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Both heavy metals and antibiotics exert selection pressure on bacterial resistance, and as they are commonly co-contaminated in the environment, they may play a larger role in bacterial resistance. This study examined how breeding cycles affect antibiotic resistance genes (ARGs) in chicken manure and the surrounding topsoils at 20, 50, 100, 200, and 300 m from twelve typical laying hen farms in the Ningxia Hui Autonomous Region of northwest China. Six antibiotics, seven heavy metals, ten mobile genetic elements (MGEs), and microbial community affected the ARGs profile in chicken dung and soil samples. Tetracycline antibiotic residues were prevalent in chicken manure, as were relatively high content of aureomycin during each culture period. Zinc (Zn) content was highest among the seven heavy metals in chicken feces. Chicken dung also enriched aminoglycosides, MLSB, and tetracycline ARGs, notably during brooding and high production. The farm had a minimal influence on antibiotics in the surrounding soil, but its effect on ARGs and MGEs closer to the farm (50 m) was stronger, and several ARGs and MGEs increased with distance. Manure microbial composition differed dramatically throughout breeding cycles and sampling distances. ARGs were more strongly related with antibiotics and heavy metals in manure than soil, whereas MGEs were the reverse. Antibiotics, heavy metals, MGEs, and bacteria in manure accounted 12.28%, 22.25%, 0.74%, and 0.19% of ARGs composition variance, respectively, according to RDA and VPA. Bacteria (2.89%) and MGEs (2.82%) only affected soil ARGs composition. These findings showed that heavy metals and antibiotics are the main factors affecting faecal ARGs and bacteria and MGEs soil ARGs. This paper includes antibiotic resistance data for large-scale laying hen husbandry in northwest China and a theoretical framework for decreasing antibiotic resistance.

This study was to investigate whether natural borneol (NB) could enhance the anti-cancer effect of demethoxycurcumin (DCur) on HepG2 cell line by MTT assay, flow cytometry, and western blotting assay. Our results demonstrated that NB/DCur resulted in a significant decrease in cell viability due to pretreatment of NB enhancing the cellular uptake of DCur. Flow cytometric assay showed that NB/DCur-induced HepG2 cells growth inhibition was mainly caused by induction of G2/M arrest, as evidenced by accumulation of the G2/M cell population. Immunoblotting assay demonstrated that NB/DCur down-regulated expression levels of cdc2 and cyclin B1, which contributed to G2/M arrest. Moreover, NB/DCur elevated the level of intracellular reactive oxygen species (ROS), indicating that NB/DCur-induced G2/M arrest was achieved by triggered ROS-mediated DNA damage involving MAPK and Akt signaling pathways. Taken together, our results suggested that the combination of NB and DCur induced G2/M phase arrest in HepG2 through ROS overproduction. This study demonstrated that NB had the potential to be further developed into a chemosensitizer of DCur in the treatment of human cancers.

Naringin palmitate is an acylated product of naringin with palmitic acid, which is an effective substance for enhancing naringin lipophilicity. Lysozyme has strong ability to carry drugs and functional compounds in mammals. Herein, the ability of lysozyme to carry naringin palmitate was investigated by fluorescence and UV spectroscopy, and the differences in affinities of naringin and naringin palmitate for lysozyme were compared. Naringin palmitate was found to quench the fluorescence of lysozyme via static quenching. The binding constant and number of binding sites of naringin palmitate–lysozyme were more sensitive to high temperature than naringin–lysozyme. van der Waals forces and hydrogen bond formation played a major role in stabilizing naringin palmitate–lysozyme. No significant change of the structure and microenvironment of lyzozyme were obtained by addition of naringin palmitate. Thus, transport of naringin palmitate by lysozyme was verified. These findings are of importance and are attractive for the practical applications of naringin palmitate.

Long periods of sleep deprivation (SD) have serious effects on health. While the α2 adrenoceptor agonist dexmedetomidine (DEX) can improve sleep quality for patients who have insomnia, the effect of DEX on cognition and mechanisms after SD remains elusive. C57BL/6 mice were subjected to 20 h SD daily for seven days. DEX (100 μg/kg) was administered intravenously twice daily (at 1:00 p.m. and 3:00 p.m.) during seven days of SD. We found that systemic administration of DEX attenuated cognitive deficits by performing the Y maze and novel object recognition tests and increased DCX+, SOX2+, Ki67+, and BrdU+NeuN+/NeuN+ cell numbers in the dentate gyrus (DG) region of SD mice by using immunofluorescence, western blotting, and BrdU staining. DEX did not reverse the decrease in DCX+, SOX2+, or Ki67+ cell numbers in SD mice after administration of the α2A-adrenoceptor antagonist BRL-44408. Furthermore, the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) expression was upregulated in SD+DEX mice compared with SD mice. Luminex analysis showed that the neurogenic effects of DEX were possibly related to the inhibition of neuroinflammation, including IL-1α, IL-2, CCL5, and CXCL1. Our results suggested that DEX alleviated the impaired learning and memory of SD mice potentially by inducing hippocampal neurogenesis via the VEGF-VEGFR2 signaling pathway and by suppressing neuroinflammation, and α2A adrenoceptors are required for the neurogenic effects of DEX after SD. This novel mechanism may add to our knowledge of DEX in the clinical treatment of impaired memory caused by SD.

Stress is well known to contribute to the development of both neurological and psychiatric diseases. In the central nervous system, a role for STING (stimulator of interferon genes) in modulating immunological responses has been widely suggested, and this protein possesses both neurotoxic and neuroprotective properties. However, the potential role of the STING signalling pathway and the underlying regulatory mechanism in chronic stress have not been well established. In this study, C57BL/6 mice were subjected to intermittent restraint stress for 14 days (6 h/day), and sucrose preference, elevated plus maze, and tail suspension tests were performed by mice subjected to chronic restraint stress (RST). Here, we showed that RST mice displayed depression-like behaviours, accompanied by increased levels of proinflammatory cytokines in the brain. We also observed remarkably decreased levels of the pathway components STING, p-TBK1 (phospho-TANK-binding kinase-1), and p-IRF3 (phospho-interferon regulatory factor-3) in the hippocampus and the prefrontal cortex of RST mice. Significant reductions in STING fluorescence intensity were also observed in the hippocampus and the prefrontal cortex of RST mice. Next, fluorescently labelled latex beads, flow cytometry, and CD68-positive cell counts were utilized to evaluate the phagocytic abilities of microglia in vivo and in vitro. Importantly, our results first indicated that activation of the STING pathway by administration of the STING agonist 2′3-cGAMP enhanced microglial phagocytosis and suppressed the release of the proinflammatory cytokines TNF-α, IL-6, and IL-1β in the brains of RST mice, which further led to antidepressant effects. Based on the results of our study, the amelioration of stress-driven depression-like behaviours by activation of the STING pathway is associated with the suppression of neuroinflammation and enhanced phagocytosis.