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This study aimed to evaluate the efficacy and safety of dapagliflozin as a monotherapy glucose-lowering drug treatment for older adults with diabetes. Randomized controlled trial reports were retrieved from PubMed, Embase Cochrane Library, and Web of Science from database inception to 8 May 2021. Publication bias and heterogeneity were assessed using the Cochrane risk-of-bias tool and the Cochrane Q statistic, respectively. Compared with placebo, dapagliflozin as a monotherapy glucose-lowering drug did improve the control of glycosylated hemoglobin and fasting plasma glucose levels in older adults. Our analysis also confirmed that the body weight of older adults was well controlled under treatment of dapagliflozin as a monotherapy glucose-lowering drug. Patients in older adults with diabetes took a higher risk of genital infection and renal impairment or failure after treatment of dapagliflozin. In addition, treatment with dapagliflozin reduced the risk of hypoglycemia, and did not reveal increased risk of urinary tract infection and developing fractures compared to placebo in older adults. Dapagliflozin as a monotherapy glucose-lowering drug appeared to be an effective treatment for older adults with diabetes, although it might increase risk of genital infection and renal impairment or failure.

Osimertinib is the only third-generation epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI) approved by Food and Drug Administration (FDA). This study aimed to know the inhibitory effect of osimertinib on human UDP-glucosyltransferases (UGTs) and human liver microsomes (HLMs), as well as to identify its potential to cause drug-drug interaction (DDI) arising from the modulation of UGT activity. High inhibitory effect of osimertinib was shown towards UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A10, 2B7 and 2B15. Especially, osimertinib exhibited competitive inhibition against UGT1A1 with a Ki,u of 0.87 ± 0.12 μM. It also noncompetitively inhibited SN-38 glucuronidation in pooled HLMs with a Ki,u of 3.32 ± 0.25 μM. Results from quantitative prediction study indicated that osimertinib administered at 80 mg/day may result in a 4.83 % increase in the AUC of drugs mainly metabolized by UGT1A1, implying low risk of DDI via liver metabolism. However, the ratios of [I]gut/Ki,u are much higher than 11 in HLMs and recombinant UGT1A1, indicating a risk for interaction in intestine. The effects of osimertinib on intestinal UGT should be paid more attention on to avoid unnecessary clinical DDI risks.

Quantification of endogenous steroids and their precursors is essential for diagnosis of a wide range of causes for female infertility. However, immunoassays often overestimate concentrations due to assay interference by other endogenous steroids, especially at low concentrations. In addition, it still lacks of diagnostic reference intervals for five sex steroid hormones, including estradiol (Esub2/sub), 11-deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OHPsub4/sub), pregnenolone (Psub5/sub) and progesterone (Psub4/sub), which are crucial for distinguishing between normal individuals and female infertility. Therefore, we developed and validated a reliable and rapid ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination and quantification of five sex hormones, giving the reference intervals to accurately evaluate and diagnose female infertility. Our results showed that the developed UPLC-MS/MS assay was fast, high throughput, reproducible, specific, accurate, highly sensitive, and fully validated for simultaneous determination of Psub5/sub, Psub4/sub, 17-OHPsub4/sub, DOC and Esub2/subin human follicular fluid. The simple sample preparation procedure in the current study gave reproducible and consistent recoveries. The validation results show that the UPLC-MS/MS assay has acceptable accuracy and precision at low concentrations, which permits their use in clinical study. In addition, our data gave the concentration range of five steroid hormones quantification in patients with female infertility and normal individuals. Our data can be used to accurately evaluate and diagnose female infertility.

Resonance, a natural phenomenon, is a fundamental physical property of any object [...]

We have reported the comparison of thermoelectric properties of Zn2GeO4 samples grown on ITO and Au coated Si substrates. Mixed powder of Zn and Ge with 1:1 ratio was evaporated in the tube furnace on ITO and Si substrates using identical experimental conditions. After growth, as grown samples were annealed at different temperatures in oxygen environment. Seebeck and Hall data suggested that the sample grown on Au coated Si substrate (Au/Si) has higher values of electromotive force, electrical conductivity and power factor as compared to sample grown on ITO substrate, because the sample grown on Au/Si substrate has high density of secondary phases. The presence of secondary phases resulted in the enhancement of Seebeck coefficient and mobility of charge carriers. It is also observed that thermoelectric properties of Zn2GeO4 samples were also improved due to increased of annealing temperature due the emergence of cracks and secondary phases in the annealed samples. This argument was further supported by various characterizations tools. XRD data confirmed the formation of Zn2GeO4 crystal along with the generation of new phases as the annealing temperature increased up to 900 °C. Furthermore, XRD data demonstrated that the sample grown on Au/Si has prominent Zn2GeO4 phases but the sample grown on ITO substrate has weak Zn2GeO4 peak along with ZnO phases. SEM images demonstrated the generation of cracks on the surface of Zn2GeO4 with annealing temperature due to thermal stress. Raman spectroscopy measurements also supported the XRD and SEM results.

