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1.
Am J Hum Genet ; 105(4): 836-843, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564437

RESUMO

Osteogenesis imperfecta (OI) comprises a genetically heterogeneous group of skeletal fragility diseases. Here, we report on five independent families with a progressively deforming type of OI, in whom we identified four homozygous truncation or frameshift mutations in MESD. Affected individuals had recurrent fractures and at least one had oligodontia. MESD encodes an endoplasmic reticulum (ER) chaperone protein for the canonical Wingless-related integration site (WNT) signaling receptors LRP5 and LRP6. Because complete absence of MESD causes embryonic lethality in mice, we hypothesized that the OI-associated mutations are hypomorphic alleles since these mutations occur downstream of the chaperone activity domain but upstream of ER-retention domain. This would be consistent with the clinical phenotypes of skeletal fragility and oligodontia in persons deficient for LRP5 and LRP6, respectively. When we expressed wild-type (WT) and mutant MESD in HEK293T cells, we detected WT MESD in cell lysate but not in conditioned medium, whereas the converse was true for mutant MESD. We observed that both WT and mutant MESD retained the ability to chaperone LRP5. Thus, OI-associated MESD mutations produce hypomorphic alleles whose failure to remain within the ER significantly reduces but does not completely eliminate LRP5 and LRP6 trafficking. Since these individuals have no eye abnormalities (which occur in individuals completely lacking LRP5) and have neither limb nor brain patterning defects (both of which occur in mice completely lacking LRP6), we infer that bone mass accrual and dental patterning are more sensitive to reduced canonical WNT signaling than are other developmental processes. Biologic agents that can increase LRP5 and LRP6-mediated WNT signaling could benefit individuals with MESD-associated OI.

2.
Lifetime Data Anal ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31576491

RESUMO

In evaluating the benefit of a treatment on survival, it is often of interest to compare post-treatment survival with the survival function that would have been observed in the absence of treatment. In many practical settings, treatment is time-dependent in the sense that subjects typically begin follow-up untreated, with some going on to receive treatment at some later time point. In observational studies, treatment is not assigned at random and, therefore, may depend on various patient characteristics. We have developed semi-parametric matching methods to estimate the average treatment effect on the treated (ATT) with respect to survival probability and restricted mean survival time. Matching is based on a prognostic score which reflects each patient's death hazard in the absence of treatment. Specifically, each treated patient is matched with multiple as-yet-untreated patients with similar prognostic scores. The matched sets do not need to be of equal size, since each matched control is weighted in order to preserve risk score balancing across treated and untreated groups. After matching, we estimate the ATT non-parametrically by contrasting pre- and post-treatment weighted Nelson-Aalen survival curves. A closed-form variance is proposed and shown to work well in simulation studies. The proposed methods are applied to national organ transplant registry data.

3.
Perit Dial Int ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582465

RESUMO

BACKGROUND: The optimal treatment for managing anemia in peritoneal dialysis (PD) patients and best clinical practices are not completely understood. We sought to characterize international variations in anemia measures and management among PD patients. METHODS: The Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) enrolled adult PD patients from 6 countries from 2014 to 2017. Hemoglobin (Hb), ferritin levels, and transferrin saturation (TSAT), as well as erythropoiesis stimulating agents (ESAs) and iron use were compared cross-sectionally at study enrollment in Australia and New Zealand (A/NZ), Canada, Japan, the United Kingdom (UK), and the United States (US). RESULTS: Among 3,603 PD patients from 193 facilities, mean Hb ranged from 11.0 - 11.3 g/dL across countries. The majority of patients (range 53% - 59%) had Hb 10 - 11.9 g/dL, with 4%- 12% patients ≥ 13 g/dL and 16% - 23% < 10 g/dL. Use of ESAs was higher in Japan (94% of patients) than elsewhere (66% - 79% of patients). In the US, 63% of patients had a ferritin level > 500 ng/mL, compared with 5% - 38% in other countries. In the US and Japan, 87% - 89% of PD patients had TSAT ≥ 20%, compared with 73% - 76% in other countries. Intravenous (IV) iron use within 4 months of enrollment was higher in the US (55% of patients) than elsewhere (6% - 17% patients). CONCLUSIONS: In this largest international observational study of anemia and anemia management in patients receiving PD, comparable Hb levels across countries were observed but with notable differences in ESA and iron use. Peritoneal dialysis patients in the US have higher ferritin levels and higher IV iron use than other countries.

