ABSTRACT Objective: Both pulsatile gonadotropin-releasing hormone (GnRH) and combined gonadotropin therapy are effective to induce spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). This study aimed to evaluate the effect of pulsatile GnRH therapy on spermatogenesis in male patients with CHH who had poor response to combined gonadotropin therapy. Materials and methods: Patients who had poor response to combined gonadotropin therapy ≥ 6 months were recruited and shifted to pulsatile GnRH therapy. The rate of successful spermatogenesis, the median time to achieve spermatogenesis, serum gonadotropins, testosterone, and testicular volume were used for data analysis. Results: A total of 28 CHH patients who had poor response to combined gonadotropin (HCG/HMG) therapy for 12.5 (6.0, 17.75) months were recruited and switched to pulsatile GnRH therapy for 10.0 (7.25, 16.0) months. Sperm was detected in 17/28 patients (60.7%). The mean time for the appearance of sperm in semen was 12.0 (7.5, 17.5) months. Compared to those who could not achieve spermatogenesis during pulsatile GnRH therapy, the successful group had a higher level of LH60min (4.32 vs. 1.10 IU/L, P = 0.043) and FSH60min (4.28 vs. 1.90 IU/L, P = 0.021). Testicular size increased during pulsatile GnRH therapy, compared to previous HCG/HMG therapy (P < 0.05). Conclusion: For CHH patients with prior poor response to one year of HCG/HMG therapy, switching to pulsatile GnRH therapy may induce spermatogenesis. Objective gonadotropinreleasing releasing (GnRH CHH. . (CHH) methods gonadotropins testosterone analysis Results 2 HCGHMG HCG HMG (HCG/HMG 125 12 5 12. 6.0, 60 0 (6.0 17.75 1775 17 75 100 10 10. 7.25, 725 7 25 (7.25 16.0 160 16 1728 17/2 60.7%. 607 60.7% (60.7%) 120 7.5, (7.5 17.5 175 LHmin LH min 4.32 432 4 32 (4.3 vs 110 1 1.1 IUL IU L IU/L 0.043 0043 043 FSHmin FSH 4.28 428 (4.2 190 90 1.9 0.021. 0021 0.021 021 0.021) 0.05. 005 0.05 05 0.05) Conclusion (CHH 6.0 (6. 17.7 177 7.25 72 (7.2 16. 172 17/ 60.7 (60.7% 7.5 (7. 17. 4.3 43 3 (4. 11 1. 0.04 004 04 4.2 42 19 9 002 0.02 02 00 0.0 6. (6 7.2 60. (60.7 7. (7 4. (4 0. ( (60. (60

Abstract Objectives Tripartite Motif 47 (TRIM47) protein plays a prominent role in many cancers. This study aimed to investigate the biological roles of TRIM47 in ovarian cancer. Methods TRIM47 was knocked down and overexpressed in ovarian cancer cell lines SKOV3 and OVCAR3, and the effects on proliferation, clone formation, apoptosis, invasion, and growth of xenograft tumors in nude mice were determined. The expression levels of the selected candidates were tested by western blotting and quantitative real-time PCR. Results TRIM47 knockdown suppressed proliferation and encourages apoptosis of ovarian cancer cells. Similarly, TRIM47 knockdown suppressed ovarian cancer cell invasion, migration, and epithelial-mesenchymal transition. Ovarian cancer cell xenograft assays demonstrated that TRIM47 knockdown significantly inhibited tumor growth. Mechanistically, TRIM47 knockdown suppressed STAT3 phosphorylation and the expression of several downstream genes, including MCL-1, MMP2, and c-MYC. Silencing of STAT3 partially prevented TRIM47-induced tumor cell proliferation and invasion. Conclusion The present study's findings demonstrate that by activating STAT3 signaling, TRIM47 functions as an oncogene in ovarian cancer. TRIM47, therefore, appears to be a potential target for ovarian cancer prevention and/or therapy.

