RESUMEN
The presence of microorganisms on biomedical devices and food packaging surfaces poses an important threat to human health. Superhydrophobic surfaces, a powerful tool to combat pathogenic bacterial adhesion, are threatened by their poor robustness. As a supplement, photothermal bactericidal surfaces may be expected to kill adhered bacteria. Using copper mesh as a mask, we prepared a superhydrophobic surface with a homogeneous conical array. The surface shows synergistic antibacterial properties, including a superhydrophobic character against bacterial adhesion and photothermal bactericidal activity. As a result of the excellent liquid repellency, the surface could highly repel the adherence of bacteria after immersing in a bacterial suspension for 10 s (95%) and 1 h (57%). Photothermal graphene can easily eliminate most adhered bacteria during the subsequent treatment of near-infrared (NIR) radiation. After a self-cleaning wash, the deactivated bacteria were easily rinsed off the surface. Furthermore, this antibacterial surface exhibited an approximately 99.9% resisted bacterial adhesion rate regardless of planar and various uneven surfaces. The results offer promising advancement of an antibacterial surface combining both adhesion resistance and photothermal bactericidal activity in fighting microbial infections.
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Antibacterianos , Adhesión Bacteriana , Humanos , Antibacterianos/farmacología , Antibacterianos/química , BacteriasRESUMEN
BACKGROUND : The effectiveness of endoscopic screening on gastric cancer has not been widely investigated in China and the screening interval of repeated screening has not been determined. METHODS : In a population-based prospective study, we included 375,800 individuals, 14,670 of whom underwent endoscopic screening (2012-2018). We assessed the associations between endoscopic screening and risk of incident gastric cancer and gastric cancer-specific mortality, and examined changes in overall survival and disease-specific survival following screening. The optimal screening interval for repeated endoscopy for early detection of gastric cancer was explored. RESULTS : Ever receiving endoscopic screening significantly decreased the risk of invasive gastric cancer (age- and sex-adjusted relative risk [RR] 0.69, 95â% confidence interval [CI] 0.52-0.92) and gastric cancer-specific mortality (RR 0.33, 95â%CI 0.20-0.56), particularly for noncardia gastric cancer. Repeated screening strengthened the beneficial effect on invasive gastric cancer-specific mortality of one-time screening. Among invasive gastric cancers, screening-detected individuals had significantly better overall survival (RR 0.18, 95â%CI 0.13-0.25) and disease-specific survival (RR 0.18, 95â%CI 0.13-0.25) than unscreened individuals, particularly for those receiving repeated endoscopy. For individuals with intestinal metaplasia or low grade intraepithelial neoplasia, repeated endoscopy at an interval of <â2 years, particularly within 1 year, significantly enhanced the detection of early gastric cancer, compared with repeated screening after 2 years (P-trendâ=â0.02). CONCLUSION : Endoscopic screening prevented gastric cancer occurrence and death, and improved its prognosis in a population-based study. Repeated endoscopy enhanced the effectiveness. Screening interval should be based on gastric lesion severity.
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Neoplasias Gástricas , Detección Precoz del Cáncer/métodos , Endoscopía Gastrointestinal , Humanos , Tamizaje Masivo/métodos , Estudios Prospectivos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/prevención & controlRESUMEN
Viral myocarditis (VMC) commonly triggers heart failure, for which no specific treatments are available. This study aims to explore the specific role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) in VMC. A VMC mouse model was induced by Coxsackievirus B3 (CVB3). Then, MEG3 and TNF receptor-associated factor 6 (TRAF6) were silenced and microRNA-223 (miR-223) was over-expressed in the VMC mice, followed by determination of ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). Dual-luciferase reporter assay was introduced to test the interaction among MEG3, TRAF6 and miR-223. Macrophages were isolated from cardiac tissues and bone marrow, and polarization of M1 or M2 macrophages was induced. Then, the expressions of components of NLRP3 inflammatory body (NLRP3, ASC, Caspase-1), M1 markers (CD86, iNOS and TNF-α) and M2 markers (CD206, Arginase-1 and Fizz-1) were measured following MEG3 silencing. In the VMC mouse model, MEG3 and TRAF6 levels were obviously increased, while miR-223 expression was significantly reduced. Down-regulation of MEG3 resulted in the inhibition of TRAF6 by promoting miR-223. TRAF6 was negatively correlated with miR-223, but positively correlated with MEG3 expression. Down-regulations of MEG3 or TRAF6 or up-regulation of miR-223 was observed to increase mouse weight, survival rate, LVEF and LVFS, while inhibiting myocarditis and inflammation via the NF-κB pathway inactivation in VMC mice. Down-regulation of MEG3 decreased M1 macrophage polarization and elevated M2 macrophage polarization by up-regulating miR-223. Collectively, down-regulation of MEG3 leads to the inhibition of inflammation and induces M2 macrophage polarization via miR-223/TRAF6/NF-κB axis, thus alleviating VMC.
