High expression of RTEL1 predicates worse progression in gliomas and promotes tumorigenesis through JNK/ELK1 cascade.

Gliomas are the most common primary intracranial tumor worldwide. The maintenance of telomeres serves as an important biomarker of some subtypes of glioma. In order to investigate the biological role of RTEL1 in glioma. Relative telomere length (RTL) and RTEL1 mRNA was explored and regression analysis was performed to further examine the relationship of the RTL and the expression of RTEL1 with clinicopathological characteristics of glioma patients. We observed that high expression of RTEL1 is positively correlated with telomere length in glioma tissue, and serve as a poor prognostic factor in TERT wild-type patients. Further in vitro studies demonstrate that RTEL1 promoted proliferation, formation, migration and invasion ability of glioma cells. In addition, in vivo studies also revealed the oncogene role of RTEL1 in glioma. Further study using RNA sequence and phospho-specific antibody microarray assays identified JNK/ELK1 signaling was up-regulated by RTEL1 in glioma cells through ROS. In conclusion, our results suggested that RTEL1 promotes glioma tumorigenesis through JNK/ELK1 cascade and indicate that RTEL1 may be a prognostic biomarker in gliomas.

[Research Progress in Adjacent Anatomical Structure and Location of Cricothyroid Membrane].

Cricothyroid membrane puncture and incision,the key techniques to save the lives of the patients in the Can't Intubate,Can't Oxygenate (CICO) emergency,need to be mastered by all the airway management staff.However,the decision to carry out cricothyroid membrane puncture or incision is often delayed due to the unfamiliarity with the adjacent anatomical structure of the cricothyroid membrane and the inability to accurately locate the cricothyroid membrane.As a result,serious complications and rescue failure occur.Therefore,airway management staff should be familiar with the adjacent structure and positioning methods of the cricothyroid membrane,so as to improve the success rate of emergency airway rescue,reduce complications,and protect the airway and life safety of the patients.

Summary of Turbocharging as a Waste Heat Recovery System for a Variable Altitude Internal Combustion Engine.

The increase in altitude causes the decrease in internal combustion engine power and the increase in pollutant emission. Converting waste heat into more useful forms of energy through the recovery of waste heat from internal combustion engines is the most promising mechanism for improving both of these goals. This paper comprehensively reviews the development and research of waste heat recovery technology of an internal combustion engine in a variable altitude environment. It is found that exhaust gas turbocharging is the most promising waste heat recovery technology to restore high-altitude internal combustion engine power. Turbochargers are affected by low temperature and low pressure at high altitudes, resulting in poor environmental adaptability, inadequate supercharging ratios, and decreased supercharging efficiency. Therefore, it is very important to select the high pressurization system facing the plateau area and its reasonable matching characteristics. The quality of exhaust energy determines how much waste heat a turbine can recover, and only the exergy part of exhaust energy can realize heat/work conversion. The main disadvantage of turbocharging technology applied in the plateau area is that the speed ratio deviates from the design value, leading to the increase of flow loss inside the supercharger. Therefore, optimizing the internal flow field of a high-altitude supercharger is a key problem to improve the efficiency of energy recovery. The conclusion drawn from this Review is that a two-stage turbocharging system will be a key technology to improve the thermal efficiency and reduce the fuel consumption of high-altitude internal combustion engines in the coming decades. In addition, the efficient utilization of the exhaust energy of the two-stage turbine and the influence of the variable compression process of the two-stage compressor on the working medium in the cylinder will be the focus of future research.

Improvement of hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) by enzyme-digested poultry by-product: Growth performance, amino acid and peptide transport capacity, and intestinal morphology.

