Search

Connected insulin pens have potential utility as diagnostic tools to objectively assess MBDs and their impact on glycemic outcomes. This cross-sectional study enrolled 68 people with T1D or insulin-using T2D (A1C ≥ 8%, ≥ 3 insulin boluses/day reported at enrollment). Mean (± SD) age of participants was 48 years (± 12), 44% female, 59% T1D, 51% BMI ≥ 30 and 65% with A1C ≥ 9.0%. Connected pen and blinded CGM data (21 days collected) were used to calculate MBDs (no insulin dose from 2 hrs prior to and 4 hrs after the start of a glucose excursion [defined as > 70 mg/dl rise within 2 hrs, not preceded by a value < 70 mg/dl]). On average, participants had 21.6 MBDs/30 days (range 0-55.8); time-in-range (TIR) was relatively low, 42.6% (± 18.8%) while time-above-range (TAR) was high, 52.8% (± 21.3%). MBD daily frequency was significantly associated with TIR (Spearman's correlation coefficient [rS] = -0.28, p = 0.02) and TAR (rS = 0.26, p = 0.03). Baseline predictors of MBD included A1C (incidence rate ratio, IRR = 1.118, p = 0.003) and BMI (IRR = 0.969, p = 0.008). Due to differences between T1D and T2D populations (age: 42.5 vs. 55.2 yrs, p < 0.001; BMI: 27.7 vs. 34.1, p < 0.001; diabetes duration: 22.7 vs. 16.0 yrs, p = 0.015, respectively), the groups were analyzed separately. For T2D, MBDs were associated with the Worry, Avoidance, and Maintain High subscales of the Hypoglycemic Fear Survey (HFS-W, A, and MH). MBDs were significantly more common among those with lower HFS-W (IRR = 0.940, p = 0.004), but with higher HFS-A (IRR = 1.140, p = 0.004) and higher HFS-MH (IRR = 1.075, p = 0.040). For T1D, none of the HFS subscales were significantly associated with MBDs. Given the differences in behavioral factors associated with MBDs in T1D and T2D, customized therapeutic approaches to reduce MBDs and improve TIR are likely needed. Disclosure: S.S. Edwards: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. X. He: Employee; Self; Eli Lilly and Company. J. Johnson: Employee; Self; Eli Lilly and Company. E. Meadows: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. W. Wang: None. H. Wolpert: Employee; Self; Eli Lilly and Company. W. Polonsky: Advisory Panel; Self; Intarcia Therapeutics, Roche Diabetes Care. Consultant; Self; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk Inc., Onduo, Sanofi US, Xeris Pharmaceuticals, Inc. Funding: Eli Lilly and Company [ABSTRACT FROM AUTHOR]

Potential mechanisms of luteolin to improve ICH-induced SBI. Luteolin can engage with TRAF6 and inhibit TLR4/TRAF6/NF-κB signaling pathway activation, finally improving the neuroinflammation induced by ICH. • Luteolin alleviates intracerebral hemorrhage induced secondary brain injury. • Luteolin inhibits the activation of microglia and inflammatory response induced by ICH. • Luteolin downregulates TLR4/TRAF6/NF-κB pathway activation. • Luteolin targets TRAF6 and prevents the ubiquitination of TRAF6. The activation of microglia and inflammatory responses is essential for the process of intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI). In this study, we investigated the effects of luteolin on ICH-induced SBI and the potential mechanisms. Autologous blood was injected to establish the ICH model in vivo , and oxyhemoglobin (OxyHb) was used to mimic the ICH model in vitro. We found that the administration of luteolin significantly improved motor and sensory impairments and inhibited neuronal cell degeneration in vivo. In the in vitro study, the decrease of the neuronal cell viability induced by activated microglia was alleviated by luteolin treatment. Furthermore, by antagonizing the activation of the Toll-like receptor 4 (TLR4)/TNF receptor-associated factor 6 (TRAF6)/nuclear transcription factor-κB (NF-κB) signaling pathway, the ICH-induced elevation of cytokine release was decreased after treatment with luteolin, which was confirmed both in vivo and in vitro. Additionally, we found that luteolin engaged with TRAF6 and inhibited the ubiquitination of TRAF6. Taken together, our findings demonstrate the neuroprotective effects of luteolin after ICH and the potential mechanisms, which suggest that luteolin is a potential therapeutic candidate for ICH treatment. [ABSTRACT FROM AUTHOR]

