[Effects of Cathepsin K on spatial learning and memory in rats].

OBJECTIVE: To investigate the effects of Cathepsin K(CatK) on spatial learning and memory in rat hippocampus and its mechanisms. METHODS: Twenty male SD rats were randomly divided into Control group and CatK inhibitor group(CatKⅡ group), which were microinjected with Cathepsin K specific inhibitor(0.5 µg/µl) and artificial cerebrospinal fluid in hippocampal DG area respectively with 5 days. The cultured hippocampal neuron cells were divided into control group (CON group), negative control group(NC group), siRNA interference group(siCatK group). Three re-wells were set for each group, and samples were collected 18～20 h after siRNA transfection. Morris water maze was used to evaluate spatial learning and memory function of rats. Meanwhile, dynamic changes of glutamate(Glu) content in extracellular fluid of DG region during learning and memory were observed by microdialysis and high performance liquid chromatography in conscious rats. Western blot was used to detect CatK-mediated Notch1 activation and other signal molecules. RESULTS: Animal experiments showed that compared with the control group, the spatial learning and memory ability were decreased significantly in CatKII group, and the hippocampus protein expressions of c-Notch1, p-Akt, p-CREB and BDNF were also decreased significantly(P＜0.05); the levels of Glu in DG area of control group and CatK II group were increased significantly with Morris water maze training days, but the increase of CatK II group was significantly weaker than that of control group(P＜ 0.05). The results of cell experiment showed that the expressions of CatK, c-Notch1, p-CREB and BDNF in siCatK group were significantly lower than other groups (P＜0.05). CONCLUSION: CatK can affect the spatial learning and memory function of rats by activating Notch1 and its memory related signal protein in hippocampus.

Clinical Impact of Thrombus Aspiration and Interaction With D-Dimer Levels in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Objectives: To evaluate the effect of thrombus aspiration (TA) strategy on the outcomes and its interaction with D-dimer levels in patients with ST-segment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (PCI) in "real-world" settings. Materials and Methods: This study included 1,295 patients with STEMI who had undergone primary PCI with or without TA between January 2013 and June 2017. Patients were first divided into a TA+PCI group and a PCI-only group, and the baseline characteristics and long-term mortality between the two groups were analyzed. Furthermore, we studied the effect of TA on the clinical outcomes of patients grouped according to quartiles of respective D-dimer levels. The primary outcome was all-cause mortality, and the secondary outcomes were new-onset heart failure (HF), rehospitalization, re-PCI, and stroke. Results: In the original cohort, there were no significant differences in all-cause mortality between the TA+PCI and PCI-only groups (hazard ratio, 0.789; 95% confidence interval, 0.556-1.120; p = 0.185). After a mean follow-up of 2.5 years, the all-cause mortality rates of patients in the TA + PCI and PCI-only groups were 8.5 and 16.2%, respectively. Additionally, differences between the two groups in terms of the risk of HF, re-PCI, rehospitalization, and stroke were non-significant. However, after dividing into quartiles, as the D-dimer levels increased, the all-cause mortality rate in the PCI group gradually increased (4.3 vs. 6.0 vs. 7.0 vs. 14.7%, p < 0.001), while the death rate in the TA+PCI group did not significantly differ (4.6 vs. 5.0 vs. 4.0 vs. 3.75%, p = 0.85). Besides, in the quartile 3 (Q3) and quartile 4 (Q4) groups, the PCI-only group was associated with a higher risk of all-cause mortality than that of the TA+PCI group (Q3: 4.0 vs. 7.0%, p = 0.029; Q4: 3.75 vs. 14.7%, p < 0.001). Moreover, the multivariate logistic regression analysis demonstrated that TA is inversely associated with the primary outcome in the Q4 group [odds ratio (OR), 0.395; 95% CI, 0.164-0.949; p = 0.038]. Conclusions: The findings of our real-world study express that routine manual TA during PCI in STEMI did not improve clinical outcomes overall. However, patients with STEMI with a higher concentration of D-dimer might benefit from the use of TA during primary PCI. Large-scale studies are recommended to confirm the efficacy of TA.

Dual-gate MoS2phototransistor with atomic-layer-deposited HfO2as top-gate dielectric for ultrahigh photoresponsivity.

