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1.
Theranostics ; 11(2): 555-566, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391492

RESUMO

Glioblastoma (GBM) is the most lethal primary brain tumor in adults with a median survival of around 15 months. A potential treatment strategy involves targeting glioma stem-like cells (GSCs) that are able to initiate, maintain, and repopulate the tumor mass. Here, we identify ACT001, a parthenolide derivative, targeting GSCs through regulation of adipocyte enhancer binding protein 1 (AEBP1) signaling. Methods: The effects of ACT001 on cell survival of normal human astrocytes (NHA) and patient-derived glioma stem-like cells (GSCs) were evaluated. RNA-Seq were performed to detect differentially expressed genes. ACT001 efficacy as a single agent or in combination with SHP-2 inhibitor SHP099 was assessed using a GSC orthotopic xenograft model. Results: GSCs exhibit high response to ACT001 in compared with normal human astrocytes. AEBP1 is a putative target of ACT001 by RNA-Seq analysis, which expression associates with prognosis of GBM patients. Knockdown of AEBP1 inhibits GSC proliferation and glioma sphere formation. Treatment with ACT001 or PI3K inhibitor or AEBP1 depletion would impair AKT phosphorylation and GSC proliferation, whereas constitutive AKT activation rescues ACT001 treatment or AEBP1 depletion-inhibited cell proliferation. Moreover, ACT001 blocks TGF-ß-activated AEBP1/AKT signaling in GSCs. ACT001 exhibits antitumor activity either as a single agent or in combination with SHP099, which provides significant survival benefits for GSC tumor xenograft-bearing animals. Conclusions: Our data demonstrate AEBP1 as a new druggable target in GBM and ACT001 as a potential therapeutic option for improving the clinical treatment of GBM in combination with SHP099.

2.
Nat Commun ; 11(1): 6101, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33257693

RESUMO

The heating and cooling energy consumption of buildings accounts for about 15% of national total energy consumption in the United States. In response to this challenge, many promising technologies with minimum carbon footprint have been proposed. However, most of the approaches are static and monofunctional, which can only reduce building energy consumption in certain conditions and climate zones. Here, we demonstrate a dual-mode device with electrostatically-controlled thermal contact conductance, which can achieve up to 71.6 W/m2 of cooling power density and up to 643.4 W/m2 of heating power density (over 93% of solar energy utilized) because of the suppression of thermal contact resistance and the engineering of surface morphology and optical property. Building energy simulation shows our dual-mode device, if widely deployed in the United States, can save 19.2% heating and cooling energy, which is 1.7 times higher than cooling-only and 2.2 times higher than heating-only approaches.

