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1.
Stem Cell Rev Rep ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33011925

RESUMO

Crohn's disease (CD) with externally fistulizing openings indicates the aggressive and relapsing manifestation and results in undesirable long-term outcomes of patients. MSC-based approach combined with multidisciplinary strategy has mandated a redefinition of the administration and management of numerous recurrent and refractory diseases whereas the spatio-temporal evaluation of the metabolokinetics and efficacy of MSCs on intractable CD with enterocutaneous fistula (EF) are largely inaccessible and dauntingly complex. Herein, we primitively established dual-fluorescence expressing placenta-derived MSCs (DF-MSCs) and explored their multidimensional attributes, including cytomorphology, immunophenotying, multilineage differentiation and long-term proliferation, together with the recognition of bifluorescence intensity (BLI). Then, with the aid of in vivo living imaging, clinicopathological or inflammatory cytokine examinations and in vitro analyses, we systematically and meticulously dissected the metabolokinetics and curative effect of MSCs on mice with refractory Crohn's-like EF (EF mice), together with revealing the underlying mechanism including reactive oxygen species (ROS) and neovascularization. Strikingly, the DF-MSCs exhibited stabilized BLI and biological properties. The spatio-temporal distribution and therapeutic process of MSCs in EF mice were intuitively delineated. Meanwhile, our data indicated the curative mechanisms of DF-MSCs by simultaneously downregulating ROS and accelerating neovascularization. Collectively, we systematically illuminated the spatio-temporal biofunction and mechanism of DF-MSCs on EF mice. Our findings have supplied new references for safety and effectiveness assessments as well as the establishment of guidelines for optimal administrations of MSC-based cytotherapy in preclinical studies, which collectively indicates the prospect of P-MSC administration in clinical trials during a wide spectrum of disease remodeling including the fistulizing CD. Graphical abstract.

2.
Ann Palliat Med ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33040556

RESUMO

BACKGROUND: Glycosylated hemoglobin (HbA1c) is directly proportional to the level of glucose in the blood, and it has been the gold standard to evaluate the status of long-term blood glucose levels. Exploring the factors that lead to HbA1c improvement is beneficial for effectively controlling of HbA1c levels. METHODS: Data collected from 52 hospitals in five cities in northern China were divided into training and test sets at a ratio of 7:3. The training set was used to build models, and the test set was used to evaluate the generalizability of the models. The performance of multivariate adaptive regression splines (MARS) models and logistic regression was evaluated, namely, the accuracy, Youden's index, recall rate, G-mean and area under the ROC curve (AUC) with 95% confidence intervals (CIs). RESULTS: The prevalence of improvements in HbA1c levels was 38.35%. Doses of insulin less than 13 U, more than 3 kinds of oral medicine, exercise frequency greater than once per week and 2 h postprandial blood glucose (2hPBG) less than 10.56 mmol/L were found to improve HbA1c. The following interactions were negatively associated with improvement in HbA1c levels: patients with relative complications and 2hPBG less than 10.56 mmol/L, type 2 diabetes mellitus (T2DM) duration more than 7 years and insulin dose less than 13U. Compared to logistic regression, the MARS model performed better in the above aspects, except for accuracy. CONCLUSIONS: Given the interaction between factors affecting HbA1c improvement, medical staff should conduct comprehensive interventions to further reduce HbA1c levels in patients. In this study, the MARS model was superior to the traditional logistic regression in improving HbA1c levels. MARS had greater generalizability because it not only considered nonlinear relations in the process of model fitting but also adopted cross-validation. Nevertheless, more studies are needed to provide evidence for this result.

