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1.
Neurol Ther ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34855160

RESUMO

INTRODUCTION: Acute traumatic intraparenchymal hematoma (tICH) expansion is a major cause of clinical deterioration after brain contusion. Here, an accurate prediction tool for acute tICH expansion is proposed. METHODS: A multicenter hospital-based study for multivariable prediction model was conducted among patients (889 patients in a development dataset and 264 individuals in an external validation dataset) with initial and follow-up computed tomography (CT) imaging for tICH volume evaluation. Semi-automated software was employed to assess tICH expansion. Two multivariate predictive models for acute tICH expansion were developed and externally validated. RESULTS: A total of 198 (22.27%) individuals had remarkable acute tICH expansion. The novel Traumatic Parenchymatous Hematoma Expansion Aid (TPHEA) model retained several variables, including age, coagulopathy, baseline tICH volume, time to baseline CT time, subdural hemorrhage, a novel imaging marker of multihematoma fuzzy sign, and an inflammatory index of monocyte-to-lymphocyte ratio. Compared with multihematoma fuzzy sign, monocyte-to-lymphocyte ratio, and the basic model, the TPHEA model exhibited optimal discrimination, calibration, and clinical net benefits for patients with acute tICH expansion. A TPHEA nomogram was subsequently introduced from this model to facilitate clinical application. In an external dataset, this device showed good predicting performance for acute tICH expansion. CONCLUSIONS: The main predictive factors in the TPHEA nomogram are the monocyte-to-lymphocyte ratio, baseline tICH volume, and multihematoma fuzzy sign. This user-friendly tool can estimate acute tICH expansion and optimize personalized treatments for individuals with brain contusion.

2.
Radiother Oncol ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34808228

RESUMO

BACKGROUND AND PURPOSE: The delineation of the gross tumor volume (GTV) is a critical step for radiation therapy treatment planning. The delineation procedure is typically performed manually which exposes two major issues: cost and reproducibility. Delineation is a time-consuming process that is subject to inter- and intra-observer variability. While methods have been proposed to predict GTV contours, typical approaches ignore variability and therefore fail to utilize the valuable confidence information offered by multiple contours. MATERIALS AND METHODS: In this work we propose an automatic GTV contouring method for softtissue sarcomas from X-ray computed tomography (CT) images, using deep learning by integrating inter- and intra-observer variability in the learned model. Sixty-eight patients with soft tissue and bone sarcomas were considered in this evaluation, all underwent pre-operative CT imaging used to perform GTV delineation. Four radiation oncologists and radiologists performed three contouring trials each for all patients. We quantify variability by defining confidence levels based on the frequency of inclusion of a given voxel into the GTV and use a deep convolutional neural network to learn GTV confidence maps. RESULTS: Results were compared to confidence maps from the four readers as well as groundtruth consensus contours established jointly by all readers. The resulting continuous Dice score between predicted and true confidence maps was 87% and the Hausdorff distance was 14 mm. CONCLUSION: Results demonstrate the ability of the proposed method to predict accurate contours while utilizing variability and as such it can be used to improve clinical workflow.

3.
Mater Horiz ; 8(1): 234-243, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821302

RESUMO

Novel applications of waste thermosetting resins are developed by facile mechanical crushing, and their excellent performances are demonstrated in oil-water separation, superhydrophobic coatings with diverse water adhesion, acid liquid/gas monitoring and information storage. This work provides new ideas for waste treatments and functional material design, as well as speeds up the transformation of waste resins from laboratory achievements to industrial applications. Moreover, it can also improve the utilization efficiency of non-renewable resources and meet the requirements of energy conservation and environmental protection.

