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1.
Sensors (Basel) ; 24(13)2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-39000890

RESUMEN

Unveiling the mechanical properties and damage mechanism of the complex composite structure, comprising backfill and surrounding rock, is crucial for ensuring the safe development of the downward-approach backfill mining method. This work conducts biaxial compression tests on backfill-rock under various loading conditions. The damage process is analyzed using DIC and acoustic emission (AE) techniques, while the distribution of AE events at different loading stages is explored. Additionally, the dominant failure forms of specimens are studied through multifractal analysis. The damage evolution law of backfill-rock combinations is elucidated. The results indicate that DIC and AE provide consistent descriptions of specimen damage, and the damage evolution of backfill-rock composite specimens varies notably under different loading conditions, offering valuable insights for engineering site safety protection.

2.
Sensors (Basel) ; 24(13)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39001143

RESUMEN

Mobile robots play an important role in the industrial Internet of Things (IIoT); they need effective mutual communication between the cloud and themselves when they move in a factory. By using the sensor nodes existing in the IIoT environment as relays, mobile robots and the cloud can communicate through multiple hops. However, the mobility and delay sensitivity of mobile robots bring new challenges. In this paper, we propose a dynamic cooperative transmission algorithm with mutual information accumulation to cope with these two challenges. By using rateless coding, nodes can reduce the delay caused by retransmission under poor channel conditions. With the help of mutual information accumulation, nodes can accumulate information faster and reduce delay. We propose a two-step dynamic algorithm, which can obtain the current routing path with low time complexity. The simulation results show that our algorithm is better than the existing heuristic algorithm in terms of delay.

3.
Nat Commun ; 14(1): 6362, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37821477

RESUMEN

The fine-scale seismic features near the inner core boundary (ICB) provide critical insights into the thermal, chemical, and geodynamical interactions between liquid and solid cores, and may shed light on the evolution mechanism of the Earth's core. Here, we utilize a dataset of pre-critical PKiKP waveforms to constrain the fine structure at the ICB, considering the influence of various factors such as source complexity, structural anomalies in the mantle, and properties at the ICB. Our modeling suggests a sharp ICB beneath Mongolia and most of Northeast Asia, but a locally laminated ICB structure beneath Central Asia, Siberia, and part of Northeast Asia. The complex ICB structure might be explained by either the existence of a kilometer-scale thickness of mushy zone, or the localized coexistence of bcc and hcp iron phase at the ICB. We infer that there may be considerable lateral variations in the dendrites growing process at ICB, probably due to the complicated thermochemical and geodynamical interaction between the outer and inner core.

4.
Discov Nano ; 18(1): 110, 2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37676446

RESUMEN

Various doping concentrations of boron (B)-doped germanium nanocrystal (Ge NC) films were prepared using the plasma-enhanced chemical vapor deposition (PECVD) technique followed by thermal annealing treatment. The electronic properties of B-doped Ge NCs films combined with the microstructural characterization were investigated. It is worthwhile mentioning that the Hall mobilities [Formula: see text] of Ge NCs films were enhanced after B doping and reached to the maximum of 200 cm2 V-1, which could be ascribed to the reduction in surface defects states in the B-doped films. It is also important to highlight that the temperature-dependent mobilities [Formula: see text] exhibited different temperature dependence trends in the Ge NCs films before and after B doping. A comprehensive investigation was conducted to examine the distinct carrier transport properties in B-doped Ge NC films, and a detailed discussion was presented, focusing on the scattering mechanisms involved in the transport process.

