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1.
FASEB J ; 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31908069

RESUMO

Aging-related organ degeneration is driven by multiple factors including the cell maintenance mechanisms of autophagy, the cytoprotective protein αKlotho, and the lesser known effects of excess phosphate (Pi), or phosphotoxicity. To examine the interplay between Pi, autophagy, and αKlotho, we used the BK/BK mouse (homozygous for mutant Becn1F121A ) with increased autophagic flux, and αKlotho-hypomorphic mouse (kl/kl) with impaired urinary Pi excretion, low autophagy, and premature organ dysfunction. BK/BK mice live longer than WT littermates, and have heightened phosphaturia from downregulation of two key NaPi cotransporters in the kidney. The multi-organ failure in kl/kl mice was rescued in the double-mutant BK/BK;kl/kl mice exhibiting lower plasma Pi, improved weight gain, restored plasma and renal αKlotho levels, decreased pathology of multiple organs, and improved fertility compared to kl/kl mice. The beneficial effects of heightened autophagy from Becn1F121A was abolished by chronic high-Pi diet which also shortened life span in the BK/BK;kl/kl mice. Pi promoted beclin 1 binding to its negative regulator BCL2, which impairs autophagy flux. Pi downregulated αKlotho, which also independently impaired autophagy. In conclusion, Pi, αKlotho, and autophagy interact intricately to affect each other. Both autophagy and αKlotho antagonizes phosphotoxicity. In concert, this tripartite system jointly determines longevity and life span.

2.
Support Care Cancer ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912364

RESUMO

PURPOSE: Chemotherapy-induced alopecia is a common and emotionally traumatic side effect on breast cancer patients. In order to make up for the deficiency of measuring tools in China, our study aims at translating the chemotherapy-induced alopecia distress scale (CADS) into Chinese and evaluating the psychometric properties of the Chinese version of CADS (CADS-C) in breast cancer patients. METHODS: The validity and reliability of CADS-C were measured by a questionnaire survey among 301 breast cancer patients from Chinese mainland. Construct validity was assessed through factor analysis and contrasted group comparisons. The validity of the content was examined by an experts group. The internal consistency and test-retest reliability were evaluated by calculating Cronbach's alpha and the intraclass correlation coefficient. RESULTS: The content validity index was 0.94; a structure with three factors was revealed by exploratory factor analysis which explained 65.40% of the variance and proved by confirmatory factor analysis. The contrasted group comparisons showed significant differences among different degrees of alopecia. The average variance extracted and composite reliability and correlations between CADS and body image, quality of life and self-esteem proved the convergent validity. The Cronbach's alpha and the intraclass correlation coefficient of the total scale were 0.90 and 0.89 respectively, indicating satisfactory internal consistency and time stability. CONCLUSION: The scale appears to be a reliable and valid tool to measure chemotherapy-induced alopecia distress among breast cancer patients in China.

3.
Nat Commun ; 11(1): 161, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919426

RESUMO

Chiral recognition, such as enantioselective interactions of enzyme with chiral agents, is one of the most important issues in the natural world. But artificial chiral receptors are much less efficient than natural ones. For tackling the chiral recognition and enantiomer excess (ee) analysis, up until now all the fluorescent receptors have been developed based on fluorescence intensity changes. Here we report that the chiral recognition of a large number of chiral carboxylic acids, including chiral agrochemicals 2,4-D, is carried out based on fluorescent colour changes rather than intensity changes of AIEgen rotors. Moreover, the fluorescence wavelength of the AIEgen rotor linearly changes with ee of the carboxylic acid, enabling the ee to be accurately measured with average absolute errors (AAE) of less than 2.8%. Theoretical calculation demonstrates that the wavelength change is ascribed to the rotation of the AIEgen rotor upon interaction with different enantiomers.

