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1.
Huan Jing Ke Xue ; 45(8): 4733-4743, 2024 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-39168691

RESUMO

The Bohai Rim Plain is an important grain-producing area in China. The cultivated land resources have great potential for production, but there are many influencing factors. Understanding the spatiotemporal change characteristics and driving factors of the net primary productivity (NPP) of cultivated land vegetation in this region is of great significance to improve the regional cultivated land production conditions, excavate and enhance the production capacity of cultivated land, and ensure national food security. In this study, Theil-Sen Median trend analysis, Mann-Kendall significance test, Hurst index, and other methods were used to explore the spatiotemporal change characteristics, stability, and sustainability of regional cultivated land NPP. The influence of driving factors on the spatial heterogeneity of cultivated land NPP was analyzed by using optical parameters-based geographical detectors. The results showed that: ① From 2001 to 2019, due to the expansion of construction land during industrialization and urbanization, the cumulative decrease in the area of cultivated land in the Shandong area around the Bohai Sea was 2 004.51 km2. ② During the selected research period, the interannual variation of average cultivated land NPP showed a fluctuating and increasing trend. In terms of spatial distribution, the NPP of cultivated land was bounded by the Dongying District, with the spatial heterogeneity in the north being significantly lower than that in the south. ③ The area with increasing NPP of cultivated land accounted for 88.06% of the total area of cultivated land, mainly with low and medium fluctuations. The NPP of cultivated land will maintain an overall sustained trend of increase across the region in the future. ④ The average annual relative humidity study area had the strongest explanatory power for the spatial variability of NPP in cropland, with a q-value of 0.26, followed by surface soil salinity and subsoil salinity, with q-values greater than 0.2. The interactions between the different drivers all showed either nonlinear enhancement or bifactorial enhancement. The results of this study will help to reveal the characteristics of the changes in cultivated land production capacity and its driving forces in the Bohai Sea region and also provide a theoretical basis for the ecological protection and sustainable development of the region.

2.
Huan Jing Ke Xue ; 45(7): 4293-4301, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022974

RESUMO

Quantitative analysis of the spatial non-stationary characteristics of soil salinization influencing factors and the prediction of its spatial distribution are of great significance for the rational use of coastal saline soil resources and the formulation of local prevention and control measures. In this study, the Hekou District of Dongying City, Shandong Province, was used as the study area, and the descriptive statistics of soil salinization status were conducted using classical statistical methods. Spatial autocorrelation theory was used to explore the characteristics of global and local spatial structure of soil salinization in the study area. Influential factors related to soil salinity were selected, and multivariate linear regression (MLR), geographically weighted regression (GWR), and multi-scale geographically weighted regression (MGWR) methods were used to model and predict the spatial distribution of soil salinity in the study area and to analyze the spatial heterogeneity of the effects of different influencing factors on soil salinity. The results showed that: ① The mean value of soil salinity in the study area was 5.84 g·kg-1, indicating severe salinization, with a global Moran's I index of 0.19 (P<0.00) and obvious spatial aggregation characteristics. ② Among the three models, the MGWR model had the highest modeling accuracy. Compared with that of the MLR model, the Radj2 of GWR and MGWR improved by 0.05 and 0.07, respectively, and the RSS decreased by 210.13 and 179.95, respectively. ③ The results of MGWR regression showed that the spatial distribution of soil salinity appeared to be mainly affected by the middle soil salinity, soil clay content, and vegetation cover from the mean values of standardized regression coefficients of different influencing factors. Different influencing factors had significant spatial non-stationary characteristics on soil salinization. ④ The results of the spatial distribution prediction of soil salinity in MGWR showed that the areas of high soil salinity (≥6 g·kg-1) were mainly distributed in the northern part of the study area, with an overall spatial trend of decreasing from the coast to the interior. The results of the study can be used as a reference for the analysis and predictive mapping of factors affecting soil salinization in the county and on a larger scale using MGWR.