5.
Sci Total Environ ; 904: 166955, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37704144

RESUMEN

Cadmium (Cd) is a commonly found environmental pollutant and is known to damage multiple organs with kidneys being the most common one. N-methyl-d-aspartate receptor 1 (NMDAR1) is a ligand-gated ion channel that is highly permeable to calcium ion (Ca2+). Because Cd2+ and Ca2+ have structural and physicochemical similarities, whether and how Cd could interfere NMDAR1 function to cause renal epithelial cells dysfunction remains unknown. In this study, we investigated the role of NMDAR1 in Cd-induced renal damage and found that Cd treatment upregulated NMDAR1 expression and promoted epithelial-mesenchymal transition (EMT) in mouse kidneys in vivo and human proximal tubular epithelial HK-2 cells in vitro, which were accompanied with activation of the inositol-requiring enzyme 1 (IRE-1α) / spliced X box binding protein-1 (XBP-1s) pathway, an indicative of endoplasmic reticulum (ER) stress. Mechanistically, NMDAR1 upregulation by Cd promoted Ca2+ channel opening and Ca2+ influx, resulting in ER stress and subsequently EMT in HK-2 cells. Inhibition of NMDAR1 by pharmacological antagonist MK-801 significantly attenuated Cd-induced Ca2+ influx, ER stress, and EMT. Pretreatment with the IRE-1α/XBP-1s pathway inhibitor STF-083010 also restored the epithelial phenotype of Cd-treated HK-2 cells. Therefore, our findings suggest that NMDAR1 activation mediates Cd-induced EMT in proximal epithelial cells likely through the IRE-1α/XBP-1s pathway, supporting the idea that NMDAR1 could be a potential therapeutic target for Cd-induced renal damage.


Asunto(s)
Cadmio , Transición Epitelial-Mesenquimal , Ratones , Animales , Humanos , Cadmio/toxicidad , Cadmio/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Línea Celular , Células Epiteliales
6.
J Gene Med ; 25(8): e3518, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37403412

RESUMEN

BACKGROUND: The overwhelming majority of subjects in the current silicosis mRNA and microRNA (miRNA) expression profile are of human blood, lung cells or a rat model, which puts limits on the understanding of silicosis pathogenesis and therapy. To address the limitations, our investigation was focused on differentially expressed mRNA and miRNA profiles in lung tissue from silicosis patients to explore potential biomarker for early detection of silicosis. METHODS: A transcriptome study was conducted based on lung tissue from 15 silicosis patients and eight normal people, and blood samples from 404 silicosis patients and 177 normal people. Three early stage silicosis, five advanced silicosis and four normal lung tissues were randomly selected for microarray processing and analyze. The differentially expressed mRNAs were further used to conduct Gene Ontology and pathway analyses. Series test of cluster was performed to explore possible changes in differentially expressed mRNA and miRNA expression patterns during the process of silicosis. The blood samples and remaining lung tissues were used in a quantitative real-time PCR (RT-qPCR) (RT-qPCR). RESULTS: In total, 1417 and 241 differentially expressed mRNAs and miRNAs were identified between lung tissue from silicosis patients and normal people (p < 0.05). However, there was no significant difference in most mRNA or miRNA expression between early stage and advanced stage silicosis lung tissues. RT-qPCR validation results in lung tissues showed expression of four mRNAs (HIF1A, SOCS3, GNAI3 and PTEN) and seven miRNAs was significantly down-regulated compared to those of control group. Nevertheless, PTEN and GNAI3 expression was significantly up-regulated (p < 0.001) in blood samples. The bisulfite sequencing PCR demonstrated that PTEN had significantly decreased the methylation rate in blood samples of silicosis patients. CONCLUSIONS: PTEN might be a potential biomarker for silicosis as a result of low methylation in the blood.


Asunto(s)
MicroARNs , Silicosis , Humanos , Ratas , Animales , ARN Mensajero/genética , ARN Mensajero/metabolismo , Pulmón/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Silicosis/genética , Silicosis/metabolismo , Biomarcadores/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Perfilación de la Expresión Génica
7.
Diabetes Care ; 46(1): 75-82, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36378879

RESUMEN

OBJECTIVE: The temporal pattern of cognitive and functional change before and after incident diabetes remains unknown. RESEARCH DESIGN AND METHODS: Data from wave 2 to wave 9 (2004-2018) of the English Longitudinal Study of Ageing were used. Global cognition (assessed by orientation, memory, and executive function) and daily functioning (calculated as the sum of impaired basic and instrumental activities of daily living) were measured in each wave. Incident diabetes was defined as glycated hemoglobin A1c ≥6.5% (47.5 mmol/mol), self-reported doctor diagnosis of diabetes, or glucose-lowering medication use during follow-up. RESULTS: Among the 6,342 participants (mean age 65.0 years, 57.8% women) included, 576 participants (9.1%) with incident diabetes were identified during a median follow-up of 13.3 years. The annual rates of change in global cognition (ß = -0.035 SD/year; 95% CI -0.054 to -0.015), orientation (-0.031 SD/year; -0.060 to -0.002), memory (-0.016 SD/year; -0.029 to -0.003), and executive function (-0.027 SD/year; -0.042 to -0.013) were accelerated after diabetes diagnosis compared with before the event. The postdiabetes annual changes in daily functioning (0.093 points/year; 95% CI 0.056-0.131) were also accelerated compared with the prediabetes diagnosis. However, the rate of cognitive and functional decline before the diabetes diagnosis in participants with future incident diabetes was similar to the rate in participants without diabetes. Also, no significant acute change was observed during its onset. CONCLUSIONS: Incident diabetes is associated with accelerated cognitive and functional decline after, but not before, the event. We suggest careful monitoring for cognitive and physical dysfunction after a diabetes diagnosis.