3.
J Stroke Cerebrovasc Dis ; 29(11): 105221, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33066883

RESUMO

INTRODUCTION: Cerebral small-vessel disease (CSVD) is an extensive cerebrovascular disease associated with many poor outcomes. Previous studies have shown that brachial-ankle pulse wave velocity (baPWV) is related to various neuroimaging signatures, but its association with the total CSVD burden remains unknown. We aimed to explore whether baPWV is related to the total CSVD score and to establish a cutoff for detecting the presence and severity of CSVD, which may guide clinical preventive measures. METHODS: We retrospectively selected 684 neurologically healthy participants to explore correlations between baPWV and the total CSVD score and each of its components (lacunes, white matter hyperintensity (WMH), perivascular space (PVS), and cerebral microbleeds (CMBs)). Subsequently, we established two receiver operating characteristic (ROC) curves to study the effectiveness of baPWV in predicting CSVD (scores 1-4) and severe CSVD (scores 3-4). RESULTS: The median baPWV was 13.16 m/s, which increased significantly with increasing scores (0-4). BaPWV was significantly higher among persons with each component of the total CSVD score than among those without any components. Multivariable ordinal logistic regression analyses showed that a one-unit (m/s) change in baPWV significantly increased the total CSVD score by 0.012. The optimal baPWV cutoffs for detecting CSVD and severe CSVD were 13.12 m/s and 15.63 m/s, respectively. CONCLUSIONS: BaPWV was positively correlated with the total CSVD score, suggesting that baPWV measurement is a useful method for early diagnosis of CSVD, which may contribute to preventing and controlling CSVD progression in the general population of China.

4.
BMJ Open ; 10(10): e033759, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33033007

RESUMO

OBJECTIVES: We aim to describe the social network members of participants of a behavioural intervention, and examine how the effects of the intervention may spillover among network members. DESIGN: Secondary analysis of a step-wedge randomised controlled trial. SETTING: Change agents (CAs) were recruited from waiting rooms of HIV treatment facilities in Dar es Salaam, Tanzania, and their network members (NMs) were recruited directly by CAs. PARTICIPANTS: We enrolled 662 CAs in an HIV behavioural intervention. They, along with 710 of their NMs, completed baseline and follow-up interviews from 2011 to 2013. PRIMARY AND SECONDARY OUTCOMES: The primary outcome of this study was change in NMs' HIV knowledge, and the secondary outcome was whether the NM was lost to follow-up. RESULTS: At baseline, many characteristics were different between NMs and CAs. We found a number of NM characteristics significantly associated with follow-up of NMs, particularly female gender (OR=1.64, 95% CI: 1.02 to 2.63) and HIV knowledge (OR=20.0, 95% CI: 3.70 to 125); only one CA variable was significantly associated with NM follow-up: having a private source of water (OR=2.17, 95% CI: 1.33 to 3.57). The 14.2% increase in NMs' HIV knowledge was largely due to CAs feeling empowered to pass on prior knowledge, rather than transmitting new knowledge to their NMs. CONCLUSIONS: Characteristics of social network members of persons living with HIV persons living with HIV may play a role in study retention. Additionally, the HIV knowledge of these NMs increased largely as a function of CA participation in the intervention, suggesting that intervening among highly-connected individuals may maximise benefits to the potential population for whom spillover can occur. TRIAL REGISTRATION NUMBER: Clinical Trial: NCT01693458; Post-results.

5.
Aging (Albany NY) ; 12(19): 19147-19158, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051401

RESUMO

Activation of the PI3K/AKT/mTOR pathway promotes the progression of renal cell carcinoma (RCC). This study tested the anti-RCC cell activity of the PI3K/mTOR dual inhibitor, VS-5584. We show that VS-5584 inhibited PI3K/AKT/mTORC1/2 activation in established (786-O and A498 lines) and primary RCC cells, thereby suppressing cell survival, proliferation, migration and cell cycle progression. VS-5584 induced significant apoptosis in RCC cells. A daily single oral dose of VS-5584 (20 mg/kg) significantly inhibited 786-O tumor growth in vivo. VS-5584 treatment of 786-O tumor xenografts and RCC cells resulted in feedback upregulation of bromodomain-containing protein 4 (BRD4). Furthermore, BRD4 inhibition (by JQ1 and CPI203), knockdown or complete knockout potentiated VS-5584-induced RCC cell death and apoptosis. Conversely, forced overexpression of BRD4 attenuated the cytotoxicity of VS-5584 in 786-O cells. Collectively, VS-5584 potently inhibits RCC cell proliferation and survival. Its anti-tumor activity is further enhanced by the targeted inhibition of BRD4.

