Influences of point defects on electron transport of two-dimensional gep semiconductor device.

The quantum transport properties of defective two-dimensional (2D) GeP semiconductor nanodevice consisting of typical point defects, such as antisite defect, substitutional defect, and Schottky defect, have been studied by using density functional theory combined with non-equilibrium Green's function calculation. The antisite defect has indistinctive influences on electron transport. However, both substitutional and Schottky defect have introduced promising defect state at the Fermi level, indicating the possibility of improvement on the carrier transport. Our quantitative quantum transport calculations ofI-Vbbehavior have revealed that the electrical characters are enhanced. Moreover, the P atom vacancy could induce significant negative differential resistance phenomenon, and the physical mechanism is unveiled by detailed analysis. The transfer characteristic properties could be prominently improved by substitutional defect and vacancy defect. Most importantly, we have proposed a computational design of GeP-based electronic device with improved electrical performance by introducing vacancy defect. Our findings could be helpful to the practical application of novel 2D GeP semiconductor nanodevice in future.

Effect of advanced paternal age on reproductive outcomes in IVF cycles of non-male-factor infertility: a retrospective cohort study.

Advanced paternal age has been overlooked, and its effect on fertility remains controversial. Previous studies have focused mainly on intracytoplasmic sperm injection (ICSI) cycles in men with oligozoospermia. However, few studies have reported on men with semen parameters within reference ranges. Therefore, we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization (IVF) cycles. In total, 381 cycles included were subgrouped according to paternal age (<35-year-old, 35-39-year-old, or ≥40-year-old), and maternal age was limited to under 35 years. Data on embryo quality and clinical outcomes were analyzed. The results showed that fertilization and high-quality embryo rates were not significantly different (all P > 0.05). The pregnancy rate was not significantly different in the 35-39-year-old group (42.0%; P > 0.05), but was significantly lower in the ≥40-year-old group (26.1%; P < 0.05) than that in the <35-year-old group (40.3%). Similarly, the implantation rate significantly decreased in the ≥40-year-old group (18.8%) compared with that in the <35-year-old group (31.1%) and 35-39-year-old group (30.0%) (both P < 0.05). The live birth rate (30.6%, 21.7%, and 19.6%) was not significantly different across the paternal age subgroups (<35-year-old, 35-39-year-old, and ≥40-year-old, respectively; all P > 0.05), but showed a declining trend. The miscarriage rate significantly increased in the 35-39-year-old group (44.8%) compared with that in the <35-year-old group (21.0%; P < 0.05). No abnormality in newborn birth weight was found. The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters, although it has no impact on embryo development.

Vitamin K2-Dependent GGCX and MGP Are Required for Homeostatic Calcium Regulation of Sperm Maturation.

A low-calcium microenvironment is essential for spermatozoa to mature in the epididymis; however, it remains unclear how dysregulation of epididymal luminal calcium is associated with male infertility. Using a warfarin-induced vitamin K2 deficiency rat model, we found that vitamin-K-dependent γ-glutamyl carboxylase (GGCX) and matrix Gla protein (MGP) were essential in extracellular calcium signaling of the intercellular communication required for epididymal sperm maturation. We found that GGCX and MGP co-localized in the vesicular structures of epididymal cells and spermatozoa. Calcium-regulated MGP binds to proteins in a biphasic manner; sub-millimolar calcium enhances, whereas excessive calcium inhibits, the binding. Bioinformatic analysis of the calcium-dependent MGP-bound proteome revealed that vesicle-mediated transport and membrane trafficking underlie the intercellular communication networks. We also identified an SNP mutation, rs699664, in the GGCX gene of infertile men with asthenozoospermia. Overall, we revealed that the GGCX-MGP system is integrated with the intercellular calcium signaling to promote sperm maturation.

Computationally unraveling how ceritinib overcomes drug-resistance mutations in ALK-rearranged lung cancer.

Anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase, has been implicated in the pathogenesis of several cancers. The small molecule ceritinib can overcome drug-resistance mutations that are observed in crizotinib-resistant patients, although the detailed mechanism for this ability of ceritinib remains elusive. Here, molecular dynamics (MD) simulations of six systems (including the apo ALK, the wild-type ALK-ceritinib complex, as well as four complexes of ceritinib with the I1171T, L1196M, S1206Y, and G1269A mutants of ALK, respectively) together with the subsequent molecular mechanics-generalized Born/surface area binding free energy calculations were performed to answer this question. Principal component analysis and domain cross-correlation analysis of MD trajectories revealed that ceritinib binding stabilized the conformational dynamics of both the wild-type and the four mutated ALKs as compared to the apo ALK. Moreover, the mutations had subtle effects on the conformation of ALK compared to that of the wild-type ALK. Importantly, binding free energy calculations demonstrated that, compared its effect on the wild-type ALK, ceritinib showed slightly increased potency towards the I1171T, L1196M, S1206Y, and G1269A mutants. Therefore, the binding of ceritinib to the four mutants can overcome crizotinib-resistant mutations. These data provide a structural and energetic explanation of how ceritinib overcomes mutation-induced drug resistance.

[Clinical observation of dog days moxibustion plaster therapy in treatment of allergic rhinitis of different patterns/syndromes].

OBJECTIVE: To explore the efficacy and feasibility of dog days moxibustion plaster therapy in treatment of allergic rhinitis of different patterns/syndromes. METHODS: Allergic rhinitis of lung deficiency and invasion of cold, spleen qi deficiency and kidney yang deficiency, 56 patients for each pattern/syndrome were randomized into a plaster therapy group and a nasal spray group, 28 cases in each one. In the plaster therapy group, according to the pattern/syndrome differentiation, with literature retrieval method, 3 acupoints of high frequency utility in clinic were selected as one group in acupoint plaster therapy. For lung deficiency and invasion of cold pattern/syndrome, Feishu (BL 13), Fengmen (BL 12) and Hegu (LI 4) were selected. For spleen qi deficiency pattern/syndrome, Pishu (BL 21), Zusanli (ST 36) and Dazhui (GV 14) were selected. For kidney yang deficiency pattern/ syndrome, Shenshu (BL 23), Dingchuan (EX-B 1) and Bailao (EX-HN 15) were selected. Separately, on July 13, 2013, July 23, 2013, August 2, 2013 and August 12, 2013, the aucpoint plaster therapy was applied, 2 to 4 h (1 to 2 h for children) each time. In the nasal spray group, beclometasone dipropionate aqueous nasal spray, 2 presses one nostril each time, 2 to 3 times a day, continuously for 4 weeks. The symptom score and efficacy were compared before and after treatment in the patients of the two groups. RESULTS: The symptom scores of 3 patterns/syndromes were all apparently improved after treatment as compared with those before treatment in the patients of the two groups (all P<0.05), and the result in the plaster therapy group was better than that of the nasal spray group (P<0.05, P<0.01). For lung deficiency and invasion of cold pattern/syndrome, the total effective rate was 87.3% (20/24) in the plaster therapy group, better than 84.6% (22/26) in the nasal spray group (P<0.05). For spleen qi deficiency pattern/syndrome, the total effective rate was 83.3% (20/24) in the plaster therapy group, obviously better than 76.9% (22/26) in the nasal spray group (P<0.05). For kidney yang deficiency pattern/syndrome, the total effective rate was 79.2% (19/24) in the plaster therapy group, better than 76.9% (22/26) in the nasal spray group (P<0.05). CONCLUSION: The dog days moxibustion plaster therapy achieves definite efficacy on allergic rhinitis at the acupoints selected based on the differentiation of different patterns/syndromes and the efficacy is better than beclometasone dipropionate aqueous nasal spray.

Sedimentary records of PAHs in a sediment core from tidal flat of Haizhou Bay, China.

The concentrations and depositional fluxes of polycyclic aromatic hydrocarbons (PAHs) were investigated in a dated sediment core collected from a tidal flat in Haizhou Bay, China. The USEPA's 16 priority PAH concentrations ranged from 72.51 ng g(-1) dw in 1969 to 805.21 ng g(-1) dw in 2010, while the deposition fluxes were in the range of 102.36-861.02 ng cm(-2) yr(-1). The PAH concentrations and fluxes changed dramatically with depth, suggesting changes in energy usage and corresponding closely with the historical economic development of eastern China. The levels of PAHs slightly increased from the late 1970s, following China's "Reform and Open" policy of 1978; however, a drastic increase in the concentration of PAHs observed in 1990 was indicative of the rapid growth in coal and petroleum incomplete combustion byproducts, which was associated with the increase in economic development in this area. Furthermore, isomer ratio analysis and principle component analysis revealed the main anthropogenic pyrolytic source that causes PAH contamination in the coastal sediment.