Abstract To investigate the effect of corosolic acid treatment on erectile function in metabolic syndrome induced rat model. Fifty male 3-week-old SD rats were fed a high fat and high sugar diet. Six months later, metabolic variables were determined. Metabolic syndrome induced erectile function (MED) rats were confirmed by an apomorphine test. Then MED rats were treated with corosolic acid daily by oral gavage for 4 weeks. To evaluate erectile function, intracavernosal pressure (ICP)/mean arterial blood pressure (MAP) ratio was measured. Thiobarbituric acid reactive substances assay and dihydroethidium staining were used to assess reactive oxygen species (ROS) level. Protein expressions of gp91phox and eNOS were examined by western blotting and immunohistochemistry. Fasting blood glucose, body weight, total cholesterol and insulin were markedly increased in metabolic syndrome rats compared with those of the control rats (p < 0.05). The ratios of max ICP/MAP and area under curve (AUC)/MAP was markedly reduced in MED rats compared with the control rats (p < 0.05). The concentration of cyclic guanosine mono-phosphate (cGMP) and the expression of eNOS were significantly decreased in MED rats compared with the control group (p < 0.05). Moreover, ROS level and the expression of gp91phox were significantly increased in MED rats. Treatment with corosolic acid reversed these changes (each p < 0.05). Corosolic acid reduces the level of ROS, ameliorating endothelial dysfunction and improvement of erectile function in MED rats.

Abstract The butt welding tests of 5.5mm thick pure nickel N6 plate were carried out by plasma arc welding (PAW) and ERNi-1wire-filled PAW. And the differences in microstructure and properties between two kinds of joints were studied. The results show that the wire-filled pure nickel N6 joint has good appearance without defects such as pores, cracks, and undercuts. Pure nickel N6 weld is single-phase austenite structure, and no phase transformation occurs during heating or cooling. The weld zone of PAW joint is characterized by coarse columnar grain with average grain size of 125.8 μm, while the weld zone of wire-filled joint is equiaxed grain with average grain size of 54.8 μm. The tensile strength of the wire-filled PAW joint is 337MPa and the elongation after fracture is 44%, which is 11.6% and 85.5% higher than that of the PAW joint. The corrosion rate of wire-filled PAW joint is 2.6908g/m2h, which is lower than that of PAW joint of2.8820g/m2h, and the corrosion rates of both joint are higher than the base metal. The alloy elements in the welding wire can supplement the alloy elements burned in the welding process. As the filler metal, the melted wire forms the joint with the melted base metal, avoiding the defects such as undercut and depression. Al and Ti elements in ERNi-1 wire have deoxidation and nitrogen fixation effect during welding thermal cycle process, which improves the resistance of weld to carbon monoxide and nitrogen porosity. In the process of nitrogen fixation, TiN particles are formed in the crystal or grain boundary. TiN particles at the grain becomes heterogeneous nucleation particles in the grain, which makes a large number of nucleation and increases the nucleation rate. TiN particles at grain boundaries act as "nails" to hinder the migration of austenite grain boundaries. In the deoxidization process, the deoxidized products Al2O3 and TiO2 are formed. However, large-size inclusions are formed owing to the high content of Al and Ti in the molten pool, which affects the performance of the joint. Therefore, the structure and performance of filler wire-filled PAW joint are better than those of PAW joint.

Abstract Background: Snakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required. Methods: Cases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database. Results: Principal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity. Conclusions: Our results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.

Abstract This study aimed to determine the association between the polymorphisms and haplotypes in the xeroderma pigmentosum group D (XPD) gene and the risk of pancreatic cancer in the Chinese Han population. SNaPshot was used for genotyping six SNP sites of the XPD gene. Comparisons of the correlations between different genotypes in combination with smoking and the susceptibility to pancreatic cancer were performed. Individual pancreatic cancer risk in patients who carry mutant C alleles (AC, CC, and AC+CC) at rs13181 increased (p < 0.05). Taking non-smoking individuals who carry the AA genotype as a reference, and non-smoking individuals who carry mutant allele C (AC+CC), the risk of pancreatic cancer increased by 3.343 times in individuals who smoked ≥ 20 cigarettes daily, 3.309 times in individuals who smoked ≥ 14 packs per year, 5.011 times in individuals who smoked ≥ 24 packs per year, and 4.013 times in the individuals who smoked ≥ 37 packs per year (P < 0.05). In addition, haplotype analysis revealed that haplotype AGG, which comprised rs13181, rs3916874 and rs238415, was associated with a 1.401-fold increase in pancreatic cancer risk (p < 0.05). We conclude that the polymorphism of XPD Lys751Gln (rs13181) in combination with smoking contributes to increased risk of pancreatic cancer in the Chinese Han population. Haplotype AGG might be a susceptibility haplotype for pancreatic cancer.

