Adrenal gland responses surgical castration and immunocastration by different compensatory manners to increase DHEA secretion.

Androgen from the testis and weak androgens from the adrenal cortex may interact with each other and affect their synthesis and secretion due to their similar functions. The purpose of this study was to investigate the compensatory effect of adrenal in rats after immunocastration and surgical castration, and the interaction between the hypothalamic-pituitary-testis (HPT) axis and the hypothalamic-pituitary-adrenal (HPA) axis. 24 male SD rats aged 8 weeks were randomly divided into three groups and accepted treatments: surgical castration group, immunocastration group and control group. In both surgical castration and immunocastration groups, the secretion of adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone (DHEA) hormones was significantly increased compared with the control group (p < 0.05). In the HPT axis of the immunocastration group, the KISS1 expression was up-regulated, whereas GPR54, LH and LHR expression were down-regulated (p < 0.05). The expression levels of CRH, POMC and MC2R genes were also significantly up-regulated (p < 0.05). In addition, in the immunocastration group, the expression of adrenal LHR mRNA expression was decreased (p < 0.05). The expression of HPT axis genes and adrenal LHR were up-regulated in the surgical castration group (p < 0.05). These results show that in both immunocastration and surgical castration, adrenal androgen is increased, suggesting that the adrenal gland plays a compensatory role. Moreover, it also shows that different castration treatments have effects on adrenal steroid secretion through different mechanisms.

Changes in colostrum ingredients of Hu sheep, as well as the missense mutation genes associated with colostrum yield.

This study focused on the changes in the composition and immune evolution in milk from birth to 144 h postpartum and the genes associated with the colostrum yield of Hu sheep. Twelve Hu sheep, which were bred carefully under animal health standards and have a litter size of two kids and similar gestation length (149 ± 1 days), were used. Lambs were transferred into their own cots to avoid interference. The compositional content (i.e., fat, protein, and lactose) and some other properties, including daily colostrum yield, DM, and SNF, were determined. In addition, immunity molecules (IgG, IgA, and IgM concentrations) received remarkable attention. The DM, SNF, fat, and protein contents were higher in the first days postpartum and then dropped quickly from the time of birth to 144 h postpartum. However, the lactose content displayed an increasing pattern and reached normal milk percentage at 48 h. The highest IgG (103.17 mg/mL), IgA (352.82 µg/mL), and IgM (2.79 mg/mL) colostrum concentrations were observed at partum, decreased quickly, and finally stabilized. The change law of concentration of IgA and IgM in colostrum are the same with IgG. Furthermore, the whole-genome resequencing was performed, and a missense variant locus in the SRC gene and two missense locus variants in the HIF1A gene were significantly associated with the colostrum yield of sheep by using the whole-genome selection signal detection analysis. In conclusions, colostrum contains abundant nutrients especially immunoglobulin, and the HIF1A gene may be used as candidate genes for colostrum yield, which has important information as a basic knowledge for the Hu sheep breeding program.

Neuroprotective Effect of Ponicidin Alleviating the Diabetic Cognitive Impairment: Regulation of Gut Microbiota.

Cognitive impairment is a major complication of diabetes mellitus, which is caused by constitutive hyperglycaemia. Ponicidin is a diterpenoid isolated from a Chinese traditional herb (Rabdosia rubescens) and demonstrates the various pharmacological effects. The goal of this study was to scrutinise the neuroprotective effect of ponicidin against diabetic nephropathy (DN) induced by streptozotocin (STZ). Intraperitoneal administration of STZ (55 mg/kg) was used for the induction of diabetes and rats were received oral administration of ponicidin (5, 10 and 15 mg/kg) until 28 days. The body weight, food intake, water intake and blood glucose level were assessed at regular time interval. Plasma insulin level, antioxidant, inflammatory cytokines, apoptosis marker and faecal gut microbiota compositions were estimated. DN-induced group rats revealed the augmented glucose level, water intake, food intake and reduced body weight. Ponicidin significantly (P < 0.001) repressed the glucose level and water food intake and improved the body weight and plasma insulin. Ponicidin significantly (P < 0.001) repressed the malonaldehyde (MDA) level and boosted the level of glutathione (GSH), glutathione reductase (GR) and superoxide dismutase (SOD) in the brain and serum level. Ponicidin significantly (P < 0.001) repressed the level of interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and enhanced the level of interleukin-4 (IL-4), interleukin-10 (IL-10) in the brain and serum level. DN group rats exhibited the enhanced relative abundance of Firmicutes, along with enhancing the Firmicutes/Bacteroidetes ratio and repressing the Bacteroidetes relative abundance. Ponicidin effectually restored the relative abundance of Allobaculum, Lactobacillus and Ruminococcus genera. Our findings clearly demonstrated that ponicidin has a neuroprotective effect against diabetic cognitive impairment through modulating the gut microbiome.

