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ABSTRACT To explore the functions of Txnip and its mechanism in adipocyte differentiation, the preadipocytes were isolated from subcutaneous adipose tissue of three-day-old piglets and induced into adipogenic differentiation. The expression of Txnip and ChREBP was silenced, and the Txnip overexpression was achieved in the cells with transfection of the recombinant lentivirus strategies. Txnip silencing promoted the differentiation of porcine preadipocytes and PPARγ expression, and a PPARγ inhibitor reduced this facilitation. Instead, Txnip overexpression exerted a suppressive effect on the cell differentiation and PPARγ expression, and the PPARγ agonist offset this inhibition. High glucose stimulated the preadipocyte differentiation and expressions of ChREBP and Txnip. In contrast, Txnip expression was reduced by ChREBP silencing, suggesting glucose-regulated Txnip expression through the mediation of ChREBP. Moreover, the expressions of ChREBP and Glut4 induced by high glucose and glucose uptake of the cells were reduced by Txnip-overexpression, but increased by Txnip silencing, while these changes of Txnip did not alter their expressions under low glucose. Collectively, Txnip could be an inhibitor of porcine preadipocyte differentiation, which attenuated the adipogenesis through the negative feedback regulation on PPARγ. Txnip impaired the induction of glucose on the preadipocyte differentiation through decreasing Glut4 expression and glucose uptake and subsequent decrease of the expression and transcriptional activity of ChREBP.

Three hundred 21-day-old male Qingjiaoma broilers were randomly assigned to six groups to investigate the effect of dietary stems and leaves of Astragalus mongholicus (AMSLs), Astragalus polysaccharides (APSs), Lactobacillus (Lac) and their combinations on finishing broilers in a 42-day feeding experiment. Supplementary 1% AMSLs, 1 000 mg/kg APSs and 4.5 × 1010 CFU/kg Lac improved significantly growth performance. Dietary AMSLs, APSs and Lac increased the serum concentrations of immunoglobulins IgA, IgG and complements C3 and C4. Furthermore, AMSLs increased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities and total antioxidation capacity (T-AOC) and decreased the malondialdehyde (MDA) content in both serum and liver tissue. Compared with individual supplementation, the combination of Lac and AMSLs or APSs increased serum IgA, IgG, C3 and C4 concentrations. The combination of AMSLs and Lac increased serum GSH-Px activity and reduced the MDA content in the serum and liver tissue. These results suggested that AMSLs, APSs and Lac are beneficial feed additives, and the applications of combined Lac and AMSLs or APSs could synergistically improve immunity in broilers.

Biological control by antagonistic microorganisms are an effective and environmentally friendly approach in postharvest disease management. In order to develop a biocontrol agent for fresh walnut fruit preservation, the potential biocontrol effects of Bacillus amyloliquefaciens RD.006 and Hanseniaspora uvarum FA.006 against the main fungal pathogen of walnuts were evaluated. Botryosphaeria species showed the highest detection, and the JNHT01 strain showed the strongest pathogenicity. Bot. dothidea JNHT01 caused gray mold and brown rot on fresh walnuts, and its incidence rate reached 100% after an 8 days incubation. The growth of this fungal strain can be promoted by lighting, with a maximum growth rate achieved at a pH of 7 and at 28 °C. B. amyloliquefaciens RD.006 and H. uvarum FA.006 supernatants at a concentration of 1–15% v/v showed antifungal activity. The mycelial growth inhibition rates of Bot. dothidea JNHT01 were 23.67–82.61% for B. amyloliquefaciens RD.006 and 1.45–21.74% for H. uvarum FA.006. During Bot. dothidea JNHT01 growth, the biomass, nucleic acid leakage, and malondialdehyde content gradually increased, while the DPPH scavenging capacity and SOD activity decreased. The B. amyloliquefaciens RD.006 and H. uvarum FA.006 strains showed antifungal activity by damaging fungal cell membranes and reducing fungal antioxidant activity. Moreover, the antifungal effect of B. amyloliquefaciens RD.006 was higher than that of H. uvarum FA.006. Hence, the RD.006 strain of B. amyloliquefaciens can be considered a potential biocontrol agent for the management of postharvest walnut diseases caused by Bot. dothidea.