4.
Retina ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31917731

RESUMO

PURPOSE: Characterization of leakage indices on ultra-widefield fluorescein angiography in proliferative diabetic retinopathy treated with intravitreal aflibercept. METHODS: Prospective study enrolling subjects for treatment of proliferative diabetic retinopathy randomized 1:1 to receive 2-mg intravitreal aflibercept every 4 weeks (2q4) or every 12 weeks (2q12). Ultra-widefield fluorescein angiography images obtained at baseline, 24, and 48 weeks were analyzed using a semiautomated leakage segmentation platform. Panretinal and zonal leakage indices were calculated. RESULTS: Forty eyes of 40 subjects were included, and mean age was 48 ± 12.1 years. Mean number of injections was 11 ± 1.7 in the 2q4 arm and 4 ± 0.4 in the 2q12 arm. Median baseline leakage index in the 2q4 and 2q12 groups was 5.1% and 4.3%, respectively (P = 0.28). At 24 and 48 weeks, the 2q4 group significantly improved to 1.1% (-79%, P < 0.0001). At Week 24, the 2q12 group demonstrated nonsignificant improvement (3.4%; -21%, P = 0.47); by Week 48, improvement was significant (1.4%; -68%, P = 0.02). The 2q4 group resulted in lower leakage index compared with the 2q12 group at 24 weeks (1.1% vs. 3.4%, respectively; P = 0.008), but by 48 weeks, leakage index was similar between both groups (1.1% vs. 1.4%, respectively; P = 0.34). CONCLUSION: Proliferative diabetic retinopathy treated with intravitreal aflibercept demonstrated significant leakage index reductions at 1 year. Monthly dosing provided more rapid reduction in leakage index compared with quarterly dosing. TRIAL REGISTRATION: RECOVERY study (NCT02863354); https://clinicaltrials.gov/ct2/show/NCT02863354.

5.
Inflamm Res ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31797003

RESUMO

OBJECTIVE: This study sought to evaluate short-term treatment with COX-2 inhibitors and acute changes in colonic PGE2 levels as predictors of long-term efficacy in a genetic model of colorectal cancer. METHODS: Celecoxib oral suspension (40 mg/kg BID) was dosed to Apc-mutant Pirc (F344/NTac-Apcam1137) rats for 4 days (short-term group), or the equivalent dose of 1500 ppm celecoxib was administered in the diet for 4 months (long-term group). Percent inhibition of colonic PGE2 was calculated, and the reduction in colonic PGE2 was assessed in relation to suppression of adenomatous colon polyps. RESULTS: Colonic mucosa PGE2 was fourfold higher in Pirc than in F344 wild-type rats (21 vs. 5.6 pg/mg epithelial tissue), due at least in part to higher COX-2 expression, and this was confirmed by elevated PGE2-d11 levels in Pirc colonic S9 incubations. In the 4-day study, dose-dependent reductions in PGE2 were observed in colonic epithelium (-33% (P>0.05) and -57% (P=0.0012)), after low- and high-dose celecoxib treatments of 4 mg/kg and 40 mg/kg (bid), respectively. In the 4-month study, 1500 ppm celecoxib suppressed colonic epithelium PGE2 by 43.5%, and tumor multiplicity by 80% (P<0.0015). Suppression of plasma 6-keto PGF1α also was corroborated following long-term treatment with 1500 ppm celecoxib (P<0.05). CONCLUSIONS: Acute changes in colonic mucosa PGE2 provided a rapid means of predicting long-term chemopreventive effects from celecoxib, and might be useful for screening of new COX-2 inhibitor compounds.

6.
Acta Trop ; 202: 105285, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31786108

RESUMO

Dipstick Dye Immunoassay (DDIA) and Indirect Haemagglutination Assay (IHA), are two commercially available kits which have been widely used for screening Schistosoma japonicum in P.R. China. Whether they can be used for screening of Schistosoma haematobium are not clear. In order to evaluate the diagnostic efficiency of DDIA and IHA for screening Schistosoma haematobium, serum samples were collected from pupils in endemic areas in Zambia, Southern Africa, and tested by DDIA and IHA by single-blind manner. Meanwhile, the pupils were microscopically examined by infection with Schistosoma and soil-transmitted helminths, visually observed for parasite eggs. Of the enrolled 148 pupils, 61% tested positive for S. haematobium infection, while 31% and 36% of pupils were infected with hookworm and Ascaris respectively. Regarding the parasitological tests as reference standard, for the diagnosis of S. haematobium infection, IHA performed higher sensitivity (74%, 95% CI: 65%-83%) than that of DDIA (60%, 95%CI: 49%-70%). The sensitivities of IHA and DDIA are significant higher in 10-14 years old students than those of 7-9 years old group. The specificity of DDIA and IHA were 61% (95%CI: 49%-74%) and 72% (95%CI: 60%-84%), respectively. The co-infection with STHs decreased the specificity of DDIA but had no impact on that of IHA. Our study indicated that IHA has more potential as an alternative diagnostic tool for identifying schistosomiasis haematobium but need further improvement.