An asymmetric dual-gate (DG) MoS2field-effect transistor (FET) with ultrahigh electrical performance and optical responsivity using atomic-layer-deposited HfO2as a top-gate (TG) dielectric was fabricated and investigated. The effective DG modulation of the MoS2FET exhibited an outstanding electrical performance with a high on/off current ratio of 6 × 108. Furthermore, a large threshold voltage modulation could be obtained from -20.5 to -39.3 V as a function of the TG voltage in a DG MoS2phototransistor. Meanwhile, the optical properties were systematically explored under a series of gate biases and illuminated optical power under 550 nm laser illumination. An ultrahigh photoresponsivity of 2.04 × 105AW-1has been demonstrated with the structure of a DG MoS2phototransistor because the electric field formed by the DG can separate photogenerated electrons and holes efficiently. Thus, the DG design for 2D materials with ultrahigh photoresponsivity provides a promising opportunity for the application of optoelectronic devices.

High-energy x-ray radiation effects on the exfoliated quasi-two-dimensional ß-Ga2O3 nanoflake field-effect transistors.

The effects of x-ray irradiation on the mechanically exfoliated quasi-two-dimensional (quasi-2D) ß-Ga2O3 nanoflake field-effect transistors (FETs) under the condition of biasing voltage were systematically investigated for the first time. It has been revealed that the device experienced two stages during irradiation. At low ionizing doses (<240 krad), the device performance is mainly influenced by the photo-effect and the subsequent persistent photocurrent (PPC) effect as a result of the pre-existing electron traps (e-trap) in the oxides far away from the SiO2/ß-Ga2O3 interface. At larger doses (>240 krad), the device characteristics are dominated by the radiation-induced structural or compositional deterioration. The newly-generated e-traps are found located at the SiO2/ß-Ga2O3 interface. This study shed light on the future radiation-tolerant device fabrication process development, paving a way towards the feasibility and practicability of ß-Ga2O3-based devices in extreme-environment applications.

Fabrication of a Nb-Doped ß-Ga2O3 Nanobelt Field-Effect Transistor and Its Low-Temperature Behavior.

For the first time, we report the successful fabrication of well-behaved field-effect transistors based on Nb-doped ß-Ga2O3 nanobelts mechanically exfoliated from bulk single crystals. The exfoliated ß-Ga2O3 nanobelts were transferred onto a purified surface of the 110 nm SiO2/Si substrate. These Nb-doped devices showed excellent electrical performance such as an ultrasmall cutoff current of ∼10 fA, a high current on/off ratio of >108, and a quite steep subthreshold swing (SS, ∼120 mV/decade). Furthermore, we investigated the temperature dependence down to 200 K, providing insightful information for its operation in a harsh environment. This work lays a foundation for wider application of Nb-doped ß-Ga2O3 in nano-electronics.

Investigation of the Mechanism for Ohmic Contact Formation in Ti/Al/Ni/Au Contacts to ß-Ga2O3 Nanobelt Field-Effect Transistors.

The issue of contacts between the electrode and channel layer is crucial for wide-bandgap semiconductors, especially the ß-Ga2O3 due to its ultra-large bandgap (4.6-4.9 eV). It affects the device performance greatly and thus needs special attention. In this work, the high-performance ß-Ga2O3 nanobelt field-effect transistors with Ohmic contact between multilayer metal stack Ti/Al/Ni/Au (30/120/50/50 nm) and unintentionally doped ß-Ga2O3 channel substrate have been fabricated. The formation mechanism of Ohmic contacts to ß-Ga2O3 under different annealing temperatures in an N2 ambient is systematically investigated by X-ray photoelectron spectroscopy. It is revealed that the oxygen vacancies at the interface of ß-Ga2O3/intermetallic compounds formed during rapid thermal annealing are believed to induce the good Ohmic contacts with low resistance. The contact resistance (Rc) between electrodes and unintentionally doped ß-Ga2O3 reduces to ∼9.3 Ω mm after annealing. This work points to the importance of contact engineering for future improved ß-Ga2O3 device performance and lays a solid foundation for the wider application of ß-Ga2O3 in electronics and optoelectronics.

Low-Temperature One-Step Growth of AlON Thin Films with Homogenous Nitrogen-Doping Profile by Plasma-Enhanced Atomic Layer Deposition.