4.
Dis Colon Rectum ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34759241

RESUMO

BACKGROUND: The characteristics of colorectal cancer patients with benign mesenteric lymph node enlargement are not well documented. OBJECTIVE: The aim of this study is to assess clinical and prognostic significance of benign mesenteric lymph node enlargement in colorectal cancer patients. DESIGN: This is a prospective cohort study. SETTING: This study was conducted at multi-tertiary institutions. PATIENTS: We included 601 colorectal cancer patients of stage 0, I, II in Tianjin, Shandong and Zhejiang from January 2010 to April 2014. Patients underwent curative surgery and were separated into two groups by presence of benign mesenteric lymph node enlargement: enlargement group (n=275) and control group (n=326). MAIN OUTCOME MEASURES: Univariate log rank and multivariate Cox regression analysis were constructed to identify risk factors for recurrence and mortality. RESULTS: The risk of recurrence in enlargement group after curative resection was significantly lower than control group, with the 1-, 3-, and 5-year disease free survival rates being 97.1, 91.6, 86.9% in enlargement group and 95.7, 86.2, 78.2% in control group respectively (p=0.004). The postoperative 1-, 3-, and 5-year overall survival rates were 99.6, 94.9, 90.5% in enlargement group and 99.4, 91.4, 82.1% in control group respectively (p=0.001). Patients of enlargement group had a higher percentage of younger age, family tumor history, right sided tumors and larger tumor size compared with control group. For enlarged patients, no significant correlation was observed between the number of enlarged lymph nodes and disease free survival or overall survival (p=0.113 and 0.386). Adjusted Cox regression model showed benign mesenteric lymph node enlargement was an independent prognostic risk factor for both disease free survival (hazard ratio 0.587; 95% CI 0.399-0.861; p=0.007) and overall survival (hazard ratio 0.506; 95% CI 0.328-0.779; p=0.002). IMITATIONS: No immunological results could be compared with clinicopathological findings. CONCLUSIONS: The study indicates that benign mesenteric lymph node enlargement can be a useful positive factor in predicting recurrence and long-term survival concerning colorectal cancer patients. See Video Abstract at http://links.lww.com/DCR/B785.

5.
J Hazard Mater ; 424(Pt C): 127576, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34736208

RESUMO

Soybean paste is manufactured through microbial fermentation and may become contaminated with aflatoxins. Herein, we conducted nationwide large-scale monitoring (n = 1436) over three years (2018-2020) to investigate aflatoxin levels according to geographic, demographic, manufacturing, quality factors, and risk characteristics of homemade soybean paste produced through fermentation. The mean level of total aflatoxins was 5.88 µg/kg (range, 0.01-281.92), with the most common contaminating type being the B type. Aflatoxin levels significantly differed according to the region, age of the manufacturer, type of starter used, and the amino-type nitrogen content and pH of the homemade soybean paste (p < 0.05). Aflatoxin levels was significantly higher when starters were manufactured using the traditional method (inoculation with a naturally occurring strain in the surrounding environment). The aflatoxin exposure level estimated through the average intake of homemade soybean paste in all age groups was 0.1012 ng/kg body weight/day. The risk assessment for the genotoxic and carcinogenic potential of aflatoxins using the margin of exposure approach revealed values of 3705-3954 for average intake of homemade soybean paste, indicating public health concern. These results suggest that follow-up studies and safety management strategies are needed to reduce aflatoxin levels in homemade soybean paste.

6.
Nonlinear Dyn ; : 1-15, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34728898

RESUMO

Current explosive outbreak of COVID-19 around the world is a complex spatiotemporal process with hidden interactions between viruses and humans. This study aims at clarifying the transmission patterns and the driving mechanism that contributed to the COVID-19 prevalence across the provinces of China. Thus, a new dynamical transmission model is established by an ordinary differential system. The model takes into account the hidden circulation of COVID-19 virus among/within humans, which incorporates the spatial diffusion of infection by parameterizing human mobility. Theoretical analysis indicates that the basic reproduction number is a unique epidemic threshold, which can unite infectivity in each region by human mobility and can totally determine whether COVID-19 proceeds among multiple regions. By validating the model with real epidemic data in China, it is found that (1) if without any intervention, COVID-19 would overrun China within three months, resulting in more than 1.1 billion clinical infections and 0.2 billion subclinical infections; (2) high frequency of human mobility can trigger COVID-19 diffusion across each province in China, no matter where the initial infection locates; (3) travel restrictions and other non-pharmaceutical interventions must be implemented simultaneously for disease control; and (4) infection sites in central and east (rather than west and northeast) of China would easily stimulate quick diffusion of COVID-19 in the whole country. Supplementary Information: The online version supplementary material available at 10.1007/s11071-021-07001-1.

