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1.
Int J Mol Sci ; 21(3)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028614

RESUMO

The BRI1-EMS suppressor 1 (BES1)/brassinazole-resistant 1 (BZR1) transcription factors, key components in the brassinosteroid signaling pathway, play pivotal roles in plant growth and development. However, the function of BES1/BZR1 in crops during stress response remains poorly understood. In the present study, we characterized ZmBES1/BZR1-5 from maize, which was localized to the nucleus and was responsive to abscisic acid (ABA), salt and drought stresses. Heterologous expression of ZmBES1/BZR1-5 in transgenic Arabidopsis resulted in decreased ABA sensitivity, facilitated shoot growth and root development, and enhanced salt and drought tolerance with lower malondialdehyde (MDA) content and relative electrolyte leakage (REL) under osmotic stress. The RNA sequencing (RNA-seq) analysis revealed that 84 common differentially expressed genes (DEGs) were regulated by ZmBES1/BZR1-5 in transgenic Arabidopsis. Subsequently, gene ontology and KEGG pathway enrichment analyses showed that the DEGs were enriched in response to stress, secondary metabolism and metabolic pathways. Furthermore, 30 DEGs were assigned to stress response and possessed 2-15 E-box elements in their promoters, which could be potentially recognized and bound by ZmBES1/BZR1-5. Taken together, our results reveal that the ZmBES1/BZR1-5 transcription factor positively regulates salt and drought tolerance by binding to E-box to induce the expression of downstream stress-related genes. Therefore, our study contributes to the better understanding of BES1/BZR1 function in the stress response of plants.

2.
World J Surg ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002583

RESUMO

BACKGROUND: Observational studies have demonstrated improved outcomes in TBI patients receiving in-hospital beta-blockers. The aim of this study is to conduct a randomized controlled trial examining the effect of beta-blockers on outcomes in TBI patients. METHODS: Adult patients with severe TBI (intracranial AIS ≥ 3) were included in the study. Hemodynamically stable patients at 24 h after injury were randomized to receive either 20 mg propranolol orally every 12 h up to 10 days or until discharge (BB+) or no propranolol (BB-). Outcomes of interest were in-hospital mortality and Glasgow Outcome Scale-Extended (GOS-E) score on discharge and at 6-month follow-up. Subgroup analysis including only isolated severe TBI (intracranial AIS ≥ 3 with extracranial AIS ≤ 2) was carried out. Poisson regression models were used. RESULTS: Two hundred nineteen randomized patients of whom 45% received BB were analyzed. There were no significant demographic or clinical differences between BB+ and BB- cohorts. No significant difference in in-hospital mortality (adj. IRR 0.6 [95% CI 0.3-1.4], p = 0.2) or long-term functional outcome was measured between the cohorts (p = 0.3). One hundred fifty-four patients suffered isolated severe TBI of whom 44% received BB. The BB+ group had significantly lower mortality relative to the BB- group (18.6% vs. 4.4%, p = 0.012). On regression analysis, propranolol had a significant protective effect on in-hospital mortality (adj. IRR 0.32, p = 0.04) and functional outcome at 6-month follow-up (GOS-E ≥ 5 adj. IRR 1.2, p = 0.02). CONCLUSION: Propranolol decreases in-hospital mortality and improves long-term functional outcome in isolated severe TBI. This randomized trial speaks in favor of routine administration of beta-blocker therapy as part of a standardized neurointensive care protocol. LEVEL OF EVIDENCE: Level II; therapeutic. STUDY TYPE: Therapeutic study.