3.
Front Endocrinol (Lausanne) ; 11: 608422, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33362722

RESUMO

Most pituitary adenomas (PAs) are considered benign tumors, but approximately 0.2% can present metastasis and are classified as pituitary carcinomas (PCs). Refractory PAs lie between benign adenomas and true malignant PC and are defined as aggressive-invasive PAs characterized by a high Ki-67 index, rapid growth, frequent recurrence, and resistance to conventional treatments, including temozolomide. It is notoriously difficult to manage refractory PAs and PC because of the limited therapeutic options. As a promising therapeutic approach, cancer immunotherapy has been experimentally used for the treatment of many tumors, including pituitary tumors. The purpose of this review is to report the progress of immunotherapy in pituitary tumors, including refractory PAs and PCs. The tumor immune microenvironment has been recognized as a key contributor to tumorigenesis, progression, and prognosis. One study indicated that the number of CD68+ macrophages was positively correlated with tumor size and Knosp classification grade for tumor invasiveness. The infiltration of CD4+ and CD8+ T cells was relatively scant in these adenomas, but pituitary growth hormone (GH) adenomas exhibited significantly more CD4+ and CD8+ T cells than non-GH adenomas. These results suggest an association of CD68+ macrophage infiltration with an increase in pituitary tumor size and invasiveness. Another study suggested that a lower number of CD8+ lymphocytes is associated with cavernous sinus invasion and resistance to treatment with first-generation somatostatin analogs in acromegaly patients, highlighting a potential role of the tumor immune microenvironment in determining the prognosis of somatotroph pituitary tumors. Preclinical studies have indicated that widely varying degrees of programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) are found among different subtypes. Functional PAs and aggressive PAs express significantly higher levels of PD-L1 and TILs than other subtypes, indicating that PD-1 blockade might be a promising alternative therapy for patients with aggressive PAs. PD-L1 transcript and protein levels were found to be significantly increased in functioning (GH and prolactin-expressing) pituitary tumors compared to nonfunctioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary tumors harbored higher levels of PD-L1 mRNA than recurrent tumors. These findings suggest the possibility of considering checkpoint blockade immunotherapy for functioning pituitary tumors refractory to conventional management. Animal models of Cushing's disease also demonstrated PD-L1 and TIL expression in cultured tumors and murine models, as well as the effectiveness of checkpoint blockade therapy in reducing the tumor mass, decreasing hormone secretion, and increasing the survival rate. Clinical studies show that immunotherapy may be an effective treatment in patients with pituitary tumors. One corticotroph carcinoma patient showed a significant reduction in hormone levels and shrinkage of the tumor size of primary and metastatic lesions immediately after investigational treatment with ipilimumab and nivolumab. However, another patient with corticotroph adenoma progressed rapidly after four cycles of anti-PD-1 (pembrolizumab) treatment. To date, there are two registered clinical trials of immunotherapy for pituitary tumors. One of them is the phase II clinical trial of nivolumab combined with ipilimumab for patients with aggressive pituitary tumors (NCT04042753). The other one is also a phase II clinical trial of the combination of nivolumab and ipilimumab for rare tumors, including pituitary tumors (NCT02834013). Both clinical trials are in the stage of recruiting patients and have not been completed. In summary, the results from preclinical research and clinical studies indicated that immunotherapy might be a promising alternative therapy for PCs and refractory PAs resistant to conventional treatments. The combination of immunotherapy and radiotherapy or temozolomide may have synergistic effects compared to a single treatment. More preclinical and clinical studies are needed to further indicate the exact efficacy of immunotherapy in pituitary tumors.

4.
Front Microbiol ; 11: 573302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162954

RESUMO

In maritime Antarctica, sea animals, such as penguins or seals, provide a large amount of external nitrogen input into tundra soils, which greatly impact nitrogen cycle in tundra ecosystems. Denitrification, which is closely related with the denitrifiers, is a key step in nitrogen cycle. However, effects of sea animal activities on tundra soil denitrification and denitrifier community structures still have received little attention. Here, the abundance, activity, and diversity of nirS- and nirK-encoding denitrifiers were investigated in penguin and seal colonies, and animal-lacking tundra in maritime Antarctica. Sea animal activities increased the abundances of nirS and nirK genes, and the abundances of nirS genes were significantly higher than those of nirK genes (p < 0.05) in all tundra soils. Soil denitrification rates were significantly higher (p < 0.05) in animal colonies than in animal-lacking tundra, and they were significantly positively correlated (p < 0.05) with nirS gene abundances instead of nirK gene abundances, indicating that nirS-encoding denitrifiers dominated the denitrification in tundra soils. The diversity of nirS-encoding denitrifiers was higher in animal colonies than in animal-lacking tundra, but the diversity of nirK-encoding denitrifiers was lower. Both the compositions of nirS- and nirK-encoding denitrifiers were similar in penguin or seal colony soils. Canonical correspondence analysis indicated that the community structures of nirS- and nirK-encoding denitrifiers were closely related to tundra soil biogeochemical processes associated with penguin or seal activities: the supply of nitrate and ammonium from penguin guano or seal excreta, and low C:N ratios. In addition, the animal activity-induced vegetation presence or absence had an important effect on tundra soil denitrifier activities and nirK-encoding denitrifier diversities. This study significantly enhanced our understanding of the compositions and dynamics of denitrifier community in tundra ecosystems of maritime Antarctica.