7.
ChemSusChem ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34747148

RESUMO

Plastic has now become a contradiction between civilization and pollution which human society has to resolve. The recycling of thermosetting plastics in waste plastics is even more a huge challenge since they are difficult to remold like thermoplastic plastics due to their high crosslinking density. Here, a new strategy is presented to achieve multicycling of anhydride-cured epoxy thermosets. The process consists of mild and high-efficiency alcoholysis catalyzed by potassium phosphate/low-boiling alcohol system, and subsequent fast hydrolysis to obtain degradation products rich of carboxyl groups. The degradation products are reused as curing agent to prepare new anhydride-cured epoxy thermosets without sacrifice of high strength and high stability. Moreover, the new epoxy thermosets can still be repeatedly recycled using the same protocol. The insoluble property of the potassium phosphate in the ethanol at room temperatures makes the separation and reuse of the catalyst more convenient. Meanwhile low-boiling alcohol not only allows high-efficiency degradation, but also enables easy separation from the degradation products. The excellent degradation performance is attribute to the improved swelling of the thermoset and the increased solubility of potassium phosphate induced by the small water in the alcohol. This research provides a recycling method that can reintegrate thermoset waste plastics into remodeling ones under the background of circular economy.

9.
J Sport Rehabil ; : 1-6, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34784583

RESUMO

CONTEXT: Many methods used to evaluate knee proprioception have shortcomings that limit their use in clinical settings. Based on an inexpensive 3D camera, a new portable device was recently used to evaluate the joint position sense (JPS) of the knee joint. However, the test-retest reliability of the new method remains unclear. This study aimed to evaluate the test-retest reliability of the new device and a long-arm goniometer for assessing knee JPS, and to compare the variability of the 2 methods. DESIGN: Prospective observational study of the test-retest reliability of knee JPS measurements. METHODS: Twenty-one healthy adults were tested in 2 sessions with a 1-week interval. Three target knee flexion angles (30°, 45°, and 60°) were reproduced in each session. Target and reproduced angles were measured with both methods. Intraclass correlation coefficients, standard error of the measurement, and Bland-Altman plots were used to quantify test-retest reliability. Paired t tests were used to compare knee JPS (absolute error of the target-reproduced angle) between the methods. RESULTS: The new device (good to excellent intraclass correlation coefficients .74-.80; standard error of the measurement 0.52°-0.61°) demonstrated better test-retest reliability than the goniometer (poor to fair intraclass correlation coefficients .23-.43; standard error of the measurement 0.89°-2.07°) and better test-retest agreement (respective mean differences for the 30°, 45°, and 60° knee angles: 0.11°, 0.13°, and 0.41° for the new system; 0.84°, 1.52°, and 1.18° for the goniometer). The measurements (absolute errors of the target-reproduced angles) with the goniometer were significantly greater than those with the new device (P < .05); the SDs of repeated measurements with the goniometer (1.50°-2.41°) were greater than with the new device (1.08°-1.38°). CONCLUSIONS: Given that the new device has good reliability and sufficient precision, it is the better alternative for evaluating knee JPS. Goniometers should be used with caution to assess knee JPS.

