Discovering new and effective drugs for the treatment of Alzheimer’s disease (AD) is a major clinical challenge. This study focuses on chemical modulation of the gut microbiome in an established murine AD model. We used the 16S rDNA sequencing technique to investigate the effect of xanthohumol (Xn) on the diversity of intestinal microflora in 2-month- and 6-month-old APP/PS1 mice, respectively. APP/PS1 and wild-type mice were treated by gavage with corn oil with or without Xn every other day for 90 days. Prior to and following treatment, animals were tested for spatial learning, cognitive and memory function. We found Xn reduced cognitive dysfunction in APP/PS1 mice and significantly regulated the composition and abundance of gut microbiota both in prevention experiments (with younger mice) and therapeutic experiments (with older mice). Differential microflora Gammaproteobacteria were significantly enriched in APP/PS1 mice treated with Xn. Nodosilineaceae and Rikenellaceae may be the specific microflora modulated by Xn. The penicillin and cephalosporin biosynthesis pathway and the atrazine degradation pathway may be the principal modulation pathways. Taken together, oral treatment with Xn may have a neuroprotective role by regulating the composition of intestinal microflora, a result that contributes to the scientific basis for a novel prophylactic and therapeutic approach to AD.

Background: Trichloroethylene (TCE) hypersensitivity syndrome (THS) is a dose-independent and potentially life-threatening disease. In this study, we sought to identify THS-related miRNAs and evaluate its potential clinical value. Methods: Serum samples of five patients and five matched TCE contacts were used for screening differential miRNAs. Another 34 patients and 34 matched TCE contacts were used for verifying significantly differential miRNAs with SYBR™ Green PCR and MGB PCR. The diagnostic model based on these miRNAs was established via the support vector machine (SVM) algorithm. Correlation between differential miRNAs and liver function was analyzed via the Spearman correlation test. Results: A total of 69 miRNAs was found to be differentially expressed. MiR-21-5p and miR-339-5p were verified to have significant higher expressions in patients. The sensitivity, specificity and accuracy of disease model were 100, 75 and 86%, respectively. The two miRNAs showed significant correlations with liver function. Conclusion: These findings suggested that miRNAs profiles in serum of THS patients had changed significantly, and miR-21-5p and miR-339-5p were associated with THS.

Alzheimer's disease (AD) is a complex disease with unknown etiology and pathogenesis. We described a combined analysis of murine proteomics and microbiomics to find potential therapeutic targets of different doses of xanthohumol (Xn), with the goal of providing a biological basis for the treatment of early AD. Xn improved the spatial learning and memory ability of APP/PS1 mice; this was associated with an increased number of newborn neurons in the subgranular zone (SGZ) and dentate gyrus (DG) and a decreased inflammatory response. 108 proteins were significantly changed after 0.5 mg/kg Xn treatment while only 72 proteins changed by 5 mg/kg Xn. Eight significant microbiota were modulated by different doses of Xn at line discriminant analysis (LDA) score 3.0, but only three of which were regulated by 0.5 mg/kg Xn at LDA score 4.0. In addition, Xn treatment could significantly regulate the pathways of neurodegeneration- multiple diseases in the hippocampus and the penicillin and cephalosporin biosynthesis and atrazine degradation pathways in the gut. Interestingly, Nefl protein validated by correlation analysis was found in the common signaling pathway. 0.5 mg/kg Xn was able to reverse the correlation between hippocampal proteins and gut microbiota. Xn treatment significantly improved cognitive function in AD transgenic mice. Different doses of Xn caused significant differences in protein expression and flora composition and abundance, suggesting that the doses of Xn should be selected with caution, and low dose may be better in the prevention of AD.