3.
Clinics (Sao Paulo) ; 79: 100394, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38820696

RESUMO

BACKGROUND AND PURPOSE: Intravenous Thrombolysis (IVT) prior to Mechanical Thrombectomy (MT) for Acute Ischaemic Stroke (AIS) due to Large-Vessel Occlusion (LVO) remains controversial. Therefore, the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy (BT) compared with direct MT in patients with AIS due to LVO. METHODS: Four databases were searched until 01 February 2023. Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included. Odds Ratios (ORs) and 95 % Confidence Intervals (CIs) for efficacy and safety outcomes were pooled using a random-effects model. RESULTS: Of the 12 studies, 86,695 patients were included. In patients with AIS due to LVO, BT group was associated with higher odds of achieving excellent functional outcome (modified Rankin Scale score 0-1) at 90 days (OR = 1.48, 95 % CI 1.25-1.75), favorable discharge disposition (to the home with or without services) (OR = 1.33, 95 % CI 1.29-1.38), and decreased mortality at 90 days (OR = 0.62, 95 % CI 0.56-0.70), as compared with the direct MT group. In addition, the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group. CONCLUSION: The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO. These findings support the current practice in a real-world setting and strengthen their validity. For patients eligible for both IVT and MT, BT remains the standard treatment until more data are available.


Assuntos
AVC Isquêmico , Trombectomia , Terapia Trombolítica , Humanos , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Trombectomia/métodos , Resultado do Tratamento , Terapia Trombolítica/métodos , Fibrinolíticos/uso terapêutico , Fibrinolíticos/administração & dosagem , Trombólise Mecânica/métodos
4.
J Environ Manage ; 359: 120782, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38669884

RESUMO

Capturing CO2 using clamshell/eggshell-derived CaO adsorbent can not only reduce carbon emissions but also alleviate the impact of trash on the environment. However, organic acid was usually used, high-temperature calcination was often performed, and CO2 was inevitably released during preparing CaO adsorbents from shell wastes. In this work, CaO-based CO2 adsorbent was greenly prepared by calcium-induced hydrogenation of clamshell and eggshell wastes in one pot at room/moderate temperature. CO2 adsorption experiments were performed in a thermogravimetric analyzer (TGA). The adsorption performance of the adsorbents obtained from the mechanochemical reaction (BM-C/E-CaO) was superior to that of the adsorbents obtained from the thermochemical reaction (Cal-C/E-CaO). The CO2 adsorption capacity of BM-C-CaO at 650 °C is up to 36.82 wt%, but the adsorption decay rate of the sample after 20 carbonation/calcination cycles is only 30.17%. This study offers an alternative energy-saving method for greenly preparing CaO-based adsorbent from shell wastes.


Assuntos
Dióxido de Carbono , Química Verde , Eliminação de Resíduos , Química Verde/métodos , Dióxido de Carbono/análise , Dióxido de Carbono/química , Hidrogenação , Temperatura , Exoesqueleto/química , Casca de Ovo/química , Eliminação de Resíduos/métodos , Adsorção
5.
Aging Dis ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38300641

RESUMO

Increased endothelial permeability plays an important role in blood-brain barrier (BBB) dysfunction and is implicated in neuronal injury in many diseased conditions. BBB disruption is primarily determined by dysfunction of endothelial cell-cell junctions. Deprivation of oxygen supply or hypoxia, a common feature of a variety of human diseases, is a major risk factor for BBB disruption. The molecular regulatory mechanisms of hypoxia-induced BBB dysfunction remain incompletely understood. The mitochondrial enzyme, arginase type II (Arg-II), has been shown to promote endothelial dysfunction. However, its role in hypoxia-induced BBB dysfunction has not been explored. In the C57BL/6J mouse model, hypoxia (8% O2, 24 hours) augments vascular Arg-II in the hippocampus, decreases cell-cell junction protein levels of Zonula occludens-1 (ZO-1), occludin, and CD31 in endothelial cells, increases BBB leakage in the brain in old mice (20 to 24 months) but not in young animals (3 to 6 months). These effects of hypoxia in aging are suppressed in arg-ii-/- mice. Moreover, the age-associated vulnerability of endothelial integrity to hypoxia is demonstrated in senescent human brain microvascular endothelial cell (hCMEC/D3) culture model. Further results in the cell culture model show that hypoxia augments Arg-II, decreases ZO-1 and occludin levels, and increases endothelial permeability, which is prevented by arg-ii gene silencing or by inhibition of mitochondrial reactive oxygen species (mtROS) production. Our study demonstrates an essential role of Arg-II in increased endothelial permeability and BBB dysfunction by promoting mtROS generation, resulting in decreased endothelial cell-cell junction protein levels under hypoxic conditions particularly in aging.