Enzyme-linked immunosorbent assay (ELISA) is a powerful analytical method for biomolecular analysis due to high sensitivity and specificity. The large background fluorescence can be eliminated by using optofluidic laser-based ELISA. However, the detection time is too long, especially for the detection of low concentration of analyte. Such a drawback can potentially be overcome by using particle with high surface-to-volume ratio. The effect of particle on the lasing threshold of optofluidic laser based on Fabry–Pérot microcavity was demonstrated, which is a fundamental issue on magnetic particle-based optofluidic laser ELISA. The 1 mM R6G ethanol solution and different concentrations of magnetic particles (Fe 3 O 4) solution (5, 10, 20, 40 and 80 μ g/ml) with the diameter 30 or 100 nm was be tested the effect of particle on optofluidic laser. The results show that the lasing threshold increases with the concentration and diameter of particles increasing, but the adverse effect is very small for the detection of low concentration of analyte. Our work will lead to the development of magnetic particle-based optofluidic laser ELISA, which can shorten the detection time and push the detection limit. [ABSTRACT FROM AUTHOR]

• An optically transparent metasurface with high-efficiency microwave absorption and low IR emission simultaneously was investigated. • The proposed device is an ITO/dielectric/ITO sandwiched structure. It does not require a special low emissivity layer to reduce IR emission. • The effect of sheet resistance to microwave absorbing performance and IR emissivity is also discussed. • The IR response of the sample was analyzed qualitatively. An ultrathin optically transparent metasurface with simultaneous high-efficiency microwave absorptivity and low infrared (IR) emissivity is proposed. The proposed metasurface is an ITO/dielectric/ITO sandwiched structure. By properly tuning the structural parameters and sheet resistance of ITO, a wide microwave absorption band (5.8–8.3 GHz) greater than 90% is achieved. Furthermore, a low IR emissivity of 0.52 was obtained by adjusting the filling ratio of the ITO part. Thus, the proposed metasurface does not require a special low emissivity layer to reduce IR radiation. The perfect consistency between experimental and simulation results demonstrates that the proposal has practical application of multifunctional stealth technology. [ABSTRACT FROM AUTHOR]

• A new method is proposed during the growth of InGaN/InGaN multiple quantum well. • This method promotes the luminescence and material homogeneity of InGaN alloy. • The influence of different pretreatment duration is investigated. • This method works by partially releasing the strain in the InGaN well layer. A new pretreatment method is adopted during the metal-organic chemical vapor deposition (MOCVD) epitaxial growth of InGaN/(In) GaN multiple quantum well (MQW), in which when the growth of under barrier of each QW is finished, i. e. before the growth of each well layer, the gallium precursor flow is switched off while indium and nitrogen precursor flows are kept on for an extra period of time. The structural and luminescence properties of samples with different pretreatment duration are investigated by high resolution X-ray diffraction, electroluminescence, temperature dependent photoluminescence and micro-photoluminescence. The results show that a better homogeneity of quantum wells can be achieved by this preprocess. This method operates mainly due to partially releasing the deformation energy and thus attenuating the composition pulling effect in InGaN well layer growth. [ABSTRACT FROM AUTHOR]

Polyaniline (PANI)-based supercapacitor electrode materials are attracting great research interests due to their easy preparation, low cost and high theoretical capacitance. However, the irreversible structural changes and mechanical degradation of PANI during the redox processes result in rapid capacitance decay. To overcome this drawback of PANI, a vulcanized PANI polymer backbone (S-PANI) is fabricated through a vulcanization process in this paper. For the obtained S-PANI, PANI chains are interconnected by the sulfide and/or disulfide bonds, and form a stable, cross-linked porous structure. The special cross-linked structure can effectively accommodate the volumetric expansion and shrinkage of PANI during the charge and discharge process. Consequently, the S-PANI sample shows excellent electrochemical cycle stability with capacitance retention of approximately 96% after 5000 cycles, which is much higher than that of PANI (51%). Moreover, in a symmetric two-electrode full cell system, the S-PANI electrode still possesses a high capacitance retention ratio of approximately 96% even after 10,000 cycles at 3 A g−1. Thus, S-PANI is a very attractive material for highly stable supercapacitor application. • A vulcanized PANI (S-PANI) was fabricated through a vulcanization process. • The obtained S-PANI possesses a stable, cross-linked porous structure. • The S-PANI electrode shows high specific capacitance and excellent cycling stability. [ABSTRACT FROM AUTHOR]

