechin (13), apigetrin (18), and quercetin (20) were major compounds with a significant content of 395.8–2481.5 μg/g of dried extract. According to docking-based simulation, compounds (11–19, and 21) demonstrated more effective inhibitory activity than berberine chloride, with good binding energy (DS values: −12.3 to −14.4 kcal/mol) and acceptable RMSD values (0.77–1.75 Å). In general, these identified compounds processed drug properties and were non-toxic for human use, based on Lipinski’s rule of five and ADMET analyses.

Among various organic wastes, shrimp shell powder (SSP) was the most suitable carbon/nitrogen source for producing antinematode compounds (ANCs) via Bacillus veleznesis RB.EK7 fermentation. The fermentation process for the enhancement of antinematode activity was investigated. B. veleznesis RB.EK7 produced the highest antinematode activity in the medium containing 0.8% SSP with an initial pH of 6.5–7.0, and fermentation was performed at 35–37 °C with a saking speed of 150 rpm for 72 h. Targeting ANCs were purified from the fermented culture broth and identified as thymine (1) and hexahydropyrrolo [1,2-a]pyrazine-1,4-dione (2) based on nuclear magnetic resonance (NMR) and mass spectra analysis and were compared to those of the reported compounds. Notably, for the first time, these compounds were found as novel ANCs. Thymine (1) demonstrated a potential nematicidal effect with near 100% mortality of second-stage juvenile (J2) nematodes and anti-egg hatching effects of 70.1%, while hexahydropyrrolo [1,2-a]pyrazine-1,4-dione showed moderate antinematode activities with 64.2% mortality of J2 nematodes and anti-egg hatching effects of 57.9%. The docking study coupled with experimental enzyme inhibition results indicated that the potent nematicidal effect of these compounds may be possibly due to the inhibition of the targeting enzyme acetylcholinesterase. The data of this study suggest that SSP can be potentially reused for the eco-friendly production of ANCs for the management of black pepper nematodes.

Fishery by-products (FBPs) have been increasingly investigated for the extraction and production of a vast array of active molecules. The aim of this study was to produce phenazine compounds from FBPs via microbial fermentation and assess their novel antinematode effect. Among various FBPs, squid pen powder (SPP) was discovered as the most suitable substrate for phenazine production by Pseudomonas aeruginosa TUN03 fermentation. Various small-scale experiments conducted in flasks for phenazine production indicated that the most suitable was the newly designed liquid medium which included 1% SPP, 0.05% MgSO4, and 0.1% Ca3(PO4)2 (initial pH 7). Phenazines were further studied for scale-up bioproduction in a 14 L bioreactor system resulting in a high yield (22.73 µg/mL) in a much shorter cultivation time (12 h). In the fermented culture broth, hemi-pyocyanin (HPC) was detected as a major phenazine compound with an area percentage of 11.28% in the crude sample. In the bioactivity tests, crude phenazines and HPC demonstrate novel potential nematicidal activity against black pepper nematodes, inhibiting both juveniles (J2) nematodes and egg hatching. The results of this work suggest a novel use of SPP for cost-effective bioproduction of HPC, a novel potential nematodes inhibitor. Moreover, the combination of MgSO4 and Ca3(PO4)2 was also found to be a novel salt composition that significantly enhanced phenazine yield by P. aeruginosa fermentation in this work.

α-Amylase inhibitors (aAIs) have been applied for the efficient management of type 2 diabetes. The aim of this study was to search for potential aAIs produced by microbial fermentation. Among various bacterial strains, Pseudomonas aeruginosa TUN03 was found to be a potential aAI-producing strain, and shrimp heads powder (SHP) was screened as the most suitable C/N source for fermentation. P. aeruginosa TUN03 exhibited the highest aAIs productivity (3100 U/mL) in the medium containing 1.5% SHP with an initial pH of 7–7.5, and fermentation was performed at 27.5 °C for two days. Further, aAI compounds were investigated for scaled-up production in a 14 L-bioreactor system. The results revealed a high yield (4200 U/mL) in a much shorter fermentation time (12 h) compared to fermentation in flasks. Bioactivity-guided purification resulted in the isolation of one major target compound, identified as hemi-pyocyanin (HPC) via gas chromatography-mass spectrometry and nuclear magnetic resonance. Its purity was analyzed by high-performance liquid chromatography. HPC demonstrated potent α-amylase inhibitory activity comparable to that of acarbose, a commercial antidiabetic drug. Notably, HPC was determined as a new aAI. The docking study indicated that HPC inhibits α-amylase by binding to amino acid Arg421 at the biding site on enzyme α-amylase with good binding energy (−9.3 kcal/mol) and creating two linkages of H-acceptors.