7.
Int J Behav Nutr Phys Act ; 16(1): 119, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791364

RESUMO

BACKGROUND: Frail older adults are predisposed to multiple comorbidities and adverse events. Recent interventional studies have shown that frailty can be improved and managed. In this study, effective individualized home-based exercise and nutrition interventions were developed for reducing frailty in older adults. METHODS: This study was a four-arm, single-blind, randomized controlled trial conducted between October 2015 and June 2017 at Miaoli General Hospital in Taiwan. Overall, 319 pre-frail or frail older adults were randomly assigned into one of the four study groups (control, exercise, nutrition, and exercise plus nutrition [combination]) and followed up during a 3-month intervention period and 3-month self-maintenance period. Improvement in frailty scores was the primary outcome. Secondary outcomes included improvements in physical performance and mental health. The measurements were performed at baseline, 1 month, 3 months, and 6 months. RESULTS: At the 6-month measurement, the exercise (difference in frailty score change from baseline: - 0.23; 95% confidence interval [CI]: - 0.41, - 0.05; p = 0.012), nutrition (- 0.28; 95% CI: - 0.46, - 0.11; p = 0.002), and combination (- 0.34; 95% CI: - 0.52, - 0.16; p <  0.001) groups exhibited significantly greater improvements in the frailty scores than the control group. Significant improvements were also observed in several physical performance parameters in the exercise, nutrition, and combination groups, as well as in the 12-Item Short Form Health Survey mental component summary score for the nutrition group. CONCLUSIONS: The designated home-based exercise and nutrition interventions can help pre-frail or frail older adults to improve their frailty score and physical performance. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov (identifier: NCT03477097); registration date: March 26, 2018.

8.
Annu Rev Immunol ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31800327

RESUMO

DNA has been known to be a potent immune stimulus for more than half a century. However, the underlying molecular mechanisms of DNA-triggered immune response have remained elusive until recent years. Cyclic GMP-AMP synthase (cGAS) is a major cytoplasmic DNA senor in various types of cells that detect either invaded foreign DNA or aberrantly located self-DNA. Upon sensing of DNA, cGAS catalyzes the formation of cyclic GMP-AMP (cGAMP), which in turn activates the ER-localized adaptor protein MITA (also named STING) to elicit the innate immune response. The cGAS-MITA axis not only plays a central role in host defense against pathogen-derived DNA but also acts as a cellular stress response pathway by sensing aberrantly located self-DNA, which is linked to the pathogenesis of various human diseases. In this review, we summarize the spatial and temporal mechanisms of host defense to cytoplasmic DNA mediated by the cGAS-MITA axis and discuss the association of malfunctions of this axis with autoimmune and other diseases. Expected final online publication date for the Annual Review of Immunology, Volume 38 is April 26, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

9.
Eur Spine J ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31834484

RESUMO

PURPOSE: No standard strategy exists for managing cervical spondylotic myelopathy (CSM). The efficacy of spinous process-splitting laminoplasty, its impact on cervical alignment change and the incidence of postoperative neck pain remain unclear. We analyzed the parameters of cervical alignment and cord morphology in CSM. METHODS: The radiographic parameters investigated were pre- and postoperative C2-C7 lordosis (CL), C2-C7 sagittal vertical axis (CSVA), T1 slope (TS), TS minus CL (TS - CL) and cervical spinal cord morphology. Myelopathy severity was measured using two different functional scores. Statistical analysis was performed to determine significant differences between preoperative and follow-up radiological findings and change in functional scores. RESULTS: This retrospective study comprised 85 CSM patients from a single institute, with a minimum follow-up of 24 months. Overall, 63.5% (n = 54) of patients had improvement in their postoperative cervical lordotic alignment; 36.5% (n = 31) developed progressive aggravation of the cervical kyphotic alignment. Pearson correlation analysis showed that CSVA, TS and T1-CL were independent predictors of CL curve change. Based on the receiver operating characteristic curve, the cutoff value for CSVA was 2.89 cm with a postoperative visual analog scale (VAS) > 4. The cutoff value of the TS - CL was 20 degrees with a postoperative VAS > 4. CSVA, TS and TS - CL had a significant association with variation in CL. CSVA and TS - CL had a significant association with postoperative neck pain. CONCLUSIONS: CSVA, T1 slope and T1-CL are good predictors of postoperative degenerative kyphotic change and neck pain. Careful consideration of their preoperative cutoff values can improve postoperative outcomes. LEVEL OF EVIDENCE: IV. These slides can be retrieved under Electronic Supplementary Material.