Hybrid nanostructures, comprising of a metal core and a semiconductor shell layer, show great potential for a new generation of low-cost solar cells due to their unique electronic and optical properties. However, experimental results have fallen far short of the ultra-high efficiency (i.e. beyond Shockley-Queisser limit) predicted by theoretical simulations. This limits the commercial application of these materials. Here, a non-transparent organic solar cell with an array of Ag/ZnO nanowires has been experimentally fabricated to increase the internal quantum efficiency (IQE) by a factor of 2.5 compared to a planar counterpart. This result indicates a significant enhancement of charge collection efficiency due to the ultrafast Ag nanowire channels. This hybrid nanostructure can also serve as a perfect back reflector for semi-transparent solar cells, which can result in enhanced light absorption by a factor of 1.8 compared to the reference samples. The enhanced charge collection and light absorption can make these Ag/ZnO nanostructures available for the application of modern optoelectronic devices. Keywords: Vertically aligned nanowires, Silver, Core-shell, Charge collection efficiency, Light harvesting, Semi-transparent organic solar cells

Objectives: To assess the efficiency and safety profiles of levetiracetam and (fos)phenytoin (phenytoin or fosphenytoin) for second-line treatment of seizures by performing a meta-analysis of RCTs. Methods: We systematically searched PubMed, Embase, Cochrane, FDA.gov, and ClinicalTrials.gov for RCTs (published before July 31, 2020; no language restrictions). Two independent reviewers screened abstracts and titles against inclusion and exclusion criteria published previously in the PROSPERO: CRD42020202736. Eleven studies fulfilled the established criteria. We assessed pooled data by using a random-effects model. Quality analysis was performed by using version 2 of the Cochrane risk-of-bias tool (RoB 2). RevMan v.5.3 was used to perform statistical analyses, and publication bias (egger's test) was assessed with Stata MP v.14.0. Results: Levetiracetam was similar to (fos)phenytoin in seizure termination rate (risk ratio [RR] 0.94; 95% CI 0.87 to 1.01), time of seizure termination (mean difference [MD] 0.44; -0.60 to 1.49), and drug resistance ([RR] 1.12, 0.86 to 1.45). The safety outcome showed a significant statistical difference between fosphenytoin group and levetiracetam group ([RR] 1.44, 1.14 to 1.81), while there was no significant difference observed between phenytoin treatment and levetiracetam treatment ([RR] 1.26, 0.99 to 1.60). Conclusion: Levetiracetam was similar to (fos)phenytoin in cessation rate convulsive status epilepticus, and drug resistance, while it was superior (fos)phenytoin in pooled safety outcome. Further exploration is still needed as to whether it is the first choice for second-line drugs.

Background: The survival of patients with chronic myeloid leukemia (CML) has improved substantially in the last decade with the development of BCR-ABL tyrosine kinase inhibitors (BCR-ABL TKIs). However, clinically apparent liver disease and even death has been found with the treatment of ponatinib, and serious cases of liver injury were also associated with imatinib, nilotinib and dasatinib. The aim of this systematic review and meta-analysis was to compare the relative risk (RR) of hepatotoxicity of new-generation BCR-ABL TKIs with that of imatinib, and to provide an overall assessment of the clinical benefit. Methods: Two independent investigators selected citations and clinical trials from PubMed, Embase, Cochrane library databases and clinicaltrials.gov from January 2000 to April 2020 to include RCTs comparing four new-generation BCR-ABL TKIs (dasatinib, bosutinib, nilotinib and ponatinib) with the first generation BCR-ABL TKI imatinib. Data extracted included study characteristics, baseline patient information, interventions and data on all grades and high grades alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, overall survival (OS), and major molecular response (MMR). The relative risk (RR) and 95% confidence interval (CI) were calculated using the inverse variance method. Findings: Nine trials involving 3475 patients were analyzed. Increased risks were observed for each new-generation TKI except for dasatinib. The pooled RRs of all grades ALT and grade 3-4 ALT elevation were 2.89 (95% CI 1.78-4.69; P