Cases of simultaneous inrush of high-temperature water and harmful gases are infrequently reported in areas without geothermal anomalies, hydrocarbon source rock, or coal measures. For this, we investigated the origin, development, and formation of the high-temperature water and harmful gases that rushed into Bangfu tunnel, Southwest China. During excavation of the Bangfu tunnel through the F1-2 fault in sandstone, a significant incident occurred involving a sudden influx of high-temperature water (45.4 °C) of Na–HCO3 type and harmful gases (CO2, H2S). An extensive geological examination uncovered a fault network extending from the crust to the mantle in the tunnel site area. The site features a substantial presence of both surface water and groundwater. Furthermore, within the middle crust at depths ranging from 19 km to 23 km, there are high-temperature ductile melts enriched with fluids and gases. Monitoring and experiments conducted on the harmful gases reveal that the primary source is identified in the crust, with the mantle source being secondary, followed by the atmospheric source being a minimal contribution. The hydrochemical and isotopic composition characteristics of the high-temperature rushed water indicate its evolution was formed through the infiltration of atmospheric precipitation from cold groundwater of the Ca–HCO3 type. The mechanism underlying the formation of the inrush high-temperature water and harmful gases can be outlined as follows. The fault network, spanning from the crust to the mantle, serves as a migration pathway for the inflow substances. Mantle-derived volatiles and high-temperature melts make heat energy facilitate the inrush activity, while groundwater contributes to heat transfer and acts as a medium for gas transport. As mantle-derived volatiles migrate towards the surface through the fault network, they mix with high-temperature melts and crust-derived gases, forming a crust-mantle mixed gas. Through processes such as deep hydrothermal circulation, shallow hydrothermal circulation, water/rock reaction, near-surface mixing, and dilution, Ca–HCO3 type cold groundwater transforms into high-temperature water of Na–HCO3 type. The methodologies and findings of our research offer insights into the route selection, investigation, and construction of mountain tunneling projects under similar geological conditions.

The effects of cyclic heat treatments on the fracture shear behaviors are rarely reported. To enhance our understanding, granite fractures having almost the same roughness were first exposed to cyclic heating at 400 °C and air-cooling treatments, and then direct shear tests were performed under four levels of normal loading. The influences of thermal cycles on roughness degradation and shear properties are analyzed. The roughness degradation in the joint roughness coefficient and the three-dimensional (3D) roughness metric exhibit linear increasing tendency with increasing thermal cycles. Typical fracture shear properties, including cohesion and friction angle, peak and residual shear strength, peak and residual shear displacement, and initial and secant shear stiffness, fluctuate generally within the first 10 thermal cycles, followed by gradual decreasing tendencies. The thermal effect on the shear properties become weaker as the number of heat treatments increases from 10 to 80. Nonuniform expansion and shrinkage of mineral grains after thermal treatments produce micro-cracks within the rock matrix and on the rock surface, suggesting that asperities are easier to be sheared-off. Thermal alteration in fracture peak-shear strength could be attributed to the deterioration in rock strengths and the mismatch in opposing fracture walls. The observations would provide better insights into rock friction after high temperatures in geothermal energy exploitation.

Composite Mo–Mo2C powders with varying contents of Mo and Mo2C were synthesized through in situ carbothermal reduction of MoO3 followed by hydrogen reduction. TiC-10(Mo + Mo2C)–10WC–20Ni (wt%) cermets were produced using self-synthesized TiC and Mo–Mo2C composite powders as well as WC and Ni powders. All sintered samples exhibited a uniformly distributed core-rim structure. As the proportion of Mo2C in composite powder increased, the rim of cermets became thinner, and the grain size was finer. The hardness of cermets increased with increasing Mo2C content in composite powders, and decreased with extended holding time. In contrast, the fracture toughness (KIC) of cermets exhibited the opposite trend. The transverse rupture strength (TRS) initially increased but then decreased as the increase of Mo2C content. Sintered sample using composite powder of Mo-94.1 wt% Mo2C exhibited the smallest grain size of 0.66 μm and the highest hardness of 1576 HV30 after sintering for 0.5 h. Whereas, the sintered sample of TiC–10Mo–10WC–20Ni demonstrated the highest KIC of 16.44 MPa m1/2 and a hardness of 1449 HV30 after a sintering time of 2 h. As the Mo2C content in composite powder increased, the fracture mechanism of cermets changed from a mixed mode of intergranular fracture and transgranular fracture to predominantly intergranular fracture, resulting in a reduction in KIC. The complexity of fracture morphology was quantified via the fractal dimension. Sintered samples with simpler fracture morphologies had smaller fractal dimensions, whereas those with more intricate surface features exhibited larger fractal dimensions, reflecting complex fracture mechanisms and higher TRS.