5.
Free Radic Biol Med ; 161: 23-31, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33011276

RESUMO

Oxidative stress and apoptosis of vascular smooth muscle cells (VSMCs) are key to vascular calcification in patients with chronic kidney disease (CKD). The mitochondria-targeted antioxidant, mitoquinone (MitoQ), which reduces oxidative stress and apoptosis, has a protective effect in acute models of renal injury but whether MitoQ can attenuate vascular calcification in CKD patients is unknown. This study was conducted to investigate whether MitoQ can prevent calcification, both in vitro and in vivo. Adenine was used to induce calcification in rats, and inorganic phosphate was used to induce calcification in VSMCs. To elucidate the underlying molecular mechanism, a specific inhibitor of Nrf2, ML385, was used 1 h before MitoQ administration. Histological staining, ELISA, flow cytometry, alizarin red staining and western blotting were used to test this hypothesis. Administration of MitoQ alleviated calcification and oxidative stress. The anti-apoptotic effect of MitoQ was associated with upregulation of Bcl-2, downregulation of Bax, and increased Nrf2 expression. The effects of MitoQ were reversed by treatment with ML385. This study offers evidence that MitoQ attenuates vascular calcification by suppressing oxidative stress and apoptosis of VSMCs through the Keap1/Nrf2 pathway. MitoQ should be further investigated as a potential therapy to prevent vascular calcification in CKD patients.

6.
Antioxidants (Basel) ; 9(9)2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32854194

RESUMO

Chronic kidney disease (CKD) is characterized by the accumulation of protein-bound uremic toxins (PBUTs), which play a pathophysiological role in renal fibrosis (a common pathological process resulting in CKD progression). Accumulation of the PBUT hippuric acid (HA) is positively correlated with disease progression in CKD patients, suggesting that HA may promote renal fibrosis. Oxidative stress is the most important factor affecting PBUTs nephrotoxicity. Herein, we assessed the ability of HA to promote kidney fibrosis by disrupting redox homeostasis. In HK-2 cells, HA increased fibrosis-related gene expression, extracellular matrix imbalance, and oxidative stress. Additionally, reactive oxygen species (ROS)-mediated TGFß/SMAD signaling contributed to HA-induced fibrotic responses. HA disrupted antioxidant networks by decreasing the levels of nuclear factor erythroid 2-related factor 2 (NRF2), leading to ROS accumulation and fibrotic responses, as evidenced by NRF2 activation and knockdown. Moreover, NRF2 levels were reduced by NRF2 ubiquitination, which was regulated via increased interactions of Kelch-like ECH-associated protein 1 with Cullin 3 and NRF2. Finally, renal fibrosis and redox imbalance promoted by HA were confirmed in rats. Importantly, sulforaphane (NRF2 activator) reversed HA-promoted renal fibrosis. Thus, HA promotes renal fibrosis in CKD by disrupting NRF2-driven antioxidant system, indicating that NRF2 is a potential therapeutic target for CKD.

7.
Environ Sci Pollut Res Int ; 27(26): 33052-33064, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32529625

RESUMO

A temperature control curtain can effectively mitigate the negative effect of outflow temperature on the river eco-environment downstream. To investigate the response of outflow temperature to influence factors (i.e., installation position of temperature control curtain, submerged depth, temperature distribution, and outflow discharge), experiments were conducted in a nonlinearly stratified fluid. The important degree of influence factors was determined by entropy weight method. The results indicated that the effect extent of influence factors on the outflow temperature was temperature distribution, submerged depth, outflow discharge, and installation position in turn. The installation position had little effect on the outflow temperature. Increasing the outflow discharge could withdraw more warm water near the surface and increase the outflow temperature. The outflow temperature also rose with decreasing submerged depth, and more warm water above the temperature control curtain level tended to be extracted when the submerged depth was enough. Although the outflow temperature increased, its variation amplitude depended on the temperature gradient of temperature distribution and was not affected by the structural form of selective withdrawal. From the point of operation management, the minimum submerged depth was determined using sensitivity analysis to obtain maximum improvement of outflow temperature.