10.
Biochem Pharmacol ; : 113753, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31837310

RESUMO

Glucuronidation, catalyzed by UDP-glucuronosyltransferases (UGTs), is a crucial substance metabolism and elimination process that mostly occurs in the liver to protect the body from toxic substances and maintain homeostasis. The reaction functions well in a uridine diphosphate glucuronic acid (UDPGA) -dependent manner in vivo. However, the mechanism for recognizing UDPGA or analog has not been reported so far. Here, through X-ray crystallography, we present a 1.78 Å cocrystal structure of the C-terminal domain of UDP-glucuronosyltransferase 2B15 (2B15CTD, K284-H451) bound by tartrate, which reveals the detailed recognition mechanism of UDPGA analog at the active site. Using surface plasmon resonance techniques, protein thermal shift studies, and limited proteolysis, we determine that tartrate stabilizes the conformation of 2B15CTD thermodynamically. The biochemical analysis further elucidates that two residues, S312 and T374, are essential for the interactions between 2B15CTD and tartrate. We also investigate the pharmacological effects of tartrate on UGTs based on the cocrystal structure of UGT2B15 and experiments performed in vitro and in vivo. In brief, the LC-MS/MS analysis shows that tartrate has a significant inhibitory effect towards UGT2B15 (Ki = 91 µM), and oral administration of tartrate to FVB mice can reduce the relative plasma concentration of glucuronide. These results reveal an unexpected physiological role of tartrate in the maintenance of UGTs function. Therefore, tartrate is a potential inhibitor of UGTs, and the excess tartrate in the diet may disturb body homeostasis and inhibit the metabolism of UGT substrates by interfering with glucuronidation.

11.
Int J Behav Nutr Phys Act ; 16(1): 136, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31870384

RESUMO

Following publication of the original article [1], the author reported that an abbreviation was incorrect in the original article.

12.
Drug Alcohol Depend ; 207: 107814, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31887603

RESUMO

BACKGROUND: Sex differences in the development of alcohol dependence (AD) among patients with panic disorder (PD) remain unexplored. The study investigated sex as an effect modifier in the incidence of AD among patients with PD. METHOD: We included 9480 patients with PD from the Taiwan National Health Insurance Research Database. A total of 169 patients (89 men and 80 women) developed incident AD during the follow-up period. Standardized incidence ratios (SIRs) were used to represent the relative risks of incident AD compared with the general population. Based on a nested case-control study design, 10 controls were selected for each case. Medical utilization and psychiatric comorbidity before diagnosing AD were analyzed using conditional logistic regression. RESULTS: The SIR of incident AD was 3.36 for men and 6.29 for women. Women with PD and incident AD had more visits to the outpatient department than the controls did, whereas men exhibited no significant differences. Women with incident AD were more likely to comorbid with depressive disorder (adjusted risk ratio [aRR] = 2.94), personality disorder (aRR = 5.03), and sleep disorder (aRR = 1.72), whereas men with incident AD were more likely to comorbid with sleep disorder (aRR = 1.85) and other substance use disorders (aRR = 3.08). CONCLUSION: Patients with PD have an additional risk of developing AD compared with the general population, and that risk is higher in women. Women and men exhibited dissimilar patterns of medical utilization and psychiatric comorbidity before developing AD. Sex differences should be taken into consideration when establishing preventive measures.