4.
J Acoust Soc Am ; 146(3): 1556, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31590542

RESUMO

Temperature-induced variations of elastic moduli in solid media are generally characterized by a strong nonlinear dependence on temperature associated with complex deformations under thermal treatments. Conventional thermoelasticity with third-order elastic constants for the one-order temperature dependence has been extensively studied for crystals, but encountering problems of divergent and limited velocity variations for rocks as a polycrystal mixture, especially at high temperatures. The extension of the theory beyond high-order elastic constants to solid media is addressed in this article to describe the nonlinear temperature dependence of both elastic constants and wave velocities. The total strain is divided into the background component associated with temperature variations and the infinitesimal component induced by propagating waves. A third-order temperature dependence of velocity variations is formulated by taking into account fourth-order elastic constants. Applications to solid rocks (sandstone, granite, and olivine) demonstrate an accurate description of temperature-induced variations, especially for high temperatures. Unlike crystals, the synthetic averaging elastic constants for a solid rock (as a polycrystal mixture) change less than 10% with temperatures. The thermal sensitivity of P-wave velocities is much more than that of S-wave velocities over the vast majority of temperatures examined.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31591881

RESUMO

Thermally conductive yet electrically insulating two-dimensional boron nitride nanosheet (BNNS) has been an ideal choice of the enhanced filler for improving thermal properties of polymer-based composites. As a nanofiller with ultra-high aspect ratio, BNNS results in a conspicuous stacking along the planar direction in the preparation of composites, which results in a strong anisotropy of heat transfer and suppresses out-plane thermal dissipation. Thus, it is necessary to facilitate the out-plane heat transfer by building favorable microstructure. Focusing on the structural design of nanofillers itself, here we have fabricated a novel three-dimensional nanofiller with improved out-plane connections. Carbon nanotubes (CNTs) have been grown in-situ on the surface of BNNSs using chemical vapor deposition (CVD). Utilizing this BNNS/CNT as fillers in composites, we have assembled diverse sorts of composites, such as the flexible films, scleroid 3D mats, painted ink, and viscous grease. Simultaneously, their thermal and insulating properties have been evaluated. The results indicate that the BNNS/CNT filler has superior thermal performance over the original BNNS while maintaining a satisfactory electrical resistivity to avoid short-circuits in high-power electronics. Furthermore, the prepared grease used as a thermal interface material shows an impressive heat dissipation performance when being applied on a computer running.

6.
Dalton Trans ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577301

RESUMO

A new tellurium(vi) oxycompound, Ca10Na10[Te9O42](H2O), was synthesized by a high-temperature, high-pressure hydrothermal reaction at 550 °C, its structure determined by single-crystal X-ray diffraction, and further characterized by energy dispersive, infrared, and X-ray photoelectron spectroscopy. The compound crystallizes in the centrosymmetric trigonal space group R3[combining macron]c (no. 167) with a = 9.743(2), c = 66.337(13) Å, and Z = 6. The structure consists of discrete linear edge-sharing octahedral trimers with the composition Te3O1410-, which is a new type of finite Te-O oligomer with Te6+ only. The large complex anions form a hexagonal close-packed lattice with the octahedral and tetrahedral interstices being filled with Ca2+ and Na+ cations and water molecules. The octahedral trimers in every other h.c.p. layer rotate around the 31 screw axis for 120°; therefore the unit cell has a very long c axis. This work is one of the few examples of the synthesis of metal tellurates by supercritical hydrothermal techniques.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31600595

