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The new xanthine dipeptidyl peptidase-4 inhibitor yogliptin has exhibited excellent hypoglycemic activity in experimental disease models. The present work aimed to assess the efficacy of yogliptin as a monotherapy in individuals with type 2 diabetes mellitus (T2DM).A 12-week, double-blind, placebo-controlled phase II study was performed. T2DM patients (new diagnosis or inadequately controlled) were randomly divided into groups (1:1:1:1) and administered either a placebo or weekly doses of 200, 300, or 400 mg yogliptin, respectively. The primary efficacy end point in this analysis was hemoglobin A1c (HbA1c) change at 12 weeks relative to baseline. Relevant secondary outcomes were also examined, including fasting plasma glucose (FPG), 2 h-postprandial plasma glucose (PPG), body weight, and the rate of individuals who achieved the treatment goal of HbA1c ≤ 7% at 12 weeks from baseline.A total of 81 cases who received either the placebo (20 cases) or 200 (20 cases), 300 (20 cases), or 400 (21 cases) mg yogliptin were examined in the full analysis set. At 12 weeks, changes in HbA1c levels from baseline were 0.17 (-0.22, 0.57) in the placebo group, and -0.75 (-1.15, -0.35), -0.52 (-0.93, -0.11) and -1.02 (-1.41, -0.64) (mean % [95% confidence interval], p .001 vs. placebo) in the 200, 300, and 400 mg yogliptin groups, respectively. From week four, significant improvements in secondary efficacy outcomes among patients administered the yogliptin monotherapy were observed. FPG showed markedly more pronounced reduction after treatment with yogliptin at 200, 300, and 400 mg in comparison with placebo patients at 4, 8, and 12 weeks. At 12 weeks, goal attainment (HbA1c ≤ 7%) was reached in 0%, 20.00%, 15.80%, and 33.33% of the placebo and three Yogliptin dosage groups, respectively. Adverse events were comparable in all groups.This study demonstrated that yogliptin controlled glycemia in Chinese T2DM cases, with a great safety profile. The current findings supported that any of the three doses of yogliptin, administered once a week, could be used for phase III clinical studies.

Advances in femtosecond laser-material interaction facilitate the extension of maskless optical processing to the high efficiency and deep-subwavelength scale. Here, a hybrid plasmon lithography technique has been demonstrated by irradiating near-infrared femtosecond laser pulses onto the Si material coated with thin Cr films in a vacuum chamber, and superior nanograting structures are found to deeply penetrate through the thin Cr film into the underlying Si substrate. In stark contrast to the common ripple structures formed on the Si surface, the Cr-layer mediated Si nanograting structures not only exhibit the spatially super-regular arrangements with a deep-subwavelength period of 355 nm but also present the nonsinusoidal sharp-edged groove geometry with a large depth-to-width aspect ratio of 2.1. Theoretical analyses and calculations reveal that the anomalous structure characterizations are physically ascribed to the excitation of dual-interface coupled plasmons in the thin metal layer, which possess the squeezed spatial wavelength and the periodic columnar intensity distributions. Moreover, the further deepening of periodic nanostructures into the Si substrate is also elucidated by the simulation of electric field enhancements at the bottom of shallow grooves under irradiation of subsequent laser pulses. In combination with a wet etching process, the Si nanograting structures can be modified into the smooth and narrow-mouthed V-profiles, whose optical measurements show a near omnidirectional antireflection especially in the visible range of 565–750 nm, which is expected for the design of advanced photonic devices.

The direct photocurrent detection capability of light orbital angular momentum (OAM) has recently been realized with topological Weyl semimetals, but it is limited to the near-infrared wavelength range. The extension of the direct OAM detection capability to the mid-infrared band, which is a wave band that plays an important role in a vast range of applications, has not yet been realized. This is because the photocurrent responses of most photodetectors are neither sensitive to the phase information nor efficient in the mid-infrared region. In this study, a photodetector based on the type-II Weyl semimetal tantalum iridium telluride (TaIrTe

We present analytic expressions for the electronic contributions to the linear conductivity $\sigma^{(1)}_{3d}(\omega)$ and the third order optical conductivity $\sigma^{(3)}_{3d}(\omega_1,\omega_2,\omega_3)$ of three dimensional massless Dirac fermions, the quasi-particles relevant for the low energy excitation of topological Dirac semimetals and Weyl semimetals. Although there is no gap for massless Dirac fermions, a finite chemical potential $\mu$ can lead to an effective gap parameter, which plays an important role in the qualitative features of interband optical transitions. For gapless linear dispersion in three dimension, the imaginary part of the linear conductivity diverges as a logarithmic function of the cutoff energy, while the real part is linear with photon frequency $\omega$ as $\hbar\omega>2|\mu|$. The third order conductivity exhibits features very similar to those of two dimensional Dirac fermions, i.e., graphene, but with the amplitude for a single Dirac cone generally two orders of magnitude smaller in three dimension than in two dimension. There are many resonances associated with the chemical potential induced gap parameters, and divergences associated with the intraband transitions. The details of the third order conductivity are discussed for third harmonic generation, the Kerr effect and two-photon carrier injection, parametric frequency conversion, and two-color coherent current injection. Although the expressions we derive are limited to the clean limit at zero temperature, the generalization to include phenomenological relaxation processes at finite temperature is straightforward and is presented.