3.
BMC Cardiovasc Disord ; 20(1): 77, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046640

RESUMO

BACKGROUND: Identification of early signs of atherosclerosis in young adults have the potential to guide early interventions to prevent later cardiovascular disease. We therefore analyzed measures of vascular structure and function and biomarkers of cardiovascular risk in a sample of young healthy adults. METHODS: Pulse-wave velocity (PWV), carotid-intima media thickness (cIMT) and augmentation index (AIX) were measured in 834 healthy non-smokers (ages 18.0-25.9). Emphasis was put on discriminating between individuals having a vascular structure and function associated with a higher or lower risk, and cluster analysis algorithms were employed to assign the subjects into groups based on these vascular measurements. In addition, a vascular status score (VSS) was calculated by summarizing the results according to quintiles of the vascular measurements. The associations between VSS and cardiovascular biomarkers were examined by regression analyses. RESULTS: The cluster analyses did not yield sufficiently distinct clustering (groups of individuals that could be categorized unequivocally as having either a vascular structure and function associated with a higher or lower CVD risk). VSS proved a better classificatory variable. The associations between VSS and biomarkers of cardiovascular risk were analyzed by univariable and multivariable regressions. Only body fat percentage and C-reactive protein (CRP) were independently associated with VSS. CONCLUSIONS: A VSS calculation, which integrates PWV, cIMT, and AIX measurements is better suited for cardiovascular risk evaluation in young adults than cluster analyses. The independent associations of VSS with body fat percentage and CRP highlight the decisive role of adiposity and systemic inflammation in early atherosclerotic progression and suggests a subordinate role of insulin and lipid metabolism in this age span.

4.
Autophagy ; : 1-17, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32013726

RESUMO

Histone deacetylases (HDACs) are important for global gene expression and contribute to numerous physiological events. Deacetylase Rpd3 in yeast and its conserved homolog HDAC1 in mammals oppositely regulate autophagy; however, how Rpd3/HDAC1 is regulated to mediate autophagy remains unclear. Here, we showed autophagy occurrence in silkworm (Bombyx mori) required BmRpd3, wherein steroid hormone 20-hydroxyecdysone (20E) signaling regulated its protein level and nuclear localization negatively. Inhibition of MTOR led to dephosphorylation and nucleo-cytoplasmic translocation of BmRpd3/HsHDAC1. Besides, cholesterol, 20E, and 27-hydroxycholesterol could all induce massive dephosphorylation and cytoplasmic localization of BmRpd3/HsHDAC1, and thus autophagy by affecting MTORC1 activity. In addition, three phosphorylation sites (Ser392, Ser421, and Ser423) identified in BmRpd3 were conserved in HsHDAC1. Single or triple phosphorylation-site mutation attenuated the phosphorylation levels of BmRpd3/HsHDAC1, leading to their cytoplasmic localization and autophagy activation. In general, cholesterol derivatives, especially hydroxylated cholesterol, caused dephosphorylation and nucleo-cytoplasmic shuttling of BmRpd3/HsHDAC1 through inhibition of MTOR signaling to facilitate autophagy in B. mori and mammals. These findings improve our understandings of BmRpd3/HsHDAC1-mediated autophagy induced by cholesterol derivatives and shed light on their potential as a therapeutic target for neurodegenerative diseases and autophagy-related studies.Abbreviations: 20E: 20-hydroxyecdysone; 27-OH: 27-hydroxycholesterol; ACTB: actin beta; AMPK: AMP-activated protein kinase; Atg: autophagy-related; BmSqstm1: Bombyx sequestosome 1; CQ: chloroquine; HDAC: histone deacetylase; LMNB: Lamin B1; MTOR: mechanistic target of rapamycin kinase; PE: phosphatidylethanolamine; SQSTM1/p62: sequestosome 1; TUBA1A: tubulin alpha 1a.

5.
FEBS Open Bio ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32053740

RESUMO

Iron overload affects the cell cycle of various cell types, but the effect of iron overload on human pluripotent stem cells (hPSCs) has not yet been reported. Here, we show that the proliferation capacities of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) were significantly inhibited by ferric ammonium citrate (FAC) in a concentration-dependent manner. Additionally, deferoxamine (DFO) protected hESCs/hiPSCs against FAC-induced cell cycle arrest. However, iron overload did not affect pluripotency in hESCs/hiPSCs. Further, treatment of hiPSCs with FAC resulted in excess reactive oxygen species production and DNA damage. Collectively, our findings provide new insights into the role of iron homeostasis in the maintenance of self-renewal in hPSCs.