RESUMO

Low levels of stresses cause eustress while high stressful situations results in distress. Female rainbow trout (Oncorhynchus mykiss) was reared under crowded conditions to mimic the stressful environment of intensive fishery production. Trout was stocked for 300 days with initial densities of 4.6 ±â€¯0.02 (final: 31.1 ±â€¯0.62), 6.6 ±â€¯0.03 (final: 40.6 ±â€¯0.77), and 8.6 ±â€¯0.04 (final: 49.3 ±â€¯1.09) kg/m3 as SD1, SD2 and SD3. We assessed molecular, cellular and organismal parameters to understand the flexibility of neuro-endocrine-immune network during stress. Trout with higher initial density (SD3) displayed the slightly activated hypothalamus-pituitary-interrenal (HPI) axis with positively increased antioxidant enzyme activities and anti-inflammatory cytokine transcriptions on day 60 or 120. These results indicated that low level of stress was capable of exerting eustress by activating neuro-endocrine-immune network with beneficial adaptation when the mild stress was observed. Transition from eustress to distress was induced by the increased intensity and duration of crowding stress on day 240 and 300. The prolonged activation of HPI axis resulted in suppressed growth hormone-insulin-like growth factor (GH-IGF) axis, up-regulated cytokine transcriptions and severe reactive oxygen species stress. Stress means reset of neuro-endocrine-immune network with energy expenditure and redistribution. Digestive ability of trout with distress was also inhibited on day 240 and 300, indicating a decreased total energy supplement and energy distribution for functions are not necessary for surviving such as growth and reproduction. Consequently, we observed the dyshomeostasis of energy balance and neuro-endocrine-immune network of trout during long-term crowding conditions.

8.
Dalton Trans ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602451

RESUMO

Correction for 'Ca10Na10[Te9O42](H2O): a hydrothermally synthesized quaternary tellurium(vi) oxide containing edge-sharing octahedral trimers' by Li-Yun Zhang, et al., Dalton Trans., 2019, DOI: 10.1039/c9dt03521d.

9.
Ann Palliat Med ; 8(4): 469-475, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31594375

RESUMO

BACKGROUND: This study aimed to investigate the effects of dexmedetomidine on the post-operative recovery and mental status in patients receiving robotic-assisted thoracic surgery (RATS). METHODS: One hundred patients who received selective RATS under general anesthesia were recruited and assigned into control group (C) and dexmedetomidine group (D). The anesthesia induction and maintenance were consistent between groups. Midazolam, sufentanil, propofol and rocuronium were intravenously injected for anesthesia induction, followed by mechanical ventilation after endotracheal intubation. Sevoflurane inhalation at a minimum alveolar concentration (MAC) of 0.5 was administered, propofol and remifentanil were intravenously injected to maintain the bispectral index (BIS) at 40-60, and rocuronium was intravenously injected once every 30 min. In the D group, dexmedetomidine was intravenously injected after endotracheal intubation, and then it was injected before the end of surgery. In the C group, normal saline of equal volume was injected. The hemodynamic parameters, blood loss, urine volume, time of surgery, time of anesthesia, total dose of propofol, time of thoracic tube indwelling, hospital stay and pulmonary complications were recorded; blood gas analysis was performed after extubation; the QoR-15 and mini-mental state examination (MMSE) questionnaires were employed for the assessment of mental status at 1 and 3 days after surgery. RESULTS: The mean arterial pressure (MAP), heart rate (HR) and brain oxygenation were similar between groups at different time points (P>0.05). There were no significant differences in the operation time, time of anesthesia and intra-operative urine volume between groups. As compared to the C group, the blood loss and dose of propofol reduced significantly (P<0.05). After extubation, the respiratory frequency reduced and PaO2 increased markedly (P<0.05). After surgery, the time of thoracic tube indwelling and hospital stay reduced dramatically in the D group as compared to the C group (P<0.05). The QoR-15 score and MMSE score in the D group were markedly higher than in the C group (P<0.05). CONCLUSIONS: Dexmedetomidine can improve the post-operative recovery and mental status after RATS.

10.
Chin Med J (Engl) ; 132(19): 2269-2277, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31567477

RESUMO

BACKGROUND: Air pollutants and their pathogenic effects differ among regions and seasons. We aimed to explore the relationship between fine particulate matter (PM2.5), sulfur dioxide (SO2), and ozone-8 hours (O3-8h) concentrations in heating and non-heating seasons and the associated death risk due to cardiovascular diseases (CDs), respiratory diseases (RDs), and malignant tumors. METHODS: Data were collected in Shenyang, China, from April 2013 to March 2016. We analyzed the correlation or lagged effect of atmospheric pollutant concentration, meteorological conditions, and death risk due to disorders of the circulatory system, respiratory system, and malignant tumor in heating and non-heating seasons. We also used multivariate models to analyze the association of air pollutants during holidays with the death risk due to the evaluated diseases while considering the presence or absence of meteorological factors. RESULTS: An increase in the daily average SO2 concentration by 10 µg/m increased the death risk by CDs, which reached a maximum of 2.0% (95% confidence interval [CI]: 1.3%-2.7%) on lagging day 4 during the non-heating season and 0.2% (95% CI: 0.1%-0.4%) on lagging day 3 during the heating season. The risk of death caused by RDs peaked on lagging day 1 by 0.8% (95% CI: 0.4%-1.2%) during the heating season. An increase in O3-8h concentration by 10 µg/m increased the risk of RD-related death on lagging day 2 by 1.0% (95% CI: 0.4%-1.7%) during the non-heating season, which was significantly higher than the 0.1% (95% CI: 0-0.9%) increase during the heating season. Further, an increase in the daily average PM2.5 concentration by 10 µg/m increased the risk of death caused by RDs by 0.3% and 0.8% during heating and non-heating seasons, respectively, which peaked on lagging day 0. However, air pollution was not significantly associated with the risk of death caused by malignant tumors. CONCLUSION: Short-term exposure to PM2.5, SO2, and O3 during the non-heating season resulted in higher risks of CD-related death, followed by RD-related death.