Introduction Different types of ketosis-prone obese diabetic patients are seen in the clinic. At present, the mechanism responsible for ketosis onset in these patients remains unclear, and we do not know how these patients should be optimally treated to prevent recurrent ketosis. Therefore, this study aims to investigate risk factors of ketosis in obese ketosis-prone diabetic (OB-KPD) patients. Methods In an observational case-control study, primary OB-KPD patients [body mass index (BMI) ≥ 28 kg/m2] were selected as the study group (OB-KPD group), and primary obese type 2 diabetes patients served as the control group (OB-T2DM group). Clinical diagnostic assessments of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), blood lipid, area under curve of serum C-peptide (AUCC-P) after steamed bread meal, insulin sensitivity index (ISI), β-hydroxybutyric acid (β-HB) and free fatty acid (FFA) vlaues of the subjects were collected. Subjects in the OB-KPD group were followed up for 1 year to determine the likelihood of insulin therapy cessation and whether ketosis recurred by assessing clinical chemistry parameters at 1-year follow-up. Results Seventy-five subjects were screened, of which 15 were not included in the study for several identified clinical reasons. On enrollment, the OB-KPD group displayed significantly higher FPG, HbA1c and FFA levels than the OB-T2DM group (p

Water-repellent superhydrophobic (SH) surfaces promise a wide range of applications, from increased buoyancy to drag reduction, but their practical use is limited. This comes from the fact that an SH surface will start to lose its efficiency once it is forced into water or damaged by mechanical abrasion. Here, we circumvent these two most challenging obstacles and demonstrate a highly floatable multifaced SH metallic assembly inspired by the diving bell spiders and fire ant assemblies. We study and optimize, both theoretically and experimentally, the floating properties of the design. The assembly shows an unprecedented floating ability; it can float back to the surface even after being forced to submerge under water for months. More strikingly, the assembly maintains its floating ability even after severe damage and piercing in stark contrast to conventional watercrafts and aquatic devices. The potential use of the SH floating metallic assembly ranges from floating devices and electronic equipment protection to highly floatable ships and vessels.

The thermoelectric effects of topological semimetals have attracted tremendous research interest because many topological semimetals are excellent thermoelectric materials and thermoelectricity serves as one of their most important potential applications. In this work, we reveal the transient photothermoelectric response of Dirac semimetallic Cd

openaire: EC/H2020/820423/EU//S2QUIP | openaire: EC/H2020/834742/EU//ATOP | openaire: EC/H2020/965124/EU//FEMTOCHIP All-optical control of nonlinear photonic processes in nanomaterials is of significant interest from a fundamental viewpoint and with regard to applications ranging from ultrafast data processing to spectroscopy and quantum technology. However, these applications rely on a high degree of control over the nonlinear response, which still remains elusive. Here, we demonstrate giant and broadband all-optical ultrafast modulation of second-harmonic generation (SHG) in monolayer transition-metal dichalcogenides mediated by the modified excitonic oscillation strength produced upon optical pumping. We reveal a dominant role of dark excitons to enhance SHG by up to a factor of ∼386 at room temperature, 2 orders of magnitude larger than the current state-of-the-art all-optical modulation results. The amplitude and sign of the observed SHG modulation can be adjusted over a broad spectral range spanning a few electronvolts with ultrafast response down to the sub-picosecond scale via different carrier dynamics. Our results not only introduce an efficient method to study intriguing exciton dynamics, but also reveal a new mechanism involving dark excitons to regulate all-optical nonlinear photonics.

We theoretically investigate the one-color injection currents and shift currents in zigzag graphene nanoribbons by applying a static electric field across the ribbon, which breaks the inversion symmetry to generate nonzero second-order optical responses by dipole interaction. These two types of currents can be separately excited by specific light polarization, circularly polarized lights for injection currents and linearly polarized lights for shift currents. Based on a tight binding model formed by carbon $2{p}_{z}$ orbitals, we numerically calculate the spectra of injection coefficients and shift conductivities, as well as their dependence on the static field strength and ribbon width. The spectra show many peaks associated with the optical transition between different subbands, and the positions and amplitudes of these peaks can be effectively controlled by the static electric field. By constructing a simple two band model, the static electric fields are found to modify the edge states in a nonperturbative way, and their associated optical transitions dominate the current generation at low photon energies. For typical parameters, such as a static field ${10}^{6}$ V/m and light intensity 0.1 GW/${\mathrm{cm}}^{2}$, the magnitude of the injection and shift currents for a ribbon with width of 5 nm can be as large as the order of 1 $\ensuremath{\mu}\mathrm{A}$. Our results provide a physical basis for realizing passive optoelectronic devices based on graphene nanoribbons.

