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Bile acid homeostasis is critical to human health. Low-level exposure to antibiotics has been suggested to potentially disrupt bile acid homeostasis by affecting gut microbiota, but relevant data are still lacking in humans, especially for the level below human safety threshold. We conducted a cross-sectional study in 4247 Chinese adults by measuring 34 parent antibiotics and their metabolites from six common categories (i.e., tetracyclines, qinolones, macrolides, sulfonamides, phenicols, and lincosamides) and ten representative bile acids in fasting morning urine using liquid chromatography coupled to mass spectrometry. Daily exposure dose of antibiotics was estimated from urinary concentrations of parent antibiotics and their metabolites. Urinary bile acids and their ratios were used to reflect bile acid homeostasis. The estimated daily exposure doses (EDED) of five antibiotic categories with a high detection frequency (i.e., tetracyclines, qinolones, macrolides, sulfonamides, and phenicols) were significantly associated with urinary concentrations of bile acids and decreased bile acid ratios in all adults and the subset of 3898 adults with a cumulative ratio of antibiotic EDED to human safety threshold of less than one. Compared to a negative detection of antibiotics, the lowest EDED quartiles of five antibiotic categories and four individual antibiotics with a high detection frequency (i.e., ciprofloxacin, ofloxacin, trimethoprim, and florfenicol) in the adults with a positive detection of antibiotics had a decrease of bile acid ratio between 6.6% and 76.6%. Except for macrolides (1.2×102 ng/kg/day), the medians of the lowest EDED quartile of antibiotic categories and individual antibiotics ranged from 0.32 ng/kg/day to 10 ng/kg/day, which were well below human safety thresholds. These results suggested that low-level antibiotic exposure could disrupt bile acid homeostasis in adults and existing human safety thresholds may be inadequate in safeguarding against the potential adverse health effects of low-level exposure to antibiotics. [Display omitted] • Daily exposure doses of antibiotic were estimated from urinary concentrations in 4247 adults. • Urinary bile acids and their ratios were used to reflect bile acid homeostasis. • A cumulative EDED of antibiotics below the safety threshold was observed in 91.8% of adults. • Antibiotic EDED was significantly associated with urinary bile acids and their ratios. • The lowest EDED disturbing bile acid homeostasis may be well below the safety threshold. [ABSTRACT FROM AUTHOR]

Previous studies have shown that early-life exposure to fine particulate matter (PM2.5) is associated with an increasing risk of autism spectrum disorder (ASD), however, the specific sensitive period of ASD is unknown. Here, a model of dynamic whole-body concentrated PM2.5 exposure in pre- and early-postnatal male offspring rats (MORs) was established. And we found that early postnatal PM2.5 exposed rats showed more typical ASD behavioral characteristics than maternal pregnancy exposure rats, including poor social interaction, novelty avoidance and anxiety disorder. And more severe oxidative stress and inflammatory responses were observed in early postnatal PM2.5 exposed rats. Moreover, the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) was down-regulated and the ratios of p-PI3K/PI3K and p-AKT/AKT were up-regulated in early postnatal PM2.5 exposed rats. This study suggests that early postnatal exposure to PM2.5 is more susceptible to ASD-like phenotype in offspring than maternal pregnancy exposure and the activation of PI3K-AKT signaling pathway may represent underlying mechanisms. • Early postnatal PM2.5 exposure induced more pronounced ASD-like phenotype in male offspring rats than maternal exposure. • Early postnatal period may be a sensitive window for PM2.5 to trigger autism spectrum disorder development. • PM2.5 exposure caused neuroinflammation and reduced anti-inflammatory melatonin levels in offspring rat brains. • PI3K-AKT pathway activation may link developmental PM2.5 exposure and autism spectrum disorder pathogenesis. [ABSTRACT FROM AUTHOR]