Endoplasmic reticulum (ER) stress is a critical molecular mechanism involved in the pathogenesis of sepsis. Hence, strategies for alleviating this stress may be essential for preventing cardiovascular injuries under sepsis. Adiponectin is secreted by adipocytes and its levels are decreased in sepsis. The purpose of this study was to investigate the protective effects of adiponectin treatment on endothelial cells and its mechanism. Male Wistar rats underwent cecal ligation and puncture (CLP) before being treated with adiponectin (72 and 120 μg/kg). The levels of malondialdehyde (MDA) in plasma, histological structure, and apoptosis of endothelial cells were evaluated. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with adiponectin at 10 and 20 μg/mL for 24 h after stimulation by lipopolysaccharide (LPS). The levels of reactive oxygen species (ROS), ultrastructure, rate of apoptosis, the expression of inositol-requiring enzyme 1α (IRE1α) protein, and its downstream molecules (78 kDa glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), and caspase-12) were detected. The results showed that the levels of MDA and ROS induced by CLP or LPS stimulation were increased. Furthermore, endothelial cell apoptosis was increased under sepsis. The IRE1α pathway was initiated, as evidenced by activated IRE1α, increased GRP78, and up-regulated CHOP and caspase-12 in HUVECs. Following treatment with adiponectin, the number of apoptotic endothelial cells was markedly decreased. These findings demonstrated that treatment with adiponectin decreased apoptosis of endothelial cells caused by sepsis by attenuating the ER stress IRE1α pathway activated by oxidative stress.

Abstract Dunaliella salina, a single-celled marine alga with extreme salt tolerance, is an important model organism for studying fundamental extremophile survival mechanisms and their potential practical applications. In this study, two-dimensional differential in-gel electrophoresis (2D-DIGE) was used to investigate the expression of halotolerant proteins under high (3 M NaCl) and low (0.75 M NaCl) salt concentrations. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and bioinformatics were used to identify and characterize the differences among proteins. 2D-DIGE analysis revealed 141 protein spots that were significantly differentially expressed between the two salinities. Twenty-four differentially expressed protein spots were successfully identified by MALDI-TOF/TOF MS, including proteins in the following important categories: molecular chaperones, proteins involved in photosynthesis, proteins involved in respiration and proteins involved in amino acid synthesis. Expression levels of these proteins changed in response to the stress conditions, which suggests that they may be involved in the maintenance of intracellular osmotic pressure, cellular stress responses, physiological changes in metabolism, continuation of photosynthetic activity and other aspects of salt stress. The findings of this study enhance our understanding of the function and mechanisms of various proteins in salt stress.

OBJECTIVE: Epstein-Barr virus (EBV) is a ubiquitous human γ-herpes virus, which can adapt and evade host immune defense. Dendritic cells (DCs) play a pivotal role in the initiation and maintenance of immune responses. This study investigated the effects of EBV on cord blood monocytes derived DCs (CBDC). METHODS: Monocytes were isolated from cord blood and cultured in medium containing recombinant IL-4 and GM-CSF to induce DCs development. B95-8 supernatant was added in monocytes culture medium for EBV infection at day 0. Phenotypic characterization of DCs, apoptotic cells, and mitochondrial membrane potential (MMP) were detected by flow cytometry. The morphology was observed by Hoechst 33258 staining and TUNEL staining, the expression of X-linked inhibitor of apoptosis protein (XIAP) was detected by Western blotting assay and caspase 3, 8 and 9 activity was measured. RESULTS: Phenotypic characterization of DCs was changed in EBV-treated group. Chromatin condensation and DNA fragmentation were observed in EBV induced CBDC apoptosis. In addition, caspase 3, caspase 8, and caspase 9 activation were enhanced in the EBV-treated group. This was accompanied by the loss of MMP. Furthermore, XIAP expression was down-regulated in the EBV-treated group and compared to mock-infected group. CONCLUSION: These results suggested that EBV could inhibit CBDC phenotypic differentiation, and induce CBDC apoptosis in caspase-dependent manner with involvement of the mitochondrial pathway. This might help EBV to evade host immune responses to establish persistent infection.