6.
Physiol Meas ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33080588

RESUMO

OBJECTIVE: Coronary artery disease (CAD) is a common fatal disease. At present, an accurate method to screen CAD is urgently needed. This study aims to provide optimal detection models for suspected CAD detection according to the differences in medical conditions, so as to assist physicians to make accurate judgments on suspected CAD patients. APPROACH: Electrocardiogram (ECG) and phonocardiogram (PCG) signals of 32 CAD patients and 30 patients with chest pain and normal coronary angiograms (CPNCA) were simultaneously collected in this paper. For each subject, the ECG and PCG multi-domain features were extracted, and the results of Holter monitoring, echocardiography (ECHO), and biomarker levels (BIO) were obtained to construct a multi-modal feature set. Then, a hybrid feature selection method was developed using mutual information, recursive feature elimination, random forest, and weight of support vector machine to obtain the optimal feature subset. The support vector machine with nested cross-validation was used for classification. MAIN RESULTS: Results showed that the Holter model achieved the best performance as a single-modal feature model with an accuracy of 82.67%. In terms of multi-modal feature models, PCG-Holter, PCG-Holter-ECHO, PCG-Holter-ECHO-BIO, and ECG-PCG-Holter-ECHO-BIO were the optimal bimodal, three-modal, four-modal, and five-modal models, with accuracies of 90.38%, 91.92%, 95.25%, and 96.67%, respectively. Among them, the ECG-PCG-Holter-ECHO-BIO model, which was constructed by combining ECG and PCG signals features with Holter, ECHO, and BIO examination results, achieved the best classification results with an average accuracy, sensitivity, specificity, and F1-measure of 96.67%, 96.67%, 96.67%, and 96.64%, respectively. SIGNIFICANCE: The study indicated that multi-modal feature fusion and hybrid feature selection can obtain more effective information for CAD detection and provide reference for physicians to diagnose CAD patients.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33052670

RESUMO

Grätzel's dye-sensitized solar cells (DSSCs) can readily convert sunlight into electricity, attracting considerable attention of global scientists. The fabrication efficiency of DSSCs was greatly limited by the slow fabrication (∼3.5-24 h) of quasi-solid (QS) electrolytes to date. In this study, novel composites of SiO2 aerogel with graphene (GR), multi-walled carbon nanotubes, or polyaniline were proposed in the fabrication of QS-state electrolytes. The morphology of these composites was characterized. The gels with SiO2 aerogels as QS electrolytes of DSSCs can be rapidly cured in ∼3 s. Using the screen-printing technology, these QS electrolytes can be readily utilized to construct the QS-DSSC to provide high efficiency and great stability. The photovoltaic parameters and interfacial charge-transfer resistances of the QS-DSSC incorporated with our synthetic composites were investigated in detail. Specifically, the SiO2 aerogel composed of GR (SiO2@GR) as a gel can greatly improve the performance of QS-DSSCs up to 8.25%. It is likely that these SiO2 aerogel composite electrolytes could provide a rapid curing process in the preparation of QS-state DSSCs, which might be useful to promote the development of DSSCs for future industrialization.