6.
Biomed Pharmacother ; 125: 109878, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32006898

RESUMO

This study aimed to investigate the efficacy and mechanism of decitabine (DAC) and all-trans retinoic acid (ATRA) in elderly acute myeloid leukemia (AML) patients and cultured cells. Our clinical trial enrolled 36 elderly patients who were judged ineligible for conventional chemotherapy, receiving DAC and ATRA regimen (DAC 20 mg/m2 days 1-5; ATRA 20 mg/m2 days 4-28 in the first cycle and days 1-28 in the subsequent cycle). Treated with a median of 3 cycles (range 1-6), 44.4 % of patients achieved complete remission (CR), 11.1 % achieved CR with incomplete peripheral count recovery (CRi) and 13.9 % achieved partial remission (PR). The median overall survival (OS) was 12.1 months; the 1-year and 2-year OS rates were 49.6 % and 17.2 %. In addition, our in vitro studies indicated that the antineoplastic activities of DAC and ATRA mutually reinforced, which induced growth inhibition, cell cycle arrest and apoptosis of AML cells. Meanwhile, we found DAC and ATRA inhibited DNMT1, activated miR-34a via promoter hypomethylation, down-regulated its target MYCN and thus exerted a synergistic antineoplastic effect. In conclusion, DAC plus ATRA regimen might be effective and well-tolerated for elderly patients partially through modulating miR-34a/MYCN axis.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32050549

RESUMO

Background: Exposures to both ambient fine particulate matter (PM2.5) and extreme weather conditions have been associated with cardiovascular disease (CVD) deaths in numerous epidemiologic studies. However, evidence on the associations with CVD deaths for interaction effects between PM2.5 and weather conditions is still limited. This study aimed to investigate associations of exposures to PM2.5 and weather conditions with cardiovascular mortality, and further to investigate the synergistic or antagonistic effects of ambient air pollutants and synoptic weather types (SWTs). Methods: Information on daily CVD deaths, air pollution, and meteorological conditions between 1 January 2012 and 31 December 2014 was obtained in Shanghai, China. Generalized additive models were used to assess the associations of daily PM2.5 concentrations and meteorological factors with CVD deaths. A 15-day lag analysis was conducted using a polynomial distributed lag model to access the lag patterns for associations with PM2.5. Results: During the study period, the total number of CVD deaths in Shanghai was 59,486, with a daily mean of 54.3 deaths. The average daily PM2.5 concentration was 55.0 µg/m3. Each 10 µg/m3 increase in PM2.5 concentration was associated with a 1.26% (95% confidence interval (CI): 0.40%, 2.12%) increase in CVD mortality. No SWT was statistically significantly associated with CVD deaths. For the interaction between PM2.5 and SWT, statistically significant interactions were found between PM2.5 and cold weather, with risk for PM2.5 in cold dry SWT decreasing by 1.47% (95% CI: 0.54%, 2.39%), and in cold humid SWT the risk decreased by 1.45% (95% CI: 0.52%, 2.36%). In the lag effect analysis, statistically significant positive associations were found for PM2.5 in the 1-3 lag days, while no statistically significant effects were found for other lag day periods. Conclusions: Exposure to PM2.5 was associated with short-term increased risk of cardiovascular deaths with some lag effects, while the cold weather may have an antagonistic effect with PM2.5. However, the ecological study design limited the possibility to identify a causal relationship, so prospective studies with individual level data are warranted.

8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 60-66, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31950791

RESUMO

Objective: To optimize the preparation parameters of the new silk birth-canal microecology transporter (BMT) for transferring the symbiotic bacteria of the birth canal efficiently. Methods: Birth canal microbial samples of 30 full term pregnant women at admission were collected as the control group (NC, n=30). The experimental group included 18 pregnant women terminated by Cesarean section, who were divided into 6 sub-groups (M1-M6, n=3) to complete the transfer tests of the birth-canal microecology. The new silk BMT was processed in the sterile liquid of the different osmotic pressure with the different immersion depth, and was placed in the vagina of the pregnant women for 1 h before sealed. All extracted DNA specimens were amplified in the V3-V4 region of the 16S rDNA, and were sequenced by Illumina Hiseq2500. Microbial diversity analysis was performed by Mothur, QIIME, Lefse and Metastat. Welch's t-test and Anosim nonparametric test were used to compare the difference between groups. Results: The new silk BMT with 70% immersion depth could be fully covered by the solution, and had good solution preserving and adhesion. The subjects had no foreign body sensation with satisfied experience. Both of the microbes on the new BMT and the control group were lactobacillus as the dominant bacteria genus. The microbial diversity and bacteria constitution in the new BMT was similar to the control group in the condition of 0.45% NaCl solution and 70% immersion depth, and there was no significant difference between the two groups ( P>0.05). Conclusion: The new silk BMT can transfer the symbiotic microbes of the birth canal efficiently, and the optimal preparation parameters were 0.45% hypotonic saline solution and 70% immersion depth.