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Macrófagos/metabolismo , MicroARNs/metabolismo , Miocarditis/virología , ARN Largo no Codificante/metabolismo , Factor 6 Asociado a Receptor de TNF/metabolismo , Animales , Regulación hacia Abajo , Silenciador del Gen , Hibridación Fluorescente in Situ , Inflamación , Activación de Macrófagos , Masculino , Ratones , Ratones Endogámicos BALB C , Miocarditis/metabolismo , Miocitos Cardíacos/metabolismoRESUMEN
Halohydrin dehalogenases (HHDHs) have attracted much attention due to their ability to synthesize enantiomerically enriched epoxides and ß-haloalcohols. However, most of the HHDHs exhibit low enantioselectivity. Here, a HHDH from the alphaproteobacteria isolate 46_93_T64 (AbHHDH), which shows only poor enantioselectivity in the catalytic resolution of rac-PGE (E = 9.9), has been subjected to protein engineering to enhance its enantioselectivity. Eight mutants (R89K, R89Y, V137I, P178A, N179Q, N179L, F187L, F187A) showed better enantioselectivity than the wild type. The best single mutant N179L (E = 93.0) showed a remarkable 9.4-fold increase in the enantioselectivity. Then, the single mutations were combined to produce the double, triple, quadruple, and quintuple mutants. Among the combinational mutants, the best variant (R89Y/N179L) showed an increased E value of up to 48. The E values of the variants N179L and R89Y/N179L for other epoxides 2-7 were 12.2 to > 200, which showed great improvement compared to 1.2 to 10.5 for the wild type. Using the variant N179L, enantiopure (R)-PGE with > 99% ee could be readily prepared, affording a high yield and a high concentration.
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Proteínas Bacterianas/metabolismo , Compuestos Epoxi/química , Compuestos Epoxi/metabolismo , Hidrolasas/metabolismo , Alphaproteobacteria/enzimología , Alphaproteobacteria/genética , Alphaproteobacteria/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/aislamiento & purificación , Biocatálisis , Hidrolasas/química , Hidrolasas/genética , Hidrolasas/aislamiento & purificación , Cinética , Modelos Moleculares , Mutación , Ingeniería de Proteínas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Estereoisomerismo , Especificidad por SustratoRESUMEN
Numerous epidemiological studies have shown that diabetes mellitus (DM) is associated with dementia and cognition decline. However, there is currently no effective treatment for diabetes-induced cognitive dysfunction. The neuroprotective effect of L-3-n-butylphthalide (L-NBP) has been demonstrated in vascular dementia animal models. The purpose of this study was to determine whether L-NBP can ameliorate cognitive deficits in db/db mice, a model of obesity and type 2 diabetes. The mice were administered with vehicle or L-NBP (120 mg/kg) by gavage daily for 6 weeks. Then, Morris water maze tasks were performed, and hippocampal LTP was recorded in vivo. Next, the synaptic structure of the CA1 hippocampus region was investigated via electron microscopy. Finally, the expression levels of MDA, SOD, 8-OHdG, and NADPH oxidase subunits gp91 and p67, as well as the expression of NF-κB p65, TNF-α, IL-1ß and caspase-3 were measured by Western blot, RT-PCR and ELISA. Treatment with L-NBP significantly attenuated the learning and memory deficits in db/db mice. Concomitantly, L-NBP also increased hippocampus synaptic plasticity, characterized by an enhanced in vivo LTP, and suppressed oxidative stress, as indicated by increased SOD activity and decreased MDA, 8-OHdG, and NADPH oxidase subunits p67 and gp91. L-NBP also significantly decreased NF-κB p65, TNF-α, IL-1ßand caspase-3 levels in the hippocampus. L-NBP significantly ameliorated cognitive decline in type 2 diabetic mice, and this effect was accompanied by an improvement in hippocampal plasticity and an amelioration of oxidative stress, inflammation and apoptosis cascades. Thus, L-NBP may be a promising therapeutic agent against DM-mediated cognitive dysfunction.
