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1.
Biomolecules ; 11(5)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946207

RESUMO

Persistent injury and the following improper repair in bronchial epithelial cells are involved in the pathogenesis of airway inflammation and airway remodeling of asthma. E-cadherin (ECAD) has been shown to be involved in airway epithelium injury repair, but its underlying mechanisms to this process is poorly understood. Here, we describe a previously undetected function of ECAD in regulating the balance of EMT and MET during injury repair. Injury in mice and human bronchial epithelial cells (HBECs) was induced by successive ozone stress for 4 days at 30 min per day. ECAD overexpression in HBECs was induced by stable transfection. EMT features, transforming growth factor beta1 (TGF-ß1) secretion, transcriptional repressor Snail expression, and ß-catenin expression were assayed. Ozone exposure and then removal successfully induced airway epithelium injury repair during which EMT and MET occurred. The levels of TGF-ß1 secretion and Snail expression increased in EMT process and decreased in MET process. While ECAD overexpression repressed EMT features; enhanced MET features; and decreased TGF-ß1 secretion, Snail mRNA level, and ß-catenin protein expression. Moreover, activating ß-catenin blocked the effects of ECAD on EMT, MET and TGF-ß1 signaling. Our results demonstrate that ECAD regulates the balance between EMT and MET, by preventing ß-catenin to inhibit TGFß1 and its target genes, and finally facilitates airway epithelia repair.

2.
Arch Toxicol ; 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963423

RESUMO

Cigarette smoking is the major cause of chronic obstructive pulmonary disease. Considerable attention has been paid to the reduced harm potential of nicotine-containing inhalable products such as electronic cigarettes (e-cigarettes). We investigated the effects of mainstream cigarette smoke (CS) and e-vapor aerosols (containing nicotine and flavor) generated by a capillary aerosol generator on emphysematous changes, lung function, and molecular alterations in the respiratory system of female Apoe-/- mice. Mice were exposed daily (3 h/day, 5 days/week) for 6 months to aerosols from three different e-vapor formulations-(1) carrier (propylene glycol and vegetable glycerol), (2) base (carrier and nicotine), or (3) test (base and flavor)-or to CS from 3R4F reference cigarettes. The CS and base/test aerosol concentrations were matched at 35 µg nicotine/L. CS exposure, but not e-vapor exposure, led to impairment of lung function (pressure-volume loop area, A and K parameters, quasi-static elastance and compliance) and caused marked lung inflammation and emphysematous changes, which were confirmed histopathologically and morphometrically. CS exposure caused lung transcriptome (activation of oxidative stress and inflammatory responses), lipidome, and proteome dysregulation and changes in DNA methylation; in contrast, these effects were substantially reduced in response to the e-vapor aerosol exposure. Compared with sham, aerosol exposure (carrier, base, and test) caused a slight impact on lung inflammation and epithelia irritation. Our results demonstrated that, in comparison with CS, e-vapor aerosols induced substantially lower biological and pathological changes in the respiratory tract associated with chronic inflammation and emphysema.

3.
Adv Mater ; : e2005910, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33852764

RESUMO

Two of the key questions to be addressed are whether and how one can turn cocoon silk into fascinating materials with different electronic and optical functions so as to fabricate the flexible devices. In this review, a comprehensive overview of the unique strategy of mesoscopic functionalization starting from silk fibroin (SF) materials to the fabrication of various meso flexible SF devices is presented. Notably, SF materials with novel and enhanced properties can be achieved by mesoscopically reconstructing the hierarchical structures of SF materials. This is based on rerouting the refolding process of SF molecules by meso-nucleation templating. As-acquired functionalized SF materials can be applied to fabricate bio-compatible/degradable flexible/implantable meso-optical/electronic devices of various types. Consequently, functionalized SF can be fabricated into optical elements, that is, nonlinear photonic and fluorescent components, and make it possible to construct silk meso-electronics with high-performance. These advances enable the applications of SF-material based devices in the areas of physical and biochemical sensing, meso-memristors, transistors, brain electrodes, and energy generation/storage, applicable to on-skin long-term monitoring of human physiological conditions, and in-body sensing, information processing, and storage.