Asunto(s)
Trastornos del Conocimiento , Disfunción Cognitiva , Diabetes Mellitus , Humanos , Femenino , Anciano , Masculino , Estudios Longitudinales , Actividades Cotidianas , Cognición , Diabetes Mellitus/epidemiología , Disfunción Cognitiva/epidemiología
8.
Front Aging Neurosci ; 14: 895188, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36118703

RESUMEN

Background and aim: Previous studies on cardiovascular risk burden assessed by the Framingham General Cardiovascular Risk Score (FGCRS) and cognitive trajectories mainly focus on Western populations and most of them have used a single measure of cardiovascular risk. In this study, among middle-aged and older Chinese, we investigated (i) the association of baseline FGCRS with subsequent cognitive decline and (ii) the association of FGCRS change with concomitant cognitive decline. Materials and methods: In wave 1 to wave 4 (2011-2018) of the China Health and Retirement Longitudinal Study, global cognition was assessed by orientation, memory, and executive function. FGCRS was assessed and categorized into tertiles (low, intermediate, and high) at baseline (2011) and 4 years after (2015). Furthermore, external validation was performed to check its generalizability using the English Longitudinal Study of Ageing (ELSA) 2008-2018. Results: In total, 6,402 participants with a mean [standard deviation (SD) age of 57.8 (8.4) years, 49.0% women] with complete baseline data and at least one reassessment of cognitive function were included. A 10% increment in baseline FGCRS was associated with a faster decline in global cognition (-0.010 SD/year, 95% CI -0.013, -0.008). Among 4,336 participants [mean (SD) age of 57.8 (8.2) years, 50.0% women] with data on FGCRS changes, compared to individuals with the consistently low FGCRS (reference group), a faster global cognition decline rate was observed in the low to intermediate group (-0.026 SD/year, 95% CI -0.045, -0.007), the low to high group (-0.052 SD/year, 95% CI -0.102, -0.001), the consistently intermediate group (-0.019 SD/year, 95% CI -0.033, -0.005), the intermediate to high group (-0.040 SD/year, 95% CI -0.058, -0.022), the high to intermediate group (-0.024 SD/year, 95% CI -0.047, -0.002), and the consistently high group (-0.047 SD/year, 95% CI -0.060, -0.034). Similar trends were observed for individual cognitive domains. Results from the external validation using the ELSA remained consistent. Conclusion: Higher baseline FGCRS was associated with faster cognitive decline. However, there was no consistent relationship between the direction of changes in FGCRS and cognitive decline.

9.
Ecotoxicol Environ Saf ; 245: 114098, 2022 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-36137422

RESUMEN

Cadmium (Cd), the common environmental pollutant, primarily targets at renal proximal tubules and induces nephrotoxicity. Cellular senescence, a phenomenon of cell growth arrest and a characteristics of maladaptive cell self-repair, is associated with renal disease progression. However, whether and how Cd induces renal tubular cells premature senescence is unknown. In our study, we found that Cd induced kidney damage and dysfunctions, which correlated with exacerbated tubular cell senescence, evidenced by increased senescence-associated ß-galactosidase activity, the upregulated protein expression of p53 and p21Waf1/Cip1 proteins, and elevated expression and secretion of cytokines in human proximal tubular epithelial HK-2 cells in vitro and in Cd-treated mice in vivo. Moreover, a S-phase arrest and decrease in Edu positive rate were found in Cd-treated HK-2 cells. Mechanistically, Cd suppressed the expression and activity of Sirtuin-1 (SIRT1), an anti-senescence deacetylase, resulting in the accumulation of acetylated p53 and upregulation of p21Waf1/Cip1. Activation of SIRT1 significantly abolished Cd-induced premature senescence and S-phase arrest. Finally, silencing p21Waf1/Cip1 efficiently delayed premature senescence and recovered cell cycle progression. These findings indicate that Cd promotes tubular cells senescence and impairs tubular cells regeneration, resulting in kidney dysfunctions, which could be ameliorated by SIRT1 activation.