Assuntos
Técnicas Microbiológicas , Microbiota , Seda , Vagina , Bactérias/classificação , Biodiversidade , Cesárea , Feminino , Humanos , Lactobacillus/fisiologia , Técnicas Microbiológicas/métodos , Microbiota/fisiologia , Gravidez , Vagina/microbiologia
9.
Int J Hyg Environ Health ; 224: 113427, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31978725

RESUMO

BACKGROUND: Early life exposure to triclosan, an emerging endocrine disrupting chemical, may adversely impact childhood neurodevelopment, but limited epidemiologic studies have examined the associations. OBJECTIVE: We evaluated the associations between prenatal and postnatal triclosan exposure and child neurodevelopment at 3 years. METHODS: The study included 377 mother-child pairs who participated in Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. Triclosan concentrations in maternal and 3-year-old child urine samples were quantified using gas chromatography-tandem mass spectrometry (GC-MS/MS). Gesell Developmental Schedules (GDS) were used to assess child neurodevelopment at 3 years of age. Multivariate linear regression models were applied to estimate associations of prenatal and postnatal urinary triclosan concentrations with children's developmental quotients (DQs). RESULTS: Detection frequencies of triclosan in maternal and childhood urine samples were 100% and 99.5%, respectively. The median values of prenatal and postnatal urinary triclosan levels were 0.65 and 0.44 µg/L, respectively. One ln-unit increase of maternal urinary triclosan concentration was associated with increase of DQ scores in motor area of children (regression coefficient, ß = 0.28, 95% confidence interval, CI: 0.03, 0.54; p = 0.03). In sex-stratified analyses, maternal urinary triclosan levels were significantly related to increases in DQ scores in motor area among boys (ß = 0.25, 95%CI: 0.01, 0.50; p = 0.04), while postnatal urinary triclosan concentrations were inversely associated with DQ scores in social area in boys (ß = -0.37, 95%CI: -0.72, -0.03; p = 0.03). CONCLUSIONS: The findings suggested that prenatal triclosan exposure predicted increases in motor scores, while postnatal triclosan exposure was related to reductions in social scores of 3-year-old children. These associations were only observed in boys. The biological mechanisms linking triclosan exposure to neurodevelopment await further studies.

10.
J Hazard Mater ; 387: 122021, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31927254

RESUMO

The overuse of sulfonamides, causing serious pollution of water bodies, has drawn great attention from society. To address these problems, a novel CuFe2O4/MXene (CFO/Ti3C2) heterojunction photocatalyst was used to photodegrade the antibiotic sulfamethazine (SMZ, a typical pollutant) under visible light, and the synergy and coupling function of the two components in the heterojunction system were analyzed. With the aid of time-resolved photoluminescence (TRPL) and transient surface photovoltage (TPV) spectra, the carrier lifetimes and kinetic behaviors were studied, revealing that the lifetime of photoinduced carriers was prolonged by loading Ti3C2, inhibiting the reorganization of photogenerated electron holes. More importantly, the organic intermediates and mineralization degree were identified by high-performance liquid chromatography (HPLC)-mass spectrometry (MS) and total organic carbon (TOC) techniques. The results show that the breaking of SN bonds, the oxidation of aniline and deamination were dominated by the attack of •OH. This work shows a new model for the degradation mechanism of SMZ over CFO/MXene heterostructures.