4.
Neurotherapeutics ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33791970

RESUMO

Abnormal redox regulation is thought to contribute to schizophrenia (SCZ). Accumulating studies have shown that the plasma antioxidant enzyme activity is closely associated with the course and outcome in antipsychotics-naïve first-episode (ANFE) patients with SCZ. The main purpose of this study was to investigate the effect of risperidone on oxidative stress markers in ANFE patients and the relationship between risperidone response and changes in oxidative stress markers. Plasma activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) enzyme, total antioxidant status (TAS), and malondialdehyde (MDA) levels were measured in 354 ANFE patients and 152 healthy controls. The clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). Patients received risperidone monotherapy for 12 weeks and oxidative stress markers and PANSS were measured at baseline and at follow-up. Compared with healthy controls, the patients exhibited higher activities of SOD, CAT, and TAS levels, but lower MDA levels and GPx activity. A comparison between 168 responders and 50 non-responders at baseline and 12-week follow-up showed that GPx activity decreased in both groups after treatment. Moreover, GPx activity decreased less in responders and was higher in responders than in non-responders at follow-up. These results demonstrate that the redox regulatory system and antioxidant defense enzymes may have predictive value for the response of ANFE patients to risperidone treatment.

5.
BMC Cancer ; 21(1): 383, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836675

RESUMO

BACKGROUND: Malignant struma ovarii (MSO) is a unique type of ovarian malignancy that data on the survival outcome is limited and management strategy remains controversial due to its extreme rarity. METHODS: To investigate the clinical characteristics and treatment options in patients with MSO confined to the ovary, while also evaluating the recurrent-free survival (RFS) and overall survival (OS) rate in this population, a retrospective study was conducted. One hundred twenty-five cases of MSO confined to the ovary were enrolled and their clinical characteristics, treatment strategies, and results of follow-up were analyzed. OS and RFS were assessed by Kaplan-Meier analyses and Cox regression models. RESULTS: The most common pathological subtype in this cohort was papillary carcinoma (44.8%). Other reported subtypes, in order of prevalence, were follicular variant of papillary carcinoma, follicular carcinoma, and mixed follicular-papillary carcinoma. Surgical treatment options varied in this cohort that 8.0% of the patients received ovarian cystectomy, 33.6% underwent unilateral salpingo-oophorectomy (USO), 5.6% received bilateral salpingo-oophorectomy (BSO), 21.6% received total abdominal hysterectomy with BSO (TAH/BSO), and 17.6% were treated with debulking surgery; 20.0% of them received radioiodine therapy (RAI). Twenty-seven patients experienced recurrence with a median RFS of 14.0 years (95% confidence interval [CI], 9.5-18.5). The 5-year and 10-year recurrent rate were 27.1, 35.2%, respectively. Eight patients died during follow-up, with five attributed to MSO; the 5-year, 10-year, and 20-year OS rate was 95.3, 88.7 and 88.7%, respectively. However, the univariate and multivariate Cox regression showed no potential risk factor for RFS and OS. CONCLUSION: Patients with MSO confined to the ovary had an excellent survival outcome, despite varied treatment strategies, and the recurrent rate was relatively high. We recommend USO as the preferred surgical option in this population since more aggressive surgery does not improve outcomes and the benefits of RAI are uncertain.

6.
Int J Psychiatry Clin Pract ; : 1-7, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879034

RESUMO

OBJECTIVE: Cognitive impairment is an essential feature of schizophrenia; however, the relationship between clinical psychiatric symptoms with cognitive impairment is still unclear. Therefore, we aimed to assess cognitive deficits and the relationship between clinical symptoms and cognitive function in patients with chronic schizophrenia, which provide a reference guide for psychiatrists. METHODS: We compared the cognitive function in 312 schizophrenia inpatients and 397 healthy controls by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The positive and negative symptom scale (PANSS) was used to assess the clinical symptoms of the patients. RESULTS: Analysis of covariance showed that the RBANS total and four index scores (all p < 0.001) were significantly lower in patients than healthy controls. After Bonferroni correction, Pearson correlation analysis showed that there was a significant negative association between PANSS negative symptom subscale and RBANS total score and all 5 domain scores (all p < 0.01). Further regression analysis showed that negative symptoms, age, age of onset, and antipsychotic dose were important independent predictors of cognitive deficits. CONCLUSIONS: Our findings suggest that patients with chronic schizophrenia exhibit cognitive deficits compared with healthy people. Negative symptoms and some clinical variables are associated with cognitive impairment in patients with schizophrenia.KEYPOINTSThis study indicates that patients with chronic schizophrenia have extensive cognitive impairment shown on RBANS except for the visuospatial/constructional domain.Cognitive impairment in patients is associated with age, negative symptoms, age of onset, and antipsychotic dose.There is a significant negative association between cognitive deficits and negative symptoms in patients with chronic schizophrenia.The results of this study need to be confirmed in future studies with longitudinal designs with a large and sex-balanced sample in first-episode drug naïve patients with schizophrenia.