Correlation between the Molecular Structure and Viscosity Index of CTL Base Oils Based on Ridge Regression.

In China, coal-to-liquid (CTL) lube base oils with ultrahigh viscosity index (VI) are very popular. Since it consists of chain alkanes only and can be precisely characterized by molecular structures alone, quantitative 13C nuclear magnetic resonance (NMR) data are used to generate the average structural parameters (ASPs) of CTL base oil. In this work, the ASPs and bulk properties of CTL base oils were tested and compared with those of mineral base oils. Based on the test results, the correlation between the unique property of CTL base oil VI and ASPs was analyzed. To eliminate the effect of significant multicollinearity among the input variables, statistical methods such as ordinary least-squares (OLS), stepwise regression, and ridge regression methods were used to build the VI prediction model. The main findings are as follows: according to the 13C NMR spectrum, CTL base oils had a significantly higher content of isomeric chain alkanes (including several branching structures) than mineral base oil, while the content of cycloalkanes was zero; among several branched structures, the one with the largest difference in content is structure S67, which has the highest percentage in the iso-paraffin structures, all above 25.5% in CTL base oils and below 21.39% in mineral oils; according to the distillation curve of the simulated distillation (SimDist) analysis, CTL base oils with similar carbon number distribution showed lower boiling points, narrower distillation ranges, and higher distillation efficiencies than mineral base oil; correlation analysis showed that the average chain length (ACL), normal paraffins (NPs), and structure S67 caused the CTL base oil to exhibit a higher VI; and from 13C NMR data, the ridge regression model was used to obtain regression coefficients consistent with reality, and the expected VI could be well predicted with a correlation coefficient of 0.935.

The c.612A>G mutation of MC4R affects constitutive activity and signaling in domestic goats.

As a key gene for balancing energy and regulating feeding behavior, MC4R is relevant to the growth of ruminants. In this presentation, a highly conserved c.612A>G site in the coding sequence (CDS) of MC4R has been selected during a selective sweep analysis of 35 Yiling goats and 20 other wild goats. This site mutation results in an amino acid change from Ile to Met. The genotyping analysis of the c.612A>G site revealed that the A allele was the dominant allele in the domestic goat populations, while the wild goat individuals only had the G allele. For a better understanding of the biological significance of this site, we examined the protein localization and signal detection to explain the function of the two MC4R receptors. The results showed that both the M204 and I204 receptors can normally localize on the membrane. When stimulating the M204 type without α-MSH, it was defective at the level of basal cAMP and decreased significantly against the I204 type. In contrast, the signaling capacity of the M204 receptor was also lower than that of I204 under the stimulation of α-MSH. In the ERK1/2 pathway, stimulating MC4R with NDP-α-MSH, both the M204 and I204 receptors had normal pERK1/2 levels. These results indicate that the p.I204M mutation may change the function by damaging the constitutive activity and signaling, and thus may regulate goats' appetite. This study has potential application for rearing domestic goats.

The Facile Preparation of PBA-GO-CuO-Modified Electrochemical Biosensor Used for the Measurement of α-Amylase Inhibitors' Activity.

Element doping and nanoparticle decoration of graphene is an effective strategy to fabricate biosensor electrodes for specific biomedical signal detections. In this study, a novel nonenzymatic glucose sensor electrode was developed with copper oxide (CuO) and boron-doped graphene oxide (B-GO), which was firstly used to reveal rhubarb extraction's inhibitive activity toward α-amylase. The 1-pyreneboronic acid (PBA)-GO-CuO nanocomposite was prepared by a hydrothermal method, and its successful boron doping was confirmed by transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS), in which the boron doping rate is unprecedentedly up to 9.6%. The CuO load reaches ~12.5 wt.%. Further electrochemical results showed that in the enlarged cyclic voltammograms diagram, the electron-deficient boron doping sites made it easier for the electron transfer in graphene, promoting the valence transition from CuO to the electrode surface. Moreover, the sensor platform was ultrasensitive to glucose with a detection limit of 0.7 µM and high sensitivity of 906 µA mM-1 cm-2, ensuring the sensitive monitoring of enzyme activity. The inhibition rate of acarbose, a model inhibitor, is proportional to the logarithm of concentration in the range of 10-9-10-3 M with the correlation coefficient of R2 = 0.996, and an ultralow limit of detection of ~1 × 10-9 M by the developed method using the PBA-GO-CuO electrode. The inhibiting ability of Rhein-8-b-D-glucopyranoside, which is isolated from natural medicines, was also evaluated. The constructed sensor platform was proven to be sensitive and selective as well as cost-effective, facile, and reliable, making it promising as a candidate for α-amylase inhibitor screening.