11.
Eur J Pain ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31976585

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional disease characterized by chronic abdominal pain and changes in bowel movements. Effective therapy for visceral hypersensitivity in IBS patients remains challenging. This study investigated the roles of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) and the effect of ANA-12 (a selective antagonist of TrkB) on chronic visceral hypersensitivity in an IBS-like rat model. METHODS: An IBS-like rat model was established through neonatal maternal separation (NMS), and visceral hypersensitivity was assessed by electromyographic (EMG) responses of the abdominal external oblique muscles to colorectal distention (CRD). Different doses of ANA-12 were injected intrathecally to investigate the effect of that drug on visceral hypersensitivity, and the open field test was performed to determine whether ANA-12 had side effects on movement. Thoracolumbar spinal BDNF, TrkB receptor and Protein kinase Mζ (PKMζ) expression were measured to investigate their roles in chronic visceral hypersensitivity. Whole-cell recordings were made from thoracolumbar superficial dorsal horn (SDH) neurons of lamina II. RESULTS: The expression of BDNF and TrkB was enhanced in the thoracolumbar spinal cord of the NMS animals. ANA-12 attenuated visceral hypersensitivity without side effects on motricity in NMS rats. PKMζ expression significantly decreased after the administration of ANA-12. The frequency of spontaneous excitatory postsynaptic currents (sEPSCs) increased in the thoracolumbar SDH neurons of lamina II in NMS rats. The amplitude and frequency of sEPSCs were reduced after perfusion with ANA-12 in NMS rats. CONCLUSIONS: Neonatal maternal separation caused visceral hypersensitivity and increased synaptic activity by activating BDNF-TrkB-PKMζ signalling in the thoracolumbar spinal cord of adult rats. PKMζ was able to potentiate AMPA receptor (AMPAR)-mediated sEPSCs in NMS rats. ANA-12 attenuated visceral hypersensitivity and synaptic activity by blocking BDNF/TrkB signalling in NMS rats. SIGNIFICANCE: ANA-12 attenuates visceral hypersensitivity via BDNF-TrkB-PKMζ signalling and reduces synaptic activity through AMPARs in NMS rats. This knowledge suggests that ANA-12 could represent an interesting novel therapeutic medicine for chronic visceral hypersensitivity.

12.
BMJ ; 368: l7057, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996343

RESUMO

OBJECTIVE: To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life. DESIGN: National register based birth cohort study with a sibling comparison design. SETTING: Sweden. PARTICIPANTS: 1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014. MAIN OUTCOME MEASURE: Fractures by attained age up to 32 years. RESULTS: During a median follow-up of 21.1 years, 377 970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and ≥10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models. CONCLUSION: Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.


Assuntos
Fraturas Ósseas , Gestantes/psicologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar , Adulto , Fatores Etários , Criança , Correlação de Dados , Feminino , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/epidemiologia , Humanos , Lactente , Masculino , Gravidez , Sistema de Registros/estatística & dados numéricos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Suécia/epidemiologia
13.
J Biol Chem ; 295(6): 1646-1657, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31907282

RESUMO

Legionella pneumophila is the causative agent of the lung malady Legionnaires' disease, it modulates host function to create a niche termed the Legionella-containing vacuole (LCV) that permits intracellular L. pneumophila replication. One important aspect of such modulation is the co-option of the host ubiquitin network with a panel of effector proteins. Here, using recombinantly expressed and purified proteins, analytic ultracentrifugation, structural analysis, and computational modeling, along with deubiquitinase (DUB), and bacterial infection assays, we found that the bacterial defective in organelle trafficking/intracellular multiplication effector Ceg23 is a member of the ovarian tumor (OTU) DUB family. We found that Ceg23 displays high specificity toward Lys-63-linked polyubiquitin chains and is localized on the LCV, where it removes ubiquitin moieties from proteins ubiquitinated by the Lys-63-chain type. Analysis of the crystal structure of a Ceg23 variant lacking two putative transmembrane domains at 2.80 Å resolution revealed that despite very limited homology to established members of the OTU family at the primary sequence level, Ceg23 harbors a catalytic motif resembling those associated with typical OTU-type DUBs. ceg23 deletion increased the association of Lys-63-linked polyubiquitin with the bacterial phagosome, indicating that Ceg23 regulates Lys-63-linked ubiquitin signaling on the LCV. In summary, our findings indicate that Ceg23 contributes to the regulation of the association of Lys-63 type polyubiquitin with the Legionella phagosome. Future identification of host substrates targeted by Ceg23 could clarify the roles of these polyubiquitin chains in the intracellular life cycle of L. pneumophila and Ceg23's role in bacterial virulence.