7.
Nat Commun ; 12(1): 2030, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795678

RESUMO

Microglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPα, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPα in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPα results in decreased synaptic density. In human tissue, we observe that microglial SIRPα expression declines alongside the progression of Alzheimer's disease. To investigate the role of SIRPα in neurodegeneration, we modulate the expression of microglial SIRPα in mouse models of Alzheimer's disease. Loss of microglial SIRPα results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPα regulates synaptic pruning in neurodegeneration.


Assuntos
Doença de Alzheimer/genética , Modelos Animais de Doenças , Microglia/metabolismo , Plasticidade Neuronal/genética , Receptores Imunológicos/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Animais , Células Cultivadas , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Microglia/citologia , Receptores Imunológicos/metabolismo , Sinapses/metabolismo , Sinapses/fisiologia
8.
Medicine (Baltimore) ; 100(14): e25240, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832084

RESUMO

BACKGROUND: Bilateral unicompartmental knee arthroplasty (UKA) can be divided into one or two stages clinically. Compared with staged bilateral UKA, whether simultaneous bilateral UKA has better clinical efficacy remains to be verified. METHODS: PubMed, EBSCO, and Web of Science were searched by us for meta-analysis. Studies were considered eligible for inclusion if they included simultaneous and staged UKA. We excluded studies unrelated to the research question, studies in non-selected languages, and studies where the full-text was not available. The data were extracted by two independent investigators, and disagreements were resolved through discussions with a third party. If important data or information about the content of the paper were not available, authors were contacted. Publication bias in studies has been assessed. Meta-analysis was done using Review Manager 5.3. RESULTS: The systematic review and meta-analysis identified 3370 trials, of which 8 studies (963 patients) compared simultaneous with staged bilateral UKA. The meta-analysis showed that the clinical outcomes of simultaneous bilateral UKA goes down in operating time (weighted mean difference [WMD] = -19.34, 95% confidence interval [CI] -22.44 to -16.25, P < .00001), postoperative hemoglobin (Std. mean difference [SMD] = -0.46, 95% CI -0.71 to -0.20, P = .0004), length of stay (LOS) (WMD = -4.73, 95% CI -6.39 to -3.06, P < .00001), hospital cost (SMD = -5.42, 95% CI -6.54 to -4.30, P < .00001). There were no significant difference in blood transfusion, venous thrombosis, infection, cardiac complications, pulmonary complications, Oxford Knee Score (OKS) between simultaneous and staged bilateral UKA. CONCLUSION: Simultaneous bilateral UKA can effectively reduce the operating time, LOS, and hospital cost without increasing postoperative complications compared to stage bilateral UKA. REGISTRATION NUMBER: CRD42020160056 (www.crd.york.ac.uk/prospero/).


Assuntos
Artroplastia do Joelho/métodos , Idoso , Artroplastia do Joelho/economia , Artroplastia do Joelho/estatística & dados numéricos , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-33890239

RESUMO

This paper theoretically and empirically investigates the role of noisy cognition in perceptual judgment, focusing on the central tendency effect: the well-known empirical regularity that perceptual judgments are biased towards the center of the stimulus distribution. Based on a formal Bayesian framework, we generate predictions about the relationships between subjective confidence, central tendency, and response variability. Specifically, our model clarifies that lower subjective confidence as a measure of posterior uncertainty about a judgment should predict (i) a lower sensitivity of magnitude estimates to objective stimuli; (ii) a higher sensitivity to the mean of the stimulus distribution; (iii) a stronger central tendency effect at higher stimulus magnitudes; and (iv) higher response variability. To test these predictions, we collect a large-scale experimental data set and additionally re-analyze perceptual judgment data from several previous experiments. Across data sets, subjective confidence is strongly predictive of the central tendency effect and response variability, both correlationally and when we exogenously manipulate the magnitude of sensory noise. Our results are consistent with (but not necessarily uniquely explained by) Bayesian models of confidence and the central tendency.

