Effect of High-Pressure Micro-Fluidization on the Inactivation of Staphylococcus aureus in Liquid Food.

High-pressure homogenization has been extensively studied for its excellent homogenization effect and the prospect of continuous liquid food production, but its sterilization ability still needs to be improved. In this study, we replaced the homogenization valve with two opposing diamond nozzles (0.05 mm inner diameter) so that the fluid collided at high velocity, corresponding to high-pressure micro-fluidization (HPM). Moreover, HPM treatment significantly inactivated Staphylococcus aureus ~7 log in the liquid with no detectable sub-lethal state at a pressure of 400 MPa and a discharge temperature of 50 °C. The sterilization effect of HPM on S. aureus subsp. aureus was attributed to a significantly disrupted cell structure and increased membrane permeability, which led to the leakage of intracellular proteins, resulting in bacterial death. At the same time, HPM treatment was able to significantly reduce the ability of S. aureus subsp. aureus to form biofilms, which, in turn, reduced its virulence. Finally, compared to the simulated system, more effective sterilization was observed in apple juice, with its color and pH remaining unchanged, which suggested that HPM can be used to process other liquid foods.

Discovery of novel AdipoRon analogues as potent anti-inflammatory agents against nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a rising public health burden, and there is a lack of effective therapeutic drugs in clinical practice. Sustained hepatic inflammation is considered as the key histopathological feature and dangerous fact for NASH. Different causes vary from one NASH patient to another, while sustained hepatic inflammation affects all NASH patients. AdipoRon is the first small-molecule AdipoR agonist, exerting antidiabetic and anti-inflammatory effect. In order to find novel AdipoRon analogues with more potent anti-inflammatory activity, we designed, synthesized and biologically evaluated 32 analogues. Among them, Q7 exerted potent anti-inflammatory activity and less cytotoxicity. Q7 could dose-dependently stimulate the increasing of AMPK phosphorylation, the widely recognized downstream effector of AdipoR1 activation. In NASH model mice, Q7 showed significant anti-inflammatory, anti-fibrotic and lipid-lowering effect in mice liver, and was superior to AdipoRon. Together, Q7 holds promise for developing anti-inflammatory and anti-NASH agents.

Discovery of a Novel Macrocyclic ATP Citrate Lyase Inhibitor.

ATP citrate lyase (ACLY) is an important metabolic enzyme involved in the synthesis of fatty acid and cholesterol. The inhibition of ACLY is considered as a promising therapeutic strategy for various metabolic diseases and numerous malignancies. In this study, a novel macrocyclic compound 2 has been identified as a potent ACLY inhibitor with the "ring closing" strategy for conformational restriction based on NDI-091143. It showed potent ACLY inhibitory activity and binding affinity comparable to the positive control. Furthermore, compared with the positive control (T1/2 = 3.36 min), the metabolic stability of 2 in HLMs (T1/2 = 531.22 min) was significantly improved. All of these results characterized 2 as a promising lead compound worthy of further study.

Inactivation of Bacillus subtilis by Curcumin-Mediated Photodynamic Technology through Inducing Oxidative Stress Response.

Photodynamic sterilization technology (PDT) is widely used in disease therapy, but its application in the food industry is still at the research stage because of the limitations of food-grade photosensitizers. Curcumin exhibits photosensitivity and is widely used as a food additive for its natural color. This study aimed to determine the effect of curcumin-mediated photodynamic technology (Cur-PDT) on Bacillus subtilis and to elucidate the anti-bacterial mechanism involved. First, the effects of curcumin concentration, duration of light irradiation, light intensity, and incubation time on the inactivation of B. subtilis were analyzed. It was found that Cur-PDT inactivated 100% planktonic cells with 50 µmol/L curcumin in 15 min (120 W). Then, the cell morphology, oxidation state and the expression of membrane structure- and DNA damage-related genes of B. subtilis vegetative cells were investigated under different treatment conditions. The membrane permeability of cells was enhanced and the cell membrane structure was damaged upon treatment with Cur-PDT, which were exacerbated with increases of treatment time and curcumin concentration. Meanwhile, the production of reactive oxygen species increased and the activities of the antioxidant enzymes SOD, GPX, and CAT decreased inside the cells. Furthermore, the Cur-PDT treatment significantly downregulated the mRNA of the membrane protein TasA and upregulated the DNA damage recognition protein UvrA and repair protein RecA of B. subtilis. These results suggested that curcumin-mediated PDT could effectively inactivate B. subtilis by inducing cell redox state imbalance, damaging DNA, and disrupting membrane structures.