Assuntos
Rios , Abastecimento de Água , Temperatura , Água
8.
Langmuir ; 36(23): 6345-6351, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32388995

RESUMO

Cutting off the energy supply by glucose oxidase (GOx) to starve cancer cells has been a feasible and efficient oncotherapy strategy. The employment of GOx can effectively starve tumor cells by aerobic hydrolysis of glucose hopefully strengthening the abnormality (including the decrease in pH, the increase of hypoxia, and toxic hydrogen peroxide) in the tumor microenvironment (TME). On this basis, we designed and fabricated a GOx-conjugated yolk-shell Ag@mSiO2 nanoframe with Ag NPs and GOx-conjugated mesoporous silica as the yolk and the shell, respectively, to make full use of changes the GOx induces in TME. Specifically, lower pH and H2O2 could accelerate the transformation of Ag nanoparticles to poisonous Ag ions. At the same time, the anabatic hypoxia condition in turn activated chemotherapy drug tirapazamine (TPZ) to exert a chemotherapeutic effect, thereby achieving effective chemo/starvation and metal ion multimodality therapy. The drug release experiment in vitro demonstrated that the GOx is the key to the nanocarriers, which can activate the whole system. The excellent cellular uptake performances of nanocarriers were corroborated by a confocal laser scanning microscope (CLSM). In addition, its superb cancer-killing effect has been confirmed by cytotoxicity and apoptosis experiments. These results indicated that the drug-delivery system achieved the cascade cancer-killing process in situ and synergistic chemo/starvation/metal ion therapy, which has a bright prospect for treating cancer.

9.
Gut ; 69(12): 2131-2142, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32241904

RESUMO

OBJECTIVE: Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD). DESIGN: Characterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity. RESULTS: A group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species, Eggerthella lenta and Fusobacterium nucleatum, increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic Bifidobacterium animalis decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats. CONCLUSION: Aberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients. TRIAL REGISTRATION NUMBER: This study was registered at ClinicalTrials.gov (NCT03010696).

10.
Environ Pollut ; 259: 113918, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32023794

RESUMO

Natural sources, such as soil and wind-erosion dust (SWD), biomass open burning (BOB), sea salt spray (SSAS) and biogenic source (BIO), are major contributors to atmospheric emissions of trace elements (TEs) globally. In this study, we used a comprehensive approach to account for area-, production- and biofuel consumption-based emission factor calculation methods, and thus developed an integrated high-resolution emission inventory for 15 types of TEs (As, B, Cd, Co, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Sb, Se, V and Zn) originated from natural sources in China for the year 2015. The results show that national emissions of TEs in 2015 range from 7.45 tons (Hg) to 1, 400 tons (Zn) except for the extremely high emissions of Mn (10, 677 tons). SWD and BIO are identified as the top two source contributors, accounting for approximately 67.7% and 26.1% of the total emissions, respectively. Absolute emissions of TEs from natural sources are high in the Xinjiang, Inner Mongolia and Tibet autonomous regions with large areas of bare soil and desert. However, emission intensity of TEs per unit area in the Southern provinces of China is higher than those in Northern China and Southwestern China, with the Yunnan and Sichuan provinces displaying the highest emission intensity. Our results suggest that controlling SWD can play a significant role in reducing fugitive particulate matter and the associated emissions of TEs from natural sources in China; and desertification control is particularly critical in the Northwest provinces where the majority of deserts are located.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Metais Pesados , Oligoelementos , China , Material Particulado , Tibet
11.
Oncogene ; 39(1): 50-63, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462705