Insulin autoimmune syndrome (IAS) is characterized by the presence of hyperinsulinemia, with high insulin levels and endogenous insulin autoantibody (IAA) in individuals without previous exposure to exogenous insulin1. Drugs composed of sulfhydryl groups have been considered as important factors. Among sulfhydryl-containing compounds, alpha lipoic acid (ALA) has been reported frequently as a potential determinant of IAS 2. Here we describe a case of Chinese woman diagnosed as IAS after using ALA for trigeminal neuralgia.

Objective There is currently no consensus regarding the optimal management of acute suppurative thyroiditis (AST) secondary to pyriform sinus fistula (PSF). To investigate the benefits and adverse events of aspiration with or without lavage for the treatment of AST secondary to PSF. Subjects and methods This was a retrospective analysis of consecutive patients with AST secondary to PSF who were admitted at the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University between August 2012 and December 2018. Clinical information, procedural data, and imaging data were analyzed. Results Seven patients (five women; mean age, 16.9 ± 6.3 years; range, 8-26 years) were included. The patients most presented with anterior neck pain and swelling (n = 7), fever (n = 7), or odynophagia (n = 5). Six cases of AST occurred on the left side of the thyroid and 1 on the right. All patients had thyroid abscess. AST was diagnosed by ultrasound-guided needle aspiration cytology in all cases. PSF was diagnosed during the inflammatory stage in five patients and during the quiescent stage in two. All patients were treated with empiric antibiotics. Needle aspiration without lavage was performed in three cases. Needle aspiration with lavage was performed in four cases. Repeat aspiration was performed in three cases. All patients recovered completely, with no procedure-related complications. During 18.3 ± 7.8 months of follow-up, AST recurred in one case. Excision of the PSF was performed in another case. Conclusion Ultrasound-guided aspiration with or without lavage had a good treatment effect and without adverse events for the management of AST secondary to PSF.

Organolead trihalide perovskites have attracted significant attention for optoelectronic applications due to their excellent physical properties in the past decade. Generally, both grain boundaries in perovskite films and the device structure play key roles in determining the device performance, especially for horizontal-structured device. Here, the first optimized vertical-structured photodetector with the perovskite single crystal MAPbBr3 as the light absorber and graphene as the transport layer is shown. The hybrid device combines strong photoabsorption characteristics of perovskite and high carrier mobility of flexible graphene, exhibits excellent photoresponse performance with high photoresponsivity (≈1017.1 A W-1 ) and high photodetectivity (≈2.02 × 1013 Jones) in a low light intensity (0.66 mW cm-2 ) under the actuations of 3 V bias and laser irradiation at 532 nm. In particular, an ultrahigh photoconductive gain of ≈2.37 × 103 is attained because of fast charge transfer in the graphene and large recombination lifetime in the perovskite single crystal. The vertical architecture combining perovskite crystal with highly conductive graphene offers opportunities to fulfill the synergistic effect of perovskite and 2D materials, is thus promising for developing high-performance electronic and optoelectronic devices.

The linkage of neurodegenerative diseases with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), including oxidative stress, mitochondrial dysfunction, excessive inflammatory responses and abnormal protein processing, and the correlation between cerebrovascular diseases and hyperglycemia has opened a new window for novel therapeutics for these cognitive disorders. Various antidiabetic agents have been studied for their potential treatment of cognitive disorders, among which the dipeptidyl peptidase-4 (DPP-4) inhibitors have been investigated more recently. So far, DPP-4 inhibitors have demonstrated neuroprotection and cognitive improvements in animal models, and cognitive benefits in diabetic patients with or without cognitive impairments. This review aims to summarize the potential mechanisms, advantages and limitations, and currently available evidence for developing DPP-4 inhibitors as a treatment of cognitive disorders.

Graphene is considered a record-performance nonlinear-optical material on the basis of numerous experiments. The observed strong nonlinear response ascribed to the refractive part of graphene’s electronic third-order susceptibility χ(3) cannot, however, be explained using the relatively modest χ(3) value theoretically predicted for the 2D material. Here we solve this long-standing paradox and demonstrate that, rather than χ(3)-based refraction, a complex phenomenon which we call saturable photoexcited-carrier refraction is at the heart of nonlinear-optical interactions in graphene such as self-phase modulation. Saturable photoexcited-carrier refraction is found to enable self-phase modulation of picosecond optical pulses with exponential-like bandwidth growth along graphene-covered waveguides. Our theory allows explanation of these extraordinary experimental results both qualitatively and quantitatively. It also supports the graphene nonlinearities measured in previous self-phase modulation and self-(de)focusing (Z-scan) experiments. This work signifies a paradigm shift in the understanding of 2D-material nonlinearities and finally enables their full exploitation in next-generation nonlinear-optical devices., Graphene enables extraordinary nonlinear-optical refraction, far exceeding predictions based on conventional nonlinear-susceptibility theory. Here, Vermeulen et al. show that rather than the nonlinear susceptibility, a complex saturable refraction process is central to graphene’s unusual behavior.