10.
J Biomater Sci Polym Ed ; : 1-13, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830881

RESUMO

The application of 3D printing technology in tissue engineering has become increasingly important. However, due to the limitations of bio-ink, there are still some remaining problems. For example, the major challenge for ideal bio-ink is to maintain stable 3D structure and good biocompatibility in the meantime while conventional gels are week and nearly unprintable. So, the development of new bio-ink material with improved rheological and mechanical properties is highly demanded to avoid compromising biocompatibility for tissue engineering. Silk fibroin (SF), a natural degradable polymer, is considered to be a proper material for the preparation of bio-inks. We used SF, gelatin, and polyols as raw materials to fabricate bio-inks and scaffolds. We evaluated the rheological properties and printability of bio-inks with a rotational rheometer and a 3D printer. The scaffolds were prepared by crosslinking and freeze-drying technologies. The biocompatibility and osteoinductive functions of scaffolds were investigated by evaluating proliferation, osteogenic differentiation and related cell signaling of cultured MC3T3-E1 cells. The results showed that the scaffolds using SF, Gel and propanediol (PG) not only had good rheological properties and storage modulus, but also could better enhance osteogenic specific genes expression mediated by Smad1/5/8 and Runx2 pathways. What is more, morphological characterization showed that α-mem incubation could help scaffold form porous structure on its surface, which could shed a light on a new 3D bio-printed bone repair scaffold with both naturally emerged and CAD-designed porous structure. Our findings provide a potential biomaterial for the treatment of bone tissue regeneration.

11.
Synapse ; : e22201, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797795

RESUMO

Traumatic brain injury (TBI) is a world-wide leading health problem with high morbidity and mortality rates. Emerging studies have demonstrated that TBI is the consequence of a series of inflammatory responses in the body. The alteration of Cystatin C (Cys C) was reported in a variety of chronic inflammatory diseases and was also recommended as a biomarker for predicting renal diseases. In this study, we aimed to investigate the relationship between serum Cys C and TBI, and to evaluate the prognostic role of Cys C in TBI prediction. One hundred and seventy-six patients with TBI were recruited and 102 patients were finally analyzed, with 30 healthy control subjects. The concentrations of Cys C were significantly reduced in the healthy control group compared to the TBI group, and correlated with high GCS scores. The levels of hsCRP, counts of white blood cells, and levels of IL-6 and TNF-α were remarkably elevated in the TBI patients compared with the control group in a severity-dependent manner. Moreover, the concentration of Cys C was negatively correlated with TBI severity and positively correlated with inflammatory factors. In conclusion, serum Cys is an inflammatory cytokine-related factor and might indicate the severity of TBI thus serving as a prognostic biomarker.

12.
Molecules ; 26(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801899

RESUMO

Natural products are important sources for drug discovery, especially anti-tumor drugs. ß-Elemene, the prominent active ingredient extract from the rhizome of Curcuma wenyujin, is a representative natural product with broad anti-tumor activities. The main molecular mechanism of ß-elemene is to inhibit tumor growth and proliferation, induce apoptosis, inhibit tumor cell invasion and metastasis, enhance the sensitivity of chemoradiotherapy, regulate the immune system, and reverse multidrug resistance (MDR). Elemene oral emulsion and elemene injection were approved by the China Food and Drug Administration (CFDA) for the treatment of various cancers and bone metastasis in 1994. However, the lipophilicity and low bioavailability limit its application. To discover better ß-elemene-derived anti-tumor drugs with satisfying drug-like properties, researchers have modified its structure under the premise of not damaging the basic scaffold structure. In this review, we comprehensively discuss and summarize the potential anti-tumor mechanisms and the progress of structural modifications of ß-elemene.