11.
EBioMedicine ; 47: 470-483, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474551

RESUMO

BACKGROUND: NACHT and WD repeat domain-containing protein 1 (Nwd1) is a member of the innate immune protein subfamily. Nwd1 contributes to the androgen receptor signaling pathway and is involved in axonal growth. However, the mechanisms that underlie pathophysiological dysfunction in seizures remain unclear. METHODS: Biochemical methods were used to assess Nwd1 expression and localization in a mouse model of kainic acid (KA)-induced acute seizures and temporal lobe epilepsy (TLE) patients. Electrophysiological recordings were used to measure the role of Nwd1 in regulating synaptic transmission and neuronal hyperexcitability in a model of magnesium-free-induced seizure in vitro. Behavioral experiments were performed, and seizure-induced pathological changes were evaluated in a KA-induced seizure model in vivo. GluN2B expression was measured and its correlation with Tyr1472-GluN2B phosphorylation was analyzed in primary hippocampal neurons. FINDINGS: We demonstrated high protein levels of Nwd1 in brain tissues obtained from mice with acute seizures and TLE patients. Silencing Nwd1 in mice using an adeno-associated virus (AAV) profoundly suppressed neuronal hyperexcitability and the occurrence of acute seizures, which may have been caused by reducing GluN2B-containing NMDA receptor-dependent glutamatergic synaptic transmission. Moreover, the decreased activation of Nwd1 reduced GluN2B expression and the phosphorylation of the GluN2B subunit at Tyr1472. INTERPRETATION: Here, we report a previously unrecognized but important role of Nwd1 in seizure models in vitro and in vivo, i.e., modulating the phosphorylation of the GluN2B subunit at Tyr1472 and regulating neuronal hyperexcitability. Meanwhile, our findings may provide a therapeutic strategy for the treatment of epilepsy or other hyperexcitability-related neurological disorders. FUND: The funders have not participated in the study design, data collection, data analysis, interpretation, or writing of the report.

12.
Taiwan J Obstet Gynecol ; 58(5): 614-620, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31542081

RESUMO

OBJECTIVE: To culturally adapt the self-regulation questionnaire to the Taiwan Chinese version (TC-SRQ) and to evaluate its psychometric properties for gynecologic cancer survivors. MATERIALS AND METHODS: A cross-sectional study was employed with a purposive sample of 287 gynecologic cancer survivors. The TC-SRQ was adapted from a Germany version through back-translation to ensure its quality. For construct validity, confirmatory factor analysis (CFA) was used to assess the TC-SRQ measurement model with fit indexes including the χ2 test, the root mean square error of approximation (RMSEA), and the normed fit index (NFI), the comparative fit index (CFI), and non-normed fit indices (NNFI). For concurrent validity, the Taiwanese version of the European Organization for Research and Treatment of Cancer's 30-item core quality of life (EORTC QLQ-C30) questionnaire was used as a criterion measure for quality of life (QOL). Reliability was evaluated by internal consistency and test-retest reliability. RESULTS: For a modified measurement model of TC-SRQ, the model fit (χ2 = 311.23, P = .0; RMSEA = .088; NFI = .97, CFI = .98, NNFI = .97) was acceptable. The evidence of construct validity of TC-SRQ scale was confirmed by the model estimates. TC-SRQ correlated positively with the global QOL, physical, cognitive, emotional, and social functioning domains, and negatively with fatigue and pain domains of EORTC QLQ-C30. For known groups validity, TC-SRQ was correlated with groups attributed by age, family support, health status, and sleep quality. A Cronbach's α of .91 indicated good internal consistency; the test-retest reliability was .82. CONCLUSIONS: TC-SRQ is a valid and reliable instrument for assessing self-regulation in gynecologic cancer survivors.