10.
Orthop Surg ; 13(6): 1882-1889, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34605608

RESUMO

OBJECTIVE: To investigate the relief of low back pain after hip arthroplasty in patients with hip joint and spinal degenerative diseases, and to discuss the effects of unilateral and bilateral hip surgery on the relief of low back pain. METHODS: In this retrospective study, we followed 153 patients (69 males and 84 females, age: 43-88 years) who had undergone total hip arthroplasty (THA) via a posterolateral approach and also suffered from lumbar degenerative diseases in the period of 2009 to 2019. The inclusion criteria were: (i) patients who had been diagnosed with severe hip degenerative disease and also been diagnosed with lumbar degenerative disease; (ii) patients who had undergone THA surgery; and (iii) patients who were retrospectively recruited. The exclusion criteria were: (i) patients who had undergone lumbar fusion or internal fixation surgery; or (ii) patients who had vascular claudication, history of major trauma, diabetic polyneuropathy, lumbar and pelvic infections, tumor diseases; (iii) or patients who had undergone THA because of femoral neck fracture or ankylosing spondylitis. The improvement of hip joint function and the relief of low back pain (LBP) were studied, and the effect of unilateral and bilateral THA on the relief of LBP were discussed. Hip pain and function were evaluated by the Harris Hip Score (HHS), LBP was evaluated by Visual Analog Scale (VAS), and lumbar function was evaluated by the Japanese Orthopaedic Association (JOA) scoring system. RESULTS: The average follow-up time was 44.3 months (24-108 months). All patients recovered smoothly without complications. The LBP VAS of 153 patients decreased from 4.13 ± 1.37 preoperatively to 1.90 ± 1.44 postoperatively. The average HHS increased from 45.33 ± 13.23 preoperatively to 86.44 ± 7.59 postoperatively at the latest follow-up. According to Japanese Orthopaedic Association scoring system, the proportion of patients with good response to treatment in these 153 patients reached 93.46%. LBP VAS decreased from 4.18 ± 1.38 preoperatively to 1.95 ± 1.49 postoperatively in unilateral group and from 3.94 ± 1.32 preoperatively to 1.73 ± 1.23 postoperatively in bilateral group, respectively. There were only nine patients with persistent or aggravated LBP after operation. Among them, six patients underwent subsequent lumbar surgery (five patients had pain relieved after reoperation and one patient had not) and the other three patients chose conservative treatment for pain. CONCLUSION: THA can relieve LBP while relieving hip pain and restoring hip function in patients with both hip and lumbar degenerative disease, thus possibly avoiding further spinal surgery.


Assuntos
Artroplastia de Quadril/métodos , Degeneração do Disco Intervertebral/terapia , Dor Lombar/terapia , Osteoartrite do Quadril/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Medidas de Resultados Relatados pelo Paciente , Período Pós-Operatório , Estudos Retrospectivos
11.
China CDC Wkly ; 3(23): 485-489, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34594919

RESUMO

What is already known about this topic? Previous studies have mainly focused on the relationship between temperature and mortality from stroke, but analysis on the effects on years of life lost (YLL) is limited. What is added by this report? YLLs were used as the health outcome, and cold and hot weather were found to be significantly associated with an increase in YLLs from stroke and for different groups, with a stronger effect found to be associated with low temperature. What are the implications for public health practice? These findings could help identify vulnerable regions and populations that have a more serious temperature-related burden and to guide the practical and effective measures for stroke control from a YLL perspective.

12.
Opt Express ; 29(18): 28359-28365, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34614969

RESUMO

We introduce a simple method with thermal annealing round gold disk for agglomeration to fabricate orderly arranged nanostructure arrays on diamond for single photon source applications. In the annealing process, the dependence of gold sphere size on disk thickness and diameter was investigated, showing that gold sphere diameter was decreased with decreasing gold disk thickness or diameter. The condition parameters of ICP etch were adjusted to obtain different nanostructure morphologies on diamond. The collection efficiency of nitrogen-vacancy (NV) center embedded in nanostructure as-fabricated could reach to 53.56% compared with that of 19.10% in planar case with the same simulation method.