The AlON film with homogeneous nitrogen-doping profile was grown by plasma-enhanced atomic layer deposition (PEALD) at low temperature. In this work, the precursors of the NH3 and the O2 were simultaneously introduced into the chamber during the PEALD growth at a relatively low temperature of 185 °C. It is found that the composition of the obtained film quickly changes from AlN to Al2O3 when a small amount of O2 is added. Thus, the NH3:O2 ratio should be maintained at a relatively high level (>85%) for realizing the AlON growth. Benefited from the growth method, the nitrogen can be doped evenly in the entire film. Moreover, the AlON films exhibit a lower surface roughness than the AlN as well as the Al2O3 ones. The Al 2p and N 1s X-ray photoelectron spectra show that the AlON film is composed of Al-N, Al-O, and N-Al-O bonds. Moreover, a three-layer construction of the AlON film is proposed through the Si 2p spectra analysis and reconfirmed by the transmission electron microscopy characterization. At last, the electrical and optical tests indicate that the AlON films prepared in this work can be employed as the gate dielectric in transistor application as well as the antireflection layer in photovoltaic application.

Identification of a novel gene, MSAG, regulated by high levels of glucose and insulin.

Identification and characterization of novel genes involved in derangement of metabolisms of glucose and triglycerides are important in understanding the development of metabolic syndrome (MS) and atherosclerosis. Model rats with certain phenotypes of MS were fed a high-carbohydrate diet. The rat hepatic subtracted cDNA libraries were constructed and screened. A novel cDNA of full length was identified by screening of a human hepatic cDNA library with a mixture of probes of the differentially expressed fragments from the rat hepatic subtracted cDNA libraries. The corresponding gene of the cDNA was temporarily named metabolic syndrome-associated gene (MSAG). The predicted protein encoded by MSAG contains 110 amino acids and has a theoretical molecular weight of 11667.04 and an isoelectric point of 4.91. Compared with the housekeeping gene of beta-actin, MSAG had low transcription activity. However, the mRNA level of MSAG in HepG2 cells, a human hepatoma cell line, was significantly increased by glucose and decreased by insulin concentrations higher than physiological levels. These results suggest that MSAG may be involved in the metabolism and/or its regulation of glucose, the functioning of insulin under non-physiological conditions, and further in the development of metabolic syndrome.

[Application of reverse vaccinology in Schistosoma vaccine development: advances and prospects].

OBJECTIVE: Current advances in reverse vaccinology based on the principle of "sequence-structure-function" and such integrated platform technologies as immunoinformatics, computer-aid design, and various high-throughput omics (including genomics, transcriptomics and proteomics) may pave a new way for the discovery of candidate vaccine molecules against schistosomiasis. Both theoretical prediction and experimental approaches conventionally used in the field of reverse vaccinology are briefly introduced in this review; and the applications of these approaches to screening and confirming candidate Schistosoma vaccine molecules are also summarized. Furthermore, potential research prospects of the application of reverse vaccinology to Schistosoma vaccine development are discussed by simulating immune effect mechanisms of immunization with radiation-attenuated cercaria vaccine in animal hosts and naturally acquired immunity in human population.

Relationship between malt qualities and beta-amylase activity and protein content as affected by timing of nitrogen fertilizer application.

The effects of different timing of N fertilizer application at the same rate on grain beta-amylase activity, protein concentration, weight and malt quality of barley were studied. Grain beta-amylase activity and protein concentration were significantly higher in treatments where all top-dressed N fertilizer was applied at booting stage only or equally applied at two-leaf stage and booting stage than in the treatment where all top-dressed N fertilizer was applied at two-leaf age stage only. On the other hand, grain weight and malt extract decreased with increased N application at booting stage. There were obvious differences between barley varieties and experimental years in the grain and malt quality response to the timing of N fertilizer application. It was found that grain protein concentration was significantly and positively correlated with beta-amylase activity, but significantly and negatively correlated with malt extract and Kolbach index. The effect of grain protein concentration on malt quality was predominant over the effect of grain beta-amylase activity.

Protein and hordein fraction content in barley seeds as affected by sowing date and their relations to malting quality.

The effect of sowing date on grain protein, hordein fraction content and malting quality of two-rowed spring barley was investigated by using ten commercial cultivars with different grain protein content and the relationships among these traits were examined. The results showed that grain protein content and B hordein content increased as the sowing date postponed and were significantly affected by sowing date, while C and D hordein contents were less influenced by sowing date. There were significant differences in grain protein and hordein fraction content among the ten cultivars. The coefficient of variation of D hordein content was much larger than that of B and C hordein contents, suggesting its greater variation caused by different sowing dates. Beta-amylase activity and diastatic power were also significantly affected by sowing date, with malt extract being less affected. Significant differences in measured malt quality were found among the ten cultivars. Grain protein was significantly correlated with B hordein and malt extract positively and negatively, respectively. There was no significant correlation between beta-amylase activity or diastatic power and grain protein content. B hordein was negatively and significantly correlated with malt extract, but no significant correlations between C hordein, D hordein and malting quality traits.