Despite the advantages of using photodynamic therapy (PDT) for the treatment of head and neck tumors, it can only be used to treat early stage flat lesions due to the limited tissue penetration ability of the visible light. Here, we developed near-infrared (NIR) excitable upconversion nanoparticle (UCN) based PDT agent that can specifically target epithelial growth factor receptor (EGFR) overexpressing oral cancer cells, in a bid to widen the application of PDT against thick and solid advanced or recurrent head and neck cancers. In vivo studies using the synthesized anti-EGFR-PEG-TiO₂-UCNs following systemic administration displayed no major sub-acute or long term toxic effects in terms of blood biochemical, hematological or histopathological changes at a concentration of 50 mg/kg. NIR-PDT even in the presence of a 10 mm tissue phantom placed over the xenograft tumor, showed significant delay in tumor growth and improved survival rate compared to conventional chlorin-e6 (Ce6) PDT using 665 nm red light. Our work, one of the longest study till date in terms of safety (120 d), PDT efficacy (35 d) and survival (60 d), demonstrates the usefulness of UCN based PDT technology for targeted treatment of thick and bulky head and neck tumors.

Okara is a major agro-waste produced from the soybean industry. To hydrolyze the okara and enable nutrient release, a strategy to valorize okara using solid-state fermentation with food grade Bacillus subtilis (B. subtilis) WX-17 was carried out. The study showed that fermentation of okara with B. subtilis WX-17 improved its overall nutritional content. The total amino acids content increased from 3.04 ± 0.14 mg/g in unfermented okara to 5.41 ± 1.21 mg/g in okara fermented with B. subtilis WX-17. Total fatty acids content increased from 153.04 ± 5.10 to 166.78 ± 2.41 mg/g okara, after fermentation. Antioxidant content (DPPH) also increased by 6.4 times after fermentation. To gain insight into the mechanism, gas chromatography–mass spectrometry analysis was carried out. In total, 49 metabolites were detected, which could be classified mainly into carbohydrates, TCA cycle metabolites, amino acids and fatty acids. The decrease in carbohydrate metabolites, showed that glycolysis was upregulated. This would have provided the energy and metabolic flux towards the amino acid and fatty acid pathway. This is also in line with the increased amino acids and fatty acid production seen in okara fermented with B. subtilis WX-17. The findings of this work demonstrated the potential of using B. subtilis WX-17 fermentation, to enhance the nutritional profile of okara. This could serve as a potential low-cost animal feed or incorporated into the human diet.

Brewers’ spent grains (BSG) are underutilized food waste materials produced in large quantities from the brewing industry. In this study, solid state fermentation of BSG using Bacillus subtilis WX-17 was carried out to improve the nutritional value of BSG. Fermenting BSG with the strain WX-17, isolated from commercial natto, significantly enhanced the nutritional content in BSG compared to unfermented BSG, as determined by the marked difference in the level of metabolites. In total, 35 metabolites showed significant difference, which could be categorized into amino acids, fatty acids, carbohydrates, and tricarboxylic acid cycle intermediates. Pathway analysis revealed that glycolysis was upregulated, as indicated by the drop in the level of carbohydrate compounds. This shifted the metabolic flux particularly towards the amino acid pathway, leading to a 2-fold increase in the total amount of amino acid from 0.859 ± 0.05 to 1.894 ± 0.1 mg per g of BSG after fermentation. Also, the total amount of unsaturated fatty acid increased by 1.7 times and the total antioxidant quantity remarkably increased by 5.8 times after fermentation. This study demonstrates that novel fermentation processes can value-add food by-products, and valorized food waste could potentially be used for food-related applications. In addition, the study revealed the metabolic changes and mechanisms behind the microbial solid state fermentation of BSG.

Utilization of algicidal bacteria as a biological agent have been receiving significant interest for controlling harmful algal blooms. While various algicidal bacterial strains have been identified, limited studies have explored the influence of bacterial culture conditions on its algicidal activity. Here, the effect of oxygen on the algicidal activity of a novel bacterium JK12, against a model diatom, Phaeodactylum tricornutum (P. tricornutum) was studied. Strain JK12 showed high algicidal activity against P. tricornutum and was identified as Pseudomonas chlororaphis (P. chlororaphis) by 16S ribosomal RNA gene analysis. JK12 culture supernatant exhibited strong algicidal activity while washed JK12 cells showed no obvious activity, indicating that JK12 indirectly attacks algae by secreting extracellular algicidal metabolites. Micro-aerobic culture condition dramatically enhanced the algicidal activity of JK12 by 50%, compared to that cultured under aerobic condition in 24 h. Extracellular metabolomic profiling of JK12 using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry analysis revealed significantly higher amounts of allantoic acid, urocanic acid, cytidine 2′,3′-cyclic phosphate, uridine 2′,3′-cyclic phosphate, and chlorinated tryptophan in the micro-aerobic culture. This is the first report to demonstrate the important role of oxygen on the algicidal activity of a non-pathogenic strain P. chlororaphis. In addition, the metabolomics analysis provided insights into the algicidal mechanism of P. chlororaphis.

Despite the rich nutritional content of okara, the majority remains underutilized and discarded as food waste. In this study, solid-state fermentation of okara with food-grade fungi was performed to extract and solubilize any remnant nutrients locked within the lignocellulosic matrix to produce a nutrient-rich okara fermentate. Fermented okara media (FOM) was used as the sole nutrient source for growing marine diatom, Phaeodactylum tricornutum. Results have shown a two-fold increase in biomass production when grown on FOM (0.52 g L⁻¹) as compared with conventional Guillard’s F/2 media (0.25 g L⁻¹). Furthermore, cellular fucoxanthin content was enhanced significantly by two-fold to reach a final concentration of 15.3 mg g⁻¹ compared to 7.3 mg g⁻¹. Additionally, a significantly higher amount of polyunsaturated fatty acid (PUFA) was produced, particularly eicosapentaenoic acid (EPA) which yield has increased by nearly three-fold. Metabolomics analysis of intracellular contents in fermented okara culture revealed a significantly enhanced accumulation of nitrogenous metabolites, alongside the decrease in sugar metabolites as compared to F/2 culture, thus indicating metabolic flux towards pathways involved in cellular growth. This study demonstrated an innovative and low-cost strategy of using fermented okara as a nutritious substrate for achieving a sustainable media replacement for high density algal growth with a simultaneous enhancement of production in highly valued nutraceuticals, including fucoxanthin and EPA.