8.
Brain Behav ; : e01885, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047489

RESUMO

INTRODUCTION: Our study was designed to examine the relationship between Brain-Derived Neurotrophic Factor (BDNF) genotypes (rs6265, Val66Met), BDNF plasma levels, and cognitive impairment in Chinese patients with panic disorder (PD). METHODS: Total 85 patients with PD and 91 healthy controls finally completed all assessments. The severity of panic symptoms and whole anxiety of PD was measured by Panic Disorder Severity Scale-Chinese Version (PDSS-CV) and Hamilton Anxiety Scale (HAMA-14). Montreal Cognitive Assessment (MoCA) and some neurocognitive measures were conducted to evaluate the cognitive performance. All participants were detected for the plasma BDNF levels and BDNF Val66Met polymorphism before assessment and treatment. RESULTS: No significant differences were found in the BDNF allele frequencies and the BDNF genotype distributions between healthy controls and PD patients. BDNF Met/Met genotype was associated with lower BDNF plasma levels in PD patients, and PD patients with BDNF Met/Met genotype had the lower scores in the attention and speed of processing domains compared to those with Val/Val and Met/Val genotype (p's < .05). Among PD patients, the BDNF plasma levels showed moderate positive correlations with Stroop interference (r = .60, p < .001). Using the MoCA data, the BDNF plasma levels were correlated with delayed memory (r = .50, p < .001), verbal learning (r = .45, p < .001), and total scores of MoCA (r = .51, p < .001). CONCLUSIONS: The BDNF Met/Met genotype may be associated with lower BDNF plasma levels and cognitive impairments in PD patients.

9.
Cancer Biol Ther ; : 1-7, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33092443

RESUMO

The current evidence regarding immunotherapy plus targeted therapy in esophageal neuroendocrine carcinoma (NEC) is lacking. Camrelizumab is a programmed cell death protein 1 inhibitor. Apatinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. A 50-year-old female was initially diagnosed as primary esophageal NEC. Neoadjuvant chemotherapy and Ivor Lewis esophagectomy were performed (ypT3N0M0, stage Ⅱ). Twenty months after the surgery, an isolated mediastinal lymph node recurrence of NEC was recorded. The specimen revealed a positive expression of vascular endothelial growth factor and programmed cell death ligand 1. The diseased lymph node was slightly enlarged after two cycles of first-line paclitaxel liposome and S-1. Second-line apatinib and S-1 for 2 months also resulted in progressive disease. Subsequently, third-line camrelizumab plus apatinib was continued for 5 months. The patient demonstrated a progression-free status for more than 10 months following the combination therapy. Meanwhile, relevant studies of camrelizumab in gastric or esophageal cancer were briefly reviewed. Based on the current evidence, camrelizumab is a promising agent for esophageal cancer. More prospective trials are warranted before a definite recommendation could be drawn.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33094354

RESUMO

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.

11.
Orthop Surg ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33078551

RESUMO

OBJECTIVE: To clarify the effects on and the mechanism of salvianic acid A sodium (SAAS) in the recovery of motor function after spinal cord injury. METHODS: In vivo and in vitro experiments were carried out in this research to determine the effects of SAAS on tissue damage, neuron survival, microglia polarization, and inflammation after spinal cord injury (SCI). Differentially expressed genes treated with SAAS were screened by transcriptome sequencing, and the molecular mechanism was investigated simultaneously. RESULTS: The results revealed that SAAS could promote type M2 polarization of microglia and reduce the proportion of type M1. In this way, it reduced the secretion and expression of inflammatory factors. Compared with Lipopolysaccharides(LPS), 345 genes were upregulated and 407 genes were downregulated in the LPS + SAAS treatment group. In the SAAS group, expression levels of Ndufa12, IL-6, TNF-α, and Vdac1 were significantly reduced, while a marked elevation was found in MIP2. In addition, results found in an animal model showed that SAAS could obviously facilitate motor function recovery of mice after spinal cord injury, and it had a good protective effect on spinal cord tissue and neuron cells. CONCLUSION: As a result, the present study clarified both the protective effect of SAAS on neurons after spinal cord injury and the anti-inflammatory effect of microglia, which is expected to serve as a theoretical basis for clinical treatment.

12.
Exp Biol Med (Maywood) ; : 1535370220961013, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023331

RESUMO

IMPACT STATEMENT: We investigated that CCAT1 expression was elevated in NSCLC and CCAT1 deletion was identified to inhibit cell carcinogenic phenotypes in NSCLC cells via miR-216a-5p/RAP2B axis, which reveals a novel pathway underlying progression in NSCLC cells and providing potential targets for NSCLC treatment.