Surface-mounted permanent magnet synchronous motors (SMPMSM) with high power density and good speed regulation are widely used in industrial applications. In order to further improve its power density, this paper studied the relationship between the thickness of the stator yoke, the thickness of the rotor yoke, the relative magnet span of the motor and the motor power density using the finite element simulation method. On this basis, a response surface model between the three parameters and the power density of the motor was established. Based on this model and a differential evolution algorithm, the motor was optimized and the power density was improve; finally, the optimization results were verified using the finite element simulation method. In addition, the optimization results showed that, when other structure parameters remain unchanged, there is an optimal combination of parameters that can maximize the motor's power density, including the thickness of the stator yoke, the thickness of the rotor yoke and relative magnet span of the motor. [ABSTRACT FROM AUTHOR]

Autophagy exerts a dual role in promoting cell death or survival. Recent studies have shown that it may play an important role in lipopolysaccharide (LPS)-induced acute lung injury (ALI). It was also suggested that angiotensin converting enzyme 2 (ACE2) may participate in the regulation of autophagy. The present study aims to investigate the role of autophagy in ALI and the involvement of ACE2. The regulation of the APMK/mTOR pathway was explored to clarify the underlying mechanism. The results showed that autophagy played an important role in ALI induced by LPS, as the autophagy inhibitor 3-methyladenine (3-MA) mitigated the severity of ALI. ACE2 activator resorcinolnaphthalein and inhibitor MLN-4760 significantly affected the histological appearance and wet/dry (W/D) ratio of the lung and altered the ACE2 activity of the lung, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) levels in lung tissue. Furthermore, LPS, resorcinolnaphthalein and MLN-4760 significantly affected the expression of autophagy proteins Beclin-1, LC3-I and LC3-II. To explore the mechanism of ACE2 on lung autophagy, we measured the phosphorylation of AMPK/mTOR after mice were treated with LPS and resorcinolnaphthalein or MLN-4760. The results revealed that resorcinolnaphthalein and MLN-4760 both significantly altered the phosphorylation of AMPK/mTOR. Finally, we found that AMPK inhibitor (8-bAMP) and mTOR activator (propranolol) both abolished the effects of ACE2 activator (resorcinolnaphthalein) on the expression of lung autophagy proteins Beclin-1, LC3-I and LC3-II. In conclusion, these findings suggest that ACE2 could alleviate the severity of ALI, inflammation and autophagy in lung tissue through the AMPK/mTOR pathway. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a recurrent and chronic intestinal disease. Available drugs for UC are accompanied by poor effectiveness or severe adverse events and thus there is an urgent need to develop specific and effective drugs for UC treatment. HLY is a new compound synthesised from coptisine by our institute. HLY activates the transcriptional activity of X-box binding protein 1 (xbp1) and inhibits the expression of non-muscle myosin heavy chain 9 (myh9) in intestinal epithelial cells (IEC6). When the xbp1 gene was silenced by siRNA, HLY had no effect on myh9. HLY effectively reduced body weight loss and the percentage of colon contracture in vivo , decreased disease activity index (DAI) score, colon mucosal damage index (CMDI) and tissue histopathological index (THI) in dextran sulfate sodium (DSS)-induced UC mice. Furthermore, oral HLY effectively increased the expression of xbp1 and inhibited the expression of myh9 in vivo as demonstrated by western-blot and immunohistochemical assays. Taken together, HLY could alter ulcerative colitis via the xbp1-myh9 pathway. To our knowledge, this is the first report demonstrating that the monomer compound targets the xbp1-myh9 pathway in the treatment of UC. HLY may be developed as a possible therapeutic candidate for UC. [ABSTRACT FROM AUTHOR]