Background: At present, fish meal (FM) resources are in short supply, and competition for food between humans and animals is becoming increasingly critical. Finding non-grain protein sources that can replace FM is the key to solving the rapid development of aquaculture. Methods: Seven trial diets were prepared with 0 g/kg (EP0), 30 g/kg (EP3), 60 g/kg (EP6), 90 g/kg (EP9), 120 g/kg (EP12), 150 g/kg (EP15), and 180 g/kg (EP18) of enzyme-digested poultry by-product meal (EPBM) by replacing of FM. A total of 630 hybrid groupers (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) were equally portioned into 21 tanks. At 8:00 and 16:00 each day, groupers were fed until they were full for a cumulative period of 8 weeks. Results: The results showed that 30 g/kg of EPBM significantly increased the rates of weight gain and special growth (P < 0.05). Significantly higher activities of serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, catalase, and superoxide dismutase were observed in the EP3 group (P < 0.05). The categories and numbers of the top 10 dominant bacteria in the phylum and genus levels were not significantly influenced by feed (P > 0.05). In the proximal intestine and distal intestine, there were significantly higher expressions of SNAT3, LAAT1, CAT2, and CAT1 in the EP3 group compared with the EP0 group (P < 0.05). In the EP3 group, the expressions of PepT1, LAAT1, B0, +AT, and CAT2 were significantly increased in MI than those in all other groups (except the EP0 group, P < 0.05). Conclusion: When FM was replaced by 30 g/kg of EPBM, growth performance, antioxidant capacity, and the ability to transport amino acids and peptides of hybrid grouper were significantly improved.

Dexmedetomidine alleviates airway hyperresponsiveness and allergic airway inflammation through the TLR4/NF­κB signaling pathway in mice.

Dexmedetomidine (DEX) suppresses inflammatory responses and protects against organ injury. The aim of the present study was to investigate the effect of DEX on airway hyperresponsiveness (AHR) and allergic airway inflammation, as well as its underlying mechanism of action in a murine model of ovalbumin (OVA)­induced asthma. A total of 30 female BALB/c mice were divided into 6 groups (n=5 mice/group): Control, OVA, OVA + DEX (20, 30 or 50 µg/kg) and OVA + TAK­242 [a toll­like receptor 4 (TLR4) inhibitor]. The mice were intraperitoneally injected with 20, 30 or 50 µg/kg DEX 1 h before OVA challenge. AHR to inhaled methacholine (Mch) was measured, and the mice were sacrificed 24 h after the last challenge. AHR following Mch inhalation was measured using the FlexiVent apparatus. Hematoxylin and eosin, periodic acid­Schiff and Wright­Giemsa staining was performed to evaluate inflammatory cell infiltration in the lung tissue. The levels of IL­4, IL­5 and IL­13 in the bronchoalveolar lavage fluid were analyzed using ELISA, and their mRNA expression levels in the lung tissue were examined using reverse transcription­quantitative PCR. The protein expression of TLR4, NF­κB and phosphorylated (p)NF­κB in the lung tissue was also detected using immunohistochemistry. In the murine OVA­induced asthma model, DEX decreased AHR following Mch inhalation and reduced the infiltration of inflammatory cells. IL­4, IL­5 and IL­13 levels in the bronchoalveolar lavage fluid were significantly lower following DEX treatment. Furthermore, DEX treatment inhibited the expression of TLR4, NF­κB and p­NF­κB in the lung tissue and exhibited a similar effect to TAK­242 treatment. In conclusion, DEX may attenuate AHR and allergic airway inflammation by inhibiting the TLR4/NF­κB pathway. These results suggested that DEX may represent a potential anti­inflammatory agent for the treatment and management of patients with asthma.

Flesh quality of hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) fed with hydrolyzed porcine mucosa-supplemented low fishmeal diet.

Iso-nitrogenous and iso-lipidic diets containing 0%, 3%, 6%, 9%, and 12% hydrolyzed porcine mucosa (namely, HPM0, HPM3, HPM6, HPM9, and HPM12) were prepared to evaluate their effects on the growth performance, muscle nutrition composition, texture property, and gene expression related to muscle growth of hybrid groupers (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂). Groupers were fed to apparent satiation at 08:00 and 16:00 every day for a total of 56 days. It was found that the weight gain percentage in the HPM0, HPM3, and HPM6 groups did not differ (P > 0.05). The cooking loss and drip loss of the dorsal muscle in the HPM3 group were lower than those in the HPM6 and HPM9 groups (P < 0.05). The hardness and chewiness of the dorsal muscle in the HPM3 group were higher than those in the HPM0, HPM9, and HPM12 groups (P < 0.05). The gumminess in the HPM3 group was higher than that in the HPM9 and HPM12 groups (P < 0.05). The total essential amino acid content of the dorsal muscle in the HPM12 group was higher than that in the HPM0 group (P < 0.05). The contents of total n-3 polyunsaturated fatty acid and total n-3 highly unsaturated fatty acid, as well as the ratio of n-3/n-6 polyunsaturated fatty acid in the dorsal muscle was higher in the HPM0 group than in all other groups (P < 0.05). The relative expressions of gene myogenic factor 5, myocyte enhancer factor 2c, myocyte enhancer factor 2a, myosin heavy chain, transforming growth factor-beta 1 (TGF-ß1), and follistatin (FST) were the highest in the dorsal muscle of the HPM3 group. The results indicated that the growth performance of hybrid grouper fed a diet with 6% HPM and 27% fish meal was as good as that of the HPM0 group. When fish ingested a diet containing 3% HPM, the expression of genes TGF-ß1 and FST involved in muscle growth were upregulated, and then the muscle quality related to hardness and chewiness were improved. An appropriate amount of HPM could be better used in grouper feed.

