Efficacy and safety of generic exenatide injection in Chinese patients with type 2 diabetes: a multicenter, randomized, controlled, non-inferiority trial.

AIMS: This study aimed to compare the efficacy and safety of generic exenatide with branded exenatide Byetta® in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues. METHODS: A multicenter, randomized, controlled, non-inferiority trial was performed. A total of 240 patients with T2DM and glycated hemoglobin (HbA1c) ≥ 7% (53 mmol/mol) to ≤ 9.0% (75 mmol/mol) on monotherapy or combination therapy of metformin and insulin secretagogues for at least 3 months were randomized into generic exenatide or branded exenatide groups with a 1:1 ratio for 16 weeks of treatment. The primary endpoint was the change in HbA1c levels from baseline at week 16, with a non-inferiority margin of - 0.35% (- 3.83 mmol/mol) (lower bound of one-sided 95% confidence interval (CI) > - 0.35% (- 3.83 mmol/mol)). Secondary endpoints included the proportion of participants achieving HbA1c < 7% (53 mmol/mol), the changes in fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG) following a standard meal, 7-point self-monitoring blood glucose (SMBG) profiles, body weight change from baseline at week 16 and the change in HbA1c levels from baseline at week 8. Safety issues were also evaluated. RESULTS: After 16 weeks of treatment, HbA1c levels decreased significantly from baseline in the two groups, with a reduction of - 1.10% ± 1.31% (- 12.0 mmol/mol ± 14.3 mmol/mol) in the generic exenatide group and - 1.08% ± 1.11% (- 11.8 mmol/mol ± 12.1 mmol/mol) in the branded exenatide group (both P < 0.001). The least-squares mean difference of HbA1c reduction between the two groups was - 0.03% (- 0.33 mmol/mol), with a lower one-sided 95% CI limit of - 0.27% (- 2.95 mmol/mol), which was higher than the prespecified non-inferiority margin of - 0.35% (- 3.83 mmol/mol). Moreover, there were no significant differences in the proportion of participants achieving HbA1c < 7% (53 mmol/mol) and the changes in FPG, 2hPG, 7-point SMBG profiles and body weight at week 16 and the change in HbA1c levels from baseline at week 8 (all P > 0.05) between the two groups. The incidence of adverse events, including the incidence of hypoglycemia (18.3% and 17.5%, respectively), was similar for the generic and branded exenatide groups (P > 0.05). CONCLUSIONS: In patients with T2DM inadequately controlled on monotherapy or combination therapy of metformin and insulin secretagogues, add-on treatment with generic exenatide demonstrated non-inferiority to branded exenatide in terms of improvements in HbA1c after 16 weeks of treatment. Furthermore, the two drugs were also similar for other efficacy endpoints and safety profile. Trial registration Chinese Clinical Trial Registry: ChiCTR-IPR-15006558, Date registered May 27, 2015.

Organs Distribution and Injury After Repeated Intratracheal Instillations of Nano-In2O3 Particles into the Lungs of Wistar Rats.

Elevated industrial production and broaden applications of indium oxide materials have increased concerns over the occupational exposure of industry workers. Respirable In2O3 particles have been identified in the workplaces and lung of indium-processing workers. The aim of this study was to assess the indium distribution in vivo and organs injury induced by nano-In2O3 particles. More than 50% of nano-In2O3 particles were accumulated in the lungs after 8-week exposure period and caused serious pulmonary alveolar proteinosis (PAP) and pneumonia. The migration of nano-In2O3 particles from lungs to the other organs was very low and dose not steadily increase the indium burden in those organs except kidney and liver. The repeated intratracheal instillations of nano-In2O3 particles into the lungs of Wistar rats were dose-dependent increased the concentrations of serum indium.

Pressure-induced enhancement in the thermoelectric properties of monolayer and bilayer SnSe2.

The electronic structures of monolayer and bilayer SnSe2 under pressure were investigated by using first-principles calculations including van der Waals interactions. For monolayer SnSe2, the variation of electronic structure under pressure is controlled by pressure-dependent lattice parameters. For bilayer SnSe2, the changes in electronic structure under pressure are dominated by intralayer and interlayer atomic interactions. The n-type thermoelectric properties of monolayer and bilayer SnSe2 under pressure were calculated on the basis of the semi-classical Boltzmann transport theory. It was found that the electrical conductivity of monolayer and bilayer SnSe2 can be enhanced under pressure, and such dependence can be attributed to the pressure-induced changes of the Se-Sn antibonding states in conduction band. Finally, the doping dependence of power factors of n-type monolayer and bilayer SnSe2 at three different pressures were estimated, and the results unveiled that thermoelectric performance of n-type monolayer and bilayer SnSe2 can be improved by applying external pressure. This study benefits to understand the nature of the transport properties for monolayer and bilayer SnSe2 under pressure, and it offers valuable insight for designing high-performance thermoelectric few-layered SnSe2 through strain engineering induced by external pressure.

