Developmental Change of Yolk Microbiota and Its Role on Early Colonization of Intestinal Microbiota in Chicken Embryo

Although the fertilized eggs were found to contain microbes in early studies, the detailed composition of yolk microbiota and its influence on embryo intestinal microbiota have not been satisfactorily examined yet. In this study, the yolk microbiota was explored by using 16s rRNA sequencing at different developmental stages of the broiler embryo. The results showed that the relative abundance of yolk microbiota was barely changed during embryogenesis. According to the KEGG analysis, the yolk microbiota were functionally related to amino acid, carbohydrate, and lipid metabolisms during chicken embryogenesis. The yolk microbiota influences the embryonic intestinal microbiota through increasing the colonization of Proteobacteria, Firmicutes, and Bacteroidetes in the intestine, particularly. The intestinal microbes of neonatal chicks showed higher proportions of Faecalibacterium, Blautia, Coprococcus, Dorea, and Roseburia compared to the embryonic intestinal microbiota. Our findings might give a better understanding of the composition and developmental change of yolk microbiota and its roles in shaping the intestinal microbiota

The Sexual Effect of Chicken Embryos on the Yolk Metabolites and Liver Lipid Metabolism

The metabolic processes of animals are usually affected by sex. Egg yolk is the major nutrient utilized for the growth and development of a chicken embryo. In this study, we explored the differences of yolk metabolites in male and female chicken embryos by LC–MS/MS. Furthermore, we investigated the mRNA expression of lipoprotein lipase (LPL) and fatty acid synthase (FAS) in chicken embryo liver with different sexes in different embryonic stages. The results showed that the nutrient metabolites in the yolk of female chickens were mainly related to lipid metabolism and amino acid metabolism in the early embryonic stage, and vitamin metabolism in the late embryonic stage. The male yolk metabolites were mainly associated with lipid metabolism and nucleic acid metabolism in the early developmental stage, and amino acids metabolism in the late embryonic stage. There was no significant difference in the expression of LPL or FAS in livers of male and female chicken embryos at different embryonic stages. Our results may lead to a better understanding of the sexual effect on yolk nutrient metabolism during chicken embryonic development

Depression in Children and Adolescents on the Qinghai-Tibet Plateau: Associations with Resilience and Prosocial Behavior

Depression in children and adolescents has become a serious public health problem worldwide. The objectives of this study were twofold: first, to investigate the status of depression among children and adolescents on the Qinghai-Tibet Plateau, the highest plateau in the world, with an average altitude of more than 4200 m (13,776 feet), and second, to examine the associations among prosocial behavior, resilience, and depression. A cross-sectional study was conducted among children and adolescents from Yushu Prefecture on the Qinghai-Tibet Plateau. A total of 11,160 participants aged 10-17 years (M-age = 14.34 years, SD = 1.77; 51.4% girls) were included. Self-reported depression, resilience, and prosocial behavior were assessed. The prevalence of depression was 29.2% in the current study. Higher levels of prosocial behavior were significantly associated with lower levels of depression (beta = -0.25, p < 0.001). Furthermore, resilience significantly moderated the relationship between prosocial behavior and depression (beta = -0.08, p < 0.001); that is, resilience enhanced the protective role of prosocial behavior in depression. These findings indicate that resilience may play an important role in the associations between prosocial behavior and depression, which suggests that improving resilience is essential for the prevention and intervention of depression among children and adolescents on the Qinghai-Tibet Plateau

Depression in Children and Adolescents on the Qinghai-Tibet Plateau: Associations with Resilience and Prosocial Behavior (vol 18, 440 2021)

Depression in children and adolescents has become a serious public health problem worldwide. The objectives of this study were twofold: first, to investigate the status of depression among children and adolescents on the Qinghai-Tibet Plateau, the highest plateau in the world, with an average altitude of more than 4200 m (13,776 feet), and second, to examine the associations among prosocial behavior, resilience, and depression. A cross-sectional study was conducted among children and adolescents from Yushu Prefecture on the Qinghai-Tibet Plateau. A total of 11,160 participants aged 10&ndash;17 years (Mage = 14.34 years, SD = 1.77; 51.4% girls) were included. Self-reported depression, resilience, and prosocial behavior were assessed. The prevalence of depression was 29.2% in the current study. Higher levels of prosocial behavior were significantly associated with lower levels of depression (b = 0.25, p &lt; 0.001). Furthermore, resilience significantly moderated the relationship between prosocial behavior and depression (b = 0.08, p &lt; 0.001); that is, resilience enhanced the protective role of prosocial behavior in depression. These findings indicate that resilience may play an important role in the associations between prosocial behavior and depression, which suggests that improving resilience is essential for the prevention and intervention of depression among children and adolescents on the Qinghai-Tibet Plateau.</p