Ru(II) complexes [Ru(phen) 2 (PIP)]2+ (Ru 1), [Ru(phen) 2 (p-HPIP)]2+ (Ru 2), and [Ru(phen) 2 (m-HPIP)]2+ (Ru 3) have been synthesized and characterized in this work. Their binding properties of the RNA duplex poly(A)•poly(U) have been investigated. The obtained results show that the three Ru(Ⅱ) complexes bind to the RNA duplex poly(A)•poly(U) by intercalation, and destabilize the RNA duplex. [Display omitted] • Complexes [Ru(phen) 2 L]2+ (Ru 1 , L = PIP; Ru 2 , L = p-HPIP; Ru 3 , L = m-HPIP) were synthesized. • Binding of the three complexes with RNA poly(A)•poly(U) were investigated. • The three complexes destabilize RNA poly(A)•poly(U). • This work reports for the first time small molecules capable of destabilizing an RNA duplex. To further explore the binding properties of Ru(Ⅱ) polypyridine complexes with RNA, three Ru(Ⅱ) complexes [Ru(phen) 2 (PIP)]2+ (Ru 1), [Ru(phen) 2 (p-HPIP)]2+ (Ru 2), and [Ru(phen) 2 (m- HPIP)]2+ (Ru 3) have been synthesized and characterized in this work. The binding properties of three Ru(Ⅱ) complexes with RNA duplex poly(A)•poly(U) have been investigated by spectral and viscosity experiments. These studies all support that these three Ru(Ⅱ) complexes bind to poly RNA duplex poly(A)•poly(U) by intercalation, and Ru 1 without substituents has a stronger binding affinity for poly(A)•poly(U). Interestingly, the thermal melting experiments show that these three Ru(Ⅱ) complexes all destabilize RNA duplex poly(A)•poly(U), and the destabilizing effect can be explained by the conformational changes of duplex structure induced by intercalating agents. To the best of our knowledge, this work report for the first time a small molecule capable of destabilizing an RNA duplex, which reflects that the substitution effect of intercalated ligands has an important influence on the affinity of Ru(Ⅱ) complexes to RNA duplex, and that not all Ru(Ⅱ) complexes show thermal stability effects on an RNA duplex. [ABSTRACT FROM AUTHOR]

The crucial feature of chicken is real-time microbial growth detection along the supply chain. Hyperspectral imaging (HSI) is an online and nondestructive technique that is well suited to microorganism analysis applications. In this study, visible and near-infrared (Vis/NIR, 400–1000 nm) HSI were utilized to establish prediction models of the total viable count (TVC) of chicken breasts stored in vacuum, pallet, and combined packaging using partial least squares regression (PLSR) and support vector machine (SVM) after spectral pretreatments and optimal wavelength selection. The SVM algorithm was used to develop the best TVC prediction models for storage, with the following outcome: vacuum (R2 p = 0.91, RMSE p = 0.47, RPD = 2.44), pallet (R2 p = 0.90, RMSE p = 0.54, RPD = 2.32), and combined (R2 p = 0.89, RMSE p = 0.58, RPD = 2.21) packs. Successively, HSI combined with fluorescence (F–HSI) was used to predict the TVC and coliforms of chicken breasts in combined packaging. Compared to HSI, F–HSI achieved the best-predicted results for TVC (R2 p = 0.93, RMSE p = 0.44, RPD = 2.74) and coliforms (R2 p = 0.92, RMSE p = 0.46, RPD = 2.57). These results indicated that fluorescence, as a complementary technique for HSI, will be widely used in the chicken supply chain to predict microbial growth. • HSI combined with fluorescence was used to predict microbial growth of chickens. • TVC and coliforms as critical biological parameters were predicted by HSI and F–HSI. • Samples were stored in different packs and temperatures to detect microbial growth. • Comparing the effects of pretreatments and modelling methods on model performance. [ABSTRACT FROM AUTHOR]