13.
BMC Ophthalmol ; 20(1): 416, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076873

RESUMO

BACKGROUND: Proliferative diabetic retinopathy (PDR) is one of the most common cause of vision loss in diabetic patients, and the incidence age of PDR patients gradually gets younger. This study aims to compare the characteristics of PDR and outcomes following vitrectomy in young and senior patients. METHODS: This is a retrospective case series study. Data of 116 eyes of 92 patients who underwent vitrectomy for PDR from February 2012 to February 2017 were reviewed, which were divided into young and senior patient groups. All patients were followed up for 24 months at least. RESULTS: There were 62.1% of eyes with tractional retinal detachment secondary to PDR in the young patient group, while only 12.1% of eyes in the senior patient group with this surgery indication. (P < 0.001) The best corrected visual acuity increased in 41 eyes (70.7%), stable in 9 eyes (15.5%), and decreased in 8 eyes (13.8%) in young patients at the final follow-up. And it increased in 47 eyes (81.0%), stable in 2 eyes (3.4%), and decreased in 9 eyes (15.5%) in senior patients.(P = 0.085) Postoperative complications mainly included recurrent vitreous hemorrhage (24.1%), retinal detachment (3.4%), neovascular glaucoma (NVG) (27.6%) and nuclear sclerosis (53.4%) in young patients, and it was 19.0, 0.0, 1.7 and 3.4% in senior patients respectively. CONCLUSION: PDR of young patients is more severe than that of senior patients, and vitrectomy is an effective and safe method for PDR treatment. NVG is a main and severe complication besides nuclear sclerosis in young patients, and the incidence of NVG is higher compared to that in senior patients.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33090063

RESUMO

Diaporthe spp. are critical plant pathogens that cause wood cankers, wilt, dieback, and fruit rot in a wide variety of economic plant hosts and are regarded as one of the most acute threats faced by kiwifruit industry worldwide. Diaporthe phragmitis strain NJD1 is a highly pathogenic isolate of soft rot of kiwifruit. Here, we present a high-quality genome-wide sequence of D. phragmitis NJD1 that was assembled into 28 contigs containing a total size of 58.33 Mb and N50 length of 3.55 Mb. These results lay a solid foundation for understanding host-pathogen interaction and improving disease management strategies.

15.
PLoS One ; 15(9): e0238240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886666

RESUMO

The aim of the study is to compare sociodemographic characteristics, psychosocial factors, HIV knowledge and risk behaviors of people living with HIV (PLH) and their social network members (NMs) to inform HIV prevention programs that engage PLH as prevention educators in their communities. We compared baseline characteristics of PLH enrolled in an intervention to become HIV prevention Change Agents (CAs) (n = 458) and 602 NMs they recruited. CAs and NMs responded to questionnaires through a computer-driven interface with Audio Computer-Assisted Self Interview (ACASI) software. Although NMs scored higher on socio-economic status, self-esteem and general self-efficacy, they had lower HIV knowledge (AOR 1.5; 95% CI: 1.1-2.1), greater inconsistent condom use (AOR 3.2; 95% CI: 2.4-4.9), and recent experience as perpetrators of physical (AOR 2.5; 95% CI: 1.2-5.1) or sexual (AOR 4.1; 95% CI: 1.4-12.7) intimate partner violence; and as victims of physical (AOR 1.5; 95% CI: 1.0-2.3) or sexual (AOR 2.2; 95% CI: 1.3-3.8) forms of violence than CAs. Higher HIV knowledge and lower sexual risk behaviors among CAs suggest PLH's potential as communicators of HIV prevention information to NMs. CAs' training should also focus on improving self-esteem, general self-efficacy and social support to increase their potential effectiveness as HIV prevention educators and enhance their own overall health and well-being.