13.
Carbohydr Polym ; 224: 115171, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472834

RESUMO

Gynecological cancers are the most commonly diagnosed forms of cancer among the female population. Chitooligosaccharides (COS)-hydrolysis products from chitosan-display high bioavailability, high water solubility, and low molecular weight properties. Here, we investigated the influence of COS on 11 gynecological tumor cell types, and subsequently elucidated molecular mechanisms through which the observed inhibition occurred. Initially, we used a controllable enzyme-membrane coupling reactor system to obtain COS with a high degree of polymerization; the yield of high-degree-polymerized COS (DP 5-12) obtained with this reactor system accounted for ∼75% yields (w/w). Using these COS materials, cell line assays showed that COS elicited the most significant anti-tumor activity against C33A cells, with anti-tumor mechanisms related to oxidative stress, as well as activation of intrinsic mitochondrial apoptosis and autophagic signaling. Thus, we provide experimental evidence to demonstrate how the enzyme-membrane coupling reactor system can generate COS that exert bioactivity against gynecological cancers.

14.
J Nat Prod ; 82(9): 2586-2593, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31532203

RESUMO

Eleven new nitrogenous meroterpenoids, cinerols A-K (1-11), were isolated from the marine sponge Dysidea cinerea collected in the South China Sea, and their structures were determined by detailed spectroscopic analysis. Cinerols A (1) and B (2) feature a rare 5H-pyrrolo[1,2a]benzimidazole moiety, while cinerols C-G (3-7) are examples of rare meroterpene benzoxazoles. The cinerols are noncytotoxic to human melanoma A375 cells at the concentration of 32 µM; however, selected cinerols exhibit moderate inhibitory activity against one or more of protein-tyrosine phosphatase 1B, ATP-citrate lyase, and SH2 domain-containing phosphatase-1 with IC50 values of 2.8-27 µM.

15.
Immunity ; 51(3): 522-534.e7, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31471107

RESUMO

Although recent progress provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), rare anti-PF therapeutics show definitive promise for treating this disease. Repeated lung epithelial injury results in injury-repairing response and inflammation, which drive the development of PF. Here, we report that chronic lung injury inactivated the ubiquitin-editing enzyme A20, causing progressive accumulation of the transcription factor C/EBPß in alveolar macrophages (AMs) from PF patients and mice, which upregulated a number of immunosuppressive and profibrotic factors promoting PF development. In response to chronic lung injury, elevated glycogen synthase kinase-3ß (GSK-3ß) interacted with and phosphorylated A20 to suppress C/EBPß degradation. Ectopic expression of A20 or pharmacological restoration of A20 activity by disturbing the A20-GSK-3ß interaction accelerated C/EBPß degradation and showed potent therapeutic efficacy against experimental PF. Our study indicates that a regulatory mechanism of the GSK-3ß-A20-C/EBPß axis in AMs may be a potential target for treating PF and fibroproliferative lung diseases.

16.
Brain Res Bull ; 153: 162-170, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31472184

RESUMO

(3ß,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX-001), a structural analogue of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effects of JLX001 on ischemic stroke (IS) and research its induction of autophagy function via 5'-AMP-activated protein kinase (AMPK)-Human Serine/threonine-protein kinase (ULK1) signaling pathway activation. The therapeutic effects of JLX001 were evaluated by infarct sizes, brain edema, neurological scores and proportion of apoptotic neurons in Sprague-Dawley (SD) rats with middle cerebral artery occlusion/reperfusion (MCAO/R). The number of autophagosomes was obtained by transmission electron microscopy. The expression of LC3-II was measured by immunofluorescence. p-AMPK and activated ULK1 were detected by western blots. Results showed that JLX001 treatment markedly alleviated cerebral infarcts, edema, neurological scores and proportion of apoptotic neurons in MCAO/R rats. The number of autophagosomes was increased, accompanying with the increased expressions of LC3-II, p-AMPK and ULK1. In summary, JLX001 attenuates cerebral ischemia injury and the underlying mechanisms may relate to inducing autophagy via AMPK-ULK1 signaling pathway activation.