Materials with massless Dirac fermions can possess exceptionally strong and widely tunable optical nonlinearities. Experiments on graphene monolayer have indeed found very large third-order nonlinear responses, but the reported variation of the nonlinear optical coefficient by orders of magnitude is not yet understood. A large part of the difficulty is the lack of information on how doping or chemical potential affects the different nonlinear optical processes. Here we report the first experimental study, in corroboration with theory, on third harmonic generation (THG) and four-wave mixing (FWM) in graphene that has its chemical potential tuned by ion-gel gating. THG was seen to have enhanced by ~30 times when pristine graphene was heavily doped, while difference-frequency FWM appeared just the opposite. The latter was found to have a strong divergence toward degenerate FWM in undoped graphene, leading to a giant third-order nonlinearity. These truly amazing characteristics of graphene come from the possibility to gate-control the chemical potential, which selectively switches on and off one- and multi-photon resonant transitions that coherently contribute to the optical nonlinearity, and therefore can be utilized to develop graphene-based nonlinear optoelectronic devices., Comment: submitted for publication on August 14th, 2017

Insulin resistance is generally responsible for the pathogenesis of type 2 diabetes mellitus (T2DM). Early growth response proteins-2 (Egr2) has been reported to be able to increase the expression of the suppressors of cytokine signaling-1 (SOCS-1), and impair insulin signaling pathway through suppression of insulin receptor substrates (IRS), including IRS-1 and IRS-2. However, whether Egr2 is directly involved in the development of insulin resistance, and how its potential contributions to insulin resistance still remain unknown. Here, our present investigation found that the expression levels of Egr2 were up-regulated when insulin resistance occurs, and knockdown of Egr2 abolished the effect of insulin resistance in HepG2 cells induced with palmitate (PA). Importantly, inhibition of Egr2 decreased the expression of SOCS-1 as well as reduced phosphorylation of JAK2 and STAT3. And, our data indicated that silencing of Egr2 accelerated hepatic glucose uptake and reversed the impaired lipid metabolism upon insulin resistance. In summary, the present study confirms that Egr2 could deteriorate insulin resistance via the pathway of JAK2/STAT3/SOCS-1 and may shed light on resolving insulin resistance and further the pathogenesis of T2DM.

Single-crystalline hybrid perovskites have important photoelectronic properties for advanced semiconductor devices, such as solar cells and photodetectors. However, neither the surface-enhanced Raman scattering (SERS) property nor the correlation between SERS and photoelectronic properties for single-crystalline perovskites have ever been studied. Here, for the first time, we observed a 105 enhancement in SERS for 4-mercaptopyridine (MPY) adsorbed on a methylamine lead chlorine (MAPbCl3) single crystal. Compared to the Raman spectrum of bulk MPY molecules, the b2 mode of the MPY molecule was selectively enhanced. This is attributed to the charge transfer (CT) resonance mechanism at the interface between the single crystal and the adsorbed molecules, which benefit from the Herzberg–Teller contribution. UV–vis spectra demonstrated that the modification with the MPY molecules leads to the formation of a new interfacial transition state, which matches the excitation laser photon energy and results in a CT res...

Background/Aims: Microbes reside in a number of body sites, including the oral cavity, and are associated with the progression of many systemic diseases. In this study, we aimed to investigate the effects of gout and hyperuricemia (HUA) on the composition of oral microbiomes. Methods: Analysis of the oral microbiota from 12 gout patients, 11 HUA patients, and 19 healthy control subjects was performed using a deep sequencing approach, and validation of significant changes in Prevotella intermedia and Serratia marcescens in new patient cohorts was performed using quantitative PCR (qPCR). Results: Our analysis indicated that both gout and HUA significantly altered the composition of the oral microbiome in patients. Patients with gout or HUA had significantly greater levels of salivary Prevotella intermedia but significantly lower levels of Serratia marcescens than healthy control subjects. Conclusion: We demonstrated the association between the oral microbiome and gout and HUA for the first time. In particular, 16S sequencing and qPCR analysis revealed significantly higher levels of oral Prevotella intermedia in gout/HUA patients, which suggests that these patients might be at risk for the development of periodontitis.