6.
Environ Sci Pollut Res Int ; 31(11): 16388-16400, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38315338

RESUMO

Gasification is widely regarded as one of the most practical, economical, and environmentally friendly waste disposal technologies for municipal solid waste (MSW). The pyrolysis stage (300-500 °C) is crucial for weight loss during MSW gasification, as a considerable amount of organic matter breaks down, producing high-value synthesis gas. This study investigated the product distribution and pollutant emission characteristics within this temperature range and its influencing factors during MSW gasification using a self-designed MSW gasification device. Results indicated that MSW underwent approximately 70% weight loss within this temperature range, yielding low amounts of inorganic and short-chain organic products, with mainly long-chain organic compounds of C16-C34. The atmosphere variation had minimal effect on the elemental composition and content of solid phase products. X-ray fluorescence spectrometry (XRF) and inductively coupled plasma mass spectrometry (ICP-MS) analyses showed that Mn and Zn were the primary components of heavy metal leaching toxicity in solid phase products, with their contents increasing as temperature increased. Synthesis gas showed the highest content of heavy metal As element, reaching a peak at 400 °C. Higher gasification temperature and lower oxygen flow rate significantly reduced the dioxin content and I-TEQ values, with highly chlorinated isomers being the predominant dioxin isomers. Nonetheless, low-chlorinated dioxins accounted for more than 50% of the I-TEQ. This study improves our understanding of the gasification process of MSW.


Assuntos
Dioxinas , Metais Pesados , Eliminação de Resíduos , Humanos , Resíduos Sólidos/análise , Dioxinas/análise , Temperatura , Pirólise , Metais Pesados/análise , Redução de Peso , Eliminação de Resíduos/métodos , Incineração/métodos
7.
Clinics ; 79: 100394, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1564359

RESUMO

Abstract Background and purpose Intravenous Thrombolysis (IVT) prior to Mechanical Thrombectomy (MT) for Acute Ischaemic Stroke (AIS) due to Large-Vessel Occlusion (LVO) remains controversial. Therefore, the authors performed a meta-analysis of the available real-world evidence focusing on the efficacy and safety of Bridging Therapy (BT) compared with direct MT in patients with AIS due to LVO. Methods Four databases were searched until 01 February 2023. Retrospective and prospective studies from nationwide or health organization registry databases that compared the clinical outcomes of BT and direct MT were included. Odds Ratios (ORs) and 95 % Confidence Intervals (CIs) for efficacy and safety outcomes were pooled using a random-effects model. Results Of the 12 studies, 86,695 patients were included. In patients with AIS due to LVO, BT group was associated with higher odds of achieving excellent functional outcome (modified Rankin Scale score 0-1) at 90 days (OR = 1.48, 95 % CI 1.25-1.75), favorable discharge disposition (to the home with or without services) (OR = 1.33, 95 % CI 1.29-1.38), and decreased mortality at 90 days (OR = 0.62, 95 % CI 0.56-0.70), as compared with the direct MT group. In addition, the risk of symptomatic intracranial hemorrhage did not increase significantly in the BT group. Conclusion The present meta-analysis indicates that BT was associated with favorable outcomes in patients with AIS due to LVO. These findings support the current practice in a real-world setting and strengthen their validity. For patients eligible for both IVT and MT, BT remains the standard treatment until more data are available.