14.
J Coll Physicians Surg Pak ; 30(1): 73-78, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31931937

RESUMO

OBJECTIVE: To compare the results of the intramedullary nail (IMN) and compression plate fixation performed for humeral shaft fracture as to determine a better option out of the two. STUDY DESIGN: Comparative study. PLACE AND DURATION OF STUDY: First Affiliated Hospital of Jinzhou Medical University, Liaoning, PR China, from October 2016 to January 2019. METHODOLOGY: Patients treated with IMN (n=26) or plate fixation (n=30) for humeral shaft fracture were included in this study. Assessment was done in terms of perioperative parameters, complications, union time, and functional outcomes. Functional outcome were compared between the two groups at each follow-up (6 weeks, 3, 6, and 12 months) and between the subsequent follow-ups in both groups using the repeated measures ANOVA. RESULTS: Intraoperative blood loss, operative time, hospital stay, and union time were significantly lower in the IMN group. There was no significant difference in the functional outcomes when it was compared between the two groups at each follow-up. However, when it was compared between subsequent follow-ups, a significant improvement was observed in both groups. Increase incidence of individual complication and reoperation were established in the plating group, but without a significant difference. Yet, the overall complications rate was significantly higher in the plating group. CONCLUSION: IMN fixation led to a significant decrease in intraoperative blood loss, shorter operating time, hospital stay, union time, and a lower rate of overall complications. Thus, IMN may be a better choice of internal fixation as it also accelerates the patients' recovery, and increases their satisfaction.

15.
Analyst ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31894761

RESUMO

Graphene oxide (GO) is capable of quenching fluorescence in bound fuel single stranded DNA (ssDNA) labeled with dye. In the presence of target microRNA let-7a, two cascaded toehold-mediated strand displacement reactions (TSDRs) were triggered, thereby desorbing substantial π-π stacking adsorbed fuel DNA from GO through recycling amplification, simultaneously accompanied with the restoration of dye fluorescence. By coupling dsDNA-AuNPs with the GO nanosheet, the proposed strategy achieved a non-enzymatic sensitive assay with a low detection limit of 3.9 pM. Hence, the proposed approach has great potential for applications in early cancer diagnosis and clinical analysis.

16.
Biomaterials ; 234: 119771, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31951972

RESUMO

Glucose oxidase (GOx)-mediated starvation circumvents the energy supply for tumor growth, which has been proved as a potent tumor treatment modality. However, tumor hypoxia negatively affects the efficacy of oxygen-involved glucose decomposition reaction. Moreover, curative effect via glucose depletion is not usually satisfactory enough and adjuvant remedies are always required for a promoted tumor ablation. Herein, a multifunctional nanoreactor based on hollow Bi2Se3 nanoparticles was developed by loading oxygenated perfluorocarbon (PFC) and surface modification with GOx, which was exploited for an enhanced tumor starvation and highly sensitive photothermal therapy (PTT). GOx-mediated tumor starvation could impede the adenosine triphosphate (ATP) generation and further downregulate the expression of heat shock protein (HSP) to decrease the thermoresistance of cells. Afterwards, near infrared (NIR) laser irradiation was performed not only to trigger sensitized PTT but also to initiate the release of encapsulated oxygen to relieve local hypoxia. Then, such GOx-mediated tumor starvation would be further amplified, accompanying with secondary enhanced suppression of HSP. Both in vitro and in vivo investigations demonstrated that such nanoreactor can realize a fascinating therapeutic outcome with minimal adverse effects in virtue of the improved synergistic starvation therapy and PTT. Taken together, the proposed treatment paradigm may inspire the future development of more intelligent nanoplatforms toward high efficient cancer therapy.

17.
Scand J Gastroenterol ; : 1-9, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906738

RESUMO

Objective: Determine diagnostic accuracy of a quantitative faecal immunochemical haemoglobin test (QuikRead go® FIT, Orion Diagnostica Oy) in symptomatic patients referred for colonoscopy, at various cut-offs and for one or two tests.Methods: Patients referred to four endoscopy units in mid-Sweden between 2013 and 2017 provided information on lower abdominal symptoms and faecal samples from two separate days prior to colonoscopy.Results: In all, 5.4% (13/242) patients had colorectal cancer (CRC). For one FIT at cut-off 10 µg Hb/g faeces, sensitivity for CRC was 92% (95% CI 78-100%) and specificity 77% (95% CI 72-83%); equal to 74%; 95% CI 68-80 (178/242) colonoscopies potentially avoidable and one CRC missed. Based on the maximal outcome of two FITs, sensitivity was 100%, specificity 71% (66-77%) and 68%; 95% CI 62-74 (160/237) colonoscopies potentially avoidable. Among 17% (42/242) patients with one FIT of >200 µg Hb/g faeces, 85% (11/13) had CRC. Positive predictive values of FIT varied 16.9-26.2% depending on cut-off and one or two FITs, whereas NPVs were 99% and above in all scenarios.In 60 patients reporting rectal bleeding, one FIT at cut-off 10 µg Hb/g discriminated well between CRC and other conditions (p = .001). In regression models, FIT was more important than age, sex and all symptoms.Conclusion: One or two FITs in symptomatic patients referred for colonoscopy imply powerful risk stratification abilities for CRC, even among patients reporting rectal bleeding. Larger studies in various settings will clarify how to make the best use of this opportunity. Trial registration: Clinicaltrails.gov NCT02491593.