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

Aim The relationship between serum Metrnl levels and visceral fat obesity (VFO) remains unclear. This study aimed to investigate the association between serum Metrnl levels and VFO in Chinese patients with type 2 diabetes. Methods A total of 321 Chinese patients with type 2 diabetes (226 men and 95 postmenopausal women aged 61.4 ± 6.5 years, BMI 25.1 ± 3.2 kg/m2) were evaluated. Serum Metrnl levels were measured by enzyme linked-immunosorbent assay. Visceral fat area (VFA) was quantified via Dual Energy X-ray Absorptiometry (DXA). Correlation analyses were carried out for serum Metrnl levels and VFO. Results VFO groups (VFA ≧100 cm2) have lower serum Metrnl levels than non-VFO groups (VFA Conclusions Serum Metrnl levels were inversely correlated with VFO and may be a useful indicator of VFO in Chinese patients with type 2 diabetes.

In this paper, we demonstrate a simple yet effective hybrid method to fabricate lab-on-a-chip devices on aluminum (Al) foil. Instead of using conventional photoresists and lithography methods, an array of square units is first produced by femtosecond laser direct writing, followed by generating highly ordered anodized aluminum oxide (AAO) nanoporous structures within each unit. The AAO treated area becomes hydrophilic. Next, we functionalize the surrounding area outside the square units to superhydrophobic by electrochemical deposition and further chemical modification. This hydrophilic and hydrophobic pattern allows us to confine the liquid samples to be detected within the hydrophilic AAO detection area. We use rhodamine 6G (R6G) as a probe, and obtain a fluorescence intensity enhancement from R6G by 70 times over a flat surface. This leads to the detection sensitivity of R6G molecules to a concentration as low as 10−17 mol L−1. By mixing R6G with RhB molecules, the fluorescence emission bands shift significantly due to the addition of RhB molecules, showing a significantly improved spectral resolution compared to traditional fluorescence spectrometers for liquid samples. This phenomenon can be attributed to the energy transfer between R6G and RhB under laser excitation, which was enhanced by the AAO nanostructures. The array-based LOC device demonstrated in this paper is simple and convenient to fabricate, has low sample consumption and dramatically enhances the fluorescence yield with improved spectral resolution.

Background Self-monitoring of blood glucose (SMBG) systems are expected to be accurate and provide reliable results. The international standard ISO (International Organization for Standardization) 15197:2013 is widely accepted for the accuracy evaluation for SMBG systems. Accuracy evaluation was performed for 5 different SMBG systems in patients from multi-departments at the hospital. Method A total of 120 patients from Changzhou Second People’s Hospital (Changzhou, China) were randomized and enrolled in the study. Accuracy evaluation was performed for 5 different SMBG systems: Gold AQ (Sinocare), Freestyle Optium Xceed (Abbott), Contour TS (Bayer), OneTouch Ultra (J&J) and Accu-Chek Performa (Roche). For each system, comparison measurements were performed with YSI 2300 STAT PLUS Glucose and Lactate Analyzer and Roche Cobas 8000 Modular Analyzer. Results All 5 systems showed that 100% of results fall within consensus error grid Zones A and B. Compared with YSI 2300 or Roche Cobas 8000 Modular Analyzer, Gold AQ system showed the highest accuracy. The linearity analysis also showed that Gold AQ had the highest correlation coefficient. Conclusion Compared with other SMBG systems, Gold AQ Glucose Monitoring System manufactured by Sinocare Inc. had the highest accuracy in measuring blood glucose level in patients from multi-departments at this hospital.

We theoretically investigate the effects of Coulomb interaction, at the level of the unscreened Hartree-Fock approximation in an equation of motion framework, on third harmonic generation from undoped graphene. The unperturbed electronic states are described by a widely used two-band tight-binding model and the Coulomb interaction is described by the Ohno potential. The ground state is renormalized by taking into account the Hartree-Fock term and the optical conductivities are obtained by numerically solving the equations of motion. The absolute values of conductivity for third-harmonic generation depend on the photon frequency $\mathrm{\ensuremath{\Omega}}$ as ${\mathrm{\ensuremath{\Omega}}}^{\ensuremath{-}n}$ for $\ensuremath{\hbar}\mathrm{\ensuremath{\Omega}}l1$, and then show a peak as $3\ensuremath{\hbar}\mathrm{\ensuremath{\Omega}}$ approaches the renormalized energy of the $M$ point. Taking into account the Coulomb interaction, $n$ is found to be 5.5, which is significantly greater than the value of 4 found with the neglect of the Coulomb interaction. Therefore, the Coulomb interaction enhances third-harmonic generation at low photon energies---for our parameters $\ensuremath{\hbar}\mathrm{\ensuremath{\Omega}}l0.8$ eV---and then reduces it until the photon energy reaches about 2.1 eV. The effect of the background dielectric constant is also considered.