Asunto(s)
Contaminantes Ambientales , Sirtuina 1 , Animales , Cadmio/metabolismo , Cadmio/toxicidad , Senescencia Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Citocinas/metabolismo , Contaminantes Ambientales/metabolismo , Humanos , Riñón/metabolismo , Ratones , Sirtuina 1/genética , Sirtuina 1/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , beta-Galactosidasa
10.
Nat Commun ; 13(1): 1042, 2022 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-35210453

RESUMEN

Ultra-low velocity zones (ULVZs) are localized small-scale patches with extreme physical properties at the core-mantle boundary that often gather at the margins of Large Low Velocity Provinces (LLVPs). Recent studies have discovered several mega-sized ULVZs with a lateral dimension of ~900 km. However, the detailed structures and physical properties of these ULVZs and their relationship to LLVP edges are not well constrained and their formation mechanisms are poorly understood. Here, we break the degeneracy between the size and velocity perturbation of a ULVZ using two orthogonal seismic ray paths, and thereby discover a mega-sized ULVZ at the northern edge of the Pacific LLVP. The ULVZ is almost double the size of a previously imaged ULVZ in this region, but with half of the shear velocity reduction. This mega-sized ULVZ has accumulated due to stable mantle flow converging at the LLVP edge driven by slab-debris in the lower mantle. Such flow also develops the subvertical north-tilting edge of the Pacific LLVP.

11.
Toxicol Ind Health ; 38(2): 92-99, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35191764

RESUMEN

Hard metal lung disease (HMLD) drugs include dexamethasone sodium phosphate (Dex), methylprednisolone (MP) injection, N-acetylcysteine injection (NAC), and a mix of Dex, MP, and NAC (MIX). In this study, we compared the effects of these drugs on different cytokines of hard metal lung disease in a rat model. Thirty-six adult female Sprague Dawley rats were distributed equally into the control group, hard metal (HM) group, Dex group, MP group, NAC group, and MIX group. HM powder (0.5 mL, 20 mg/mL; one time) was administered by intraperitoneal injection to the HM group through the pulmonary endotracheal tube, while the control group received normal saline (0.5 mL, 20 mg/mL; one time). After 4 weeks, the drugs were administered to the experimental groups (0.5 mL, 20 mg/mL; one time). After 8 weeks, bronchoalveolar lavage fluid (BALF) and serum were examined for cytokine levels. Biochemical analysis indicated that the Dex, MP, NAC, and MIX did not improve TGF-ß1, TGF-ß2, KL-6, and MMP-1 in the BALF, while MIX increased TIMP-1 in BALF. In addition, the NAC treatment significantly increased the expression levels of TGF-ß1, TGF-ß2, KL-6, and MMP-1. The MIX treatment significantly increased the expression levels of TGF-ß1, TGF-ß2, and KL-6. The MP treatment significantly increased the expression levels of KL-6, and MMP-1. The Dex treatment significantly increased the expression levels of TGF-ß1, KL-6, and MMP-1. This study demonstrated that administered with NAC and MIX could improve TGF-ß1, TGF-ß2, and KL-6 in serum of hard metal lung disease in a rat model. Therefore, NAC injection may be considered a useful candidate in the development of a preventive agent against HMLD.


Asunto(s)
Enfermedades Pulmonares , Pulmón , Aleaciones , Animales , Líquido del Lavado Bronquioalveolar , Cobalto , Femenino , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismo , Tungsteno
12.
Sensors (Basel) ; 21(21)2021 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-34770274