Expression of cell proliferation regulatory factors bricd5, tnfrsf21, cdk1 correlates with expression of clock gene cry1 in testes of Hu rams during puberty.

BACKGROUND: Cryptochrome 1 (cry1), the core regulator of the circadian clock, is essential for ontogeny and mammalian reproduction. Unlike in other tissues, the cry1 gene have noncircadian functions in spermatogenesis, which implies the unique role of cry1 gene in the development of testis. The role of cry1 during the puberty has not been described yet. This study aimed to explore the relationship between cry1 expression and spermatogenic cell numbers. METHODS AND RESULTS: We analyzed testicular tissues from Hu sheep aged 0-180 days by hematoxylin and eosin staining, measured cry1 and cell proliferation regulatory factors (bricd5, tnfrsf21, cdk1) expression by quantitative real-time PCR and characterized the transcription factor in the 5' flanking region of cry1 gene. The data revealed that the number of spermatocytes and early spermatocytes increased rapidly from 90 to 120 dpp (day postpartum). Correspondingly, there was a marked variation in the cry1 and cell proliferation related genes (bricd5, tnfrsf21, cdk1) mRNA expression in the testes from the age of 90 days to 180 days (p < 0.05). We also identified some transcription factors (tcfl5) related to cell proliferation. CONCLUSIONS: There is a significant causal relationship between the transcription level of cry1 gene in Hu sheep testes and the number of spermatogenic cells. It is speculated that cry1 gene may regulate the proliferation of spermatogenic cells by regulating the expression of cell proliferation related genes such as bricd5, tnfrsf21 and cdk1.

Using PAMPs and DAMPs as adjuvants in cancer vaccines.

Immunotherapy for cancer has attracted considerable attention. As one of the immunotherapeutics, tumor vaccines exert great potential for cancer immunotherapy. The most important components in tumor vaccines are antigens and adjuvants, which determine the therapeutic safety and efficacy, respectively. After decades of research, many types of adjuvants have been developed. Although these adjuvants can induce strong and long-lasting immune responses in tumor immunity, they also cause more severe toxic side effects and are therefore not suitable for use in humans. With the development of innate immunity research, pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are receiving more attention in vaccine design. However, whether they have the potential to become new adjuvants remains to be elucidated. The purpose of this review is to provide newideas for the research and development of new adjuvants by discussing the mechanisms and related functions of PAMPs and DAMPs.

Co-immunizing with HMGB1 enhances anti-tumor immunity of B7H3 vaccine in renal carcinoma.

Metastatic renal carcinoma is a kind of tumor with high degree of malignancy, but there are no effective treatment methods and strategies at present. In this study, we designed a folate-grafted PEI600-CyD (H1) nanoparticle-mediated DNA vaccine containing an adjuvant of high mobility group box 1 protein (HMGB1) and a tumor-specific antigen of B7H3 (CD276) for renal carcinoma therapy. Mice bearing subcutaneous human B7H3 (hB7H3)-Renca tumor were immunized with H1-pHMGB1/pB7H3, H1-pB7H3, H1-pHMGB1, or Mock vaccine. Compared to other control groups, the growth of the tumor was significantly inhibited in H1-pHMGB1/pB7H3 vaccine group. The increased proportion and mature of CD11c+ DCs were observed in the spleen of H1-pHMGB1/pB7H3 treated mice. Likewise, HMGB1 promoted B7H3 vaccine to induce tumor-specific CD8+ T cell proliferation and CTL responses. Beyond that, H1-pHMGB1/pB7H3 vaccine strengthened the induction of functional CD8+ T cells. With the depletion of CD8+ T cells, the anti-tumor effect of H1-pHMGB1/pB7H3 also disappeared, indicating that CD8+ T cells are the key factor of the anti-tumor activity of the vaccine. So, to sum up, H1-pHMGB1/pB7H3 vaccine could achieve the desired anti-tumor effect by enhancing the response of tumor-specific functional CD8+ T cell responses. H1 nanoparticle-based vaccines may have great potential and prospect in the treatment of primary solid tumors.

Red, green, and blue fluorescent folate-receptor-targeting carbon dots for cervical cancer cellular and tissue imaging.

