Ginkgetin aglycone exerts anti-osteoporotic effect via regulation of NOX4/Akt/PI3K pathway

Purpose: To investigate the protective effect of Ginkgetin aglycone (GA) on ovariectomy-induced osteoporosis in rats, as well as the mechanism of action involved. Methods: Adult female Wistar rats (n = 40) were separated into four group: normal control, ovariectomy (OVR), 100 mg GA/kg dose, and 200 mg GA/kg dose. The rats were ovariectomized using standard procedures, except for those in normal control group. Rats in the two treatment groups received 100 or 200 mg GA/kg orally for a period of 12 weeks. Biochemical assays were performed on the urine and blood. Markers of bone formation and mediators of inflammation were assessed. Bone microarchitectural changes were examined using micro-CT scanner, while Western blotting was used to determine the expressions of NOX4, NF-κB p65, PI3K, Akt and JNK proteins in rat femurs. Results: Phosphorus and calcium levels in the serum varied among different groups. Levels of calcium, phosphorus and creatinine decreased (p < 0.01) significantly to a greater extent in the urine of GA group than in that of OVR group (p < 0.05). Interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α) and osteocalcin (OC) levels and the activity of alkaline phosphatase (ALP) decreased more in GA group than in OVR group. In GA-treated group, bone mineral density (BMD) was enhanced in a dose dependent manner than OVR group (p < 0.05). Treatment with GA ameliorated altered bone microarchitecture in OVR rats. Treatment of osteoporotic rats with GA led to significant and dosedependent decrease in the expressions of JNK, NOX4, NF-κB p65 and PI3K, and (p < 0.05) increase in the expression of Akt in femur tissue. Conclusion: In conclusion, result of study proves the anti-osteoporotic activity of GA is exerted via regulation of NOX4/PI3K/Akt pathway

Improving Fine-grained Entity Typing with Entity Linking

Fine-grained entity typing is a challenging problem since it usually involves a relatively large tag set and may require to understand the context of the entity mention. In this paper, we use entity linking to help with the fine-grained entity type classification process. We propose a deep neural model that makes predictions based on both the context and the information obtained from entity linking results. Experimental results on two commonly used datasets demonstrates the effectiveness of our approach. On both datasets, it achieves more than 5\% absolute strict accuracy improvement over the state of the art.Comment: EMNLP 201

Genetic variants in ELOVL2 and HSD17B12 predict melanoma‐specific survival

Fatty acids play a key role in cellular bioenergetics, membrane biosynthesis and intracellular signaling processes and thus may be involved in cancer development and progression. In the present study, we comprehensively assessed associations of 14,522 common single‐nucleotide polymorphisms (SNPs) in 149 genes of the fatty‐acid synthesis pathway with cutaneous melanoma disease‐specific survival (CMSS). The dataset of 858 cutaneous melanoma (CM) patients from a published genome‐wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used as the discovery dataset, and the identified significant SNPs were validated by a dataset of 409 CM patients from another GWAS from the Nurses’ Health and Health Professionals Follow‐up Studies. We found 40 noteworthy SNPs to be associated with CMSS in both discovery and validation datasets after multiple comparison correction by the false positive report probability method, because more than 85% of the SNPs were imputed. By performing functional prediction, linkage disequilibrium analysis, and stepwise Cox regression selection, we identified two independent SNPs of ELOVL2 rs3734398 T>C and HSD17B12 rs11037684 A>G that predicted CMSS, with an allelic hazards ratio of 0.66 (95% confidence interval = 0.51–0.84 and p = 8.34 × 10−4) and 2.29 (1.55–3.39 and p = 3.61 × 10−5), respectively. Finally, the ELOVL2 rs3734398 variant CC genotype was found to be associated with a significantly increased mRNA expression level. These SNPs may be potential markers for CM prognosis, if validated by additional larger and mechanistic studies

Causes of Infection after Earthquake, China, 2008

To determine which organisms most commonly cause infection after natural disasters, we cultured specimens from injured earthquake survivors in Wenchuan, China, 2008. Of 123 cultures, 46 (59%) grew only 1 type of pathogenic bacteria. Smear was more effective than culture for early diagnosis of gas gangrene. Early diagnosis and treatment of wounds are crucial

Puerarin attenuates pressure overload-induced cardiac hypertrophy

AbstractBackgroundPuerarin is the most abundant isoflavonoid in kudzu root. It has been used to treat angina pectoris and myocardial infarction clinically. However, little is known about the effect of puerarin on cardiac hypertrophy.MethodsAortic banding (AB) was performed to induce cardiac hypertrophy in mice. Puerarin premixed in diets was administered to mice after one week of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed at 7 weeks after starting puerarin treatment (8 weeks post-surgery). The extent of cardiac hypertrophy was also evaluated by pathological and molecular analyses of heart samples. Cardiomyocyte apoptosis was assessed by measuring Bax and Bcl-2 protein expression and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In addition, the inhibitory effect of puerarin (1μM, 5μM, 10μM, 20μM, 40μM) on mRNA expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in Ang II (1μM)-stimulated H9c2 cells was investigated using quantitative real-time reverse transcription-polymerase chain reaction.ResultsEchocardiography and catheter-based measurements of hemodynamic parameters at 7 weeks revealed the amelioration of systolic and diastolic abnormalities. Puerarin also decreased cardiac fibrosis in AB mice. Moreover, the beneficial effect of puerarin was associated with the normalization in gene expression of hypertrophic and fibrotic markers. Further studies showed that pressure overload significantly induced the activation of phosphoinositide 3-kinase (PI3K)/Akt signaling and c-Jun N-terminal kinase (JNK) signaling, which was blocked by puerarin treatment. Cardiomyocyte apoptosis and induction of Bax in response to AB were suppressed by puerarin. Furthermore, the increased mRNA expression of ANP and BNP induced by Ang II (1μM) was restrained to a different extent by different concentrations of puerarin.ConclusionPuerarin may have an ability to retard the progression of cardiac hypertrophy and apoptosis which is probably mediated by the blockade of PI3K/Akt and JNK signaling pathways

The cosmic ray test of MRPCs for the BESIII ETOF upgrade

In order to improve the particle identification capability of the Beijing Spectrometer III (BESIII),t is proposed to upgrade the current endcap time-of-flight (ETOF) detector with multi-gap resistive plate chamber (MRPC) technology. Aiming at extending ETOF overall time resolution better than 100ps, the whole system including MRPC detectors, new-designed Front End Electronics (FEE), CLOCK module, fast control boards and time to digital modules (TDIG), was built up and operated online 3 months under the cosmic ray. The main purposes of cosmic ray test are checking the detectors' construction quality, testing the joint operation of all instruments and guaranteeing the performance of the system. The results imply MRPC time resolution better than 100$ps$, efficiency is about 98$\%$ and the noise rate of strip is lower than 1$Hz/$($scm^{2}$) at normal threshold range, the details are discussed and analyzed specifically in this paper. The test indicates that the whole ETOF system would work well and satisfy the requirements of upgrade