16 pags., 11 figs., Plasmonic metamaterials enable extraordinary manipulation of key constitutive properties of light at a subwavelength scale and thus have attracted significant interest. Here, we report a simple and convenient nanofabrication method for a novel meta-device by glancing deposition of gold into anodic aluminum oxide templates on glass substrates. A methodology with the assistance of ellipsometric measurements to examine the anisotropy and optical activity properties is presented. A tunable polarization conversion in both transmission and reflection is demonstrated. Specifically, giant broadband circular dichroism for reflection at visible wavelengths is experimentally realized by oblique incidence, due to the extrinsic chirality resulting from the mutual orientation of the metamaterials and the incident beam. This work paves the way for practical applications for large-area, low-cost polarization modulators, polarization imaging, displays, and bio-sensing., Beijing Municipal Commission of Education (BJJWZYJH01201910007022); National Natural Science Foundation of China (61775019).

Cancer therapy with tyrosine kinase inhibitors (TKIs) is a rapidly developing field, and several TKIs have been reported to have an impact on the activities of UDP-glucosyltransferases (UGTs), implying a potential risk for drug-drug interaction (DDI). Herein, we investigated the inhibitory effects of two commonly used TKIs, midostaurin and ruxolitinib, on human UGTs and quantitatively evaluated their DDI potential via UGT inhibition. It was found that midostaurin was a potent inhibitor of the majority of human UGTs, including UGT1A3, 1A4, 1A7, 1A8, 1A9, 1A10, 2B7, 2B15, and 2B17, with IC50 values lower than 4 μM (IC50 0.0128-3.85 μM), while ruxolitinib exhibited weak inhibition towards the activity of almost all the tested UGT isoforms. Furthermore, based on reversible inhibition, the co-administration of midostaurin at the clinical available dose was predicted to increase the plasma exposure to sensitive UGT1A3, 1A7, and 1A8 substrates by at least 61.4%, 25.6%, and 651%, respectively. In summary, our data identify that midostaurin is a potent inhibitor of the majority of human UGTs and may bring a potential risk of DDI via inhibition against UGT1A3, 1A7, and 1A8, while ruxolitinib cannot trigger UGT-mediated DDI due to its weak inhibition towards UGTs.

Importance Although BCR-ABL fusion oncoprotein tyrosine kinase inhibitors (BCR-ABL TKIs) can substantially improve the survival rate of chronic myeloid leukemia (CML), they are clinically accompanied by severe hepatotoxicity. Objective To compare the relative risk (RR) of hepatotoxicity of new-generation BCR-ABL TKIs with that of imatinib, and to provide an overall assessment of the clinical benefit. Data Sources PubMed, Embase, Cochrane library databases, and ClinicalTrials.gov were searched for clinical trials published between January 2000 and April 2020. Study Selection Study selection was conducted independently by 2 investigators according to the inclusion and exclusion criteria published previously in the protocol: only randomized phase 2 or phase 3 clinical trials that compared bosutinib, dasatinib, nilotinib, or ponatinib with imatinib were included. Among the 2666 records identified, 9 studies finally fulfilled the established criteria. Data Extraction and Synthesis Two investigators extracted study characteristics and data independently using a standardized data extraction form. Data were extracted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. When substantial heterogeneity was observed, pooled estimates were calculated based on the random-effect model; otherwise, the fixed-effect model was used. Main Outcomes and Measures Data extracted included study characteristics, baseline patient information, interventions and data on all-grade and high-grade (grades 3 and 4) elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, overall survival, and major molecular response (MMR). The RRs and 95% CIs were calculated using the inverse variance method. Results Nine trials involving 3475 patients were analyzed; the median (range) age was 49 (18-91) years; 2059 (59.2%) were male patients. Increased risks were observed for each new-generation TKI except for dasatinib. Patients receiving new-generation TKIs were more likely to experience all grades of ALT elevation (pooled RR, 2.89; 95% CI, 1.78-4.69;P Conclusions and Relevance When compared to imatinib, bosutinib, nilotinib, and ponatinib had higher relative risks of hepatotoxicity. Treatment with new-generation TKIs was associated with a higher MMR rate at 1 year but not with 1-year overall survival.