Abstract Background Clinically, the coadministration of opioids to enhance antinociception and decrease tolerance has attracted increasing research attention. We investigated the effects of dezocine, a mu- and kappa-opioid receptor agonist/antagonist, on morphine tolerance and explored the involvement of opioid receptor expression in a rat model of bone cancer pain. Methods Thermal nociceptive thresholds were measured after the subcutaneous injection of morphine (10 mg/kg) alone or combined with dezocine (10 or 1 mg/kg) for 7 consecutive days. Real-time PCR and western blot analysis were used to examine opioid receptor expression in the periaqueductal gray (PAG) and spinal cord. Results The analgesic effect was significantly decreased after 4 days of morphine administration. We observed that low-dose dezocine significantly attenuated morphine tolerance without reducing the analgesic effect of morphine. Low-dose dezocine coadministration significantly reversed the downregulated expression of mu (MOR) and delta (DOR) opioid receptors in the PAG and the upregulated expression of kappa (KOR) and DOR in the spinal cord induced by morphine. Moreover, low-dose dezocine coadministered with morphine significantly inhibited KOR expression in both the PAG and spinal cord. Conclusions The combination of low-dose dezocine with morphine may prevent or delay the development of morphine tolerance in a rat model of bone cancer pain. The regulation of opioid receptor expression in the PAG and spinal cord may be part of the mechanism.

The separation of Cu from the CuxO-FexO containing waste (such as copper slag and electroplating sludge) is always intractable by using pyrometallurgy method. The carbothermic reduction methods, as well as the conventional sulfurization technology by using sulfurization agent FeS2, will introduce lots of iron into the prepared Cu–Fe alloy or Cu–Fe–S matte, and this results in the difficulty in further separation of Cu from Fe. In this work, CaS is utilized as the new sulfurization agent, and the iron content of prepared Cu–Fe–S matte is lower than 5%, while the copper grade is improved to about 76–79%. Such products could be used as the raw materials for producing metallic copper. According to the experimental results, at 1450 °C, the copper oxides in CuO–Fe2O3–SiO2–CaO system is selectively sulfurized by CaS, and Cu2S dominated product is formed and separated from slags. The recovery extent of copper reaches 98% when the CaS addition is 1.15 times (1.15CaS) of the stoichiometric quantity required. However, the increase of CaS addition (1.6CaS) will lead to the sulfurization of iron oxides, and make the iron content in Cu–Fe–S matte increase to 15%. Besides, when the Cu/Fe ratio (in mass) of synthetic waste is 0.5, part of the CaS is oxidized by Fe2O3, which results in the recovery extent of Cu to only about 73.30%. However, the copper recovery extent could be improved to 97% by adding extra reductant carbon.

Nano-sized transition-metal carbides with high purities were synthesized by vacuum carbothermal reduction coupled with a novel method for the removal of free carbon by molten calcium treatment. Transition-metals oxides were firstly reduced by excessive carbon black under vacuum condition, and then the obtained product was treated in molten calcium to remove the free carbon. After acidic leaching the product, pure carbides were obtained. The excess carbon in the carbothermic reduction stage could not only increase the contact between reactants and make the reduction more thorough, but also act as barrier to restrict the grain growth of the products. The effects of carbothermic reduction temperature, calcium treatment temperature and particle sizes of oxides on the reaction products were discussed in detail. It was concluded that after carbothermic reduction of corresponding oxides at 1823 K in vacuum and the following calcium treatment at 1173 K, TiC, ZrC, HfC, V8C7, NbC and TaC with the particle sizes of 100 nm, 70 nm, 130 nm, 200 nm, 150 nm and 120 nm, could be prepared, respectively.

A simple and efficient pathway was developed to synthesize ultrafine grained oxide dispersion strengthened (ODS) Mo alloys doped with nano-scaled oxide particles. Firstly, dispersed La(NO3)3 or Al(NO3)3 nanoparticles were introduced into commercial MoO3 via a solution spraying method. Then, Mo nanopowders containing different amounts of oxides nanoparticles (La2O3 (0%, 0.5%, 1% and 2%) or Al2O3 (0.5%, 1%)) were successfully prepared by reducing the doped MoO3 with carbon black at 600 °C and 1050 °C, and hydrogen at 800 °C. Due to the high sintering activity of prepared doped Mo nanopowder, after sintering in H2 at 1300 °C for 3 h, the relative density of sintered products containing 0.5% La2O3 or Al2O3 reached to above 95.4%. Nanostructured ODS Mo alloys with Mo and La2O3 (or Al2O3) grain sizes of about 0.5 μm and 75 nm (or 50 nm for Al2O3) were successfully prepared at around 1300 °C. The obtained nanostructured Mo-oxides alloys had much high hardness values. For the Mo-La2O3 alloys, the highest value of hardness can reach to 338 HV (1% La2O3, Mo grain size, 0.51 μm; La2O3 grain size, 71.3 nm; density, 93.0%), while the highest hardness of Mo-Al2O3 alloys reached to 385 HV (1% Al2O3, Mo grain size, 0.55 μm; Al2O3 grain size, 55.9 nm; density, 94.6%), which were much higher than the ODS-Mo alloys prepared from the traditional methods. This method could also have great potential for industrially producing nanostructured ODS Mo alloys and W alloys. Keywords: Mo alloy, Nanoparticles, Microstructure, Dispersion strengthening, Hardness