We propose a metasurface-based Lithium Niobate waveguide power splitter with an ultrabroadband and polarization independent performance. The design consists of an array of amorphous silicon nanoantennas that partially converts the input mode to multiple output modes creating multimode interference such that the input power is equally split and directed to two branching waveguides. FDTD simulation results show that the power splitter operates with low insertion loss (< 1dB) over a bandwidth of approximately 800 nm in the near-infrared range, far exceeding the O, E, S, C, L and U optical communication bands. The metasurface is ultracompact with a total length of 2.7 µm. The power splitter demonstrates a power imbalance of less than 0.16 dB for both fundamental TE and TM modes. Our simulations show that the device efficiency exhibits high tolerance to possible fabrication imperfections.

BACKGROUND Whether type 2 diabetes mellitus (T2DM) is independently associated with structural heart abnormalities is controversial because of confounders associated with T2DM. This study aimed to investigate echocardiographic features in patients with newly diagnosed T2DM, exploring changes in cardiac structure and function. MATERIAL AND METHODS This was a retrospective study of new T2DM cases treated at the Second People's Hospital Affiliated to Nanjing Medical University (Changzhou) in 2014-2016. In all, 128 T2DM cases were included (62 hypertensive and 66 non-hypertensive individuals). Controls were selected among individuals who underwent examination at the same department/period. Interventricular septal thickness (IVST), left ventricular end-diastolic diameter (LVEDD), posterior left ventricular wall thickness (PWTD), left ventricle mass (LVM), end-diastolic thickness of left ventricular posterior wall (Dd), aortic root diameter, left atrial diameter (LAd), left atrial diameter fraction-shortening values, and left ventricular ejection fraction (LVEF) were determined routinely. RESULTS IVST, LVEDD, PWTD, Dd, LAd, and left atrial diameter fraction-shortening values were larger in patients with T2DM (all P0.05 vs. controls). LVM was higher in T2DM patients (median, 57.12 vs. 54.77 g, P=0.001). There were no differences in aortic root diameter and EF (both P0.05). Multivariable analysis showed that IVST (OR=1.33, 95% CI: 1.01-1.76, P=0.04), LAd (OR=1.16, 95% CI: 1.07-1.25, P0.001), TGs (OR=1.34, 95% CI: 1.09-1.63, P=0.005), and HDL (OR=1.46, 95% CI: 1.02-2.08, P=0.04) were independently associated with hypertension in patients with T2DM. CONCLUSIONS Patients with newly diagnosed T2DM already display structural heart abnormalities. LAd and IVST are independently associated with hypertension in these patients, probably contributing to increased cardiovascular risk.

AIMS To compare the efficacy and safety of saxagliptin and glimepiride in type 2 diabetes (T2D) patients who are inadequately controlled with metformin monotherapy. MATERIALS AND METHODS In this 48-week, multi-centre, open-label, randomized, parallel trial (NCT02280486, clinicaltrials.gov), a total of 388 T2D patients were randomized 1:1 to saxagliptin or glimepiride groups. The primary endpoint was achievement of HbA1c

We present a theoretical framework for nonlinear optics of graphene and other 2D materials in layered structures. We derive a key equation to find the effective electric field and the sheet current density in the 2D material for given incident light beams. Our approach takes into account the effect of the surrounding environment and characterizes its contribution as a structure factor. We apply our approach to two experimental setups, and discuss the structure factors for several nonlinear optical processes including second harmonic generation, third harmonic generation, and parametric frequency conversion. Our systematic study gives a strict extraction method for the nonlinear coefficients, and provides new insights in how layered structures influence the nonlinear signal observed from 2D materials.

We solve the long-standing discrepancy between the theoretically predicted and experimentally observed performance of nonlinear-optical refraction in graphene. Hereto we study self-phase modulation in silica-core waveguides covered with graphene.

For centrosymmetric materials such as monolayer graphene, no optical second harmonic generation (SHG) is generally expected because it is forbidden under the electric-dipole approximation. Yet we observed a strong, doping induced SHG from graphene, with its highest strength comparable to the electric-dipole allowed SHG in non-centrosymmetric 2D materials. This novel SHG has the nature of an electric-quadrupole response, arising from the effective breaking of inversion symmetry by optical dressing with an in-plane photon wave vector. More remarkably, the SHG is widely tuned by carrier doping or chemical potential, being sharply enhanced at Fermi edge resonances, but vanishing at the charge neutral point that manifests the electron-hole symmetry of massless Dirac Fermions. The striking behavior in graphene, which should also arise in graphene-like Dirac materials, expands the scope of nonlinear optics, and holds the promise of novel optoelectronic and photonic applications., Comment: to appear in PRL

Graphene exhibits extremely strong optical nonlinearity when a strong perpendicular magnetic field is applied, the response current shows strong field dependence even for moderate light intensity, and the perturbation theory fails. We nonperturbatively calculate full optical conductivities induced by a periodic field in an equation-of-motion framework based on the Floquet theorem, with the scattering described phenomenologically. The nonlinear response at high fields is understood in terms of the dressed electronic states, or Floquet states, which is further characterized by the optical conductivity for a weak probe light field. This approach is illustrated for a magnetic field at $5$ T and a driving field with photon energy $0.05$ eV. Our results show that the perturbation theory works only for weak fields $