13.
Ophthalmol Retina ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31690541

RESUMO

PURPOSE: To examine the relationship between diabetic macular edema (DME) and quantitative ultra-widefield fluorescein angiography (UWFA) metrics of ischemia, leakage, and microaneurysms. DESIGN: Retrospective image analysis study. PARTICIPANTS: Eyes with diabetic retinopathy that had undergone spectral-domain OCT, UWFA, and ultra-widefield fundus photography. METHODS: OCT images were analyzed to determine the presence or absence of DME, central subfield thickness (CST), and subretinal fluid. Using a semiautomated analysis platform, UWFA images were segmented for ischemia, leakage, and microaneurysms with manual correction as needed. Clinical variables, including age, gender, race, hemoglobin A1C levels, blood pressure, cholesterol levels, use of blood thinners, smoking status, and lens status also were evaluated. MAIN OUTCOME MEASURES: Factors associated with the presence and severity of DME. RESULTS: A total of 304 eyes (156 right eyes, 148 left eyes) from 178 diabetic patients were analyzed in the study. Panretinal leakage index, microaneurysm count, and ischemic index were not significantly different between eyes with and without DME in univariate assessment. Zonal assessments of macular microaneurysms and macular leakage index values revealed that eyes with DME showed a significantly higher microaneurysm count (P = 0.001) and leakage index (P < 0.0001) in the posterior pole compared with eyes without DME. Severity of macular thickening (i.e., CST) was associated significantly with macular leakage index and posterior pole microaneurysm count (P = 0.0002 and P = 0.03, respectively). In addition to posterior pole leakage index and microaneurysm count, DME was associated with older age (P < 0.01), higher systolic blood pressure (P < 0.001), and white race (P = 0.03). Multivariate assessment confirmed the independent association of presence of DME with macular leakage index and macular microaneurysm count (P < 0.01). CONCLUSIONS: Quantitative measures of leakage index and microaneurysm count in the posterior pole on UWFA images were associated with the presence and severity of DME. Panretinal analyses were not linked to DME as strongly. Additional research is needed to determine the role of quantitative UWFA in predicting DME development and characterizing patient prognosis.

14.
Am J Addict ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691402

RESUMO

BACKGROUND AND OBJECTIVES: Ketamine has emerged as one of the major illicit substances worldwide. Craving, a primary symptom for addiction, is a key challenge for ketamine abusers attempting abstinence. A link between craving and negative affect has been suggested previously for other substances. We examined the relationship between craving and negative effect (depression and anxiety) in patients with ketamine dependence (KD) undergoing withdrawal treatment. METHODS: We included 104 patients with KD (76 males and 28 females) who received inpatient treatment for ketamine withdrawal and assessed them by using Beck Depression Inventory (BDI), Beck Anxiety Inventory, and a visual analog scale (VAS; 0-100 mm) for ketamine craving on day 2 to 3 of admission. RESULTS: Fifty-nine (59%) and 38 (38.7%) of our patients reported moderate-to-severe depression and anxiety symptoms, respectively. Patients with greater cravings (ie, greater than the median VAS) reported spending more days on ketamine in the preceding month and displayed severer depressive symptoms than did those with lower cravings. VAS was significantly correlated with BDI scores after adjustment. Patients who stayed in the treatment longer (more than 2 weeks) experienced more cravings and depressive symptoms than those who did not. DISCUSSION AND CONCLUSIONS: We observed a high prevalence of depression in patients with KD, particularly those with higher cravings. Patients with greater cravings and severer depression might require a longer duration of withdrawal treatment. SCIENTIFIC SIGNIFICANCE: This research provides intimal evidence for an association between depression and craving in patients with KD. Screening and management of depression are recommended for this population. (Am J Addict 2019;00:00-00).