RESUMO

Resistance of breast cancer to human epidermal growth factor receptor 2 (HER2) inhibitors involves reprogramming of the kinome through HER2/HER3 signaling via the activation of multiple tyrosine kinases and transcriptional upregulation. The heterogeneity of induced kinases prevents kinase targeting by a single kinase inhibitor and presents a major challenge to the treatment of therapeutically recalcitrant HER2-positive breast cancers (HER2+ BCs). As a result, there is a critical need for effective treatment that attacks the aberrant kinome activation associated with resistance to HER2-targeted therapy. Here, we describe a novel treatment strategy that targets cyclin-dependent kinase 7 (CDK7) in HER2 inhibitor-resistant (HER2iR) breast cancer. We show that both HER2 inhibitor-sensitive (HER2iS) and HER2iR breast cancer cell lines exhibit high sensitivity to THZ1, a newly identified covalent inhibitor of the transcription regulatory kinase CDK7. CDK7 promotes cell cycle progression through inhibition of transcription, rather than via direct phosphorylation of classical CDK targets. The transcriptional kinase activity of CDK7 is regulated by HER2, and by the receptor tyrosine kinases activated in response to HER2 inhibition, as well as by the downstream SHP2 and PI3K/AKT pathways. A low dose of THZ1 displayed potent synergy with the HER2 inhibitor lapatinib in HER2iR BC cells in vitro. Dual HER2 and CDK7 inhibition induced tumor regression in two HER2iR BC xenograft models in vivo. Our data support the utilization of CDK7 inhibition as an additional therapeutic avenue that blocks the activation of genes engaged by multiple HER2iR kinases.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quinases Ciclina-Dependentes/genética , Fenilenodiaminas/farmacologia , Pirimidinas/farmacologia , Receptor ErbB-2/genética , Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Quinases Ciclina-Dependentes/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lapatinib/farmacologia , Proteína Oncogênica v-akt/genética , Fosfatidilinositol 3-Quinases/genética , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Receptor ErbB-2/antagonistas & inibidores , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genética
12.
Neurobiol Dis ; 134: 104617, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31669733

RESUMO

As the most common cause of progressive cognitive decline in humans, Alzheimer's disease (AD) has been intensively studied, but the mechanisms underlying its profound synaptic dysfunction remain unclear. Here we confirm that exposing wild-type mice to an enriched environment (EE) facilitates signaling in the hippocampus that promotes long-term potentiation (LTP). Exposing the hippocampus of mice kept in standard housing to soluble Aß oligomers impairs LTP, but EE can fully prevent this. Mechanistically, the key molecular features of the EE benefit are an upregulation of miRNA-132 and an inhibition of histone deacetylase (HDAC) signaling. Specifically, soluble Aß oligomers decreased miR-132 expression and increased HDAC3 levels in cultured primary neurons. Further, we provide evidence that HDAC3 is a direct target of miR-132. Overexpressing miR-132 or injecting an HDAC3 inhibitor into mice in standard housing mimics the benefits of EE in enhancing hippocampal LTP and preventing hippocampal impairment by Aß oligomers in vivo. We conclude that EE enhances hippocampal synaptic plasticity by upregulating miRNA-132 and reducing HDAC3 signaling in a way that counteracts the synaptotoxicity of human Aß oligomers. Our findings provide a rationale for prolonged exposure to cognitive novelty and/or epigenetic modulation to lessen the progressive effects of Aß accumulation during human brain aging.