17.
Molecules ; 24(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480235

RESUMO

To explore the transformation mechanisms of free gastrodin and combined gastrodin before and after steaming of Gastrodia elata (G. elata), a fresh G. elata sample was processed by the traditional steaming method prescribed by Chinese Pharmacopoeia (2015 version), and HPLC-ESI-TOF/MS method was used to identify the chemical composition in steamed and fresh G. elata. Finally, 25 components were identified in G. elata based on the characteristic fragments of the compounds and the changes of the 25 components of fresh and steamed G. elata were compared by the relative content. Hydrolysis experiments and enzymatic hydrolysis experiments of 10 monomer compounds simulating the G. elata steaming process were carried out for the first time. As a result, hydrolysis experiments proved that free gastrodin or p-hydroxybenzyl alcohol could be obtained by breaking ester bond or ether bond during the steaming process of G. elata. Enzymatic experiments showed that steaming played an important role in the protection of gastrodin, confirming the hypothesis that steaming can promote the conversion of chemical constituents of G. elata-inhibiting enzymatic degradation. This experiment clarified the scientific mechanism of the traditional steaming method of G. elata and provided reference for how to apply G. elata decoction to some extent.

18.
Biomed Pharmacother ; 118: 109394, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545259

RESUMO

The renin-angiotensin system (RAS) plays an important role in scar formation. We have previously shown that oral administration of ramipril and losartan could inhibit scarring. For easier application, here we developed a series of topical ramipril and losartan creams in different concentrations and formulations to explore the effect on scar formation in a C57BL/6 mouse scar model. The harvested scar tissues were analyzed with H&E staining, Masson staining and immunohistochemical staining. We found the group treated with 0.2% losartan urea cream (Prep. 1) or 0.1% ramipril cream (Prep. 2) had significantly smaller scars compared to the negative control, while the proliferation of fibroblasts was less active and the collagen fibers were more regular; both groups showed similar efficacy with the positive control (triamcinolone acetonide urea). We also found that drug transdermalness couldn't directly determine the efficacy. Our findings indicate that local application of angiotensin converting enzyme inhibitor drugs (ACEIs) and angiotensin receptor blocker drugs (ARBs) can reduce scarring by reducing the expression of collagen I, collagen III, phosphorylated small mothers against decapentaplegic 3 (p-Smad3) and transforming growth factor-ß 1 (TGF-ß1). This may provide new insight on scar treatment in clinic.

19.
Epigenetics ; : 1-13, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31506003

RESUMO

DNA methylation (DNAm) has a well-established association with age in many tissues, including peripheral blood mononuclear cells (PBMCs). Compared to DNAm, the closely related epigenetic modification known as DNA hydroxymethylation (DNAhm) was much more recently discovered in mammals. Preliminary investigations have observed a positive correlation between gene body DNAhm and cis-gene expression. While some of these studies have observed an association between age and global DNAhm, none have investigated region-specific age-related DNAhm in human blood samples. In this study, we investigated DNAhm and gene expression in PBMCs of 10 young and 10 old, healthy female volunteers. Thousands of regions were differentially hydroxymethylated in the old vs. young individuals in gene bodies, exonic regions, enhancers, and promoters. Consistent with previous work, we observed directional consistency between age-related differences in DNAhm and gene expression. Further, age-related DNAhm and genes with high levels of DNAhm were enriched for immune system processes which may support a role of age-related DNAhm in immunosenescence.

20.
Nanoscale ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31556427

RESUMO

Perovskite quantum dots (QDs) have been hotly pursued in recent decades owing to their quantum confinement effect and defect-tolerant nature. Their unique optical properties, such as high photoluminescence quantum yield (PLQY) approaching unity, narrow emission bandwidth, tunable wavelength spanning the entire visible spectrum, and compatibility with flexible/stretchable electronics, render perovskite QDs promising for next-generation solid lighting sources and information displays. Herein, the advances in perovskite QDs and their applications in LEDs are reviewed. Strategies to fabricate efficient perovskite QDs and device configuration, including material composition design, synthetic methods, surface engineering, and device optimization, are investigated and highlighted. Moreover, the main challenges in perovskite QDs of instability and toxicity (lead-based) are identified, while the solutions undertaken with respect to composition engineering, device encapsulation, and lead-replacement QDs are demonstrated. Meanwhile, perspectives for the further development of perovskite QDs and corresponding LEDs are presented.

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