15.
Int J Mol Sci ; 20(23)2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31779216

RESUMO

Brassica napus (oilseed rape) is an economically important oil crop worldwide. Sclerotinia stem rot (SSR) caused by Sclerotinia sclerotiorum is a threat to oilseed rape production. Because the flower petals play pivotal roles in the SSR disease cycle, it is useful to express the resistance-related genes specifically in flowers to hinder further infection with S. sclerotiorum. To screen flower-specific promoters, we first analyzed the transcriptome data from 12 different tissues of the B. napus line ZS11. In total, 249 flower-specific candidate genes with high expression in petals were identified, and the expression patterns of 30 candidate genes were verified by quantitative real-time transcription-PCR (qRT-PCR) analysis. Furthermore, two novel flower-specific promoters (FSP046 and FSP061 promoter) were identified, and the tissue specificity and continuous expression in petals were determined in transgenic Arabidopsis thaliana with fusing the promoters to ß-glucuronidase (GUS)-reporter gene. GUS staining, transcript expression pattern, and GUS activity analysis indicated that FSP046 and FSP061 promoter were strictly flower-specific promoters, and FSP046 promoter had a stronger activity. The two promoters were further confirmed to be able to direct GUS expression in B. napus flowers using transient expression system. The transcriptome data and the flower-specific promoters screened in the present study will benefit fundamental research for improving the agronomic traits as well as disease and pest control in a tissue-specific manner.

16.
Genome Biol ; 20(1): 255, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779666

RESUMO

BACKGROUND: The 3-dimensional (3D) conformation of chromatin inside the nucleus is integral to a variety of nuclear processes including transcriptional regulation, DNA replication, and DNA damage repair. Aberrations in 3D chromatin conformation have been implicated in developmental abnormalities and cancer. Despite the importance of 3D chromatin conformation to cellular function and human health, little is known about how 3D chromatin conformation varies in the human population, or whether DNA sequence variation between individuals influences 3D chromatin conformation. RESULTS: To address these questions, we perform Hi-C on lymphoblastoid cell lines from 20 individuals. We identify thousands of regions across the genome where 3D chromatin conformation varies between individuals and find that this variation is often accompanied by variation in gene expression, histone modifications, and transcription factor binding. Moreover, we find that DNA sequence variation influences several features of 3D chromatin conformation including loop strength, contact insulation, contact directionality, and density of local cis contacts. We map hundreds of quantitative trait loci associated with 3D chromatin features and find evidence that some of these same variants are associated at modest levels with other molecular phenotypes as well as complex disease risk. CONCLUSION: Our results demonstrate that common DNA sequence variants can influence 3D chromatin conformation, pointing to a more pervasive role for 3D chromatin conformation in human phenotypic variation than previously recognized.

17.
Materials (Basel) ; 12(21)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31731398

RESUMO

The effect of compression on the thermal conductivity of CuGaS2, CuInS2, CuInTe2, and AgInTe2 chalcopyrites (space group I-42d) was studied at 300 K using phonon Boltzmann transport equation (BTE) calculations. The thermal conductivity was evaluated by solving the BTE with harmonic and third-order interatomic force constants. The thermal conductivity of CuGaS2 increases with pressure, which is a common behavior. Striking differences occur for the other three compounds. CuInTe2 and AgInTe2 exhibit a drop in the thermal conductivity upon increasing pressure, which is anomalous. AgInTe2 reaches a very low thermal conductivity of 0.2 W·m-1·K-1 at 2.6 GPa, being beneficial for many energy devices, such as thermoelectrics. CuInS2 is an intermediate case. Based on the phonon dispersion data, the phonon frequencies of the acoustic modes for CuInTe2 and AgInTe2 decrease with increasing pressure, thereby driving the anomaly, while there is no significant pressure effect for CuGaS2. This leads to the negative Grüneisen parameter for CuInTe2 and AgInTe2, a decreased phonon relaxation time, and a decreased thermal conductivity. This softening of the acoustic modes upon compression is suggested to be due to a rotational motion of the chalcopyrite building blocks rather than a compressive oscillation. The negative Grüneisen parameters and the anomalous phonon behavior yield a negative thermal expansion coefficient at lower temperatures, based on the Grüneisen vibrational theory.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31752489

RESUMO

Halide perovskites have emerged as promising candidates as the active material in photovoltaics and light-emitting diodes. They possess unusual bulk thermal transport properties that have been the focus of a number of studies, but there is much less understanding of thermal transport in thin films where a diverse range of structures and morphologies are accessible. Here, we report on the tuning of in-plane thermal conductivity in methylammonium lead iodide thin films by morphological control. Using 3-ω measurements, we find that the room temperature thermal conductivity of thermally evaporated methylammonium lead iodide perovskite films ranges from 0.31 to 0.59 W/(m K). We measure a discontinuity in thermal conductivity at the orthorhombic-tetragonal phase transition and explore this using density functional theory and attributing it to a collapse in the phonon group velocity along the c-axis of the tetragonal crystal. Moreover, we have quantified the thermal boundary resistance (Kapitza resistance) for thermally evaporated films, allowing us to estimate the Kapitza length, which is 36 ± 2 nm at room temperature and 15 ± 2 nm at 100 K. Curiously, the Kapitza resistance has a strong temperature dependence which we also explore using density functional theory, with these results suggesting an important role of methylammonium rotational modes in scattering phonons at the crystallite boundaries.