8.
Front Nutr ; 10: 1282438, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37899841

RESUMO

To explore the effect of different microbial strains on blueberry pomace with solid-state fermentation (SSF), three fungi strains and three lactic acid bacteria (LAB) strains were utilized to investigate with respect to polyphenol profiles, antioxidant capacities, and bioaccessibility. Different strains exhibited different capacities for metabolizing polyphenolic compounds in blueberry pomace. The contents of 10 phenolic acids and 6 flavonoids (except (+)-catechin) were increased in blueberry pomace fermented by Lactobacillus acidophilus (LA). A similar tendency was observed in blueberry pomace fermented by Aspergillus niger (AN) and Lactobacillus plantarum (LP), where the concentration of 8 phenolic acids and 5 flavonoids was enhanced, with the following exceptions: (+)-catechin, ferulic acid, vanillic acid, and quercitrin. Chlorogenic acid and quercetin were the maximum phenolic acids and flavonoids in blueberry pomace with SSF, upgraded at 22.96 and 20.16%, respectively. Contrary to the growth of phenolic acids and flavonoid compounds, all individual anthocyanins showed a decreased trend. Only in the blueberry pomace fermented by AN, all anthocyanidins exhibit a rising trend. After SSF, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenylpicrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) radical scavenging abilities were increased by up to 33.56, 59.89, and 87.82%, respectively. Moreover, the simulated gastrointestinal digestion system revealed that SSF improved the bioaccessibility of polyphenolic compounds. Compared with other strains, LA, LP, and AN showed better excellent capacities for metabolizing polyphenolic compounds, which led to a greater increase in antioxidant activity and bioaccessibility in fermented blueberry pomace.

9.
Transl Neurosci ; 14(1): 20220296, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37529170

RESUMO

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease with complex pathogenesis. Although HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is upregulated in PD, its exact role in HOTAIRM1 is seldom reported. The purpose of this study is to research the effect of HOTAIRM1 on 1-methyl-4-phenylpyridonium (MPP+)-induced cytotoxicity and oxidative stress in SH-SY5Y cells. Methods: SH-SY5Y cells were treated with MPP+ at various concentrations or time points to induce SH-SY5Y cytotoxicity, so as to determine the optimal MPP+ concentration and time point. HOTAIRM1 expression upon MPP+ treatment was analyzed through qRT-PCR. Next, HOTAIRM1 was downregulated to observe the variance of SH-SY5Y cell viability, apoptosis, oxidative stress-related indexes, and protein levels of the Nrf2/HO-1 pathway. In addition, rescue experiments were carried out to assess the role of Nrf2 silencing in HOTAIRM1 knockdown on MPP+-induced oxidative stress in SH-SY5Y cells. Results: MPP+ treatment-induced cytotoxicity and upregulated HOTAIRM1 expression in SH-SY5Y cells in a dose- and time-dependent manner. Mechanically, HOTAIRM1 knockdown enhanced cell viability, limited apoptosis, and oxidative stress, therefore protecting SH-SY5Y cells from MPP+-induced SH-SY5Y cytotoxicity. On the other hand, HOTAIRM1 knockdown activated the protein levels of Nrf2 and HO-1. Nrf2 silencing could counteract the neuroprotective effect of HOTAIRM1 knockdown on in vitro PD model. Conclusion: Our data demonstrated that HOTAIRM1 knockdown could inhibit apoptosis and oxidative stress and activated the Nrf2/HO-1 pathway, therefore exerting neuroprotective effect on the PD cell model.