Ambient ozone (O 3) pollution can induce respiratory and cardiovascular toxicity. However, its impact on the metabolome and the underlying mechanisms remain unclear. This study first investigated the serum metabolite changes in rats exposed to 0.5 ppm O 3 for 3 months using untargeted metabolomic approach. Results showed chronic ozone exposure significantly altered the serum levels of 34 metabolites with potential increased risk of digestive, respiratory and cardiovascular disease. Moreover, bile acid synthesis and secretion, and arachidonic acid (AA) metabolism became the most prominent affected metabolic pathways after O 3 exposure. Further studies on the mechanisms found that the elevated serum toxic bile acid was not due to the increased biosynthesis in the liver, but the reduced reuptake from the portal vein to hepatocytes owing to repressed Ntcp and Oatp1a1 , and the decreased bile acid efflux in hepatocytes as a results of inhibited Bsep , Ostalpha and Ostbeta. Meanwhile, decreased expressions of detoxification enzyme of SULT2A1 and the important regulators of FXR, PXR and HNF4α also contributed to the abnormal bile acids. In addition, O 3 promoted the conversion of AA into thromboxane A2 (TXA2) and 20-hydroxyarachidonic acid (20-HETE) in the liver by up-regulation of Fads2 , Cyp4a and Tbxas1 which resulting in decreased AA and linoleic acid (LA), and increased thromboxane B2 (TXB2) and 20-HETE in the serum. Furthermore, apparent hepatic chronic inflammation, fibrosis and abnormal function were found in ozone-exposed rats. These results indicated chronic ozone exposure could alter serum metabolites by interfering their metabolism in the liver, and inducing liver injury to aggravate metabolic disorders. [Display omitted] • Subchronic O 3 induces characteristic changes in serum metabolites of rats especially bile acids and arachidonic acid. • O 3 reduces reuptake of bile acids from the portal vein to hepatocytes by repressing Ntcp and Oatp1a1. • O 3 decreases bile acid efflux in hepatocytes by inhibiting Bsep, Ostalpha and Ostbeta. • O 3 promotes the conversion of AA into TXA2 and 20-HETE by up-regulating Fads2 , Cyp4a and Tbxas1 in liver. • O 3 induces hepatic inflammation, fibrosis and function disturbance which may mutually reinforce with abnormal metabolites. [ABSTRACT FROM AUTHOR]

To study the regulatory relationship between ozone-induced mitophagy and pyroptosis in lung epithelial cells. First, type I primary alveolar epithelial cells and male Wistar rats were treated with ozone at different dosages. The ATP content and mitochondrial membrane potential significantly decreased in type I primary alveolar epithelial cells. The mitophagy-related markers and PINK1/Parkin pathway-related proteins, and the co-localization of LC3, Parkin, and mitochondria in type I alveolar epithelial cells indicated that ozone exposure triggered mitophagy. On the other hand, the reactive oxygen species (ROS) inhibitor NAC could significantly alleviate mitophagy in epithelial cells. After treatment with the mitophagy inhibitor MDIVI-1, the levels of the NLRP3 inflammasome, cleaved caspase-1, and N-gasdermin D (N-GSDMD) significantly decreased in the cells. Altogether, these results indicated that mitophagy can be triggered by ozone exposure, and subsequently induces cell death mediated by the NLRP3 inflammasome. Finally, the overexpression and knockdown of NLRP3 confirmed this conclusion. Ozone exposure induced oxidative damage, leading to mitochondrial structural and functional damage. Ozone-induced ROS triggered mitophagy through the activation of the PINK1/Parkin signaling pathway, then pyroptosis through activation of the NLRP3 inflammasome. • Ozone exposure can lead to pulmonary mitochondrial dysfunction in vivo and in vitro. • Ozone exposure can lead to mitophagy in lung, and ROS is involved in this process. • ROS induce mitophagy through the activation of the PINK1/Parkin signaling pathway. • Mitophagy induced by ozone can induce pyroptosis through the activation of NLRP3 inflammasome in lung. [ABSTRACT FROM AUTHOR]