This study aimed to reuse groundnut oil processing by-product, groundnut cake (GNC) for the low-cost production of prodigiosin (PG) via microbial technology and to assess its novel potential application for the management of black pepper nematodes. Serratia marcescens TUN02 was found as the most active PG-producing strain. Various small-scale experiments conducted in flasks indicated that GNC at 1% may be used as the sole carbon/nitrogen source for cost-effective PG production by fermentation. Notably, no further commercial ingredients and salts are required to supplement into the culture medium of this fermentation. PG was further investigated for scale-up production in a 14-L bioreactor system and PG was produced at high yield (6886 mg/L) with large-scale volume (4 L) in a short cultivation time (10 h). PG was then purified and its nematicidal activity was evaluated and showed effective inhibition of juveniles and egg hatching of Meloidogyne incognita species, harmful on black pepper, with low IC50 values of 0.2 and 0.32 mg/mL, respectively. The simple medium containing 1% GNC is the first report of cost-effective biosynthesis of PG, as well as potential in vitro anti-egg hatching activity of PG. These results indicated the potential application of GNC for low-cost bioproduction of PG for promising and novel use in the management of black pepper nematodes.

The purpose of this study was to reuse cassava wastewater (CW) for scaled-up production, via the fermentation of prodigiosin (PG), and to conduct an evaluation of its bioactivities. PG was produced at the yield of high 6150 mg/L in a 14 L-bioreactor system, when the designed novel medium (7 L), containing CW and supplemented with 0.25% casein, 0.05% MgSO4, and 0.1% K2HPO4, was fermented with Serratia marcescens TNU01 at 28 °C in 8 h. The PG produced and purified in this study was assayed for some medical effects and showed moderate antioxidant, high anti-NO (anti-nitric oxide), and potential α-glucosidase inhibitory activities. Notably, PG was first reported as a novel effective α-glucosidase inhibitor with a low IC50 value of 0.0183 µg/mL. The commercial anti-diabetic drug acarbose was tested for comparison and had a lesser effect with a high IC50 value of 328.4 µg/mL, respectively. In a docking study, the cation form of PG (cation-PG) was found to bind to the enzyme α-glucosidase by interacting with two prominent amino acids, ASP568 and PHE601, at the binding site on the target enzyme, creating six linkages and showing a better binding energy score (−14.6 kcal/mol) than acarbose (−10.5 kcal/mol). The results of this work suggest that cassava wastewater can serve as a low-cost raw material for the effective production of PG, a potential antidiabetic drug candidate.

Robusta coffee is a major commercial crop in the Central Highland of Vietnam with high economic and export value. However, this crop is adversely affected by various pathogens, particularly nematodes. This study aimed to screen active anti-nematode rhizobacterial strains for sustainable coffee production. Among more than 200 isolates, the isolate TUN03 demonstrated efficient biocontrol with nearly 100% mortality of J2 coffee nematodes Meloidogyne spp. and 84% inhibition of nematode egg hatching. This active strain was identified as Pseudomonas aeruginosa TUN03 based on its 16S rRNA gene sequence and phylogenetic analysis. In greenhouse tests, the strain TUN03 significantly reduced the coffee nematode population in the rhizome-soil with an 83.23% inhibition rate and showed plant growth-promoting effects. Notably, this is the first report of the nematicidal effect of P. aeruginosa against coffee nematodes. This potent strain further showed an antifungal effect against various crop-pathogenic fungi and was found to be the most effective against Fusarium solani F04 (isolated from coffee roots) with a 70.51% inhibition rate. In addition, high-performance liquid chromatography analysis revealed that this bacterial strain also secretes plant growth regulators including indole acetic acid (IAA), gibberellic acid (GA3), kinetin, and zeatin in significant amounts of 100, 2700, 37, and 9.5 µg/mL, respectively. The data from this study suggest that P. aeruginosa TUN03 may be a potential biocontrol agent and biofertilizer for the sustainable production of Robusta coffee and other crops.

NMR, X-ray analysis, and CD methods are powerful techniques for the study of absolute configuration of bioactive compounds from natural resources. This study presents the results of a joint-study between Vietnam and Taiwan on the bioactive compounds obtained from Vietnamese plants and fungi. Among the tested compounds, hexatenuin A displayed the most significant inhibition of superoxide anion generation and elastase release. These triterpenoids may be used as potential anti-inflammatory agents.