The rapidly expanding trade and ownership of exotic pets have created increasingly complex interfaces among humans, animals, and shared environments, increasing the potential for zoonotic pathogen spillover and antimicrobial resistance (AMR) dissemination. Shenzhen is a major international port city with an active hub for the exotic pet trade, yet molecular epidemiological data on exotic pet-associated pathogens and AMR genes remain limited. In this study, tNGS was used to detect pathogens and AMR genes in 23 biological samples collected from an exotic pet park in Longgang District (n = 9) and an exotic pet hospital in Longhua District (n = 14), Shenzhen. Pathogens were detected in 95.7% of samples (22/23), with 35 pathogen species identified. The dominant organisms were Escherichia coli (56.5%), Enterococcus faecium (30.4%), Enterococcus casseliflavus (30.4%), and Acinetobacter baumannii (26.1%). Notably, Mycobacterium tuberculosis complex (MTBC) was detected in one monk parakeet sample and should be regarded as a preliminary molecular screening signal requiring orthogonal confirmation. Eighteen AMR genes across seven resistance categories were detected. sul1 (56.5%) and vanD (52.2%) were the most prevalent, and carbapenemase-associated genes (GES, KPC, VIM, and IMP) were found in both exotic pet park and hospital samples. Park samples had a significantly higher total pathogen burden than hospital samples (t = 2.257, P = 0.035), whereas vancomycin resistance gene clusters were more frequent in hospital samples. These findings suggest that exotic pets in Shenzhen may serve as under-recognized reservoirs of zoonotic pathogens and clinically relevant resistance determinants, supporting the integration of exotic pet trade networks into One Health surveillance frameworks and highlighting the need to strengthen border quarantine, veterinary infection control, and AMR monitoring.

Alzheimer's disease (AD) is a neurodegenerative disorder that progressively impairs cognitive function for which there is no effective treatment. Natural dietary compounds such as xanthohumol (Xn) potentially offer a new therapeutic approach in AD. We aim to employ quantitative proteomic techniques to investigate the effects of Xn on cognitive impairment in two established murine models of AD. Treatment with 0.5mg/kg Xn significantly improved the ability of stimulating learning and memory and cognitive function of 3×Tg AD mice while 5mg/kg Xn ameliorated cognitive decline in APP/PS1 mice. We identified two common differential proteins and 12 pathways in the hippocampi of 3×Tg AD mice and 70 common differential proteins and 22 pathways in APP/PS1 mice. Moreover, Nine common signaling pathways mainly involved in energy metabolism, neurodegenerative disease, cardiovascular disease and cancer. So multi high-throughput proteomic analyses of hippocampus add to the scientific basis for development of effective drugs for AD, one candidate of which is Xn.

N-Nitrosodimethylamine (NDMA) is an environmental and food contaminant, but limited data to concern whether NDMA has adverse effects on the brain. This study first determined the concentration of NDMA in foods from aquaculture markets in Shenzhen, then analyzed the effects on C57BL/6 mice and further evaluated on the urine samples of elderly Chinese residents with normal cognition (NC, n = 144), cognitive decline (CD, n = 116) and mild cognitive impairment (MCI, n = 123). The excessive rate of NDMA in foods was 3.32% (27/813), with a exceeding range of 4.78–131.00 µg/kg. Behavioral tests showed that 60 days treatment of mice with 3 mg/kg NDMA reduced cognitive performance. Cognitive impairment in human was significantly associated with sex, educational levels, length of residence in Shenzhen, household registration, passive smoking, rice, fresh vegetables, bacon products. NDMA was detected in 55.4% (212/383) of urine samples, with a median concentration of 0.23 µg/L (1.20×10^− 7 µg/L to 157.39 µg/L). The median concentration for NC, CD and MCI were 0.32µg/L, 0.27µg/L, and 0µg/L, respectively. The urinary NDMA concentration had a strong negative correlation with cognitive impairment (Kendall's Tau-b= -0.89, P = 0.024). The median estimated daily intake (EDI) of NDMA was determined to be 6.63 ng/kg-bw/day. Taken together, there appears to be an association between NDMA and human and murine cognition, which provides a new clue to Alzheimer's disease (AD).