16.
Biomed Res Int ; 2020: 4795763, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908891

RESUMO

Nursing is a high-risk occupation with high exposure to stress. The physical and mental health of nurses is directly related to the quality of medical services. Therefore, the sleep quality of nurses should not be ignored. In this study, the method of cluster random sampling was adopted from May to September 2019, and a questionnaire survey was conducted among 521 surgical nurses from five affiliated hospitals of Xinjiang Medical University. The relationship between mental health and sleep quality was analyzed, and 20% of the participants with sleep disorders were randomly selected. The sleep disorders used 1 : 1 matching, finally providing a sample with 60 cases and 60 controls for measurement of the CLOCK gene (rs1801260, rs6850524), to analyze the effect of the interaction between mental health and the CLOCK gene on sleep. The mental health and sleep quality of the surgical nurses were evaluated using the Symptom Checklist 90 (SCL-90) and Pittsburgh Sleep Quality Index (PSQI). The study found that surgical nurses had poor sleep, and there were differences associated with age, years working, frequency of night shifts, and incidence of sleep disorders under marital status (p < 0.05). The PSQI scores of the positive psychological symptoms were higher than those of the negative psychological symptoms. The rank sum test was used to compare the sleep quality scores of different genotypes in CLOCK rs1801260 and rs6850524; the results indicated that the PSQI scores were different among different genotypes at the rs1801260 and rs6850524 loci. The logistic regression results suggested that CLOCK gene rs1801260 (TC) and positive psychological symptoms were influential factors for sleep disorders, and the interaction of positive psychological symptoms∗rs1801260 (TT) was a risk factor for sleep disorders (OR = 10.833, 95% CI: 2.987-39.288). The sleep quality of nurses is not only affected by demographic characteristics but also affected by mental health status and the CLOCK gene.

17.
Environ Sci Technol ; 54(20): 13167-13174, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32929958

RESUMO

Long-term exposure to fine particulate matter (PM2.5) is associated with kidney dysfunction. However, few studies have investigated acute effects of PM2.5 elemental constituents on renal function. We evaluated associations between personal PM2.5 and its elemental constituents and kidney function, assessed by an estimated glomerular filtration rate (eGFR) in Biomarkers of Air Pollutants Exposure in the Chinese aged 60-69 study. Seventy one older individuals were visited monthly between September 2018 and January 2019. Each participant wore a PM2.5 monitor for 72 h, responded to a questionnaire, and underwent a physical examination with blood sampling. Linear mixed-effect models were used to estimate associations between personal PM2.5 elemental constituents and eGFR. We found that significant changes in eGFR from -1.69% [95% confidence interval (CI): -3.34%, -0.01%] to -3.27% (95% CI: -5.04%, -1.47%) were associated with interquartile range (IQR) increases in individual PM2.5 exposures at various lag periods (7-12, 13-24, 0-24, 25-48, and 49-72 h). An IQR increase in 72 h moving averages of copper, manganese, and titanium in personal PM2.5 corresponded to -2.34% (95% CI: -3.67%, -0.99%) to -4.56% (95% CI: -7.04%, -2.00%) changes in eGFR. Personal PM2.5 and some of its elemental constituents are inversely associated with eGFR in older individuals.

18.
Sci Total Environ ; 751: 141738, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32882557

RESUMO

Land-use and climate changes have been repeatedly identified as important factors affecting terrestrial carbon budgets, however little is known about how deforestation and catchment development affect aquatic systems in carbonate-rich regions. Multi-proxy analyses of 210Pb-dated sediment cores from two hard-water lakes with different land-use histories were applied for assessing carbon cycling and limnological changes in response to land-use changes over the past century in southwest China. Logging of primary forests in the catchment of Lugu Lake, starting in the 1950s, led to a significant increase of catchment erosion, as well as a consistent decline in inferred lake-water total organic carbon (TOC) levels and sediment carbonate accumulation. This process of recent deforestation may significantly reduce the role of lake systems to act as carbon sinks through hampering of both the soil organic carbon flux and the dissolution of catchment carbonate. The decline in lake-water TOC in Lugu Lake further increased algal production (i.e. tracked through sediment trends in chlorophyll a and its main diagenetic products) and changes in diatom composition. In comparison, there was little variation of sediment carbonate content in Chenghai Lake, which has a long history of catchment deforestation, while both primary production and lake-water TOC increased following cultural eutrophication during the last three decades. Furthermore, regional warming was associated with an increase in small-sized diatoms in both deep lakes, likely due to enhanced thermal stability. This study highlights the significant role of vegetation cover and land use in driving aquatic carbon cycling and phototrophs, revealing that deforestation can strongly reduce both inorganic and organic carbon export to lakes and thus aquatic carbon storage in karst landscapes.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32910145