13.
Environ Sci Pollut Res Int ; 27(1): 469-481, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31797271

RESUMO

Sudden water pollution is a global environmental issue. On a large spatial scale, any pollution source may cause water pollution incidents. Dividing a large watershed into several units and giving each unit a different level would be favorable for managing sudden water pollution incidents. To scientifically divide an area into units and determine their risk grade of sudden water pollution, data of pollution sources were collected, and an area was divided into risk assessment units of sudden water pollution. The risk grade assessment was conducted following the analytic hierarchy process (AHP) and fuzzy comprehensive evaluation method. The technology combined with the AHP and fuzzy comprehensive evaluation (F-AHP) can generate the hydrology, pollution source, natural geography, and socioeconomic characteristics of each unit and provide a risk grade evaluation. A risk grade assessment was conducted using the Yongding River as a case study. The results show that the areas with high sudden water pollution risk were mainly distributed in Shanxi Datong and Hebei Zhangjiakou. Sufficient control of pollution sources in production processes and the establishment of necessary measures to strengthen inspections should reduce the risk of sudden water pollution.


Assuntos
Monitoramento Ambiental/métodos , Poluição da Água/análise , China , Lógica Fuzzy , Abordagem GRADE , Geografia , Hidrologia , Medição de Risco/métodos , Rios , Poluição da Água/estatística & dados numéricos
14.
Biomed Pharmacother ; 123: 109749, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31846840

RESUMO

OBJECTIVE: Intestinal mucosal barrier damage is an important mechanism for the development of sepsis and multiple organ dysfunction syndrome. At present, there are no satisfactory and effective methods for the protection of the intestinal mucosal barrier. Jinzhi, the first fecal microbiota transplantation worldwide, is often used to treat critically ill patients; however, the specific mechanism involved in this process remains unclear. The aim of this study was to investigate the therapeutic effect and mechanism of Jinzhi intervention on mice with sepsis induced through treatment with lipopolysaccharide (LPS). METHODS: Mice were intraperitoneally injected with LPS to simulate intestinal mucosal barrier function damage in sepsis; intervention was performed through the oral administration of Jinzhi. The effect of Jinzhi on LPS-induced sepsis was analyzed by comparing the vital signs and survival rate of mice under different treatments. Pathological staining and enzyme-linked immunosorbent assay were used to identify the effects of LPS or treatment with Jinzhi on the intestinal mucosal barrier in mice. The effect of LPS or treatment with Jinzhi on the intestinal flora was analyzed via 16S rRNA gene sequencing of ileal contents. RESULTS: Immunohistochemistry and enzyme-linked immunosorbent assay showed that treatment with LPS increased levels of inflammatory factors (interleukin-1α, interleukin-6, tumor necrosis factor-α), caspase-3, and caspase-8 in the serum and ileum, and destroyed the tight junction between epithelial cells. Intervention with Jinzhi reduced levels of serum LPS and tumor necrosis factor-α, and repaired the tight junction between epithelial cells. Furthermore, 16S rRNA gene sequencing analysis showed that treatment with Jinzhi improved the diversity and physiological function of the intestinal flora. CONCLUSIONS: These results suggest that Jinzhi may be a promising option for the treatment of sepsis caused by LPS, and emphasize that Jinzhi exerts a recovery effect on the imbalance of intestinal flora.


Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Substâncias Protetoras/farmacologia , Animais , Caspases/metabolismo , Citocinas/metabolismo , Células Epiteliais/patologia , Íleo , Intestinos/patologia , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , RNA Ribossômico 16S , Sepse/induzido quimicamente , Taxa de Sobrevida , Proteínas de Junções Íntimas/metabolismo
15.
J Diabetes Res ; 2019: 4251829, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31871946

