BiothiolFunctionalized Cuprous Oxide Warning regarding DualMode Sensitive Hg2 Recognition

PLAAT1 belongs to the PLAAT family and plays regulatory roles in cell growth, tumor suppression and phospholipid metabolism. However, whether PLAAT1 is involved in p53 mediated signaling has not been investigated. Here, we report that PLAAT1 promotes degradation of p53 in zebrafish. We found that the plaat1 gene was constitutively expressed in tissues including liver, kidney, spleen, intestine, eye and brain, with relative higher expression levels detected in the brain and eye. Overexpression of plaat1 led to inhibition of p53 and tnfα mRNA expression. Furthermore, it was shown that PLAAT1 interacted with p53 to facilitate p53 degradation via autophagy-lysosome dependent pathway. Our work indicates that PLAAT1 is involved in the interplay between p53 mediated cellular responses and autophagy.LPCAT3, a subtype of lysophosphatidylcholine acyltransferases, is a key enzyme in phosphatidylcholine remodeling pathway and plays a significant role in mediating inflammatory response in mammals. However, its inflammatory function in fish has yet to be discovered. Herein, this study aimed to investigate its role in inflammation in Larimichthys crocea. We analyzed the coding sequence of Larimichthys crocea LPCAT3 (Lc-LPCAT3) and explored the effect of Lc-LPCAT3 on palmitate (PA)-induced inflammation. We found that in macrophage cell line of Larimichthys crocea, the mRNA expression of Lc-lpcat3 was upregulated by PA with the elevated pro-inflammatory genes expression, including il1β, il6, il8, tnfα and ifnγ. Next, the role of Lc-LPCAT3 in inflammation induced by PA was further investigated. Results showed that knockdown of Lc-LPCAT3 mitigated PA-induced pro-inflammatory genes mRNA expression, including il1β, il8, tnfα and ifnγ, in which JNK signaling pathway was involved. In contrast, overexpression of Lc-LPCAT3 induced pro-inflammatory genes expression including il1β, tnfα and ifnγ. Furthermore, several transcription factors with negative regulation of Lc-LPCAT3 promoter activity were discovered including LXRα, RXRα, PPARα, PPARγ, CEBPα, CEBPβ, CEBPδ, SREBP1 and SREBP2, and SREBP1 had the strongest regulatory effect. In conclusion, we first discovered that fish LPCAT3 participated in PA-induced inflammation, and targeting SREBP1 might be an effective coping strategy.Parasitic dinoflagellates in genus Hematodinium have caused substantial economic losses to multiple commercially valuable marine crustaceans around the world. Recent efforts to better understand the life cycle and biology of the parasite have improved our understanding of the disease ecology. However, studies on the host-parasite interaction, especially how Hematodinium parasites evade the host immune response are lacking. To address this shortfall, we used the comprehensive omics approaches (miRNA transcriptomics, iTRAQ-based proteomics) to get insights into the host-parasite interaction between hemocytes from Portunus trituberculatus and Hematodinium perezi in the present study. The parasitic dinoflagellate H. perezi remodeled the miRNome and proteome of hemocytes from challenged hosts, modulated the host immune response at both post-transcriptional and translational levels and caused post-transcriptional regulation to the host immune response. Multiple important cellular and humoral immune-related pathways (ex. Apoptosis, Endocytosis, ECM-receptor interaction, proPO activation pathway, Toll-like signaling pathway, Jak-STAT signaling pathway) were significantly affected by Hematodinium parasites. Through modulation of the host miRNome, the host immune responses of nodulation, proPO activation and antimicrobial peptides were significantly suppressed. Cellular homeostasis was imbalanced via post-transcriptional dysregulation of the phagosome and peroxisome pathways. Cellular structure and communication was seriously impacted by post-transcriptional downregulation of ECM-receptor interaction and focal adhesion pathways. In conclusion, H. perezi parasites could trigger striking changes in the miRNome and proteome of crustacean hemocytes, and this parasite exhibited multifaceted immunomodulatory effects and potential immune-suppressive mechanisms in crustacean hosts.Microplastics have become a worldwide pollutant, widely discovered in soil, air and aquatic environment. Microplastics have been found in habitats where crayfish (Procambarus clarkii) cultivated, but the impact of microplastics on crayfish remains unclear. In this study, after 21-day dietary exposure, polyethylene (PE) particles were found to accumulate in intestine, hepatopancreas, gills and hemolymph of crayfish. Selleck CH6953755 Furthermore, PE particles can still be detected in these tissues after a 7-day depuration in clean water. PE retained in these tissues caused oxidative stress responses, as indicated by the change of oxidative-stress-related index, such as the increase of H2O2 level and SOD activity. PE exposure also caused hemocytic encapsulation in crayfish hepatopancreas and increase of mucus secretion in intestine. Moreover, PE exposure affected the microbiota balance in crayfish, by reducing the total microbiota abundance and altering the proportions of many bacterial families. Interestingly, results showed that PE exposure led to of lower numbers of hemocytes and declination of phenoloxidase activity. Finally, PE exposure induced the expression of immune-related genes, including transcription factors and antimicrobial peptides. Taken these together, we conclude that PE microplastics exert considerable toxic effects on crayfish and are a potential threat to crayfish aquaculture and consumption. This study provides basic toxicological data toward quantifying and illuminating the impact of PE microplastics on freshwater animals.
