Oocyte stage-specific effects of MTOR determine granulosa cell fate and oocyte quality in mice.

MTOR (mechanistic target of rapamycin) is a widely recognized integrator of signals and pathways key for cellular metabolism, proliferation, and differentiation. Here we show that conditional knockout (cKO) of Mtor in either primordial or growing oocytes caused infertility but differentially affected oocyte quality, granulosa cell fate, and follicular development. cKO of Mtor in nongrowing primordial oocytes caused defective follicular development leading to progressive degeneration of oocytes and loss of granulosa cell identity coincident with the acquisition of immature Sertoli cell-like characteristics. Although Mtor was deleted at the primordial oocyte stage, DNA damage accumulated in oocytes during their later growth, and there was a marked alteration of the transcriptome in the few oocytes that achieved the fully grown stage. Although oocyte quality and fertility were also compromised when Mtor was deleted after oocytes had begun to grow, these occurred without overtly affecting folliculogenesis or the oocyte transcriptome. Nevertheless, there was a significant change in a cohort of proteins in mature oocytes. In particular, down-regulation of PRC1 (protein regulator of cytokinesis 1) impaired completion of the first meiotic division. Therefore, MTOR-dependent pathways in primordial or growing oocytes differentially affected downstream processes including follicular development, sex-specific identity of early granulosa cells, maintenance of oocyte genome integrity, oocyte gene expression, meiosis, and preimplantation developmental competence. Proc Natl Acad Sci U S A 2018 Jun 5; 115(23):E5326-E5333

Baiji genomes reveal low genetic variability and new insights into secondary aquatic adaptations

The baiji, or Yangtze River dolphin (Lipotes vexillifer), is a flagship species for the conservation of aquatic animals and ecosystems in the Yangtze River of China; however, this species has now been recognized as functionally extinct. Here we report a high-quality draft genome and three re-sequenced genomes of L. vexillifer using Illumina short-read sequencing technology. Comparative genomic analyses reveal that cetaceans have a slow molecular clock and molecular adaptations to their aquatic lifestyle. We also find a significantly lower number of heterozygous single nucleotide polymorphisms in the baiji compared to all other mammalian genomes reported thus far. A reconstruction of the demographic history of the baiji indicates that a bottleneck occurred near the end of the last deglaciation, a time coinciding with a rapid decrease in temperature and the rise of eustatic sea level

Association between triglyceride glucose index and breast cancer in 142,184 Chinese adults: findings from the REACTION study

BackgroundThe triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women.MethodsThis cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer.ResultsMultivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19–2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13–17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09–1.68), 1.27 (1.05–1.54), 1.26 (1.05–1.52), and 1.32 (1.08–1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44–3.87).ConclusionThe TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women

Incentive contract design considering quotas production: A principal-agent perspective

The quality of primary products in a supply chain is determined by the agent and the principal. Simultaneously, there are quota production constraints on the principals. Our discourse centers on the design of incentive contracts for agents within these supply chains. We derived the parameters describing the contract, level of effort, profits for both sides, and the minimum requirements of the principal for the proportion of high-quality primary products. This study compares the decision-making paradigms of agents and principals in various contexts. The results show that decision-making mechanisms are strongly influenced by individual effort costs, various internal and external organizational variables, and the interplay of efforts on both sides. Using numerical experiments, we investigate the effects of different situations between clients and contractors on contracting and effort strategies. The results show that when the agent exerts unilateral effort, reasonable incentive contracts can spur the agent to increase effort and thus increase the proportion of high-quality primary products. In the case of bilateral efforts, a well-calibrated contract design benefits the agent (bearing less risk). For the principal, the expected profit increases in most cases. When considering the quota production, it is necessary to set an appropriate limit on the proportion of high-quality primary products

Huqi San-Evoked Rat Colonic Anion Secretion through Increasing CFTR Expression

Huqi San (HQS) is a Chinese herbal preparation of eight medicinal herbs that promote diuresis, detoxification, blood circulation, and cholestasis. Defects in transporter expression and function can cause cholestasis and jaundice. However, the mechanism of the cholestasis underlying HQS effects, especially on the gastrointestinal tract ion secretion, has not been elucidated. Real-time RT-PCR and Western blotting were used to study the expression and localization of cystic fibrosis transmembrane conductance regulator (CFTR) and α-ENaC in rat alimentary tract, and then the effect of HQS on the ion transport in rat distal colon mucosa was investigated using the short-circuit current (ISC) technique. The results showed that pretreatment with HQS significantly enhanced mRNA transcripts and protein content of CFTR in liver and distal colon but not α-ENaC in alimentary organs. HQS increases ISC and decreases the transepithelial resistance. Pretreatment with epithelial Na+ channel blocker did not affect the ISC responses elicited by HQS, but removal of extracellular Cl− or pretreatment with Cl− channel or Na+-K+-2Cl− cotransporter blocker inhibited HQS-elicited ISC responses. These findings demonstrated that HQS, RA, and RP can stimulate Cl− secretion in the distal colon by increasing the mRNA transcripts and protein content of CFTR in liver and distal colon

ROS accelerated G1/S transition and increased cyclin E/CDK2 expression in WB-F344 cells.

<p>(A) Cell cycle was assessed by flow cytometry. After starvation, cells were treated with UII (10⁻⁹ M) for 12 h, with or without apocynin (0.5 mM) pre-treatment for 30 min. The results are presented as mean ± SEM (n = 5). * <i>P</i><0.05 versus control. # <i>P</i><0.05 versus UII group. (B) Expression of cyclin E and CDK2 was examined by western blotting and normalized against GADPH. Data are presented as mean ± SEM (n = 3). * <i>P</i><0.05 versus control. # <i>P</i><0.05 versus UII group.</p

ROS level and expression of NADPH oxidase were elevated in HCC.

<p>(A) Fresh human HCC tissues and adjacent noncancerous tissues were stained with DHE. The fluorescence signals were captured by fluorescent microscopy and analyzed by Image J software. (B) Malondialdehyde content in human liver tissue was measured by thiobarbituric acid assay. (C) Activity of superoxide dismutase and glutathione peroxidase was measured by glutathione assay. (D) Expression of NADPH oxidase subunit p47phox, NOX2, p40phox and p67phox was measured by western blotting and normalized against GADPH. The results are presented as mean ± SEM. * indicates significant difference compared to adjacent liver tissues, <i>P</i><0.05.</p

Apocynin or urantide inhibited UII-elevated ROS production.

<p>(A) Flow cytometric histogram of DCF in WB-F344 cells. After starvation, cells were treated with UII (10⁻⁹ M) for 2 h, with or without apocynin (0.5 mM) or urantide (1 mM) pre-treatment for 30 min. The relative DCF fluorescence intensity was determined by flow cytometry. Data are presented as mean ± SEM (n = 6). * <i>P</i><0.05 versus control. # <i>P</i><0.05 versus UII group. (B) ROS signals were captured by fluorescent microscopy.</p