RESUMEN

Microseismic monitoring system is one of the effective means to monitor ground stress in deep mines. The accuracy and speed of microseismic signal identification directly affect the stability analysis in rock engineering. At present, manual identification, which heavily relies on manual experience, is widely used to classify microseismic events and blasts in the mines. To realize intelligent and accurate identification of microseismic events and blasts, a microseismic signal identification system based on machine learning was established in this work. The discrimination of microseismic events and blasts was established based on the machine learning framework. The microseismic monitoring data was used to optimize the parameters and validate the classification methods. Subsequently, ten machine learning algorithms were used as the preliminary algorithms of the learning layer, including the Decision Tree, Random Forest, Logistic Regression, SVM, KNN, GBDT, Naive Bayes, Bagging, AdaBoost, and MLP. Then, training set and test set, accounting for 50% of each data set, were prospectively examined, and the ACC, PPV, SEN, NPV, SPE, FAR and ROC curves were used as evaluation indexes. Finally, the performances of these machine learning algorithms in microseismic signal identification were evaluated with cross-validation methods. The results showed that the Logistic Regression classifier had the best performance in parameter identification, and the accuracy of cross-validation can reach more than 0.95. Random Forest, Decision Tree, and Naive Bayes also performed well in this data set. There were some differences in the accuracy of different classifiers in the training set, test set, and all data sets. To improve the accuracy of signal identification, the database of microseismic events and blasts should be expanded, to avoid the inaccurate data distribution caused by the small training set. Artificial intelligence identification methods, including Random Forest, Logistic Regression, Decision Tree, Naive Bayes, and AdaBoost algorithms, were applied to signal identification of the microseismic monitoring system in mines, and the identification results were consistent with the actual situation. In this way, the confusion caused by manual classification between microseismic events and blasts based on the characteristics of waveform signals is solved, and the required source parameters are easily obtained, which can ensure the accuracy and timeliness of microseismic events and blasts identification.


Asunto(s)
Inteligencia Artificial , Aprendizaje Automático , Algoritmos , Teorema de Bayes , Modelos Logísticos , Máquina de Vectores de Soporte
13.
Nanomaterials (Basel) ; 11(10)2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34685119

RESUMEN

Recent investigations of fundamental electronic properties (especially the carrier transport mechanisms) of Si nanocrystal embedded in the amorphous SiC films are highly desired in order to further develop their applications in nano-electronic and optoelectronic devices. Here, Boron-doped Si nanocrystals embedded in the amorphous SiC films were prepared by thermal annealing of Boron-doped amorphous Si-rich SiC films with various Si/C ratios. Carrier transport properties in combination with microstructural characteristics were investigated via temperature dependence Hall effect measurements. It should be pointed out that Hall mobilities, carrier concentrations as well as conductivities in films were increased with Si/C ratio, which could be reached to the maximum of 7.2 cm2/V∙s, 4.6 × 1019 cm-3 and 87.5 S∙cm-1, respectively. Notably, different kinds of carrier transport behaviors, such as Mott variable-range hopping, multiple phonon hopping, percolation hopping and thermally activation conduction that play an important role in the transport process, were identified within different temperature ranges (10 K~400 K) in the films of different Si/C ratio. The changes from Mott variable-range hopping process to thermally activation conduction process with temperature were observed and discussed in detail.

14.
JAMA Netw Open ; 4(9): e2124100, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34477849

RESUMEN

Importance: It is important to determine what frequencies and auditory perceptual measures are the most sensitive early indicators of noise-induced hearing impairment. Objectives: To examine whether hearing loss among shipyard workers increases more rapidly at extended high frequencies than at clinical frequencies and whether subtle auditory processing deficits are present in those with extensive noise exposure but little or no hearing loss. Design, Setting, and Participants: This cross-sectional study collected audiometric data (0.25-16 kHz), survey questionnaires, and noise exposure levels from 7890 shipyard workers in a Shanghai shipyard from 2015 to 2019. Worsening hearing loss was evaluated in the group with hearing loss. Speech processing and temporal processing were evaluated in 610 participants with noise exposure and clinically normal hearing to identify early biomarkers of noise-induced hearing impairment. Data analysis was conducted from November to December 2020. Main Outcomes and Measures: Linear regression was performed to model the increase in hearing loss as function of cumulative noise exposure and compared with a group who were monitored longitudinally for 4 years. Auditory processing tests included speech-in-noise tests, competing sentence tests, dichotic listening tests, and gap detection threshold tests and were compared with a control group without history of noise exposure. Results: Of the 5539 participants (median [interquartile range (IQR)] age, 41.0 [34.0-47.0] years; 3861 [86.6%] men) included in the cross-sectional analysis, 4459 (80.5%) were hearing loss positive and 1080 (19.5%) were hearing loss negative. In younger participants (ie, ≤40 years), the maximum rate of increase in hearing loss was 0.40 (95% CI, 0.39-0.42) dB per A-weighted dB-year (dB/dBA-year) at 12.5 kHz, higher than the growth rates of 0.36 (95% CI, 0.35-0.36) dB/dBA-year at 4 kHz, 0.32 (95% CI, 0.31-0.33) dB/dBA-year at 10 kHz, 0.31 (95% CI, 0.30-0.31) dB/dBA-year at 6 kHz, 0.27 (95% CI, 0.26-0.27) dB/dBA-year at 3 kHz, and 0.27 (95% CI, 0.27-0.28) dB/dBA-year at 8 kHz. In the 4-year longitudinal analysis of hearing loss among 403 participants, the mean (SD) annual deterioration in hearing was 2.70 (2.98) dB/y at 12.5 kHz, almost twice as that observed at lower frequencies (eg, at 3kHz: 1.18 [2.15] dB/y). The auditory processing scores of participants with clinically normal hearing and a history of noise exposure were significantly lower than those of control participants (eg, median [IQR] score on speech-in-noise test, noise-exposed group 1 vs control group: 0.63 [0.55-0.66] vs 0.78 [0.76-0.80]; P < .001). Conclusions and Relevance: These findings suggest that the increase in hearing loss among shipyard workers was more rapid at 12.5 kHz than at other frequencies; workers with clinically normal hearing but high cumulative noise exposure are likely to exhibit deficits in speech and temporal processing.