18.
Nanoscale ; 12(3): 1707-1718, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31894823

RESUMO

Oxygen deficient TiO2-x nanoparticles (NPs) have been recognized as a category of new-fashioned photothermal agents to offer safer PTT. However, the surface of TiO2-x NPs is deficient in free active groups or radicals to conjugate functional therapeutic molecules, which seriously impedes their in-depth development for versatile medical applications. In this study, surface activation of TiO2-x NPs was realized by the facile conjugation of (3-aminopropyl)triethoxysilane (APTES) through the formation of a stable Si-O-Ti bond, and photosensitizer chlorin e6 (Ce6) was successfully modified onto the TiO2-x NP surface and with a considerably high loading content. The resultant TiO2-x@APTES/Ce6 (TAC) NPs displayed decent biosafety, rapid tumor enrichment and outstanding performance in photoacoustic (PA) imaging. Taking advantage of the intense photo-absorption in the near-infrared (NIR) region and high dose of conjugated Ce6, a powerful antitumor effect was realized based on the combination of hyperthermia-induced cell ablation and cytotoxic reactive oxygen species (ROS)-triggered apoptosis both in vitro and in vivo. Moreover, PA imaging guidance was exceptionally useful for locating the tumor position and optimizing the treatment regimens. Apart from Ce6, this elaborate modification strategy for TiO2-x is believed to be universal for steadily binding more versatile therapeutic agents, which would definitely favor the development of multifunctional TiO2-x-based nanocomplexes for enhanced tumor treatment.

19.
Nucleic Acids Res ; 48(2): 576-588, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31799609

RESUMO

Significant improvements have been made in the efficiency and accuracy of RNA 3D structure prediction methods during the succeeding challenges of RNA-Puzzles, a community-wide effort on the assessment of blind prediction of RNA tertiary structures. The RNA-Puzzles contest has shown, among others, that the development and validation of computational methods for RNA fold prediction strongly depend on the benchmark datasets and the structure comparison algorithms. Yet, there has been no systematic benchmark set or decoy structures available for the 3D structure prediction of RNA, hindering the standardization of comparative tests in the modeling of RNA structure. Furthermore, there has not been a unified set of tools that allows deep and complete RNA structure analysis, and at the same time, that is easy to use. Here, we present RNA-Puzzles toolkit, a computational resource including (i) decoy sets generated by different RNA 3D structure prediction methods (raw, for-evaluation and standardized datasets), (ii) 3D structure normalization, analysis, manipulation, visualization tools (RNA_format, RNA_normalizer, rna-tools) and (iii) 3D structure comparison metric tools (RNAQUA, MCQ4Structures). This resource provides a full list of computational tools as well as a standard RNA 3D structure prediction assessment protocol for the community.

20.
Neural Netw ; 122: 106-116, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31677439

RESUMO

This article is deeply concerned with the effects of hybrid impulses on quasi-synchronization of neural networks with mixed time-varying delays and parameter mismatches. Hybrid impulses allow synchronizing as well as desynchronizing impulses in one impulsive sequence, so their infinite time occurrence with the system may destroy the synchronization process. Therefore, the effective hybrid impulsive controller has been designed to deal with the difficulties in achieving the quasi-synchronization under the effects of hybrid impulses, which occur all the time, but their density of occurrence gradually decrease. In addition, the new concepts of average impulsive interval and average impulsive gain have been applied to cope with the simultaneous existence of synchronizing and desynchronizing impulses. Based on the Lyapunov method together with the extended comparison principle and the formula of variation of parameters for mixed time-varying delayed impulsive system, the delay-dependent sufficient criteria of quasi-synchronization have been derived for two separate cases, viz., Ta<∞ and Ta=∞. Finally, the efficiency of the theoretical results has been illustrated by providing two numerical examples.

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