13.
Sci Total Environ ; 807(Pt 1): 150814, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34626635

RESUMO

Due to strong endocrine disrupting effects, steroids in the environment have attracted substantial attention, with studies mostly focusing on the parent steroids. Here, we conducted the first investigation on the contamination profiles, possible sources, mass inventories, and ecological risks of 27 steroids and their metabolites in 15 typical fishing ports in Southeast China. Twelve steroids were detectable in the sediment samples with the total mean concentrations of 4.6-35 ng/g. High proportions of steroid metabolites were measured in the sediments and five metabolites were newly observed. Untreated municipal sewage and aquaculture wastes constitute the possible steroid sources in the studied fishing ports. The total inventories of steroids in fishing ports ranged from 2.1-16 mg/m2, with their metabolites being important contributors. The ecological risk analysis indicated high risks across all sampling sites mainly due to the contributions of parent steroids. Furthermore, our results found that progesterone is an acceptable chemical indicator for various steroids in sediments. This study provides the first evidence of steroid metabolites in the marine environment, calling for more studies in environmental behavior and ecotoxicology of steroid metabolites.

14.
Am J Transl Res ; 13(8): 8847-8859, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539999

RESUMO

Beta-hydroxybutyric acid (BHB) exerts a protective effect in experimental of kidney disease models. However, the mechanisms underlying this activity are not well defined. BHB stands out for its ability to inhibit the Nε-lysine acetylation of histone and non-histone proteins, which may affect cellular processes and protein functions. In adriamycin-injured murine glomerular podocytes, BHB ameliorates podocyte damage and preserves actin cytoskeleton integrity, reminiscent of the effect of MS275, a highly selective inhibitor of lysine deacetylase. Further research found that adriamycin causes the reduced acetylation of nephrin, WT-1, and GSK3ß. This process is abrogated by the lysine deacetylase inhibitor or BHB, suggesting that the acetylation of these molecules regulates their activity. In contrast, anacardic acid, a selective inhibitor of acetyltransferase, decreases the acetylation of nephrin, WT-1, and GSK3ß and mitigates the podocyte protective effects of BHB. Taken together, BHB attenuates adriamycin-elicited glomerular epithelial cell injury, at least in part, by inhibiting the deacetylation of the key molecules implicated in glomerular injury.

15.
Br J Cancer ; 125(8): 1111-1121, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34365472

RESUMO

BACKGROUND AND AIMS: Computed tomography (CT) scan is frequently used to detect hepatocellular carcinoma (HCC) in routine clinical practice. The aim of this study is to develop a deep-learning AI system to improve the diagnostic accuracy of HCC by analysing liver CT imaging data. METHODS: We developed a deep-learning AI system by training on CT images from 7512 patients at Henan Provincial Peoples' Hospital. Its performance was validated on one internal test set (Henan Provincial Peoples' Hospital, n = 385) and one external test set (Henan Provincial Cancer Hospital, n = 556). The area under the receiver-operating characteristic curve (AUROC) was used as the primary classification metric. Accuracy, sensitivity, specificity, precision, negative predictive value and F1 metric were used to measure the performance of AI systems and radiologists. RESULTS: AI system achieved high performance in identifying HCC patients, with AUROC of 0.887 (95% CI 0.855-0.919) on the internal test set and 0.883 (95% CI 0.855-0.911) on the external test set. For internal test set, accuracy was 81.0% (76.8-84.8%), sensitivity was 78.4% (72.4-83.7%), specificity was 84.4% (78.0-89.6%) and F1 (harmonic average of precision and recall rate) was 0.824. For external test set, accuracy was 81.3% (77.8-84.5%), sensitivity was 89.4% (85.0-92.8%), specificity was 74.0% (68.5-78.9%) and F1 was 0.819. Compared with radiologists, AI system achieved comparable accuracy and F1 metric on internal test set (0.853 versus 0.818, P = 0.107; 0.863 vs. 0.824, P = 0.082) and external test set (0.805 vs. 0.793, P = 0.663; 0.810 vs. 0.814, P = 0.866). The predicted HCC risk scores by AI system in HCC patients with multiple tumours and high fibrosis stage were higher than those with solitary tumour and low fibrosis stage (tumour number: 0.197 vs. 0.138, P = 0.006; fibrosis stage: 0.183 vs. 0.127, P < 0.001). Radiologists' review showed that the accuracy of saliency heatmaps predicted by algorithms was 92.1% (95% CI: 89.2-95.0%). CONCLUSIONS: AI system achieved high performance in the detection of HCC compared with a group of specialised radiologists. Further investigation by prospective clinical trials was necessitated to verify this model.