Asunto(s)
Pérdida Auditiva Provocada por Ruido/diagnóstico , Enfermedades Profesionales/diagnóstico , Navíos , Adulto , Audiometría , Biomarcadores , China , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ruido/efectos adversos
15.
Hear Res ; 407: 108281, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34157653

RESUMEN

BACKGROUND: The overall genetic profile for noise-induced hearing loss (NIHL) remains elusive. Herein we proposed a novel machine learning (ML) based strategy to evaluate individual susceptibility to NIHL and identify the underlying genetic risk variants based on a subsample of participants with extreme phenotypes. METHODS: Five features (age, sex, cumulative noise exposure [CNE], smoking, and alcohol drinking status) of 5,539 shipbuilding workers from large cross-sectional surveys were included in four ML classification models to predict their hearing levels. The area under the curve (AUC) and prediction accuracy were exploited to evaluate the performance of the models. Based on the prediction error of the ML models, the NIHL-susceptible group (n=150) and NIHL-resistant group (n=150) with a paradoxical relationship between hearing levels and features were separately screened, to identify the underlying variants associated with NIHL risk using whole-exome sequencing (WES). Subsequently, candidate risk variants were validated in an additional replication cohort (n=2108), followed by a meta-analysis. RESULTS: With 10-fold cross-validation, the performances of the four ML models were robust and similar, with average AUCs and accuracies ranging from 0.783 to 0.798 and 73.7% to 73.8%, respectively. The phenotypes of the NIHL-susceptible and NIHL-resistant groups were significantly different (all p<0.001). After WES analysis and filtering, 12 risk variants contributing to NIHL susceptibility were identified and replicated. The meta-analyses showed that the A allele of CDH23 rs41281334 (odds ratio [OR]=1.506, 95% confidence interval [CI]=1.106-2.051) and the C allele of WHRN rs12339210 (OR=3.06, 95% CI=1.398-6.700) were significantly associated with increased risk of NIHL after adjustment for confounding factors. CONCLUSIONS: This study revealed two genetic variants in CDH23 rs41281334 and WHRN rs12339210 that associated with NIHL risk, based on a promising approach for evaluating individual susceptibility using ML models.


Asunto(s)
Pérdida Auditiva Provocada por Ruido , Estudios de Casos y Controles , China , Estudios Transversales , Predisposición Genética a la Enfermedad , Genotipo , Pérdida Auditiva Provocada por Ruido/etiología , Pérdida Auditiva Provocada por Ruido/genética , Humanos , Ruido en el Ambiente de Trabajo , Exposición Profesional , Polimorfismo de Nucleótido Simple
16.
Toxicology ; 456: 152769, 2021 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-33813002