10.
Int J Mol Sci ; 24(13)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37446405

RESUMO

One of the manifestations of renal aging is podocyte dysfunction and loss, which are associated with proteinuria and glomerulosclerosis. Studies show a male bias in glomerular dysfunction and chronic kidney diseases, and the underlying mechanisms remain obscure. Recent studies demonstrate the role of an age-associated increase in arginase-II (Arg-II) in proximal tubules of both male and female mice. However, it is unclear whether Arg-II is also involved in aging glomeruli. The current study investigates the role of the sex-specific elevation of Arg-II in podocytes in age-associated increased albuminuria. Young (3-4 months) and old (20-22 months) male and female mice of wt and arginase-II knockout (arg-ii-/-) were used. Albuminuria was employed as a readout of glomerular function. Cellular localization and expression of Arg-II in glomeruli were analyzed using an immunofluorescence confocal microscope. A more pronounced age-associated increase in albuminuria was found in male than in female mice. An age-associated induction of Arg-II in glomeruli and podocytes (as demonstrated by co-localization of Arg-II with the podocyte marker synaptopodin) was also observed in males but not in females. Ablation of the arg-ii gene in mice significantly reduces age-associated albuminuria in males. Also, age-associated decreases in podocyte density and glomerulus hypertrophy are significantly prevented in male arg-ii-/- but not in female mice. However, age-associated glomerulosclerosis is not affected by arg-ii ablation in both sexes. These results demonstrate a role of Arg-II in sex-specific podocyte injury in aging. They may explain the sex-specific differences in the development of renal disease in humans during aging.


Assuntos
Podócitos , Animais , Feminino , Masculino , Camundongos , Albuminúria/metabolismo , Arginase/genética , Arginase/metabolismo , Glomérulos Renais/metabolismo , Podócitos/metabolismo , Proteinúria/metabolismo
11.
Des Monomers Polym ; 26(1): 132-139, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37125223

RESUMO

ß-cyclodextrin butenate was synthesized by using N, N'-Carbonyldiimidazole (CDI) activating reagent and 4-Dimethylaminopyridine (DMAP) as catalyst. The best preparation condition of ß-CD butenate was described as below: reaction temperature was 25°C, concentration of 2-butenoic acid was 450 mmol/L, concentration of DMAP was 12.5 mmol/L and reaction time was 20 minutes and at this condition the yield of ß-CD butenate was 0.83 mmol/g. According to the results of FT-IR spectrum, NMR spectroscopy and HPLC-QTof-mass spectrum of ß-CD butenate, there were four types ß-CD butenate synthesized, which were ß-CD-2-butenoic acid monoester, ß-CD-2-butenoic acid diester, ß-CD-2-butenoic acid triester and ß-CD-2-butenoic acid tetraester, respectively.

12.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36835007

RESUMO

Hypoxia is an important risk for renal disease. The mitochondrial enzyme arginase-II (Arg-II) is expressed and/or induced by hypoxia in proximal tubular epithelial cells (PTECs) and in podocytes, leading to cellular damage. Because PTECs are vulnerable to hypoxia and located in proximity to podocytes, we examined the role of Arg-II in the crosstalk of PTECs under hypoxic conditions with podocytes. A human PTEC cell line (HK2) and a human podocyte cell line (AB8/13) were cultured. Arg-ii gene was ablated by CRISPR/Case9 in both cell types. HK2 cells were exposed to normoxia (21% O2) or hypoxia (1% O2) for 48 h. Conditioned medium (CM) was collected and transferred to the podocytes. Podocyte injuries were then analyzed. Hypoxic (not normoxic) HK2-CM caused cytoskeletal derangement, cell apoptosis, and increased Arg-II levels in differentiated podocytes. These effects were absent when arg-ii in HK2 was ablated. The detrimental effects of the hypoxic HK2-CM were prevented by TGF-ß1 type-I receptor blocker SB431542. Indeed, TGF-ß1 levels in hypoxic HK2-CM (but not arg-ii-/--HK2-CM) were increased. Furthermore, the detrimental effects of TGF-ß1 on podocytes were prevented in arg-ii-/--podocytes. This study demonstrates crosstalk between PTECs and podocytes through the Arg-II-TGF-ß1 cascade, which may contribute to hypoxia-induced podocyte damage.