Cytotoxicity Regulated by Host–Guest Interactions: A Supramolecular Strategy to Realize Controlled Disguise and Exposure

This work is aimed at providing a supramolecular strategy for tuning the cytotoxicity in chemotherapy. To this end, as a proof of concept, we employed dynamic cucurbit[7]­uril­(CB[7])-mediated host–guest interaction to control the loading and releasing of dimethyl viologen (MV) as a model antitumor agent. MV has high cytotoxicity to both normal cells and tumor cells without specificity. By encapsulating MV into the hydrophobic cavity of CB[7], the cytotoxicity of MV to normal cells can be significantly decreased. When the host–guest complex of MV-CB[7] is added into tumor cells with overexpressed spermine, the antitumor activity of MV can be recovered in tumor cell environment. There are two reasons behind this effect: on the one hand, spermine has a high affinity to CB[7], leading to releasing of MV from MV-CB[7]; on the other hand, CB[7] can soak up spermine, which is essential for tumor cell growth, therefore decreasing the cell viability furthermore. Then, it is highly anticipated that this kind of supramolecular strategy could apply to clinical antitumor agents and provide a new approach for decreasing the cytotoxicity and increasing the antitumor activity, thus opening horizons of supramolecular chemotherapy

Low WIP1 Expression Accelerates Ovarian Aging by Promoting Follicular Atresia and Primordial Follicle Activation

Our previous study demonstrated that ovarian wild-type P53-induced phosphatase 1 (WIP1) expression decreased with age. We hypothesized that WIP1 activity was related to ovarian aging. The role of WIP1 in regulating ovarian aging and its mechanisms remain to be elucidated. Adult female mice with or without WIP1 inhibitor (GSK2830371) treatment were divided into three groups (Veh, GSK-7.5, GSK-15) to evaluate the effect of WIP1 on ovarian endocrine and reproductive function and the ovarian reserve. In vitro follicle culture and primary granulosa cell culture were applied to explore the mechanisms of WIP1 in regulating follicular development. This study revealed that WIP1 expression in atretic follicle granulosa cells is significantly lower than that in healthy follicles. Inhibiting WIP1 phosphatase activity in mice induced irregular estrous cycles, caused fertility declines, and decreased the ovarian reserve through triggering excessive follicular atresia and primordial follicle activation. Primordial follicle depletion was accelerated via PI3K-AKT-rpS6 signaling pathway activation. In vitro follicle culture experiments revealed that inhibiting WIP1 activity impaired follicular development and oocyte quality. In vitro granulosa cell experiments further indicated that downregulating WIP1 expression promoted granulosa cell death via WIP1-p53-BAX signaling pathway-mediated apoptosis. These findings suggest that appropriate WIP1 expression is essential for healthy follicular development, and decreased WIP1 expression accelerates ovarian aging by promoting follicular atresia and primordial follicle activation

Supramolecular Chemotherapy: Cooperative Enhancement of Antitumor Activity by Combining Controlled Release of Oxaliplatin and Consuming of Spermine by Cucurbit[7]uril

Supramolecular chemotherapy is aimed to employ supramolecular approach for regulating the cytotoxicity and improving the efficiency of antitumor drugs. In this paper, we demonstrated a new example of supramolecular chemotherapy by utilizing the clinical antitumor drug, oxaliplatin, which is the specific drug for colorectal cancer treatment. Cytotoxicity of oxaliplatin to the colorectal normal cell could be significantly decreased by host–guest complexation between oxaliplatin and cucurbit[7]­uril (CB[7]). More importantly, oxaliplatin-CB[7] exhibited cooperatively enhanced antitumor activity than oxaliplatin itself. On the one hand, the antitumor activity of oxaliplatin can reappear by competitive replacement of spermine from oxaliplatin-CB[7]; on the other hand, CB[7] can consume the overexpressed spermine in tumor environments, which is essential for tumor cell growth. These two events can lead to the cooperatively enhanced antitumor performance. Supramolecular chemotherapy can be applied to treat with spermine-overexpressed tumors. It is highly anticipated that this strategy may be employed in many other clinical antitumor drugs, which opens a new horizon of supramolecular chemotherapy for potential applications in clinical antitumor treatments