Diabetic patients have an increased risk of osteoporosis-associated fractures. However, the results of most studies of the effects of diabetes on bone mass in patients with type 2 diabetes (T2DM) have been contradictory. To clarify these conflicting findings, we investigated the effects of diabetic serum on the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs). We used human sera from subjects with different levels of glycemic control to culture the MSCs and induce osteogenic differentiation. The rate of MSC proliferation differed when MSCs were cultured with sera from diabetic subjects with different levels of hyperglycemia. Hyperglycemic sera promoted MSC proliferation to some extent, but all the diabetic sera inhibited the differentiation of MSCs to osteoblasts. The effects of type 2 diabetic sera on the proliferation and osteogenic differentiation of MSCs are closely related to glycemic control. Our data demonstrate the importance of stratifying the study population according to glycemic control in clinical research into diabetic osteoporosis.

We present Fermi's ``golden rule'' calculations of the optical carrier injection and the coherent control of current injection in graphene nanoribbons with zigzag geometry, using an envelope function approach. This system possesses strongly localized states (flat bands) with a large joint density of states at low photon energies; for ribbons with widths above a few tens of nanometers, this system also posses large number of (nonflat) states with maxima and minima close to the Fermi level. Consequently, even with small dopings the occupation of these localized states can be significantly altered. In this work, we calculate the relevant quantities for coherent control at different chemical potentials, showing the sensitivity of this system to the occupation of the edge states. We consider coherent control scenarios arising from the interference of one-photon absorption at $2\ensuremath{\hbar}\ensuremath{\omega}$ with two-photon absorption at $\ensuremath{\hbar}\ensuremath{\omega}$, and those arising from the interference of one-photon absorption at $\ensuremath{\hbar}\ensuremath{\omega}$ with stimulated electronic Raman scattering (virtual absorption at $2\ensuremath{\hbar}\ensuremath{\omega}$ followed by emission at $\ensuremath{\hbar}\ensuremath{\omega})$. Although at large photon energies these processes follow an energy-dependence similar to that of 2D graphene, the zigzag nanoribbons exhibit a richer structure at low photon energies, arising from divergences of the joint density of states and from resonant absorption processes, which can be strongly modified by doping. As a figure of merit for the injected carrier currents, we calculate the resulting swarm velocities. Finally, we provide estimates for the limits of validity of our model.

Atherosclerosis is the main underlying cause of major cardiovascular diseases such as stroke and heart attack. Oxidized phospholipids such as oxidized 1-palmitoyl-2-arachidonoyl-sn-Glycero-3-phosphorylcholine (OxPAPC) accumulate in lesions of and promote atherosclerosis. OxPAPC activates endothelial cells, a critical early event of atherogenesis. Epoxyisoprostane E2 (EI) is an oxidized fatty acid contained at the sn-2 position of 1-palmitoyl-2-epoxyisoprostane E2-sn-glycero-3-phosphorylcholine (PEIPC), the most active component of OxPAPC in regulating inflammation. OxPAPC and its components including PEIPC activate endothelial cells to express an array of genes in different categories including oxidative stress response genes such as tumor suppressor gene OKL38 and Heme oxygenase-1 (HO-1). EI can be released by lipase from PEIPC. In this study, we examined the ability of EI to stimulate oxidative stress response in endothelial cells. EI released from OxPAPC and synthetic EI stimulated the expression of oxidative stress response gene OKL38 and antioxidant gene HO-1. Treatment of endothelial cells with EI increased the production of superoxide. NADPH oxidase inhibitor Apocynin and superoxide scavenger N-acetyl-cysteine (NAC) significantly attenuated EI-stimulated expression of OKL38 and HO-1. We further demonstrated that EI activated oxidative stress-sensitive transcription factor Nrf2. Silencing of Nrf2 with siRNA significantly reduced EI stimulated expression of OKL38 and HO-1. Thus, we demonstrated that EI induced oxidative stress in endothelial cells leading to increased expression of oxidative stress response gene OKL38 and HO-1 via Nrf2 signaling pathway relevant to atherosclerosis.