RESUMO

The correlation between serum 25-hydroxy vitamin D (25(OH)D) levels and lower extremity atherosclerotic disease and the predictive value of 25(OH)D for early-stage lower extremity atherosclerotic disease in patients with type 2 diabetes mellitus (T2DM) were explored. In total, 620 subjects (590 T2DM patients and 30 healthy subjects) completed a questionnaire. All subjects were divided into four groups according to serum 25(OH)D concentration quartile: Q1 (<12.18 ng/ml), Q2 (12.18~20.65 ng/ml), Q3 (20.65~31.97 ng/ml), and Q4 (>31.97 ng/ml). Participants were also divided into four groups based on the degree of lower extremity arteriostenosis: A1 (T2DM), A2 (T2DM with mild lower extremity vascular lesions (LEVL)), A3 (T2DM with moderate LEVL), and A4 (T2DM with severe LEVL). The incidence of lower extremity artery plaque was significantly higher in groups Q1 and Q2 than in group Q4 (both P < 0.05). The concentration of 25(OH)D was significantly lower in group A4 than in groups A1 and A2. Pearson correlation analysis revealed that the degree of lower extremity vascular stenosis was positively correlated with age, smoking, and HbA1c, CRP, and LDL-C levels and negatively correlated with 25(OH)D concentrations. Logistic regression analysis demonstrated that 25(OH)D concentrations exerted a protective effect against LEVL in T2DM patients. Serum 25(OH)D concentrations may be correlated with the incidence of macrovascular disease in T2DM patients. A low serum 25(OH)D concentration is an independent risk factor for lower extremity vascular pathological changes and acts as a prognostic index for lower extremity atherosclerotic disease.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/etiologia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , China/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Medição de Risco , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico
16.
Adv Mater ; 31(46): e1904589, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566277

RESUMO

Insertion-type anode materials with beneficial micro- and nanostructures are proved to be promising for high-performance electrochemical metal ion storage. In this work, heterostructured TiO2 shperes with tunable interiors and shells are controllably fabricated through newly proposed programs, resulting in enhanced pseudocapacitive response as well as favorable Na+ storage kinetics and performances. In addition, reasonably designed nanosheets in the extrinsic shells are also able to reduce the excess space generated by hierarchical structure, thus improving the packing density of TiO2 shperes. Lastly, detailed density functional theory calculations with regard to sodium intercalation and diffusion in TiO2 crystal units are also employed, further proving the significance of the surface-controlled pseudocapacitive Na+ storage mechanism. The structure design strategies and experimental results demonstrated in this work are meaningful for electrode material preparation with high rate performance and volume energy density.

17.
Sci Total Environ ; 694: 133633, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31386953

RESUMO

Modelling is a useful tool for comprehensively describing the processes occurring in floating treatment wetlands (FTWs). However, temperature effects and phosphorus dynamics are not considered in the current FTW models. Therefore, a process-based model comprised of a plant growth submodel, a nitrogen dynamic submodel and a phosphorus dynamic submodel was developed to understand the complicated processes occurring in FTWs. The model was fully calibrated using a mesocosm FTW system operated for 168 days. Global sensitivity analysis revealed that nitrogen removal performance was predominantly sensitive to parameters representing plant characteristics and microbial activity. Because of the high concentration of organic matter, mineralization and sedimentation played important roles in nitrogen and phosphorus removal. In addition, the coprecipitation rate of phosphate also had a significant influence on phosphorus removal performance. When further investigation was applied to understand the behavior of the model, the ratio of nitrogen to phosphorus in plant tissue was found to be an indicator of the nutrient limitation in the water column. Furthermore, the model illustrated that both FTW operating conditions and plant characteristic parameters exerted an important influence on nitrogen removal and plant uptake contribution. Therefore, the selection of appropriate operating conditions and plant species can achieve high nutrients removal and make effective use of plants in FTWs. The model provides a useful tool for assessing the nutrients removal performance of FTWs and for evaluating strategies for them in design and operation.


Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água/análise , Áreas Alagadas , Biodegradação Ambiental , Nitrogênio/análise , Fosfatos/análise , Fósforo/análise , Plantas
18.
Environ Sci Pollut Res Int ; 26(21): 21161-21171, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31119534