RESUMO

OBJECTIVES: To characterize serum microRNA (miR) and the miR interactome of active RA patients in RA aetiology and pathogenesis. METHODS: The differentially expressed miRs (DEmiRs) in serum of naïve active RA patients (NARAPs, n = 9, into three pools) vs healthy controls (HCs, n = 15, into five pools) were identified with Agilent human miR microarray analysis. Candidate driver genes in epigenetic and pathogenic signalling pathway modules for RA were analysed using miRTarBase and a molecular complex detection algorithm. The interactome of these DEmiRs in RA pathogenesis were further characterized with gene ontology and Kyoto Encyclopaedia of Genes and Genomes. RESULTS: Three upregulated DEmiRs (hsa-miR-187-5p, -4532, -4516) and eight downregulated DEmiRs (hsa-miR-125a-3p, -575, -191-3p, -6865-3p, -197-3p, -6886-3p, -1237-3p, -4436b-5p) were identified in NARAPs. Interactomic analysis from heterogeneous experimentally validated sources yielded 1719 miR-target interactions containing 5.67% strong and 94.33% less strong experimental evidence. Gene ontology and Kyoto Encyclopaedia of Genes and Genomes analyses allocated the upregulated DEmiRs in the infection modules and the downregulated DEmiRs in the immune signalling pathways. Specifically, these DEmiRs revealed the significant contributions of the intestinal microbiome dysbiosis in the infection-inflammation-immune network for activation of T cells, immune pathways of IL-17, Toll-like receptor, TNF, Janus kinase-signal transducer and activator of transcription, osteoclast cell differentiation pathway and IgA production to the active RA pathogenesis. CONCLUSIONS: Our experiment-based interactomic study of DEmiRs in serum of NARAPs revealed novel clinically relevant miRs interactomes in the infection-inflammation-immune network of RA. These results provide valuable resources for understanding the integrated function of the miR network in RA pathogenesis and the application of circulating miRs as biomarkers for early aetiologic RA diagnosis.

20.
Anal Chem ; 92(19): 12801-12808, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-32966065

RESUMO

Due to its key roles in regulating the occurrence and development of cancer, protein histidine phosphorylation has been increasingly recognized as an important form of post-translational modification in recent years. However, large-scale analysis of histidine phosphorylation is much more challenging than that of serine/threonine or tyrosine phosphorylation, mainly because of its acid lability. In this study, MoS2-Ti4+ nanomaterials were synthesized using a solvothermal method and taking advantage of the electrostatic adsorption between MoS2 nanosheets and Ti4+. The MoS2-Ti4+ nanomaterials have the advantage of the combined affinity of Ti4+ and Mo toward phosphorylation under medium acidic conditions (pH = 3), which is crucial for preventing hydrolysis and loss of histidine phosphorylation during enrichment. The feasibility of using the MoS2-Ti4+ nanomaterial for phosphopeptide enrichment was demonstrated using mixtures of ß-casein and bovine serum albumin (BSA). Further evaluation revealed that the MoS2-Ti4+ nanomaterial is capable of enriching synthetic histidine phosphopeptides from 1000 times excess tryptic-digested HeLa cell lysate. Application of the MoS2-Ti4+ nanomaterials for large-scale phosphopeptide enrichment results in the identification of 10 345 serine, threonine, and tyrosine phosphosites and the successful mapping of 159 histidine phosphosites in HeLa cell lysates, therefore indicating great potential for deciphering the vital biological roles of protein (histidine) phosphorylation.

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