Metallic nanorod metamaterials, arrays of vertically aligned nanorods embedded in an alumina matrix (diameter ~80 nm, length 100-250 nm, period ~113 nm), have recently emerged as a flexible platform for applications in photonics, opto-electronics and sensing. The optical constants for these nanostructured materials are directly associated with their crystallinity. Controlling the crystallinity of these metamaterials in a fast manner has presented a new challenge. Here we show a laser annealing with a pulsed Nd:YAG laser (λ = 532 nm, FWHM 15 ns) to rapidly change the crystallinity of the metallic nanorods. The small column X-Ray diffraction characterization shows that not only the crystallinity of the metallic nanorods is changed, but also that evaporation of the metal occurs with laser annealing.

Plasmonic metamaterials have recently received increasing attention due to their favorable optical and electrical properties. The physics of the interaction between plasmonic metamaterials and lasers are rich and open opportunities for applications, such as sensing, imaging and photovoltaics. Here, we investigate the mechanism of the interaction between Ag nanorod arrays and nanosecond (ns) pulsed laser. The experimental results show that ns laser pulses significantly improve the crystallinity of the Ag nanorod arrays. Meanwhile, the laser evaporates some of the Ag into the air. This work paves the way for future high-performance plasmonic meta-devices.

This research work has been demonstrated the growth of ZnInO thin films using thermal evaporation technique for thermoelectric power generation applications. The pure zinc powder and indium metal were evaporated on the multi-crystalline Si substrate using the vacuum tube furnace. Deposited thin films were annealed at various temperatures (500–700 °C) for 30 min in a programmable muffle furnace. XRD data concluded that the sample annealed at temperature 500 °C, has a weak structure of ZnO. But as we have increased the annealing temperature, indium atoms get thermal energy from the annealing process and reacted with ZnO molecule to form ZnInO composite. The vibrational and rotational modes of the samples were studied by the Raman spectroscopic analysis and morphology of annealed samples was verified by SEM. The Seebeck coefficient data suggested that the value of Seebeck coefficient varies between (140.9–182.2) μV/oC. The maximum value of the Seebeck coefficient was obtained for the sample annealed at 600 °C because the mobility of carriers is highest at that temperature. But the value of electrical conductivity and power factor for the sample annealed at 600 °C is minimum due to low carrier concentration. Because of these conclusions, it may be suggested that this material can be a potential choice soon for thermoelectric power generation applications.

Hybrid nanostructures, comprising of a metal core and a semiconductor shell layer, shows great potential for a new generation of low-cost solar cells, due to their unique electronic and optical properties. However, experimental results have fallen far short of unltra-high efficiency (i.e. beyond Shockley-Queisser limit) predicted by theoretical simulation, limiting commercial application. Here, we experimentally design a non-transparent organic solar cell containing an array of Ag/ZnO nanowires, increasing internal quantum efficiency (IQE) by a factor of 2.5 compared with the planar counterpart, indicating a great enhancement of charge collection efficiency, due to the ultrafast Ag nanowire channels. Furthermore, we exploit this hybrid nanostructure as a perfect back reflector for semi-transparent solar cells, resulting in enhanced light absorption by a factor of 1.8 compared with the planar counterparts. The ability to enhance the charge collection and light absorption makes these Ag/ZnO nanostructures a flexible platform for the development of modern optoelectronic devices.

Arrays of silver nanowires have received increasing attention in a variety of applications such as surface-enhanced Raman scattering (SERS), plasmonic biosensing and electrode for photoelectric devices. However, until now, large scale fabrication of device-suitable silver nanowire arrays on supporting substrates has seen very limited success. Here we show the synthesis of free-standing silver nanowire arrays on indium-tin oxide (ITO) coated glass by pulsed electrodeposition into anodic aluminum oxide (AAO) templates. We use an in situ oxygen plasma cleaning process and a sputtered Ti layer to enhance the adhesion between the template and ITO glass. An ultrathin gold layer (2 nm) is deposited as a nucleation layer for the electrodeposition of silver. An unprecedented high level of uniformity and control of the nanowire diameter, spacing and length has been achieved. The absorption measurements show that the free-standing silver nanowire arrays possess tunable plasmonic resonances. published

An electrode structured with a TiO2/Ag/TiO2 (TAT) multilayer as indium tin oxide (ITO) replacement with a superior thermal stability has been successfully fabricated. This electrode allows to directly tune the optical cavity mode towards maximized photocurrent generation by varying the thickness of the layers in the sandwich structure. This enables tailored optimization of the transparent electrode for different organic thin film photovoltaics without alteration of their electro-optical properties. Organic photovoltaic featuring our TAT multilayer shows an improvement of ∼12% over the ITO reference and allows power conversion efficiencies (PCEs) up to 8.7% in PTB7:PC71BM devices.