Excessive acetaminophen (APAP) intake causes oxidative stress and inflammation, leading to fatal hepatotoxicity; however, the mechanism remains unclear. This study aims to explore the protective effects and detailed mechanisms of sirtuin 6 (SIRT6) in the defense against APAP-induced hepatotoxicity.
Hepatocyte-specific SIRT6 knockout mice, farnesoid X receptor (FXR) knockout mice, and mice with genetic or pharmacological activation of SIRT6 were subjected to APAP to evaluate the critical role of SIRT6 in the pathogenesis of acute liver injury. RNA sequences were used to investigate molecular mechanisms underlying this process.
Hepatic SIRT6 expression was substantially reduced in the patients and mice with acute liver injury. The deletion of SIRT6 in mice and mice primary hepatocytes led to high N-acetyl-p-benzo-quinoneimine and low glutathione levels in the liver, thereby enhancing APAP overdose-induced liver injury, manifested as increased hepatic centrilobular necrosis, oxidative stress, and inflammaty, and pharmacological activation of SIRT6 may represent a novel therapeutic strategy for APAP overdose-induced liver injury.
Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are complementary techniques for large (≥20 mm) nonpedunculated rectal polyps (LNPRPs). A mechanism for appropriate technique selection has not been described.
We evaluated the performance of a selective resection algorithm (SRA) (August 2017 to April 2021) compared with a universal EMR algorithm (UEA) (July 2008 to July 2017) for LNPRPs within a prospective observational study. In the SRA, LNPRPs with features of superficial submucosal invasive cancer (SMIC) (<1000 μm; Kudo pit pattern Vi), or with an increased risk of SMIC (Paris 0-Is or 0-IIa+Is nongranular, 0-IIa+Is granular with a dominant nodule ≥10 mm) underwent ESD. The remaining LNPRPs underwent EMR. Algorithm performance was evaluated by SMIC identified after EMR, curative oncologic resection (R0 resection, superficial SMIC, absence of negative histologic features), technical success, adverse events, and recurrence at first surveillance colonoscopy.
A total of 480 LNPRPs were evaluated (290 UEA, 190 SRA). Median lesion size was 40 (interquartile range, 30-60) mm. SMIC was identified in 56 (11.7%) LNPRPs. Significant differences in SMIC after EMR (SRA 1 [1.0%] vs UEA 35 [12.1%]; P= .001) and curative oncologic resection (SRA n= 7 [33.3%] vs UEA n= 2 [5.7%]; P= .010) were identified. No significant differences in technical success or adverse events were identified (all P > .137). Among LNPRPs with SMIC amenable to curative oncologic resection and which underwent ESD, 100% (n= 7 of 7) were cured.
A rectum-specific SRA optimizes oncologic outcomes for LNPRPs and mitigates the risk of piecemeal resection of cancers.
A rectum-specific SRA optimizes oncologic outcomes for LNPRPs and mitigates the risk of piecemeal resection of cancers.Xylitol is a hygroscopic compound known to protect nasal cavity against bacteria. It has also been developed into nasal spray and evaluated as a potential candidate drug for respiratory diseases. Consequently, it is necessary to study its inhalation toxicity. Based on our previous study on its subacute inhalation toxicity, this study aimed to investigate the safety of xylitol inhalation for long-term use. According to the OECD Test Guideline 413, Sprague-Dawley rats were randomly divided into six groups and exposed with different concentrations of xylitol aerosol or air. After exposure for 90-day, the recovery groups were continued to observe for a recovery period of 28-day. No significant changes in body weight were observed between sham and xylitol groups. Several significant differences in hematological, clinical chemistry, bronchoalveolar lavage fluid were observed, which either had no dose-effect relationship for both male and female rats or were restored during the recovery period. Finally, except for high dose group of xylitol, two rats showed a small amount of inflammatory exudate in alveolar and bronchial cavities, which was restored in the recovery period. The rest of rats showed no obvious difference. For the recovery groups, no significant difference was observed between these two groups. In conclusion, the no observable adverse effect level (NOAEL) of xylitol in our subchronic inhalation toxicological experiments was 2.9 mg/L, which indicated that xylitol for rats' long-time inhalation is tolerant and safe.The present study investigates whether resveratrol could modulate the endothelial dysfunction of atherosclerosis via the Pin1/Notch1 signaling pathway. To assess the vascular endothelial cell (VECs) injury in mice, the levels of serum soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), soluble thrombomodulin (sTM), and von Willebrand factor (vWF) were measured. Expressions of Pin1 and Notch1 intracellular domain (NICD1), both mRNA and protein, were also measured. Human umbilical vein endothelial cells (HUVECs) treated with 100 μg/mL oxidized low-density lipoprotein (ox-LDL) were incubated with resveratrol at doses from 10 μM to 40 μM. Cell function was evaluated by measuring apoptosis, cell viability, lipid accumulation, and adherent human myeloid leukemia mononuclear (THP-1) cells. Resveratrol intervention in AS mice decreased the expression of serum sVCAM-1, sICAM-1, sE-selectin, sTM, and vWF and dose-dependently down-regulated Pin1 and NICD1 mRNA and protein expression in endothelial cells.