Abstract Background Vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) have been involved in tumor growth and metastasis. Sevoflurane may promote angiogenesis, whereas propofol can present an anti-angiogenic effect. In this study, we compared the effects of propofol/remifentanil-based total intravenous anesthesia (TIVA) and sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-β, as well as recurrence- free survival (RFS) rates in the patients undergoing breast cancer surgery. Methods Eighty female patients undergoing breast cancer resection were enrolled and randomized to receive either sevoflurane-based inhalational anesthesia (SEV group) or propofol/remifentanil-based TIVA (TIVA group). The serum concentrations of VEGF-C and TGF-β before and 24 h after surgery were measured and RFS rates over a two-year follow-up were analyzed in both groups. The postoperative pain scores assessed using a visual analogue scale (VAS) and the use of perioperative opioids were also evaluated. Results Although VAS scores at 2 h and 24 h after surgery were comparable between the two groups, there were more patients receiving postoperative fentanyl in the TIVA group (16[40%]) compared with the SEV group (6[15%], p = 0.023). VEGF-C serum concentrations increased after surgery from 105 (87–193) pg/ml to174 (111–281) pg/ml in the SEV group (P = 0.009), but remained almost unchanged in the TIVA group with 134 (80–205) pg/ml vs.140(92–250) pg/ml(P = 0.402). The preoperative to postoperative change for VEGF-C of the SEV group (50 pg/ml) was significantly higher than that of the TIVA group (12 pg/ml) with a difference of 46 (− 11–113) pg/ml (P = 0.008). There were also no significant differences in the preoperative and postoperative TGF-β concentrations between the two groups. The two-year RFS rates were 78% and 95% in the SEV and TIVA groups (P = 0.221), respectively. Conclusion In comparison with sevoflurane-based inhalational anesthesia, propofol/remifentanil -based total intravenous anesthesia can effectively inhibit the release of VEGF-C induced by breast surgery, but didn’t seem to be beneficial in the short-term recurrence rate of breast cancer. Trial registration Chictr.org.cn ChiCTR1800017910. Retrospectively Registered (Date of registration: August 20, 2018).

The aim of this study was to evaluate the influence of artesunate on Th1 differentiation and its anti-tumor effect on ovarian cancer. A Murine ovarian cancer model was established by ID8 cells transplantation. The expression of miR-142 and Sirt1 proteins in peripheral CD4+ T cells were quantified with qRT-PCR and western blot, respectively. Peripheral CD4+ T cells were induced for Th1 differentiation. The percentages of apoptosis of Th1/CD4+ T cells and ovarian cancer cells were analyzed by flow cytometry. The IFN-γ level was examined through enzyme-linked immunosorbent assay. Artesunate promoted miR-142 expression in peripheral CD4+ T cells and Th1 differentiation from CD4+ T cells. Artesunate promoted cell apoptosis of ovarian cancer cells by inducing Th1 differentiation. By up-regulating miR-142, artesunate suppressed Sirt1 level and promoted Th1 differentiation. Artesunate enhanced the pro-apoptotic effects of Th1 cells on ovarian cancer via the miR-142/Sirt1 pathway. Artesunate promoted Th1 differentiation from CD4+ T cells by down-regulating Sirt1 through miR-142, thereby enhancing cell apoptosis in ovarian cancer.

ABSTRACT To demonstrate the role of gonadotropin-releasing hormone (GnRH) in yaks (Bos grunniens), we characterized the expression of gonadotropin-releasing hormone receptor (GnRHR) mRNA and protein. The level of GnRHR mRNA in the hypothalamus was higher than that in the pineal gland, pituitary gland, and ovary during estrus. Immunofluorescence analysis showed that GnRHR was expressed in the pinealocyte, synaptic ribbon, and synaptic spherules of the pineal gland and that melatonin interacts with GnRHR via nerve fibers. In the hypothalamus, GnRHR was expressed in the magnocellular neurons and parvocellular neurons. In the pituitary gland, GnRHR was expressed in acidophilic cells and basophilic cells. In the ovary, GnRHR was present in the ovarian follicle and Leydig cells. Gonadotropin-releasing hormone receptor is located in the pineal gland, hypothalamus, pituitary, and gonad during estrus of yaks and is mainly expressed in the hypothalamus and ovaries during the estrus period.