Supramolecular Chemotherapy: Carboxylated Pillar[6]arene for Decreasing Cytotoxicity of Oxaliplatin to Normal Cells and Improving Its Anticancer Bioactivity Against Colorectal Cancer

We have successfully demonstrated that the host–guest complex of carboxylated pillar[6]­arene with oxaliplatin (OxPt) exhibits low cytotoxicity toward normal cells and displays higher anticancer bioactivity against colorectal cancer cells than OxPt itself. Owing to higher binding affinity of carboxylated pillar[6]­arene with spermine (SPM) than that with OxPt, the encapsulated OxPt can be thoroughly released from its host–guest complex by the competitive replacement with SPM. This supramolecular chemotherapy works well both in vitro and in vivo for SPM-overexpressed cancers, such as colorectal cancer. Compared to OxPt itself, the anticancer bioactivity of this host–guest complex is further improved by about 20%. Such an improvement results from the combined effect of controlled release of OxPt from its host–guest complex and simultaneous consumption of SPM by carboxylated pillar[6]­arene. It is anticipated that this supramolecular strategy may be extended to other clinical anticancer drugs for decreasing their severe side effects and improving their anticancer bioactivity, thus enriching the realm of supramolecular chemotherapy

miR-202-5p Inhibits Lipid Metabolism and Steroidogenesis of Goose Hierarchical Granulosa Cells by Targeting ACSL3

miRNAs are critical for steroidogenesis in granulosa cells (GCs) during ovarian follicular development. We have previously shown that miR-202-5p displays a stage-dependent expression pattern in GCs from goose follicles of different sizes, suggesting that this miRNA could be involved in the regulation of the functions of goose GCs; therefore, in this study, the effects of miR-202-5p on lipid metabolism and steroidogenesis in goose hierarchical follicular GCs (hGCs), as well as its mechanisms of action, were evaluated. Oil Red O staining and analyses of intracellular cholesterol and triglyceride contents showed that the overexpression of miR-202-5p significantly inhibited lipid deposition in hGCs; additionally, miR-202-5p significantly inhibited progesterone secretion in hGCs. A bioinformatics analysis and luciferase reporter assay indicated that Acyl-CoA synthetase long-chain family member 3 (ACSL3), which activates long-chain fatty acids for the synthesis of cellular lipids, is a potential target of miR-202-5p. ACSL3 silencing inhibited lipid deposition and estrogen secretion in hGCs. These data suggest that miR-202-5p exerts inhibitory effects on lipid deposition and steroidogenesis in goose hGCs by targeting the ACSL3 gene

<i>MiR-202-5p</i> Regulates Geese Follicular Selection by Targeting <i>BTBD10</i> to Regulate Granulosa Cell Proliferation and Apoptosis

The regulation of granulosa cells (GCs) proliferation and apoptosis is the key step in follicular selection which determines the egg production performance of poultry. miR-202-5p has been reported to be involved in regulating the proliferation and apoptosis of mammalian ovarian GCs. However, its role in regulating the proliferation and apoptosis of goose GCs is still unknown. In the present study, the GCs of pre-hierarchical follicles (phGCs, 8–10 mm) and those of hierarchical follicles (hGCs, F2–F4) were used to investigate the role of miR-202-5p in cell proliferation and apoptosis during follicle selection. In phGCs and hGCs cultured in vitro, miR-202-5p was found to negatively regulate cell proliferation and positively regulate cell apoptosis. The results of RNA-seq showed that BTB Domain Containing 10 (BTBD10) is predicted to be a key target gene for miR-202-5p to regulate the proliferation and apoptosis of GCs. Furthermore, it is confirmed that miR-202-5p can inhibit BTBD10 expression by targeting its 3′UTR region, and BTBD10 was revealed to promote the proliferation and inhibit the apoptosis of phGCs and hGCs. Additionally, co-transfection with BTBD10 effectively prevented miR-202-5p mimic-induced cell apoptosis and the inhibition of cell proliferation. Meanwhile, miR-202-5p also remarkably inhibited the expression of Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Beta (PIK3CB) and AKT Serine/Threonine Kinase 1 (AKT1), while it was significantly restored by BTBD10. Overall, miR-202-5p suppresses the proliferation and promotes the apoptosis of GCs through the downregulation of PIK3CB/AKT1 signaling by targeting BTBD10 during follicular selection. Our study provides a theoretical reference for understanding the molecular mechanism of goose follicular selection, as well as a candidate gene for molecular marker-assisted breeding to improve the geese’ egg production performance