The existence of large nonlinear optical coefficients is one of the preconditions for using nonlinear optical materials in nonlinear optical devices. For a crystal, such large coefficients can be achieved by matching photon energies with resonant energies between different bands, and so the details of the crystal band structure play an important role. Here we demonstrate that large third-order nonlinearities can also be generally obtained by a different strategy: As any of the incident frequencies or the sum of any two or three frequencies approaches zero, the doped or excited populations of electronic states lead to divergent contributions in the induced current density. We refer to these as intraband divergences, by analogy with the behavior of Drude conductivity in linear response. Physically, such resonant processes can be associated with a combination of inraband and interband optical transitions. Current-induced second order nonlinearity, coherent current injection, and jerk currents are all related to such divergences, and we find similar divergences in degenerate four wave mixing and cross-phase modulation under certain conditions. These divergences are limited by intraband relaxation parameters, and lead to a large optical response from a high quality sample; we find they are very robust with respect to variations in the details of the band structure. To clearly track all of these effects, we analyze gapped graphene, describing the electrons as massive Dirac fermions; under the relaxation time approximation, we derive analytic expressions for the third order conductivities, and identify the divergences that arise in describing the associated nonlinear phenomena., correct some typos in the formulas

MicroRNAs (miRNAs) regulate posttranscriptional gene expression usually by binding to 3′-untranslated regions (3′UTRs) of target message RNAs (mRNAs). Previous studies have demonstrated that SNPs within miRNA target sites could modulate miRNA–mRNA interaction to affect the regulation of target genes and the individual's diseases. So far, little is known about the relationship of miRNA binding site polymorphisms with the risk of metabolic syndrome (MetS) in the general population. Therefore, we conducted a case–control study in Chinese Han population to evaluate the association between SNPs within miRNA binding sites and risk of MetS. 8 SNPs in miRNA binding sites with a minor allele frequency (MAF) of ≥ 0.05 in the Chinese Han population were selected by bioinformatics software. TaqMan ®assay was performed to test the genotypes in MetS patients (n = 1026) and normal controls (n = 1032). We found rs5750146 (adjusted odds ratio (OR) = 1.24 for GA/AA, P = 0.023, compared with GG), rs5999924 (adjusted OR = 1.22 for AT/TT, P = 0.038, compared with AA) in the APOL6 3′UTR were identified to correlate with MetS in the total sample and females. Rs11724758 (adjusted OR = 0.65 for AA, P = 0.002, compared with GG) in the FABP2 3′UTR was found to correlate with MetS in the total sample and males. Correlations between FABP2 rs11724758 polymorphisms and components of MetS reveal that high-density lipoprotein cholesterol (HDL-c) levels are significantly higher in FABP2 rs11724758 AA genotype carrier compared with noncarriers, whereas triglycerides (TG) and fasting plasma glucose (FG) were to be significantly lower in the AA genotype carrier. These findings indicate that these three polymorphisms which located at the predicted miRNAs binding sites were identified to contribute to susceptibility to MetS in the Chinese Han population.

We experimentally demonstrate a negative Kerr nonlinearity for quasiundoped graphene. Hereto, we introduce the method of chirped-pulse-pumped self-phase modulation and apply it to graphene-covered silicon waveguides at telecom wavelengths. The extracted Kerr-nonlinear index for graphene equals n(2,gr) = -10(-13) m(2) = W. Whereas the sign of n(2,gr) turns out to be negative in contrast to what has been assumed so far, its magnitude is in correspondence with that observed in earlier experiments. Graphene's negative Kerr nonlinearity strongly impacts how graphene should be exploited for enhancing the nonlinear response of photonic (integrated) devices exhibiting a positive nonlinearity. It also opens up the possibility of using graphene to annihilate unwanted nonlinear effects in such devices, to develop unexplored approaches for establishing Kerr processes, and to extend the scope of the "periodic poling" method often used for second-order nonlinearities towards third-order Kerr processes. Because of the generic nature of the chirped-pulse-pumped self-phase modulation method, it will allow fully characterizing the Kerr nonlinearity of essentially any novel (2D) material.

Summary Objective To investigate exenatide, a GLP-1 analogue, compared with acarbose, for intra-abdominal fat reduction in patients with obesity and type-2 diabetes. Methods This randomized controlled trial included 36 patients with obesity and type-2 diabetes, who were metformin-unresponsive, receiving metformin/exenatide (GLP-1 group) or metformin/acarbose (control group) for 3 months. Primary end-point: intra-abdominal fat content from baseline to 3 months; Secondary end-points: changes in fasting blood glucose, glycated haemoglobin (HbAlc), fasting insulin, blood lipids, weight, body mass index, and inflammatory cytokines from baseline to 3 months. Results Intra-abdominal fat content decreased in the GLP-1 group from baseline to 3 months (17,947±5804; 13,717±3628mm 2 , P=0.001, respectively), but was not significantly reduced in the control group (P=0.197) and at 3 months post-treatment, it was significantly lower in the GLP-1 group than control group (P=0.043). Glucose control, measured by HbA1c (GLP-1: 9.72±1.38; 7.09±0.60%, P Conclusion Combined exenatide/metformin reduced intra-abdominal fat content, and enhanced insulin resistance and inflammatory status in patients with obesity and type-2 diabetes, representing a novel treatment regimen.