Assuntos
Túbulos Renais Proximais , Comunicação Parácrina , Podócitos , Humanos , Apoptose , Arginase/metabolismo , Células Epiteliais/metabolismo , Túbulos Renais Proximais/metabolismo , Comunicação Parácrina/genética , Podócitos/metabolismo , Podócitos/patologia , Fator de Crescimento Transformador beta1/metabolismo
13.
Aging Cell ; 22(4): e13790, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36794355

RESUMO

Elevated arginases including type-I (Arg-I) and type-II isoenzyme (Arg-II) are reported to play a role in aging, age-associated organ inflammaging, and fibrosis. A role of arginase in pulmonary aging and underlying mechanisms are not explored. Our present study shows increased Arg-II levels in aging lung of female mice, which is detected in bronchial ciliated epithelium, club cells, alveolar type 2 (AT2) pneumocytes, and fibroblasts (but not vascular endothelial and smooth muscle cells). Similar cellular localization of Arg-II is also observed in human lung biopsies. The age-associated increase in lung fibrosis and inflammatory cytokines, including IL-1ß and TGF-ß1 that are highly expressed in bronchial epithelium, AT2 cells, and fibroblasts, are ameliorated in arg-ii deficient (arg-ii-/- ) mice. The effects of arg-ii-/- on lung inflammaging are weaker in male as compared to female animals. Conditioned medium (CM) from human Arg-II-positive bronchial and alveolar epithelial cells, but not that from arg-ii-/- cells, activates fibroblasts to produce various cytokines including TGF-ß1 and collagen, which is abolished by IL-1ß receptor antagonist or TGF-ß type I receptor blocker. Conversely, TGF-ß1 or IL-1ß also increases Arg-II expression. In the mouse models, we confirmed the age-associated increase in IL-1ß and TGF-ß1 in epithelial cells and activation of fibroblasts, which is inhibited in arg-ii-/- mice. Taken together, our study demonstrates a critical role of epithelial Arg-II in activation of pulmonary fibroblasts via paracrine release of IL-1ß and TGF-ß1, contributing to pulmonary inflammaging and fibrosis. The results provide a novel mechanistic insight in the role of Arg-II in pulmonary aging.


Assuntos
Arginase , Fator de Crescimento Transformador beta1 , Masculino , Feminino , Camundongos , Humanos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Arginase/genética , Arginase/metabolismo , Pulmão/patologia , Citocinas/metabolismo , Fibroblastos/metabolismo , Fibrose
14.
J Asian Nat Prod Res ; 25(8): 765-782, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36394271

RESUMO

The aim of this study was to investigate the anti-inflammatory effects and mechanism of isovitexin on ulcerative colitis mice and RAW264.7 cells. The results showed that isovitexin had strong antioxidant and anti-inflammatory effects, and could restore intestinal barrier integrity (p < 0.01). In addition, isovitexin inhibited the expression of MyD88, TLR4 and NF-κB p65 proteins. At the same time, isovitexin can inhibit the activation of MAPK/NF-κB signaling pathway in RAW264.7 cells. In conclusion, isovitexin has a protective effect on UC mice, and its improvement mechanism of UC might be related to MAPK/NF-κB signaling pathway.

15.
J Natl Cancer Inst ; 115(6): 742-748, 2023 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35094066

RESUMO

BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Inibidores de Proteínas Quinases/efeitos adversos , Receptores ErbB/genética , Mutação
16.
Int J Biol Sci ; 18(16): 6008-6019, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439874

RESUMO

Cardiac fibrosis is one of the common pathological processes in many cardiovascular diseases characterized by excessive extracellular matrix deposition. SerpinE2 is a kind of protein that inhibits peptidase in extracellular matrix and up-regulated tremendously in mouse model of cardiac fibrosis induced by pressure-overloaded via transverse aortic constriction (TAC) surgery. However, its effect on cardiac fibroblasts (CFs), collagen secretion and the underlying mechanism remains unclear. In this study, DyLight® 488 green fluorescent dye or His-tagged proteins were used to label the exogenous serpinE2 protein. It was showed that extracellular serpinE2 translocated into CFs by low-density lipoprotein receptor-related protein 1 (LRP1) and urokinase plasminogen activator receptor (uPAR) of cell membrane through endocytosis. Knockdown of LRP1 or uPAR reduced the level of serpinE2 in CFs and down-regulated the collagen expression. Inhibition of the endocytosis of serpinE2 could inhibit ERK1/2 and ß-catenin signaling pathways and subsequently attenuated collagen secretion. Knockdown of serpinE2 attenuates cardiac fibrosis in TAC mouse. We conclude that serpinE2 could be translocated into cardiac fibroblasts due to endocytosis through directly interact with the membrane protein LRP1 and uPAR, and this process activated the ERK1/2, ß-catenin signaling pathways, consequently promoting collagen production.


