Phosphorylation-dependent deubiquitinase OTUD3 regulates YY1 stability and promotes colorectal cancer progression.

Yin Yang 1 (YY1) is a key transcription factor that has been implicated in the development of several malignancies. The stability of YY1 is regulated by the ubiquitin-proteasome system. The role of deubiquitinases (DUBs) and their impact on YY1 remain to be fully elucidated. In this study, we screened for ubiquitin-specific proteases that interact with YY1, and identified OTUD3 as a DUB for YY1. Over-expressed OTUD3 inhibited YY1 degradation, thereby increasing YY1 protein levels, whereas OTUD3 knockdown or knockout promoted YY1 degradation, thereby decreasing the proliferation of colorectal cancer (CRC). Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1. In CRC tissues, elevated the expression level of OTUD3 and YY1 were significantly associated with poor prognostic outcomes. These findings suggest that the OTUD3-YY1 pathway has therapeutic potential in CRC, and OTUD3 plays a critical role in regulating YY1.

Lactobacillus Ameliorates SD-Induced Stress Responses and Gut Dysbiosis by Increasing the Absorption of Gut-Derived GABA in Rhesus Monkeys.

Sleep deprivation (SD) has become a health problem in the modern society. Although probiotics supplementation has been proven to improve SD-induced gut dysbiosis, the potential neuroendocrine mechanisms remain elusive. In this study, thirty rhesus monkeys (RMs) were recruited. Paradoxical sleep, bright light, and noise were used to build an RM SD model. We examined the plasma γ-aminobutyric acid (GABA), stress hormones, and inflammatory cytokines using ELISAs. 16S ribosomal DNA sequencing and untargeted metabolomics sequencing were employed to detect gut microbial community and metabolites, respectively. The results of our study showed that RMs subjected to SD had elevated plasma stress hormones (such as cortisol and norepinephrine) and proinflammatory cytokines (such as TNF-α, IL-6, and IL-8), and a decreased anti-inflammatory cytokine IL-10 level. Additionally, SD could give rise to a significant change in gut microbiota and metabolites. The differential gut microbiota and metabolites caused by SD were enriched in the signaling pathways related to GABA metabolism. Pearson correlation analysis revealed that there is a significant correlation between plasma GABA and SD-induced stress responses and gut dysbiosis. The supplementation of GABA-producing probiotics could significantly increase the relative abundance of Lactobacillus and plasma GABA levels, and reverse SD-induced stress responses and gut dysbiosis. Therefore, we speculated that SD-induced stress response and gut dysbiosis might be an outcome of reduced gut-derived GABA absorption. The supplementation of GABA-producing Lactobacillus might be beneficial for the treatment of SD-induced intestinal dysfunction.

Insulin resistance induced by long-term sleep deprivation in rhesus macaques can be attenuated by Bifidobacterium.

Long-term sleep deprivation (SD) is a bad lifestyle habit, especially among specific occupational practitioners, characterized by circadian rhythm misalignment and abnormal sleep/wake cycles. SD is closely associated with an increased risk of metabolic disturbance, particularly obesity and insulin resistance. The incretin hormone, glucagon-like peptide-1 (GLP-1), is a critical insulin release determinant secreted by the intestinal L-cell upon food intake. Besides, the gut microbiota participates in metabolic homeostasis and regulates GLP-1 release in a circadian rhythm manner. As a commonly recognized intestinal probiotic, Bifidobacterium has various clinical indications regarding its curative effect. However, few studies have investigated the effect of Bifidobacterium supplementation on sleep disorders. In the present study, we explored the impact of long-term SD on the endocrine metabolism of rhesus monkeys and determined the effect of Bifidobacterium supplementation on the SD-induced metabolic status. Lipid concentrations, body weight, fast blood glucose, and insulin levels increased after SD. Furthermore, after 2 mo of long-term SD, the intravenous glucose tolerance test showed that the glucose metabolism was impaired and the insulin sensitivity decreased. Moreover, 1 mo of Bifidobacterium oral administration significantly reduced blood glucose and attenuated insulin resistance in rhesus macaques. Overall, our results suggested that Bifidobacterium might be used to alleviate SD-induced aberrant glucose metabolism and improve insulin resistance. Also, it might help in better understanding the mechanisms governing the beneficial effects of Bifidobacterium.NEW & NOTEWORTHY Our findings demonstrated that long-term sleep deprivation is closely associated with metabolic syndromes. Bifidobacterium administration showed a superior effect on insulin resistance caused by sleep deprivation. Overall, we provide prevention and treatment methods for long-term sleep deprivation, a bad lifestyle habit among specific occupational practitioners, such as irregular shift workers.

Nutrient removal and lipid production by Coelastrella sp. in anaerobically and aerobically treated swine wastewater.

Coelastrella sp. QY01, a microalgae species isolated from a local pond, was identified and used for the treatment of anaerobically and aerobically treated swine wastewater (AnATSW). Microalgal growth characteristics, nutrient removal and lipid accumulation of QY01 cultivated in the initial concentration of AnATSW ranged from 63 to 319mg NH3-N/L were examined. The specific growth rate of QY01 cultivated in cultures ranged from 0.269 to 0.325day(-1) with a biomass productivity from 42.77 to 57.46mgL(-1)day(-1). Removal rates for NH3-N, TP and inorganic carbon in AnATSW at the various nutrient concentrations ranged from 90% to 100%, from 90% to 100% and from 74% to 78%, respectively. The lipid content of QY01 ranged from 22.4% to 24.8%. The lipid productivity was positive correlation with the biomass productivity. 40% AnATSW was optimal for QY01 cultivation, in which nutrient removal and productivity of biomass and lipid were maximized.

[Screening of different AFLP fragments between near-isogenic lines of male sterile and fertile Salvia miltiorrhiza and their comparison analysis].

There is distinctive advantage of using male sterile lines to breed new cultivar and produce hybrids, when compared with general breeding method on yield and quality. In our previous work, near-isogenic lines (NILs) of male sterile and fertile Salvia miltiorrhiza have been obtained through continuous hybridization in many years. In this investigation, 378 primer combination were screened by using AFLP and BSA technique, in which 26 markers amplified from seven primers were found to tightly link to male sterile gene. Based on these markers, two linkage genetic maps were constructed. A 2 027,2 028 bp fragment was amplifed from NILs of fertile and sterile S. miltiorrhiza, respectively, using genome walking technique and previous E11/M4-208 marker as template. Four base mutations were found in intron when comparing both fragments. Among all different markers between NILs of male sterile and fertile S. miltiorrhiza, four was found to have 100% identities to chromosome 1, 3 and 5 of Arabidopsis, namely, E01/M09-418, E05/M13-308, E05/M04-750 and E01/M01-204. The E01/M09-418 marker was very close to male sterile gene of S. miltiorrhiza with distance of 2.1 cM, which also had 100% identities to male sterile gene MS2 in Arabidopsis. Both were distributed in chromosome 3 of Arabidopsis. The 2 028 bp fragment also had 100% identities to MS2 gene. Another E05/M04-750 marker that had 100% identities to chromosome 5 of Arabidopsis was found to have high identities to POP085-M05 gene of poplars and low affinity calcium antiporter CAX2 of Arabidopsis with very low E-value. The constructed genetic map and differential fragments with potential functions found in this study provide a solid foundation to lock male sterile genes in S. miltiorrhiza genome and to discover their functions.