Exenatide enhances INS-1 rat pancreatic ß­cell mass by increasing the protein levels of adiponectin and reducing the levels of C-reactive protein.

Type 2 diabetes mellitus (T2DM) is a complex and heterogeneous disorder affecting >220 million individuals worldwide; this is projected to reach 366 million by 2030. Exenatide, a long­acting glucagon­like peptide 1 receptor agonist, exhibits potential in the treatment of T2MD due to its ability to increase ß­cell mass. However, the molecular mechanism by which exenatide increases ß­cell mass is yet to be elucidated. Exenatide function was explored in the INS­1 rat pancreatic ß­cell line. Exenatide was found to increase adiponectin protein levels by 20% (P<0.05 versus the control group) and reduce the level of C­reactive protein (CRP) by 50% (P<0.01 versus the control group) in INS­1 cells, resulting in an increase in the INS­1 rat pancreatic ß­cell mass by 20% (P<0.01 versus the control group). These findings suggest that exenatide may ameliorate T2DM by increasing adiponectin protein levels and reducing the level of CRP.

Second-order nonlinearity in triangular lattice perforated gold film due to surface plasmas resonance.

We have studied the excitation second-order nonlinearity through a triangular lattice perforated gold film instead of square lattice in many papers. Under the excitation of surface plasmas resonance effect, the second order nonlinearity exists in the noncentrosymmetric split-ring resonators arrays. Reflection of fundamental frequency wave through a triangular lattice perforated gold film is obtained. We also described the second harmonic conversion efficiencies in the second order nonlinear optical process with the spectra. Moreover, the electric field distributions of fundamental frequency above the gold film region are calculated. The light propagation through the holes results in the enhancement of the second order nonlinearity including second harmonic generation as well as the sum (difference) frequency generation.

[Synthesis and white light emission upconversion of Tm3+, Ho3+, Yb3+ co-doped YPO4 micro-nano tubes].

Tm3+, Ho3+, Yb3+ co-doped YPO4 micro-nano tubes were synthesized by hydrothermal method. Under the 980 nm near infrared (NI) excitation, the micro-nano tubes emitted red, green, blue visible light and a near infrared emission centered at 795 nm. The optical properties and structure of the synthesized Tm3+, Ho3+, Yb3+ co-doped YPO4 micro-nano tubes were characterized by testing the TEM, XRD and fluorescence spectra. The results showed that the micro-nano tubes are pure hexagonal phase. The hydrothermal temperature had obvious effect on fluorescence spectra but little effect on phase. The intensity of the emission peaks didn't increase with the concentration of doping ions monotonously under the same reaction temperature, but changed non-monotonously due to the concentration quenching and cross relation. The possible upconversion (UC) mechanism was discussed in this paper. This UC emission intensity controllable fluorescent material has potential application in three dimension solid display, UC illumination, fluorescence detection and some other fields.

[Research on the photoelectric conversion efficiency of grating antireflective layer solar cells].

A numerical investigation of the effect of grating antireflective layer structure on the photoelectric conversion efficiency of solar cells was carried out by the finite-difference time-domain method. The influence of grating shape, height and the metal film thickness coated on grating surface on energy storage was analyzed in detail. It was found that the comparison between unoptimized and optimized surface grating structure on solar cells shows that the optimization of surface by grating significantly increases the energy storage capability and greatly improves the efficiency, especially of the photoelectric conversion efficiency and energy storage of the triangle grating. As the film thickness increases, energy storage effect increases, while as the film thickness is too thick, energy storage effect becomes lower and lower.

Evaluation of the potential cytotoxicity of metals associated with implanted biomaterials (II).

The effects of metal ions on the cell DNA and RNA synthetic functions and the destruction of cell defensive system caused by metal ions were studied on the investigation of the effects of metal ions on cell alkaline phosphatase (ALP) activity and cell metabolism ability. The poisonous behaviours of metal ions [Cr (VI), Ni, V, Cr (III), Ag, and Al] on living tissue were both quantitatively and qualitatively measured. It was shown that Cr (VI) has a notable action on both cellular DNA and RNA synthetic functions, and following that, were Ni, V. The limitation action of Cr (III) on the synthetic abilities of DNA and RNA increased with the increase of Cr (III) concentration. Different to other five metal ions, the limitation of Al ion on RNA was greater than that on DNA. The limitation of V, Ag ions on DNA was same to that on RNA. Trace Cr (VI), in culture medium resulted in the decreasing of GSH in living tissue. Similar to that, a little higher Ni ion concentration seriously reduced the GSH content in living tissue. It was suggested that Cr (VI), Ni, might destroy and/or disturb the orientation of the microtubulin in cell skeleton. For other four metal ions, together with increasing the concentration in culture medium, the osmotic pressure increased. Consequently, more metal ions entered cell membrane, more GSH were lost in cell.

Template-free method to prepare polymer nanocapsules embedded with noble metal nanoparticles.

In this paper, polymer nanocapsules embedded with noble metal nanoparticles and showing a good catalytic activity were prepared by a novel and convenient method.