13.
J Appl Toxicol ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33825214

RESUMO

Cigarette smoking is one major modifiable risk factor in the development and progression of chronic obstructive pulmonary disease and cardiovascular disease. To characterize and compare cigarette smoke (CS)-induced disease endpoints after exposure in either whole-body (WB) or nose-only (NO) exposure systems, we exposed apolipoprotein E-deficient mice to filtered air (Sham) or to the same total particulate matter (TPM) concentration of mainstream smoke from 3R4F reference cigarettes in NO or WB exposure chambers (EC) for 2 months. At matching TPM concentrations, we observed similar concentrations of carbon monoxide, acetaldehyde, and acrolein, but higher concentrations of nicotine and formaldehyde in NOEC than in WBEC. In both exposure systems, CS exposure led to the expected adaptive changes in nasal epithelia, altered lung function, lung inflammation, and pronounced changes in the nasal epithelial transcriptome and lung proteome. Exposure in the NOEC caused generally more severe histopathological changes in the nasal epithelia and a higher stress response as indicated by body weight decrease and lower blood lymphocyte counts compared with WB exposed mice. Erythropoiesis, and increases in total plasma triglyceride levels and atherosclerotic plaque area were observed only in CS-exposed mice in the WBEC group but not in the NOEC group. Although the composition of CS in the breathing zone is not completely comparable in the two exposure systems, the CS-induced respiratory disease endpoints were largely confirmed in both systems, with a higher magnitude of severity after NO exposure. CS-accelerated atherosclerosis and other pro-atherosclerotic factors were only significant in WBEC.

14.
Preprint | bioRxiv | ID: ppbiorxiv-442010

RESUMO

Antivirals are urgently needed to combat the global SARS-CoV-2/COVID-19 pandemic, supplement existing vaccine efforts, and target emerging SARS-CoV-2 variants of concern. Small molecules that interfere with binding of the viral spike receptor binding domain (RBD) to the host ACE2 receptor may be effective inhibitors of SARS-CoV-2 cell entry. Here we screened 512 pure compounds derived from natural products using a high-throughput RBD/ACE2 binding assay and identified (-)-hopeaphenol, a resveratrol tetramer, in addition to vatalbinoside A and vaticanol B, as potent and selective inhibitors of RBD/ACE2 binding and viral entry. For example, (-)-hopeaphenol disrupted RBD/ACE2 binding with a 50% inhibitory concentration (IC50) of 0.11 M in contrast to an IC50 of 28.3 M against the unrelated host ligand/receptor binding pair PD-1/PD-L1 (selectivity index = 257.3). When assessed against the USA-WA1/2020 variant, (-)-hopeaphenol also inhibited entry of a VSV{Delta}G-GFP reporter pseudovirus expressing SARS-CoV-2 spike into ACE2-expressing Vero-E6 cells and in vitro replication of infectious virus in cytopathic effect assays (IC50 = 10.2 M) without cytotoxicity. Notably, (-)- hopeaphenol also inhibited two emerging variants of concern originating from the United Kingdom (B.1.1.7) and South Africa (B.1.351) in both cytopathic effect and spike-containing pseudovirus assays with similar (B.1.1.7) or improved (B.1.351) efficacies over the USA- WA1/2020 variant. These results identify (-)-hopeaphenol and related stilbenoid analogues as potent and selective inhibitors of viral entry across multiple SARS-CoV-2 variants including those with increased infectivity and/or reduced susceptibility to existing vaccines. ImportanceSARS-CoV-2 antivirals are needed to supplement existing vaccine efforts and target emerging viral variants with increased infectivity or reduced susceptibility to existing vaccines. Here we show that (-)-hopeaphenol, a naturally-occurring stilbenoid compound, in addition to its analogues vatalbinoside A and vaticanol B, inhibit SARS-CoV-2 by blocking the interaction of the viral spike protein with the cellular ACE2 entry receptor. Importantly, in addition to inhibiting the early USA-WA1/2020 SARS-CoV-2 variant, hopeaphenol also inhibits emerging variants of concern including B.1.1.7 ("United Kingdom variant") and B.1.351 ("South Africa variant"), with improved efficacy against B.1.351. (-)-Hopeaphenol therefore represents a new antiviral lead against infection from multiple SARS-CoV-2 variants.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33895839

