Anchovy protein hydrolysates (APH) and catechin (CA) have proved to be effective in memory improvement. However, the enhancing effects of APH-CA conjugates on the memory are little investigated. The underlying mechanism and synergic effects remain unclear. Herein, relationships among memory enhancement, gut microbiota, fecal metabolites, and neurotransmitters of mice regulated by APH-CA were investigated. APH, APH-CA, and CA decreased MDA, IL-1β, and TNF-α in liver, altered levels of GPx, LDH, IL-1β, and TNF-α in serum, re-structured gut microbiota, regulated fecal metabolites, and regulated neurotransmitters in the brain. The alleviation effects of APH-CA were partially better than those of APH and CA. The 16s rRNA results illustrated that Bacteroidetes and Firmicutes were altered. Notably, memory-related metabolites and neurotransmitters were significantly up-regulated by the administration of samples. Moreover, possible connections are observed among the gut microbiota, fecal metabolites, and brain neurotransmitters. Together, the regulation of the microbiota-metabolites-brain-neurotransmitters axis may be one of the mechanisms for APH-CA against scopolamine-induced cognitive deficits. In addition, the synergic effects of APH and CA were partially confirmed.

Escherichia coli O157:H7 is one of the major foodborne pathogenic bacterial that cause infectious diseases in humans. The previous found that a combination of kojic acid and tea polyphenols exhibited better activity against E. coli O157:H7 than using either alone. This study aimed to explore responses underlying the antibacterial mechanisms of kojic acid and tea polyphenols from the gene level. The functional enrichment analysis by comparing kojic acid and tea polyphenols individually or synergistically against E. coli O157:H7 found that acid resistance systems in kojic acid were activated, and the cell membrane and genomic DNA were destructed in the cells, resulting in "oxygen starvation". The oxidative stress response triggered by tea polyphenols was inhibited both sulfur uptake and the synthesis of ATP, which affected the bacteria's life metabolic process. Interestingly, we found that kojic acid combined with tea polyphenols hindered the uptake of iron that played an essential role in the synthesis of DNA, respiration, tricarboxylic acid cycle. The results suggested that the iron uptake pathways may represent a novel approach for kojic acid and tea polyphenols synergistically against E. coli O157:H7 and provided a theoretical basis for bacterial pathogen control in the food industry.

Phenyllactic acid (PLA) generally recognized as a natural organic acid shows against Vibrio parahaemolyticus activity. In this study, V. parahaemolyticus ATCC17802 (Vp17802) was cultured under the stress of 1/2MIC PLA, and then the antibacterial mechanisms were explored via transcriptomics. The minimum inhibitory concentration (MIC) of PLA against Vp17802 was 3.2 mg/mL, and the time-kill analysis resulted that Vp17802 was inhibited. PLA was able to destroy the bacterial membrane, leading to the leakage of intracellular substances and decline of ATP levels. The RNA-sequencing analysis results indicated that 1616 significantly differentially expressed genes were identified, among which 190 were up-regulated and 1426 were down-regulated. Down-regulation of the icd2 gene in the TCA cycle mediates blockage of tyrosine metabolic, arginine biosynthesis, and oxidative phosphorylation, causing insufficient energy supply of Vp17802. Moreover, PLA could cause amino acids, metal ions, and phosphate transporters to be blocked, affecting the acquisition of nutrients. The treatment by PLA altered the expression of genes encoding functions involved in quorum sensing, flagellar assembly, and cell chemotaxis pathway, which may be interfering with the biofilm formation in Vp17802, reducing cell motility. Overall, 1.6 mg/mL PLA inhibited the growth of Vp17802 by disrupting to uptake of nutrients, cell metabolism, and the formation of biofilms. The results suggested a new direction for exploring the activity of PLA against Vp17802 and provided a theoretical basis for bacterial pathogen control in the food industry. Key points: •RNA sequencing was carried out to indicate the antibacterial mechanism of Vp17802. •The icd2 gene in the TCA cycle mediates blockage of metabolic of Vp17802. •The biofilm formation has interfered with 1.6 mg/mL PLA, which could reduce cell motility and virulence. Graphical

Cyclophosphamide (CTX)-induced premature ovarian failure (POF) is characterized by disruption of the follicular microenvironment, granulosa-cell loss, endocrine imbalance, and oxidative-inflammatory injury. Here, we evaluated two multi-bioactive formulations developed to enhance ovarian stress resilience: a base formulation containing coenzyme Q10, calcium L-5-methyltetrahydrofolate, and Vitex agnus-castus extract (Base), and a urolithin A-enriched formulation (Base + U). Using a CTX-induced female C57BL/6 mouse model, we integrated phenotypic, histological, endocrine, oxidative-inflammatory, and transcriptional readouts to assess efficacy and mechanistic consistency. CTX markedly reduced ovarian index, disrupted estrous cyclicity, shifted follicle development toward atresia, increased granulosa-cell apoptosis, and caused endocrine dysregulation, including decreased anti-Müllerian hormone and estradiol and increased GnRH, FSH, and LH. CoQ10, Base, and Base + U each partially alleviated these abnormalities, improving ovarian index and coat condition, showing a trend toward improved follicular distribution, and normalizing hormone profiles. CTX also induced an ovarian oxidative-inflammatory shift, as reflected by decreased GSH-Px, increased MDA, and elevated IL-1β, IL-6, and TNF-α, all of which were attenuated by the interventions. Notably, Base + U more effectively reduced lipid peroxidation and TNF-α than Base alone. Consistently, ovarian transcripts related to follicle responsiveness and steroid regulation, including Fshr, Esr1, and Hsd17b2, were restored, whereas hypothalamic qRT-PCR analysis did not reveal robust transcriptional alterations within the intervention window. These findings suggest that the urolithin A-enhanced formulation partially alleviates CTX-induced ovarian dysfunction by suppressing oxidative-inflammatory stress and preserving granulosa-cell and follicle fate.