Background: The JAK2-STAT signaling pathway plays a critical role in myeloproliferative neoplasms (MPN). An activating mutation in JAK2 (V617F) is present in ~ 95% of polycythemia vera, essential thrombocythemia, and primary myelofibrosis cases. This study aims to explore the selective JAK2V617F inhibitor, evaluate the efficacy and possible mechanism of ZT55 on MPN. Methods: HTRF assays were conducted to evaluate the selective inhibition of ZT55 for JAKs. Cell apoptosis, proliferation, and cycle arrest assays were performed to examine the effect of ZT55 on HEL cell line with JAK2V617F mutation in vitro. Western analysis was used to monitor the expression and activity of proteins on JAK2/STAT pathway. A mice xenograft model was established to evaluate the antitumor efficacy of ZT55 in vivo. Peripheral blood samples from patients with the JAK2V617F mutation were collected to estimate the effect of ZT55 on erythroid colony formation by colony-forming assay. Results: We found that ZT55 showed a selective inhibition of a 0.031 μM IC50 value against JAK2. It exhibited potent effects on the cellular JAK-STAT pathway, inhibiting tyrosine phosphorylation in JAK2V617F and downstream STAT3/5 transcription factors. ZT55 inhibited the proliferation of the JAK2V617F-expressing HEL cell line, leading to cell cycle arrest at the G2/M phase and induction of caspase-dependent apoptosis. Notably, ZT55 also significantly suppressed the growth of HEL xenograft tumors in vivo. Further evaluation indicated that ZT55 blocked erythroid colony formation of peripheral blood hematopoietic progenitors from patients carrying the JAK2V617F mutation. Conclusion: These results suggest that ZT55 is a highly-selective JAK2 inhibitor that can induce apoptosis of human erythroleukemia cells by inhibiting the JAK2-STAT signaling. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Neovascularization during tumorigenesis supplies oxygen and nutrients to proliferative tumor cells, and serves as a conduit for migration. Targeting oncogenes involved in angiogenesis is needed to treat organ-confined and locally advanced ESCC. Although the phospholipase C epsilon-1 (PLCE1) gene was originally identified as a susceptibility gene for ESCC, how PLCE1 is involved in ESCC is unclear. Methods: Matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to measure the methylation status of the PLCE1 promoter region. To validate the underlying mechanism for PLCE1 in constitutive activation of the NF-κB signaling pathway, we performed studies using in vitro and in vivo assays and samples from 368 formalin-fixed esophageal cancer tissues and 215 normal tissues with IHC using tissue microarrays and the Cancer Genome Atlas dataset. Results: We report that hypomethylation-associated up-regulation of PLCE1 expression was correlated with tumor angiogenesis and poor prognosis in ESCC cohorts. PLCE1 can activate NF-κB through phosphoinositide-phospholipase C-ε (PI-PLCε) signaling pathway. Furthermore, PLCE1 can bind p65 and IκBα proteins, promoting IκBα-S32 and p65-S536 phosphorylation. Consequently, phosphorylated IκBα promotes nuclear translocation of p50/p65 and p65, as a transcription factor, can bind vascular endothelial growth factor-C and bcl-2 promoters, enhancing angiogenesis and inhibiting apoptosis in vitro. Moreover, xenograft tumors in nude mice proved that PLCE1 can induce angiogenesis, inhibit apoptosis, and increase tumor aggressiveness via the NF-κB signaling pathway in vivo. Conclusions: Our findings not only provide evidence that hypomethylation-induced PLCE1 confers angiogenesis and proliferation in ESCC by activating PI-PLCε-NF-κB signaling pathway and VEGF-C/Bcl-2 expression, but also suggest that modulation of PLCE1 by epigenetic modification or a selective inhibitor may be a promising therapeutic approach for the treatment of ESCC. [ABSTRACT FROM AUTHOR]