Assuntos
beta Catenina , Camundongos , Animais , beta Catenina/metabolismo , Serpina E2/metabolismo , Serpina E2/farmacologia , Inibidores de Proteases/farmacologia , Sistema de Sinalização das MAP Quinases/genética , Fibrose , Transdução de Sinais/genética , Endocitose/genética , Colágeno/metabolismo
17.
Biomolecules ; 12(9)2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-36139052

RESUMO

Hypoxia plays a crucial role in acute and chronic renal injury, which is attributable to renal tubular and glomerular cell damage. Some studies provide evidence that hypoxia-dependent upregulation of the mitochondrial enzyme arginase type-II (Arg-II) in tubular cells promotes renal tubular injury. It is, however, not known whether Arg-II is also expressed in glomerular cells, particularly podocytes under hypoxic conditions, contributing to hypoxia-induced podocyte injury. The effects of hypoxia on human podocyte cells (AB8/13) in cultures and on isolated kidneys from wild-type (wt) and arg-ii gene-deficient (arg-ii-/-) mice ex vivo, as well as on mice of the two genotypes in vivo, were investigated, respectively. We found that the Arg-II levels were enhanced in cultured podocytes in a time-dependent manner over 48 h, which was dependent on the stabilization of hypoxia-inducible factor 1α (HIF1α). Moreover, a hypoxia-induced derangement of cellular actin cytoskeletal fibers, a decrease in podocin, and an increase in mitochondrial ROS (mtROS) generation-as measured by MitoSOX-were inhibited by adenoviral-mediated arg-ii gene silencing. These effects of hypoxia on podocyte injury were mimicked by the HIFα stabilizing drug DMOG, which inhibits prolyl hydroxylases (PHD), the enzymes involved in HIFα degradation. The silencing of arg-ii prevented the detrimental effects of DMOG on podocytes. Furthermore, the inhibition of mtROS generation by rotenone-the inhibitor of respiration chain complex-I-recapitulated the protective effects of arg-ii silencing on podocytes under hypoxic conditions. Moreover, the ex vivo experiments with isolated kidney tissues and the in vivo experiments with mice exposed to hypoxic conditions showed increased Arg-II levels in podocytes and decreased podocyte markers regarding synaptopodin in wt mice but not in arg-ii-/- mice. While age-associated albuminuria was reduced in the arg-ii-/- mice, the hypoxia-induced increase in albuminuria was, however, not significantly affected in the arg-ii-/-. Our study demonstrates that Arg-II in podocytes promotes cell injury. Arg-ii ablation seems insufficient to protect mice in vivo against a hypoxia-induced increase in albuminuria, but it does reduce albuminuria in aging.


Assuntos
Arginase , Podócitos , Actinas/metabolismo , Albuminúria , Animais , Arginase/genética , Arginase/metabolismo , Humanos , Hipóxia/metabolismo , Camundongos , Podócitos/metabolismo , Prolil Hidroxilases/metabolismo , Prolil Hidroxilases/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Rotenona/farmacologia
18.
J Environ Manage ; 319: 115617, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35803071

RESUMO

The preparation of clean fuel or CO2 adsorbents using industrial and domestic garbage is an alternative way of meeting global energy needs and alleviating environmental problems. Herein, H2-mixed CH4 fuel and CaO-based CO2 sorbent were first prepared in one pot by the mechanochemical reaction of pretreated clamshell or eggshell wastes (carbon and calcium source) with calcium hydride (hydrogen source) at room temperature. In the above reactions, CH4 was the sole hydrocarbon product, and its yield reached 78.23%. The H2/CH4 ratio of the produced H2-mixed CH4 fuel was tunable according to the need by changing the reaction conditions. It is inspiring that the simultaneously formed solid CaO/carbon products were efficient CaO-based sorbents, which possessed a higher CO2 adsorption capacity (49.81-58.74 wt.%) at 650 °C and could maintain good adsorption stability in 30 carbonation/calcination cycles (average activity loss per cycle of only 1.6%). The three achievements of the idea are that it can simultaneously eliminate clamshell or eggshell wastes, obtain valuable clean fuel, and acquire efficient CaO-based sorbents.