RESUMEN

Cadmium (Cd) is a nephrotoxicant that primarily damages renal proximal tubular cells. Endoplasmic reticulum (ER) stress is mechanistically linked to Cd-induced renal injury. Inositol-requiring enzyme 1 (IRE-1α) is the most conserved ER stress transducer protein, which has both kinase and endonuclease activities. This study aimed to investigate whether the two enzymatic activities of IRE-1α have different effects in its regulation of Cd-induced apoptosis. Human proximal tubular (HK-2) cells were treated with 20 µM CdCl2 for 0-24 h, and mice were fed with Cd-containing drinking water (100-400 mg/L) for 24 weeks. We found that Cd increased cell apoptosis in HK-2 cells and mouse kidneys in a time-dependent manner. Such cytotoxicity was correlated with activation of ER stress, evidenced by upregulation of IRE-1α and its target protein spliced X-box binding protein-1 (XBP-1 s). Interestingly, inhibition of IRE-1α kinase activity by KIRA6 was more protective against Cd-induced apoptosis than inhibition of its RNase activity by STF-083010. Mechanistically, Cd promoted the binding of IRE-1α with signal transducer and activator of transcription-3 (STAT3) leading to elevated phosphorylation of STAT3 at Ser727 and thus inactivation of STAT3 signaling, which resulted in aggravation of Cd-induced apoptosis in HK-2 cells. Collectively, our findings indicate that IRE-1α coordinate ER stress and STAT3 signaling in mediating Cd-induced renal toxicity, suggesting that targeting IRE-1α might be a potential therapeutic approach for Cd-induced renal dysfunction and disease.


Asunto(s)
Cadmio/toxicidad , Estrés del Retículo Endoplásmico/fisiología , Endorribonucleasas/metabolismo , Células Epiteliales/metabolismo , Túbulos Renales/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Relación Dosis-Respuesta a Droga , Estrés del Retículo Endoplásmico/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Humanos , Túbulos Renales/citología , Túbulos Renales/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL
17.
Med Sci Monit ; 27: e928413, 2021 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-33531453

RESUMEN

BACKGROUND To explore the efficacy of beraprost sodium combined with sildenafil and its effects on the vascular endothelial function and inflammation in left heart failure patients complicated with pulmonary arterial hypertension. MATERIAL AND METHODS A total of 80 patients with left heart failure complicated with pulmonary arterial hypertension was enrolled as the subjects of this study and assigned into an observation group (n=40) and a control group (n=40) using a random number table. The changes in pulmonary arterial hypertension-associated indicators at 3 months after treatment and the alterations in the levels of cardiac function-associated biochemical indicator brain natriuretic peptide (BNP), inflammatory factor tumor necrosis factor alpha (TNF-alpha), and mean pulmonary arterial pressure during treatment were compared between the 2 groups. RESULTS At 3 months after treatment, the pulmonary arterial hypertension-associated indicators human urotensin II and calcitonin gene-related peptide in the observation group were lower and higher, respectively, than those in control group. Moreover, the observation group had significantly lower BNP and TNF-alpha levels and mean pulmonary arterial pressure than the control group. After intervention, the echocardiographic parameters left ventricular ejection fraction (LVEF), cardiac output (CO), and stroke volume (SV) in both groups were significantly higher than those before intervention, and the observation group had significantly higher LVEF, SV, and CO than the control group after intervention. CONCLUSIONS Beraprost sodium combined with sildenafil for left heart failure complicated with pulmonary arterial hypertension can effectively improve pulmonary arterial hypertension, alleviate left heart failure, and reduce inflammatory responses, thereby achieving better clinical efficacy in patients.


Asunto(s)
Epoprostenol/análogos & derivados , Insuficiencia Cardíaca/tratamiento farmacológico , Hipertensión Arterial Pulmonar/tratamiento farmacológico , Citrato de Sildenafil/uso terapéutico , Anciano , Anciano de 80 o más Años , Ecocardiografía , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Epoprostenol/farmacología , Epoprostenol/uso terapéutico , Tolerancia al Ejercicio , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Humanos , Inflamación/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Arteria Pulmonar/fisiopatología , Citrato de Sildenafil/farmacología , Volumen Sistólico/efectos de los fármacos , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacos , Función Ventricular Derecha/efectos de los fármacos
18.
Sci Total Environ ; 765: 142740, 2021 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-33071125

