Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Metasurface photoelectrodes for enhanced solar fuel generation

Tailoring optical properties in photocatalysts by nanostructuring them can help increase solar light harvesting efficiencies in a wide range of materials. Whereas plasmon resonances are widely employed in metallic catalysts for this purpose, latest advances of nonradiative, dielectric nanophotonics also enable light confinement and enhanced visible light absorption in semiconductors. Here, a design procedure for large-scale nanofabrication of semiconductor photoelectrodes using imprint lithography is developed. Anapole excitations and metasurface lattice resonances are combined to enhance the absorption of the model material, amorphous gallium phosphide (a-GaP), over the visible spectrum. It is shown that cost-effective, high sample throughput is achieved while retaining the precise signature of the engineered photonic states. Photoelectrochemical measurements under hydrogen evolution reaction conditions and sunlight illumination reveal the contributions of the respective resonances and demonstrate an overall photocurrent enhancement of 5.7, compared to a planar film. These results are supported by optical and numerical analysis of single nanodisks and of the upscaled metasurface.https://onlinelibrary.wiley.com/doi/10.1002/aenm.20210287

Strong polarization dependent nonlinear excitation of a perovskite nanocrystal monolayer on a chiral dielectric nanoantenna array

With their unique optoelectronic properties, perovskite nanocrystals are highly advantageous semiconductor materials for tailored light applications including an interaction with circularly polarized light. Although chiral perovskite nanocrystals have been obtained by the adsorption of chiral molecules, their chiroptical response is still intrinsically weak. Alternatively, perovskites have been combined with artificial chiral surfaces demonstrating enhanced chiroptical responses. However, bulk perovskite films of considerable thickness were required, mitigating the perovskite’s photoluminescence efficiency and processability. Here we developed a hybrid system of a dielectric chiral nanoantenna array that was coated with a monolayer of cubic all-inorganic lead halide perovskite nanocrystals. By tuning the thickness of the perovskite film down to one monolayer of nanocrystals, we restricted the interactions exclusively to the near-field regime. The chiral surface built of z-shaped Si nanoantennas features pronounced chiral resonances in the visible to IR region. We demonstrate that the two-photon excited photoluminescence emission of the nanocrystals can be enhanced by up to one order of magnitude in this configuration. This emission increase is controllable by the choice of the excitation wavelength and polarization with an asymmetry in emission of up to 25% upon left and right circularly polarized illumination. Altogether, our findings demonstrate a pathway to an all-optical control and modulation of perovskite light emission via strong polarization sensitive light–matter interactions in the near-field, rendering this hybrid system interesting for sensing and display technologies

Permittivity-asymmetric quasi-bound states in the continuum.

Breaking the in-plane geometric symmetry of dielectric metasurfaces allows us to access a set of electromagnetic states termed symmetry-protected quasi-bound states in the continuum (qBICs). Here we demonstrate that qBICs can also be accessed by a symmetry breaking in the permittivity of the comprising materials. While the physical size of atoms imposes a limit on the lowest achievable geometrical asymmetry, weak permittivity modulations due to carrier doping, and electro-optical Pockels and Kerr effects, usually considered insignificant, open the possibility of infinitesimal permittivity asymmetries for on-demand, dynamically tunable resonances of extremely high quality factors. As a proof-of-principle, we probe the excitation of permittivity-asymmetric qBICs (ε-qBICs) using a prototype Si/TiO2 metasurface, in which the asymmetry in the unit cell is provided by the permittivity contrast of the materials. ε-qBICs are also numerically demonstrated in 1D gratings, where quality-factor enhancement and tailored interference phenomena of qBICs are shown via the interplay of geometrical and permittivity asymmetries

Glucosamine as carbon source for amino acid-producing Corynebacterium glutamicum

Uhde A, Youn J-W, Maeda T, et al. Glucosamine as carbon source for amino acid-producing Corynebacterium glutamicum. Applied Microbiology and Biotechnology. 2013;97(4):1679-1687

Transcriptome analysis of thermophilic methylotrophic Bacillus methanolicus MGA3 using RNA-sequencing provides detailed insights into its previously uncharted transcriptional landscape

BACKGROUND: Bacillus methanolicus MGA3 is a thermophilic, facultative ribulose monophosphate (RuMP) cycle methylotroph. Together with its ability to produce high yields of amino acids, the relevance of this microorganism as a promising candidate for biotechnological applications is evident. The B. methanolicus MGA3 genome consists of a 3,337,035 nucleotides (nt) circular chromosome, the 19,174 nt plasmid pBM19 and the 68,999 nt plasmid pBM69. 3,218 protein-coding regions were annotated on the chromosome, 22 on pBM19 and 82 on pBM69. In the present study, the RNA-seq approach was used to comprehensively investigate the transcriptome of B. methanolicus MGA3 in order to improve the genome annotation, identify novel transcripts, analyze conserved sequence motifs involved in gene expression and reveal operon structures. For this aim, two different cDNA library preparation methods were applied: one which allows characterization of the whole transcriptome and another which includes enrichment of primary transcript 5′-ends. RESULTS: Analysis of the primary transcriptome data enabled the detection of 2,167 putative transcription start sites (TSSs) which were categorized into 1,642 TSSs located in the upstream region (5′-UTR) of known protein-coding genes and 525 TSSs of novel antisense, intragenic, or intergenic transcripts. Firstly, 14 wrongly annotated translation start sites (TLSs) were corrected based on primary transcriptome data. Further investigation of the identified 5′-UTRs resulted in the detailed characterization of their length distribution and the detection of 75 hitherto unknown cis-regulatory RNA elements. Moreover, the exact TSSs positions were utilized to define conserved sequence motifs for translation start sites, ribosome binding sites and promoters in B. methanolicus MGA3. Based on the whole transcriptome data set, novel transcripts, operon structures and mRNA abundances were determined. The analysis of the operon structures revealed that almost half of the genes are transcribed monocistronically (940), whereas 1,164 genes are organized in 381 operons. Several of the genes related to methylotrophy had highly abundant transcripts. CONCLUSION: The extensive insights into the transcriptional landscape of B. methanolicus MGA3, gained in this study, represent a valuable foundation for further comparative quantitative transcriptome analyses and possibly also for the development of molecular biology tools which at present are very limited for this organism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1239-4) contains supplementary material, which is available to authorized users