16.
Chemosphere ; 285: 131481, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34265721

RESUMO

The development of slow-release phosphorus fertilizers (SRFs) with high water retention is of significance for modern agriculture. Herein, a new class of biochar-based SRFs are developed by an integrated co-pyrolysis and co-polymerization process (PSRFs). The water-retention performance and P slow-release behavior of PSRFs are evaluated, which are compared with other types of biochar-based SRFs derived from biochar-based phosphorus adsorption (MSRFs), co-pyrolysis of biomass-bentonite-nutrients (BSRFs), and the application of coating on BSRFs (CSRFs). The results show that the obtained PSRFs exhibits high water retention with the maximum swelling capacity of 94.2 g/g, far outstripping other tested SRFs. The water-retention performance of PSRFs is found to be positively correlated with their crosslinking agent contents. In addition, PSRFs has excellent P slow-release performance which is comparable with CSRFs (~51.5% of P release after 30 days), but much better than MSRFs and BSRFs with a complete P release after 30 days. Furthermore, pot experiments reveal that PSRFs has the highest P utilization efficiency (75.83% after 60 days), which can promote the growth of pepper seedlings better than other SRFs. Moreover, the soil burial tests indicate that PSRFs has a good biodegradability with the degradation ratio of 33.46% in 75 days. Finally, biological abundance analysis further reveals that Actinobacteria in soil is mainly responsible for the metabolism of starch and sodium alginate in PSRFs.


Assuntos
Fertilizantes , Pirólise , Carvão Vegetal , Fertilizantes/análise , Fósforo , Polimerização , Solo , Água
18.
Gait Posture ; 88: 231-237, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34119778

RESUMO

BACKGROUND: Knee injuries often occur during or shortly after marathon running, and are linked to altered knee kinematics. RESEARCH QUESTION: The kinematics of healthy knees during pre- and post-marathon running have not been examined with high-speed fluoroscopy. This study aimed to evaluate the effects of marathon running on knee kinematics during walking and running by using a combined high-speed fluoroscopy and MRI technique. METHODS: Ten healthy runners underwent knee MRI within 24 h before marathon running to construct three-dimensional (3D) knee models. Knee kinematics during treadmill walking and running were evaluated using high-speed fluoroscopy (200hz) within 24 h before and as soon as possible (within 5 h) after marathon running. All pre- and post-marathon measurements were compared. RESULTS: (1) For post-marathon walking, posterior femoral translation increased 1.4 mm at initial contact (p = 0.015); proximal-distal distance of tibia and femur decreased 0.7 mm and 0.8 mm at initial contact and after contact, respectively (p = 0.039, p = 0.046); and valgus femur rotation increased 1.2° after contact (p = 0.027). (2) For post-marathon running, proximal-distal distance decreased 0.7 mm and 1.0 mm at initial contact and after contact (p = 0.011, p = 0.003) respectively; knee flexion decreased 4.3° before contact (p = 0.007); knee flexion increased 1.8° and 2.6° at initial contact and after contact, respectively (p = 0.038, p = 0.011); external femoral rotation increased 1.2° and 1.8° at initial contact and after contact, respectively (p = 0.012, p = 0.037). Valgus femoral rotation after contact increased 2.3° (p = 0.001). SIGNIFICANCE: Post-marathon changes in valgus and external femoral rotation, knee flexion, posterior femoral translation, and proximal-distal distance may increase the risk of knee injury. This study provides information to better understand the response of the knee to marathon running.