Background: Previous metabolomic studies have revealed that plasma metabolic signatures may predict epithelial ovarian cancer (EOC) recurrence. However, few studies have performed metabolic profiling of pre- and post-operative specimens to investigate EOC prognostic biomarkers.Objective: The aims of our study were to compare the predictive performance of pre- and post-operative specimens and to create a better model for recurrence by combining biomarkers from both metabolic signatures.Methods: Thirty-five paired plasma samples were collected from 35 EOC patients before and after surgery. The patients were followed-up until December, 2016 to obtain recurrence information. Metabolomics using rapid resolution liquid chromatography-mass spectrometry was performed to identify metabolic signatures related to EOC recurrence. The support vector machine model was employed to predict EOC recurrence using identified biomarkers.Results: Global metabolomic profiles distinguished recurrent from non-recurrent EOC using both pre- and post-operative plasma. Ten common significant biomarkers, hydroxyphenyllactic acid, uric acid, creatinine, lysine, 3-(3,5-diiodo-4-hydroxyphenyl) lactate, phosphohydroxypyruvic acid, carnitine, coproporphyrinogen, l-beta-aspartyl-l-glutamic acid and 24,25-hydroxyvitamin D3, were identified as predictive biomarkers for EOC recurrence. The area under the receiver operating characteristic (AUC) values in pre- and post-operative plasma were 0.815 and 0.909, respectively; the AUC value after combining the two sets reached 0.964.Conclusion: Plasma metabolomic analysis could be used to predict EOC recurrence. While post-operative biomarkers have a predictive advantage over pre-operative biomarkers, combining pre- and post-operative biomarkers showed the best predictive performance and has great potential for predicting recurrent EOC. [ABSTRACT FROM AUTHOR]

BiVO4:Sx (x = 0, 0.1, 0.3, 0.5, 0.7, 0.9) photocatalysts are prepared by surfactant-free hydrothermal treatment of an aq. [ABSTRACT FROM AUTHOR]

We show a hybrid structure consisting of Si film with photonic crystal surface and random triangular gold grooves reflector at the bottom, which is capable of realizing efficient, broad-band, wide-angle optical absorption. It is numerically demonstrated that the enhanced absorption in a broad wavelength range (0.3-9.9 μm) due to the scattering effect of both sides of the structure and the created resonance modes. Larger thickness and period are favored to enhance the absorption in broader wavelength range. Substantial electric field concentrates in the grooves of surface photonic crystal and in the Si film. Our structure is versatile for solar cells, broadband photodetection and stealth coating. [ABSTRACT FROM AUTHOR]

Microbiota have recently been shown to be associated with many disease conditions. However, the microbiota associated with tuberculosis (TB) infection, recurrence and treatment outcome have not been systematically characterized. Here, we used high throughput 16S RNA sequencing to analyze the sputum microbiota associated with Mycobacterium tuberculosis infection and also to identify the microorganisms associated with different outcomes of TB treatment. We recruited 25 new TB patients, 30 recurrent TB patients and 20 TB patients with treatment failure, as well as 20 healthy controls. Streptococcus, Gramulicatella and Pseudomonas were more abundant in TB patients while Prevotella, Leptotrichia, Treponema, Catonella and Coprococcus were less abundant in TB patients than in the healthy controls. We found reduced frequency and abundance of some genera such as Bulleidia and Atopobium in recurrent TB patients compared with those in new TB patients. In addition, the ratio of Pseudomonas / Mycobacterium in recurrent TB was higher than that in new TB while the ratio of Treponema / Mycobacterium in recurrent TB was lower than that in new TB, indicating that disruption of these bacteria may be a risk factor of TB recurrence. Furthermore, Pseudomonas was more abundant and more frequently present in treatment failure patients than in cured new patients, and the ratio of Pseudomonas / Mycobacterium in treatment failure was higher than that in new TB. Our data suggest that the presence of certain bacteria and the disorder of lung microbiota may be associated with not only onset of TB but also its recurrence and treatment failure. These findings indicate that lung microbiota may play a role in pathogenesis and treatment outcome of TB and may need to be taken into consideration for improved treatment and control of TB in the future. [ABSTRACT FROM AUTHOR]