RESUMO

OBJECTIVE: Clinical trials are an essential part of the effort to find safe and effective prevention and treatment for COVID-19. Given the rapid growth of COVID-19 clinical trials, there is an urgent need for a better clinical trial information retrieval that supports searching by specifying criteria including both eligibility criteria and structured trial information. MATERIALS AND METHODS: We built a linked graph for registered COVID-19 clinical trials: the COVID-19 Trial Graph, to facilitate retrieval of clinical trials. Natural language processing (NLP) tools were leveraged to extract and normalize the clinical trial information from both their eligibility criteria free texts and structured information from ClinicalTrials.gov. We linked the extracted data using the COVID-19 Trial Graph and imported it to a graph database, which supports both query and visualization. We evaluated trial graph using case queries and graph embedding. RESULTS: The graph currently (as of 10-05-2020) contains 3,392 registered COVID-19 clinical trials, with 17,480 nodes and 65,236 relationships. Manual evaluation of case queries found high-precision and recall scores on retrieving relevant clinical trials searching from both eligibility criteria and trial-structured information. We observed clustering in clinical trials via graph embedding, which also showed superiority over the baseline (0.8704 vs. 0.8199) in evaluating whether a trial can complete its recruitment successfully. CONCLUSIONS: The COVID-19 Trial Graph is a novel representation of clinical trials that allows diverse search queries and provides a graph-based visualization of COVID-19 clinical trials. High-dimensional vectors mapped by graph embedding for clinical trials would be potentially beneficial for many downstream applications, such as trial end recruitment status prediction, and trial similarity comparison. Our methodology also is generalizable to other clinical trials, such as cancer clinical trials.

16.
Dalton Trans ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33912883

RESUMO

van der Waals heterojunctions formed by transition metal dichalcogenides (TMDs) and fullerenes are promising candidates for novel photovoltaic devices due to the excellent optoelectronic properties of both TMDs and fullerenes. However, relevant experimental and theoretical investigations remain scarce to the best of our knowledge. Herein, we have first employed static density functional theory (DFT) calculations in combination with time-domain density functional theory (TDDFT) based nonadiabatic dynamics simulations to rationally evaluate the photovoltaic performances of four TMD@fullerene heterostructures, i.e. WSe2@C60, WSe2@C70, MoTe2@C60 and MoTe2@C70, respectively. Our simulation results indicate that the C70-based heterostructures overall have better photoinduced electron transfer efficiencies than their C60-based counterparts, among which the performance of the WSe2@C70 heterostructure is the best and the electron transfer from WSe2 to C70 almost accomplishes within 1 ps. In addition, the large build-in potential of about 0.75 eV of WSe2@C70 is beneficial for the charge separation processes. Our present work not only selects the van der Waals TMD@fullerene heterojunctions that might have excellent photovoltaic properties, but also paves the way for the rational design of novel heterojunctions with better optoelectronic performances with DFT and TDDFT simulations in the future.

17.
Chin J Traumatol ; 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33863620

RESUMO

PURPOSE: Evidence suggests that the oxytocin receptor gene (OXTR) may be involved in the psychopathology of posttraumatic stress disorder (PTSD). This study aimed to investigate the effects of OXTR rs53576 genotype on PTSD symptoms introduced in the Diagnostic and Statistical Manual, Fifth Edition (DSM-5). METHODS: This study was a cross-sectional study conducted among 1140 adults who had personally experienced the Wenchuan earthquake. PTSD symptoms were measured with the PTSD checklist for DSM-5. A custom-by-design 2 × 48-Plex SNPscanTMKit were used to determine the OXTR rs53576. Multiple regression models were used to analyze the independent and interactive effects of OXTR rs53576 genotype and earthquake exposure on the severity of total PTSD symptoms and different dimensions of PTSD symptoms. RESULTS: The results revealed that the rs53576 genotype could significantly predict PTSD symptoms (ß = 0.055, p = 0.045). Further analysis showed that the rs53576 genotype was only significantly associated with dysphoric arousal symptoms of PTSD (ß = 0.080, p = 0.005). The rs53576 genotype × earthquake exposure interaction had no significant effect on different symptom clusters (p > 0.05). CONCLUSION: This study showed that the rs53576 genotype was only associated with the dysphoric arousal symptoms but not with other symptom clusters of PTSD. These findings support the role of the OXTR on the psychopathology of PTSD and help us understand the genetic basis of PTSD.