19.
Ophthalmol Retina ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31757691

RESUMO

PURPOSE: To characterize the longitudinal panretinal retinal vascular dynamics in diabetic macular edema (DME) and retinal vein occlusion (RVO) over a 12-month period while being treated with intravitreal aflibercept injections (IAIs). DESIGN: Prospective open-label study (clinicaltrials.gov identifier, NCT02503540). PARTICIPANTS: Thirty-one treatment-naive eyes with foveal-involving retinal edema secondary to DME and RVO. METHODS: Participants received 2 mg IAI every 4 weeks for the first 6 months, followed by 2 mg every 8 weeks. Ultra-widefield fluorescein angiography (UWFA; California Optos [Optos, Dunfermline, United Kingdom]) and spectral-domain OCT (Cirrus; Zeiss, Oberkochen, Germany) scans were obtained and analyzed using a novel quantitative assessment platform. Visual acuity, central subfield thickness, and adverse events also were collected. MAIN OUTCOME MEASURES: The primary end point was the mean change in panretinal leakage index at month 12 from baseline as measured by UWFA. RESULTS: Mean age was 67.1 years. At month 12, visual acuity significantly improved by a mean of 18.4±21.4 letters (P < 0.0001), and central subfield thickness also improved significantly, with a mean reduction of 301.3±250.3 µm (P < 0.0001). Mean panretinal leakage index improved significantly, decreasing from 3.4% at baseline to 0.5% at month 6 (P <0.0001) and 0.4% at month 12 (P < 0.0001). Panretinal ischemic index did not demonstrate any significant change but showed a nonsignificant increase from 5.5% at baseline to 6.1% at month 6 (P = 0.315) and 8.7% at month 12 (P = 0.193). Eyes with DME showed a decrease in leakage index from 3.5±2.7% at baseline to 1.6±0.8% at month 12 (P = 0.018) and overall stability in ischemic index from 5.0±4.1% at baseline to 4.7±3.5% at month 12 (P = 0.689). Participants with RVO showed a decrease in leakage index from 3.3±1.1% at baseline to 0.02±0.03% at 12 months (P < 0.0001) and a nonsignificant increase in ischemic index from 5.9±4.5% at baseline to 12.6±9.8% at month 12 (P = 0.172). CONCLUSIONS: Intravitreal aflibercept injections resulted in a dramatic reduction in panretinal leakage index. Panretinal ischemic index did not improve and trended toward worsening.

20.
Eur J Med Chem ; : 111891, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759730

RESUMO

In 10-15% of cancers, telomere maintenance is provided by a telomerase-independent mechanism known as alternative lengthening of telomere (ALT), making telomerase inhibitors ineffective on these cancers. Ligands that stabilize telomeric G-quadruplex (G4) are considered to be able to inhibit either the ALT process or disrupt the T-loop structure, which would be promising therapeutic agents for ALT cancers. Notably, the 3'-terminal overhang of telomeric DNA might fold into multimeric G4 containing consecutive G4 subunits, which offers an attractive target for selective ligands considering large numbers of G4s widespread in the genome. In this study, a dimeric aryl-substituted imidazole (DIZ-3) was developed as a selective multimeric G4 ligand based on a G4-ligand-dimerizing strategy. Biophysical experiments revealed that DIZ-3 intercalated into the G4-G4 interface, stabilizing the higher-order structure. Furthermore, this ligand was demonstrated to induce cell cycle arrest and apoptosis, and thus inhibited cell proliferation in an ALT cancer cell line. Cancer cells were more sensitive to DIZ-3, relative to normal cells. Notably, DIZ-3 had little effect on the transcription of several G4-dependent oncogenes. This study provides a nice example for discovering dimeric agents to potentially treat ALT cancers via targeting telomeric multimeric G4.

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