Assuntos
Articulação do Joelho , Corrida de Maratona , Fenômenos Biomecânicos , Fêmur , Fluoroscopia , Humanos , Imageamento Tridimensional , Amplitude de Movimento Articular , Tíbia
19.
Acta Pharmacol Sin ; 42(10): 1690-1702, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34112960

RESUMO

Ferroptotic cell death is characterized by iron-dependent lipid peroxidation that is initiated by ferrous iron and H2O2 via Fenton reaction, in which the role of activating transcription factor 3 (ATF3) remains elusive. Brucine is a weak alkaline indole alkaloid extracted from the seeds of Strychnos nux-vomica, which has shown potent antitumor activity against various tumors, including glioma. In this study, we showed that brucine inhibited glioma cell growth in vitro and in vivo, which was paralleled by nuclear translocation of ATF3, lipid peroxidation, and increases of iron and H2O2. Furthermore, brucine-induced lipid peroxidation was inhibited or exacerbated when intracellular iron was chelated by deferoxamine (500 µM) or improved by ferric ammonium citrate (500 µM). Suppression of lipid peroxidation with lipophilic antioxidants ferrostatin-1 (50 µM) or liproxstatin-1 (30 µM) rescued brucine-induced glioma cell death. Moreover, knockdown of ATF3 prevented brucine-induced accumulation of iron and H2O2 and glioma cell death. We revealed that brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT to prevent H2O2 degradation on the other hand. H2O2 then contributed to brucine-triggered iron increase and transferrin receptor upregulation, as well as lipid peroxidation. This was further verified by treating glioma cells with exogenous H2O2 alone. Moreover, H2O2 reversely exacerbated brucine-induced ER stress. Taken together, ATF3 contributes to brucine-induced glioma cell ferroptosis via increasing H2O2 and iron.

20.
Innovation (N Y) ; 2(3): 100139, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34189495

RESUMO

The evidence for the effects of environmental factors on COVID-19 case fatality remains controversial, and it is crucial to understand the role of preventable environmental factors in driving COVID-19 fatality. We thus conducted a nationwide cohort study to estimate the effects of environmental factors (temperature, particulate matter [PM2.5, PM10], sulfur dioxide [SO2], nitrogen dioxide [NO2], and ozone [O3]) on COVID-19 case fatality. A total of 71,808 confirmed COVID-19 cases were identified and followed up for their vital status through April 25, 2020. Exposures to ambient air pollution and temperature were estimated by linking the city- and county-level monitoring data to the residential community of each participant. For each participant, two windows were defined: the period from symptom onset to diagnosis (exposure window I) and the period from diagnosis date to date of death/recovery or end of the study period (exposure window II). Cox proportional hazards models were used to estimate the associations between these environmental factors and COVID-19 case fatality. COVID-19 case fatality increased in association with environmental factors for the two exposure windows. For example, each 10 µg/m3 increase in PM2.5, PM10, O3, and NO2 in window I was associated with a hazard ratio of 1.11 (95% CI 1.09, 1.13), 1.10 (95% CI 1.08, 1.13), 1.09 (95 CI 1.03, 1.14), and 1.27 (95% CI 1.19, 1.35) for COVID-19 fatality, respectively. A significant effect was also observed for low temperature, with a hazard ratio of 1.03 (95% CI 1.01, 1.04) for COVID-19 case fatality per 1°C decrease. Subgroup analysis indicated that these effects were stronger in the elderly, as well as in those with mild symptoms and living in Wuhan or Hubei. Overall, the sensitivity analyses also yielded consistent estimates. Short-term exposure to ambient air pollution and low temperature during the illness would play a nonnegligible part in causing case fatality due to COVID-19. Reduced exposures to high concentrations of PM2.5, PM10, O3, SO2, and NO2 and low temperature would help improve the prognosis and reduce public health burden.

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