RESUMEN

Mechanisms for hematotoxicity and health effects from exposure to low doses of benzene (BZ) remain to be identified. To address the information gap, our investigation was focused onto using appropriate populations and cell cultures to investigate novel BZ-induced effects such as disruption of DNA repair capacity (DRC). From our study, abnormal miRNAs were identified and validated using lymphocytes from 56 BZ-poisoned workers and 53 controls. In addition, 173 current BZ-exposed workers and 58 controls were investigated for key miRNA expression using RT-PCR and for cellular DRC using a challenge assay. Subsequently, the observed activities in lymphocytes were verified using human HL-60 (p53 null) and TK6 (p53 wild-type) cells via 1,4-benzoquinone (1,4-BQ) treatment and miR-222 interferences. The targeting of MDM2 by miR-222 was validated using a luciferase reporter. Our results indicate induction of genotoxicity in lymphocytes from workers with low exposure doses to BZ. In addition, miR-222 expression was up-regulated among both BZ-poisoned and BZ-exposed workers together with inverse association with DRC. Our in vitro validation studies using both cell lines indicate that 1,4-BQ exposure increased expression of miR-222 and Comet tail length but decreased DRC. Loss of miR-222 reduced DNA damage, but induced S-phase arrest and apoptosis. However, silencing of MDM2 failed to activate p53 in TK6 cells. In conclusion, our in vivo observations were confirmed by in vitro studies showing that BZ/1,4-BQ exposures caused genotoxicity and high expression of miR-222 which obstructed expression of the MDM2-p53 axis that led to failed activation of p53, abnormal DRC and serious biological consequences.


Asunto(s)
Benceno , MicroARNs , Apoptosis , Benceno/toxicidad , Daño del ADN , Reparación del ADN , Humanos , MicroARNs/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
19.
Sensors (Basel) ; 20(15)2020 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-32756357

RESUMEN

The discrimination of micro-seismic events (events) and blasts is significant for monitoring and analyzing micro-seismicity in underground mines. To eliminate the negative effects of conventional discrimination methods, a waveform image discriminant method was proposed. Principal component analysis (PCA) was applied to extract the raw features of events and blasts through their waveform images that established by the recorded field data, and transform them into the new uncorrelated features. The amount of initial information retained in the derived features could be determined quantitatively by the contribution rate. The binary classification models were established by utilizing the support vector machine (SVM) algorithm and the PCA derived waveform image features. Results of four groups of cross validation show that the optimal values for the accuracy of events and blasts, total accuracy, and quality evaluation parameter MCC are 97.1%, 93.8%, 93.60%, and 0.8723, respectively. Moreover, the computation efficiency per accuracy (CEA) was introduced to quantitatively evaluate the effects of contribution rate on classification accuracy and computation efficiency. The optimal contribution rate was determined to be 0.90. The waveform image discriminant method can automatically classify events and blasts in underground mines, ensuring the efficient establishment of high-quality micro-seismic databases and providing adequate data for the subsequent seismicity analysis.

20.
J Occup Environ Med ; 62(7): e308-e317, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32730034

RESUMEN

OBJECTIVE: This study investigates the mechanisms of benzene hematotoxicity. METHODS: We used microarray to detect expression profiles of long non-coding RNAs (lncRNAs) and mRNAs in peripheral lymphocytes from chronic benzene poisoning, acute myelocytic leukemia, and healthy controls. The lncRNAs and mRNAs were validated using real-time quantitative PCR (RT-qPCR). Cytokinesis-block micronucleus assay was used to analyze chromosomal aberration. RESULTS: We found 173 upregulated and 258 downregulated lncRNAs, and 695 upregulated and 804 downregulated mRNAs. The lncRNA CUST_40243 and mRNA PDGFC and CDKN1A associated with chronic benzene poisoning. Relevant inflammatory response, hematopoietic cell lineage, and cell cycle may be important pathways for the sifted lncRNAs and mRNAs. Furthermore, micronuclei frequency was significantly higher in off-post chronic benzene poisoning patients. CONCLUSIONS: Chromosomal aberration induced by benzene exposure is irreversible. The lncRNA CUST_40243 and mRNA PDGFC and CDKN1A are related to chronic benzene poisoning.


Asunto(s)
Benceno/envenenamiento , Leucemia Mieloide Aguda/genética , ARN Largo no Codificante/genética , Adulto , Aberraciones Cromosómicas , Femenino , Regulación de la Expresión Génica , Humanos , Leucemia Mieloide Aguda/inducido químicamente , Leucemia Mieloide Aguda/patología , Masculino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , ARN Mensajero/genética
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