Folate receptor targeted photo-luminescent quantum carbon dots (Fr-CDs) were successfully prepared from folic acid and phenylenediamine isomers through hydrothermal approaches. Fr-CDs were spherical particles smaller than 10 nm, and emit stable green, blue and red luminescence under ultraviolet region excitation (λex = 365 nm) with maximum emissive lengths at 530, 429, and 612 nm. And the corresponding photoluminescence quantum yield as 15.4%, 12.6% and 16.2% respectively. Up-converted photoluminescent properties in near infrared 800 nm spectral region located in green, blue and yellow region. In-vitro studies showed Fr-CDs had almost none cytotoxicity (cell viability over 80%) and high affinitive to the Hela celline highly-expressed-folate-receptor membranes, and lighted on cytoplasm as the fluorescent marker. It displayed long luminescent-stability with PL intensity above 90% in ultraviolet illuminant exposure over 24 h. In in-vivo studies, Fr-CDs were internalized and accumulated in targeted cancer tissues of cervical carcinoma and the emitting fluorescence maintains over 30 min.

Characterization of an α-Calcium Sulfate Hemihydrates/α-Tricalcium Phosphate Combined Injectable Bone Cement.

The artificial bone-repair materials have received extensive attention. In this study, we have prepared new α-calcium sulfate hemihydrates (α-CSH) and gelatin modified α-tricalcium phosphate (α-TCP) combined injectable bone cement (α-CSH/α-TCP bone cement). The solidification, mechanical behavior, in vitro biocompatibility and degradation were studied and a spine bone trabecular defect model in swine vertebral body was constructed to evaluate its in vivo performance. The results demonstrated that the bone cement has the appropriate in vitro initial setting time of 6-10 min and final setting time within 20 min, excellent mechanical properties up to 35 M Pa in compressive strength, no in vitro cytotoxicity and appropriate in vivo biodegradation with good bone regeneration ability as the radiological and histological examination showed. Therefore, the α-CSH/α-TCP bone cement has broad application prospects in minimally invasive surgery for the bone defects treatment.

Automated Mechanical Repositioning Treatment for Posterior Canal Benign Paroxysmal Positional Vertigo: A Single-Center Experience and Literature Review.

OBJECTIVE: To evaluate the feasibility and effectiveness of automated mechanical repositioning treatment (AMRT) for posterior canal benign paroxysmal positional vertigo -(PC-BPPV). PATIENTS AND METHODS: We reviewed all PC-BPPV patients admitted to our department between January and -December 2016. The inclusion criteria mainly required conducting a diagnosis for PC-BPPV by using the Dix-Hallpike test, a PC-BPPV history within 1 month, no intake of medications for the last 48 h. Compared with the cases who received classical manual repositioning treatment (CMRT), the proportion of patients who underwent AMRT with a resolution within the 1-week follow-up session after initial treatment and a recurrence during the 6-month follow-up were evaluated. RESULTS: A total of182 patients who underwent AMRT and 152 patients who underwent CMRT were included. Compared with the CMRT group, the AMRT group had a higher rate of complete or partial resolution and positional nystagmus at the 1 week follow-up (92.6 vs. 86.2%; p = 0.004). AMRT with less treatment cycles was more effective than CMRT (1.5 vs. 1.9; p < 0.001). After 6 months of follow-up, the cumulative recurrence rate of the AMRT group was significantly lower than that of the CMRT group (3.0 vs. 8.9%; p = 0.037). CONCLUSION: AMRT is a feasible and effective procedure for the resolution of PC-BPPV.

Tumor-Penetrating Peptide-Modified DNA Tetrahedron for Targeting Drug Delivery.

DNA self-assembling nanostructure has been considered as a promising candidate as a drug delivery vehicle because of its compactness, mechanical stability, and noncytotoxicity. In this work, we developed functional, multiform DNA nanostructures by appending a tumor-penetrating peptide to tetrahedral DNA nanostructure (p-TDN). This functional structure is able to efficiently increase the rate of uptake of glioblastoma cell U87MG compared with the DNA tetrahedron and the double-stranded DNA structures. We found that the DNA tetrahedron plays the main role in the endocytosis of U87MG cells, whereas the tumor-penetrating peptide could also bind to transmembrane glycoprotein neuropilin-1 and mediate the endocytosis of the p-TDN nanostructure. Moreover, given the high efficiency of the growth inhibitory effect of the p-TDN loading doxorubicin hydrochloride, the p-TDN distinguishes itself as a promising candidate as an effective delivery carrier.