Assuntos
Compostos de Cálcio , Óxidos , Adsorção , Animais , Cálcio , Carbono , Dióxido de Carbono , Casca de Ovo , Hidrogenação , Temperatura
19.
BMC Med Educ ; 22(1): 154, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35255878

RESUMO

BACKGROUND: Undergraduate medical (UM) students faced the difficulties inherent in medical careers due to the coronavirus (COVID-19) outbreak. Thus, imperative containment measures might affect UM students' career intentions. Information on the factors that may be associated with these students' career change intentions is limited. METHODS: We conducted a cross-sectional survey in August 2020 to investigate the impact of the COVID-19 pandemic on career intention and the associated factors in UM students. Univariate analyses and logistic regression analysis were performed to identify said factors. RESULTS: A total of 2040 medical students from the Hubei University of Medicine were surveyed. Univariate analyses showed that grade, attitude towards healthcare, and the degree of the COVID-19 pandemic's impact on the students' lives were associated with changes in career choice (P<0.05). Logistic regression analysis showed that Grade 2, Grade 5, attitude towards a medical career, and having relatives with a medical background were associated with changes in career choice. The degree of the COVID-19 pandemic's impact was a common and significant factor associated with career preference, career perspective, and ideal workplace. CONCLUSIONS: Changes in career intentions were particularly influenced by grade, attitude towards being a health worker, and the degree of COVID-19's impact on the participants' lives. Treating large-scale public health emergencies rationally, setting up correct views of occupation choice, and building reasonable career planning may reduce the loss of medical talent.


Assuntos
COVID-19 , Estudantes de Medicina , COVID-19/epidemiologia , Escolha da Profissão , Estudos Transversais , Humanos , Intenção , Ocupações , Pandemias , SARS-CoV-2 , Inquéritos e Questionários
20.
Environ Sci Pollut Res Int ; 29(35): 53755-53767, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35288857

RESUMO

Cement kiln collaborative disposal technology can not only dispose of hazardous waste but also provide energy for the cement industry. However, the addition of hazardous waste may promote the formation of dioxins in cement kilns. In this study, typical hazardous solid wastes, such as solidified fly ash, electroplating sludge, and industrial residue, were co-processed in a cement kiln with different feeding positions and different feeding amounts. The concentrations of dioxins in the flue gas, clinker, and precalciner furnace slag were investigated. The effect of adding mixed hazardous solid waste on the formation of dioxin was also studied. The results showed that the concentration of dioxin in the flue gas without added hazardous waste was 1.57 ng/m3, and the concentration varied from 1.03 to 6.49 ng/m3 after the addition of hazardous waste. In addition, the concentration of dioxin in the flue gas and solid samples increased substantially when the co-processing ratio doubled. The large amount of Cu in solidified fly ash promoted the formation of dioxins, while the higher S content in the electroplating sludge suppressed the formation of dioxins. Compared with the addition of single hazardous waste, the concentration of dioxin in precalciner furnace slag increases by about 300%. Furthermore, the distributions of isomers in the clinker and precalciner furnace slag were similar. 1,2,3,4,6,7,8-HpCDD and OCDD accounted for a large proportion of the mass concentration, and the contribution rate ranged from 48.7 to 82.0%. Most importantly, correlation analysis showed that the concentration of dioxin was closely related to the copper content, hazardous waste types and additive proportion, with correlation coefficients of 0.79, 0.83, and 0.89, respectively. This study provides a basis for exploring the high environmental benefits of disposing of hazardous solid waste by co-processing in cement kilns.


Assuntos
Dioxinas , Cinza de Carvão/química , Dioxinas/análise , Resíduos Perigosos/análise , Incineração , Esgotos/análise , Resíduos Sólidos/análise
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