18.
Cells ; 10(4)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807246

RESUMO

BACKGROUND: Percutaneous transluminal renal angioplasty (PTRA) confers clinical and mortality benefits in select 'high-risk' patients with renovascular disease (RVD). Intra-renal-delivered extracellular vesicles (EVs) released from mesenchymal stem/stromal cells (MSCs) protect the kidney in experimental RVD, but have not been compared side-by-side to clinically applied interventions, such as PTRA. We hypothesized that MSC-derived EVs can comparably protect the post-stenotic kidney via direct tissue effects. METHODS: Five groups of pigs (n = 6 each) were studied after 16 weeks of RVD, RVD treated 4 weeks earlier with either PTRA or MSC-derived EVs, and normal controls. Single-kidney renal blood flow (RBF) and glomerular filtration rate (GFR) were assessed in vivo with multi-detector CT, and renal microvascular architecture (3D micro CT) and injury pathways ex vivo. RESULTS: Despite sustained hypertension, EVs conferred greater improvement of intra-renal microvascular and peritubular capillary density compared to PTRA, associated with attenuation of renal inflammation, oxidative stress, and tubulo-interstitial fibrosis. Nevertheless, stenotic kidney RBF and GFR similarly rose in both PTRA- and EV-treated pigs compared RVD + Sham. mRNA sequencing reveled that EVs were enriched with pro-angiogenic, anti-inflammatory, and antioxidants genes. CONCLUSION: MSC-derived EVs elicit a better preservation of the stenotic kidney microvasculature and greater attenuation of renal injury and fibrosis compared to PTRA, possibly partly attributed to their cargo of vasculo-protective genes. Yet, both strategies similarly improve renal hemodynamics and function. These observations shed light on diverse mechanisms implicated in improvement of post-stenotic kidney function and position EVs as a promising therapeutic intervention in RVD.

19.
BMC Anesthesiol ; 21(1): 116, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853548

RESUMO

BACKGROUND: The intrathecal hyperbaric bupivacaine dosage for cesarean section is difficult to predetermine. This study aimed to develop a decision-support model using a machine-learning algorithm for assessing intrathecal hyperbaric bupivacaine dose based on physical variables during cesarean section. METHODS: Term parturients presenting for elective cesarean section under spinal anaesthesia were enrolled. Spinal anesthesia was performed at the L3/4 interspace with 0.5% hyperbaric bupivacaine at dosages determined by the anesthesiologist. A spinal spread level between T4-T6 was considered the appropriate block level. We used a machine-learning algorithm to identify relevant parameters. The dataset was split into derivation (80%) and validation (20%) cohorts. A decision-support model was developed for obtaining the regression equation between optimized intrathecal 0.5% hyperbaric bupivacaine volume and physical variables. RESULTS: A total of 684 parturients were included, of whom 516 (75.44%) and 168 (24.56%) had block levels between T4 and T6, and less than T6 or higher than T4, respectively. The appropriate block level rate was 75.44%, with the mean bupivacaine volume [1.965, 95%CI (1.945,1.984)]ml. In lasso regression, based on the principle of predicting a reasonable dose of intrathecal bupivacaine with fewer physical variables, the model is "Y=0.5922+ 0.055117* X1-0.017599*X2" (Y: bupivacaine volume; X1: vertebral column length; X2: abdominal girth), with λ 0.055, MSE 0.0087, and R2 0.807. CONCLUSIONS: After applying a machine-learning algorithm, we developed a decision model with R2 0.8070 and MSE due to error 0.0087 using abdominal girth and vertebral column length for predicting the optimized intrathecal 0.5% hyperbaric bupivacaine dosage during term cesarean sections.

20.
New Phytol ; 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33864702

RESUMO

Drought stress seriously limits crop productivity. Although studies have been carried out, it is still largely unknown that how plant responds to drought stress. Here we find that drought treatment can enhance the phosphorylation activity of brassinosteroid-signaling kinase 1 (ZmBSK1) in maize (Zea mays). Our genetic studies reveal that ZmBSK1 positively affects drought tolerance in maize plants. ZmBSK1 localizes in plasma membrane, interacts with calcium/calmodulin-dependent protein kinase (ZmCCaMK), and phosphorylates ZmCCaMK. Ser-67 is a crucial phosphorylation site of ZmCCaMK by ZmBSK1. Drought stress enhances not only the interaction between ZmBSK1 and ZmCCaMK but also the phosphorylation of Ser-67 in ZmCCaMK by ZmBSK1. Furthermore, Ser-67 phosphorylation in ZmCCaMK regulates its Ca2+ /CaM binding, autophosphorylation activity and transphosphorylation activity, and positively affects its function in drought tolerance in maize. Our results reveal an important role of ZmBSK1 in drought tolerance and suggest a direct regulatory mode of ZmBSK1 phosphorylating ZmCCaMK.

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