A Single- and Multiple-Dose Study To Characterize the Pharmacokinetics, Safety, and Tolerability of Imipenem and Relebactam in Healthy Chinese Participants.

Relebactam/imipenem/cilastatin is approved in the United States to treat complicated urinary tract and intra-abdominal infections in patients who have limited or no alternative treatment options and hospital-acquired bacterial pneumonia (HABP)/ventilator-associated bacterial pneumonia (VABP). Initial pharmacokinetic, safety, and tolerability studies of relebactam with and without imipenem/cilastatin included mostly Caucasian participants. This study evaluated the pharmacokinetics, safety, and tolerability of relebactam/imipenem/cilastatin in 12 healthy Chinese participants after three single doses of increasing concentrations (relebactam at 125, 250, or 500 mg; cilastatin at 250, 500, or 1,000 mg; and imipenem at 250, 500, or 1,000 mg) and after multiple doses every 6 h of a single concentration (relebactam at 250 mg, cilastatin at 500 mg, and imipenem at 500 mg) for 14 days. After single doses, the area under the concentration-time curve (AUC) extrapolated to infinity (relebactam, 15.0 to 70.7 h · mg/liter; imipenem, 24.1 to 109.8 h · mg/liter; cilastatin, 18.4 to 95.3 h · mg/liter) and the AUC from 0 to 6 h (relebactam, 14.2 to 66.3 h · mg/liter; imipenem, 23.4 to 107.3 h · mg/liter; cilastatin, 18.3 to 94.4 h · mg/liter) increased in a dose-dependent manner; clearance (relebactam, 6.9 to 8.3 liters/h; imipenem, 8.6 to 10.4 liters/h; cilastatin, 10.5 to 13.6 liters/h) and half-life (relebactam, 1.4 to 1.6 h; imipenem, 1.0 to 1.2 h; cilastatin, 0.7 to 1.0 h) were consistent between doses. Pharmacokinetic parameters after multiple doses were similar to parameters after a single dose (geometric mean ratios of 0.8 to 1.0 for all three agents). Relebactam/imipenem/cilastatin was well tolerated; mild adverse events occurred during single dosing, and one participant experienced serious adverse events after multiple doses. Pharmacokinetics and safety data are comparable with data from participants of other ethnicities, supporting the use of relebactam/imipenem/cilastatin at the approved dose and schedule in Chinese patients.

Gradient elution of organic acids on a beta-cyclodextrin column in the polar organic mode and its application to drug discovery.

A high performance liquid chromatographic method was developed that separated organic acids using the polar organic mode. The separation was obtained using a beta-cyclodextrin stationary phase with a mobile phase that was composed of acetonitrile/methanol/triethylamine (TEA)/acetic acid. The compounds were eluted under gradient conditions and the elution order depended on the number, type and position of the hydrogen bonding functional groups present in the molecule. Adjusting the acid to base ratio resulted in the biggest change in selectivity. In addition, increasing the methanol concentration decreased the retention times of the analytes, which had little effect on the selectivity. Using a certain set of conditions one could separate a large number of organic acids, which allowed these acids to be detected by UV and mass spectrometry. These conditions were used to evaluate the purity of potential pharmaceutical drug candidates that showed activity towards a kinase target vascular endothieal growth factor (Vegf). Each compound contained a carboxylic acid group that was critical to the activity. The method was able to give purity estimates of these samples, which were difficult to determine by other HPLC methods.