In this study, a natural extract from the plant Radix hedysari (ER) was proven to be useful for the green synthesis of silver nanoparticles (AgNPs) and ER-AgNPs in particular. Considering the complexity of plant extracts, high-pressure liquid chromatography (HPLC) was effective at confirming the components of ER, surprisingly, formononetin was found to comprise more than 85% of the total contents. Since formononetin was confirmed to be the primary component of ER, this compound was also used as the basis to synthesize AgNPs designated FMT-AgNPs that was highly pure and of high quality. The FMT-AgNPs functionalized by formononetin were optimized for further study. A simple, fast and sensitive colorimetric method detect formothion was achieved using FMT-AgNPs. A wide linear range from 0.1 μM to 10 μM was established with a low limit of detection (LOD) of 14.6 nM. Since formononetin performed multiple roles during the synthesis, it was confirmed that the mechanism of detection was based on aldol condensation, intermolecular hydrogen bonds and electrostatic attraction between formononetin and formothion. Finally, the green synthesized FMT-AgNPs were further applied in typical fruit and vegetable samples, indicating that FMT-AgNPs were potentially highly useful. [Display omitted] • The plant extract (ER) and formononetin was utilized to green synthesize silver nanoparticles (ER-AgNPs/FMT-AgNPs). • FMT-AgNPs were proven to be pure and of high quality. • The relevant synthesis or mechanism of detection was clearly explained. • FMT-AgNPs were sensitive and selective for the detection of formothion. • FMT-AgNPs were applied to detect formothion in typical vegetable and fruit samples. [ABSTRACT FROM AUTHOR]

The mouse WD repeat and FYVE domain containing 1 (Wdfy1) gene is located in chromosome 1qC4 and spans over 73.7 kilobases. It encodes a protein of 410-amino acid protein that shares 97.8% amino acid sequence identity with the human WDFY1 protein. However, the expression pattern of WDFY1 in reproductive organs and its function in male fertility remain unknown. In this study, we generated transgenic mice expressing FLAG-Wdfy1-mCherry cDNA driven by the Wdfy1 promoter to clarify the expression of WDFY1. The results showed that WDFY1 is highly expressed in mouse testes and located in the cytoplasm of late pachytene spermatocytes to elongated spermatids. Interestingly, the global Wdfy1 knockout (KO) male mice displayed normal growth, development, and fertility. Further histological analysis of Wdfy1 knockout mouse testes revealed that all spermatogenic cells are present in Wdfy1 KO seminiferous tubules. Together, our data demonstrate that WDFY1 is dispensable for mouse spermatogenesis and male fertility. • WDFY1 is preferentially expressed in mouse testes. • WDFY1 is located in the cytoplasm of late pachytene spermatocytes to elongated spermatids. • The global Wdfy1 knockout (KO) male mice displayed normal growth, development, and fertility. [ABSTRACT FROM AUTHOR]

The clove extract showed the best inhibitory effect on all the five spoilage bacteria of dry-cured ducks among eight commonly used spices. The proliferation of Staphylococcus simulans 2 was inhibited significantly with no logarithmic phase following the treatment of the clove extract. The MIC of clove extract against Staphylococcus simulans 2 was 9 mg/mL. The clove extract had remarkable effects on inhibiting proteins synthesis and enhancing the permeability of the cell membrane, which induced the inactivation of the spoilage bacteria and the irregular, pitted, and shriveled bacterial morphology. Besides, the clove extract showed the strongest antioxidant capacity in vitro than the other seven spices. The clove extract had the highest scavenging activity on DPPH·, OH· and O2−·, which were 95.28%, 95.88% and 62.63%, respectively. It had the unique antioxidant capacity in duck grease, which was almost equivalent to TBHQ. As the clove extract was applied in the manufacture of dry-cured duck, the peroxide value, acid value, and total bacterial colony count declined significantly, and the shelf-life extended from 3 months to 6 months. It confirmed that the clove extract had distinguished antibacterial and antioxidant properties in the manufacture of traditional dry-cured duck. • The clove extract had distinguished antibacterial effect and the mechanism was also elucidated preliminary. • The clove extract also showed distinguished antioxidant activity in vitro and in practical application. • The clove could inhibit microbial growth, decline lipid oxidation, and prolong the shelf-life of dry-cured duck effectively. • In contrast to chemical preservatives, natural plant extracts are more acceptable to consumers. [ABSTRACT FROM AUTHOR]