Taurocholic acid represents an earlier and more sensitive biomarker and promotes cholestatic hepatotoxicity in ANIT-treated rats.

Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.

Effect of co-infection with Newcastle disease virus on Mycoplasma gallisepticum pathogenesis in vivo and in vitro.

The co-infection of Newcastle disease virus (NDV) and Mycoplasma gallisepticum (MG) has a detrimental effect on chicken production performance, exerts a deleterious impact on poultry production performance, resulting in substantial economic losses. However, the exact impact and underlying mechanisms remain ambiguous. In this study, co-infection models were established both in vivo and in vitro. Through these models, it was found that the co-infection facilitated the replication of MG and NDV, as well as MG induced pathogenesis. The administration of lentogenic NDV resulted in the suppression of the innate immune response in vivo. At cellular level, co-infection promoted MG induced apoptosis through caspase-dependent mitochondrial endogenous pathway and suppressed the inflammatory secretion. This research contributes novel insights in co-infection.

The relationship between depression severity and heart rate variability in children and adolescents: A meta-analysis.

OBJECTIVE: Depression in children and adolescents has gradually attracted social attention. Heart rate variability (HRV) has been found to be influenced by depression severity, but results have not been uniformed in children and adolescents. This study investigated the relationship between depression severity and heart rate variability in children and adolescents, aiming to provide additional evidence for an objective, effective, and convenient depression screening tool in this population. METHODS: Literature searching was conducted in China National Knowledge Infrastructure (CNKI), Wanfang Data, Web of Science, PubMed, ScienceDirect, and EBSCO. Relevant studies investigating the relationship between depression severity and HRV in children and adolescents were selected for meta-analysis. RESULTS: 31 articles were included in this meta-analysis, involving 4534 participants. Depression severity in children and adolescents was significantly negatively correlated with high frequency (HF) and root mean square of successive differences (RMSSD) in HRV (HF: r = -0.10, 95% CI: -0.17 to -0.04, p = 0.001; RMSSD: r = -0.18, 95% CI: -0.30 to -0.05, p = 0.01). The relationship between HF and depression severity was moderated by age, higher among those aged >12 than among those aged <12 (r = -0.17, -0.02, Q = 7.32, p = 0.007). CONCLUSION: Heart rate variability is associated with depression severity in children and adolescents.

3D printing processes in precise drug delivery for personalized medicine.

With the advent of personalized medicine, the drug delivery system will be changed significantly. The development of personalized medicine needs the support of many technologies, among which three-dimensional printing (3DP) technology is a novel formulation-preparing process that creates 3D objects by depositing printing materials layer-by-layer based on the computer-aided design method. Compared with traditional pharmaceutical processes, 3DP produces complex drug combinations, personalized dosage, and flexible shape and structure of dosage forms (DFs) on demand. In the future, personalized 3DP drugs may supplement and even replace their traditional counterpart. We systematically introduce the applications of 3DP technologies in the pharmaceutical industry and summarize the virtues and shortcomings of each technique. The release behaviors and control mechanisms of the pharmaceutical DFs with desired structures are also analyzed. Finally, the benefits, challenges, and prospects of 3DP technology to the pharmaceutical industry are discussed.

Mineralogical transformation of arsenic at different copper smelting workshops: The impact on arsenic bioaccessibility.

Soil arsenic (As) contamination associated with the demolition of smelting plants has received increasing attention. Soil As can source from different industrial processes, and also participate in soil weathering, making its speciation rather complex. This study combined the usage of chemical sequential extraction and advanced spectroscopic techniques, e.g., time of flight secondary ion mass spectrometry (ToF-SIMS), to investigate the mineralogical transformation of soil As at different processing sites from a typical copper smelting plant in China. Results showed that the stability of arsenic species decreased following the processes of storage, smelting, and flue gas treatment. Arsenic in the warehouse area was incorporated into pyrite (FeS2) as well as its secondary minerals such as jarosite (KFe3(SO4)2(OH)6). At the smelting area, a large proportion of As was adsorbed by iron oxides from smelting slags, while some As existed in stable forms like orpiment (As2S3). At the acid-making area, more than half of As was adsorbed on amorphous iron oxides, and some were adsorbed on the flue gas desulfurization gypsum. More importantly, over 86% of the As belonged to non-specifically and specifically adsorbed fractions was found to be bioaccessible, highlighting the gypsum-adsorbed As one of the most hazardous species in smelting plant soils. Our findings indicated the importance of iron oxides in As retention and suggested the potential health risk of gypsum-adsorbed As. Such detailed knowledge of As speciation and bioaccessibility is vital for the management and remediation of As-contaminated soils in smelting plants.

NDV inhibited IFN-ß secretion through impeding CHCHD10-mediated mitochondrial fusion to promote viral proliferation.

Newcastle disease virus (NDV) is an RNA virus that can promote its own replication through the inhibition of cellular mitochondrial fusion. The proteins involved in mitochondrial fusion, namely mitofusin 1 (Mfn1) and optic atrophy 1 (OPA1) are associated with interferon-beta (IFN-ß) secretion during NDV infection. However, the precise mechanism by which NDV modulates the Mfn1-mediated or OPA1-mediated fusion of mitochondria, thereby impacting IFN-ß, remains elusive. This study revealed that the downregulation of the mitochondrial protein known as coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) exerts a negative regulatory effect on OPA1 and Mfn1 in human lung adenocarcinoma (A549) cells during the late stage of NDV infection. This reduction in CHCHD10 expression impeded cellular mitochondrial fusion, subsequently leading to a decline in the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB), ultimately resulting in diminished secretion of IFN-ß. In contrast, the overexpression of CHCHD10 alleviated infection-induced detrimental effect in mitochondrial fusion, thereby impeding viral proliferation. In summary, NDV enhances its replication by inhibiting the CHCHD10 protein, which impedes mitochondrial fusion and suppresses IFN-ß production through the activation of IRF3 and NF-κB.

Mitochondrial protein CHCHD10 inhibits NDV replication and reduces pathological changes.

Newcastle disease (ND) is a disease that threatens the world's poultry industry, which is caused by virulent Newcastle disease virus (NDV). As its pathogenic mechanism remains not fully clear, the proteomics of NDV-infected cells were analyzed. The results revealed that coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) protein displayed a significant decrease at the late stage of NDV infection. To investigate the function of CHCHD10 in NDV infection, its expression after NDV infection was detected both in vivo and in vitro. Besides, the tissue viral loads and pathological damage of C57BL/6 mice with CHCHD10 differently expressed were also investigated. The results showed that the CHCHD10 expression was significantly decreased both in vivo and in vitro at the late stage of NDV infection. The viral loads were significantly higher in CHCHD10 silenced C57BL/6 mice, along with more severe pathological damage and vice versa.