RESUMO

Artificial substrates (ASs) and floating treatment wetlands (FTWs) have been widely used in the treatment of polluted surface water. In fact, periphyton on ASs functions in nutrient removal, while the plant-periphyton complex functions in FTWs. However, the nutrient removal performance of the periphyton on ASs and the plant-periphyton complex in FTWs has not been systematically compared. Thus, ASs and FTWs were established in a mesocosm experiment to compare nitrogen and phosphorus removal between the two ecological treatment techniques. The results showed that the total nitrogen removal efficiency was 60.4% in the AS treatments and 65.3% in the FTWs, while the total phosphorus removal efficiency was 83.7% in the AS treatments and 39.45% in the FTWs. Periphyton on the ASs absorbed 2.5 g N m-2 and 0.85 g P m-2, accounting for 20.8% of the N removal and 18.7% of the P removal. Sedimentation contributed to 71.3% of the N removal and 56.1% of the P removal in the AS treatments. For the plant-periphyton complex in the FTWs, 25.1% of the N and 53.0% of the P accumulated in plant tissue. Most of the reduced N (47.1%) was removed by other pathways, which was likely the effect of periphyton attached on plant roots and floating rafts. The nutrient removal efficiencies and pathways of AS and FTW treatments showed different characteristics, providing a reference for the selection of treatment measures for polluted surface water remediation.


Assuntos
Perifíton , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Áreas Alagadas , Nitrogênio/análise , Fósforo/análise , Plantas/metabolismo , Poluição da Água
19.
Sensors (Basel) ; 19(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31071991

RESUMO

Fault identification for closed-loop control systems is a future trend in the field of fault diagnosis. Due to the inherent feedback adjustment mechanism, a closed-loop control system is generally very robust to external disturbances and internal noises. Closed-loop control systems often encourage faults to propagate inside the systems, which may lead to the consequence that faults amplitude becomes smaller and fault characteristics difference becomes more inapparent. Hence, it has been challenging to achieve fault identification for such systems. Traditional fault identification methods are not particularly designed for closed-loop control systems and thus cannot be applied directly. In this work, a new fault identification method is proposed, which is based on the deep neural network for closed-loop control systems. Firstly, the fault propagation mechanism in closed-loop control systems is theoretically derived, and the influence of fault propagation on system variables is analyzed. Then deep neural network is applied to find fault characteristics difference between different data modes, and a sliding window is used to amplify the fault-to-noise ratio and characteristics difference, with an aim to increase the identification performance. To verify this method, the simulations that are based on a numerical simulation model, the Tennessee industrial system and the satellite attitude control system are conducted. The results show that the proposed method is more feasible and more effective in fault identification for closed-loop control systems compared with traditional data-driven identification methods, including distance-based and angle-based identification methods.

20.
Endocr Connect ; 8(7): 822-828, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31137015

RESUMO

Objectives: The pathogenesis of Graves' disease (GD) remains unclear. In terms of environmental factors, GD development may be associated with chronic inflammation caused by alteration of the intestinal flora. This study explored the association of intestinal flora alteration with the development of GD among the Han population in southwest China. Design and methods: Fifteen GD patients at the Affiliated Hospital of Zunyi Medical College between March 2016 and March 2017 were randomly enrolled. Additionally, 15 sex- and age-matched healthy volunteers were selected as the control group during the same period. Fresh stool samples were collected, and bacterial 16S RNA was extracted and amplified for gene sequencing with the Illumina MiSeq platform. The sequencing results were subjected to operational taxonomic unit-based classification, classification verification, alpha diversity analysis, taxonomic composition analysis and partial least squares-discriminant analysis (PLS-DA). Results: The diversity indices for the GD group were lower than those for the control group. The GD group showed significantly higher abundances of Firmicutes, Proteobacteria and Actinobacillus and a higher Firmicutes/Bacteroidetes ratio than the control group. PLS-DA suggested the satisfactory classification of the flora between the GD group and the control group. The abundances of the genera Oribacterium, Mogibacterium, Lactobacillus, Aggregatibacter and Mogibacterium were significantly higher in the GD group than in the control group (P < 0.05). Conclusions: The intestinal flora of GD patients was significantly different from that of the healthy population. Thus, alteration of intestinal flora may be associated with the development of GD.

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