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Benzofuranos/farmacología , Cognición/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hipocampo/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Benzofuranos/uso terapéutico , Caspasa 3/metabolismo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Ratones , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacosRESUMEN
BACKGROUND: White matter hyperintensities (WMHs) are frequently detected in migraine patients. However, their significance and correlation to migraine disease burden remain unclear. This study aims to examine the correlation of WMHs with migraine features and explore the relationship between WMHs and migraine prognosis. METHODS: A total of 69 migraineurs underwent MRI scans to evaluate WMHs. Migraine features were compared between patients with and without WMHs. After an average follow-up period of 3 years, these patients were divided into two groups, according to the reduction of headache frequency: improved and non-improved groups. The percentage and degree of WMHs were compared between these two groups. RESULTS: A total of 24 patients (34.8%) had WMHs. Patients with WMHs were significantly older (39.0 ± 7.9 vs. 30.6 ± 10.4 years, P < 0.001) and had a longer disease duration (median: 180.0 vs. 84.0 months, P = 0.013). Furthermore, 33 patients completed the follow up period (15 patients improved and 18 patients did not improve). Patients in the non-improved group had a higher frequency of WMHs (55.6% vs. 13.3%, P = 0.027) and median WMHs score (1.0 vs. 0.0, P = 0.030). CONCLUSIONS: WMHs can predict unfavorable migraine prognosis. Furthermore, WMHs may have a closer association with age than migraine features.
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Trastornos Migrañosos/diagnóstico por imagen , Trastornos Migrañosos/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
Glucagon-like peptide 1 (GLP-1), a neuroendocrine hormone produced by the gastrointestinal tract, plays a significant role in blood glucose regulation; drugs derived from GLP-1 are currently used for the treatment of type 2 diabetes. In addition to regulating glucose homeostasis, the protective effects of GLP-1 on the cardiovascular system are also of interest. However, the vascular protective mechanisms of GLP-1 remain unclear. The present study was designed to evaluate the role of GLP-1 in the proliferation and migration of vascular smooth muscle cells, and the underlying mechanisms. In this study, proliferation, migration, cyclin D1 expression, and phosphorylation of MLC, as well as RhoA and Rho-associated coiled-coil forming protein kinase 2 (ROCK2) expression, were increased in rat aorta smooth muscle cells (RASMCs) following incubation with angiotensin II (Ang II). These effects were significantly attenuated by GLP-1, forskolin (a cAMP activator) and Y-27632 (a ROCK2 inhibitor). However, H89 (a PKA inhibitor) inhibited the action of GLP-1, both in terms of inhibition of RASMC proliferation and migration, and RHOA/ROCK2 expression. These results indicate that GLP-1 inhibits Ang II-induced RASMC proliferation and migration via the cAMP/PKA/RhoA/ROCK2 signaling pathway. Our data suggest that GLP-1 should be considered for use in the clinical treatment of cardiovascular diseases, in addition to its current use in the treatment of diabetes mellitus.
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Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Péptido 1 Similar al Glucagón/farmacología , Músculo Liso Vascular/efectos de los fármacos , Amidas/farmacología , Angiotensina II/administración & dosificación , Animales , Aorta/citología , Aorta/efectos de los fármacos , Células Cultivadas , Colforsina/farmacología , Péptido 1 Similar al Glucagón/administración & dosificación , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/efectos de los fármacos , Fosforilación/efectos de los fármacos , Piridinas/farmacología , Ratas , Transducción de Señal/efectos de los fármacos , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
We aim to investigate the effect of aurantiamide acetate isolated from the aerial parts of Clematis terniflora DC against gliomas. Human malignant glioma U87 and U251 cells were incubated with different concentrations (0-100 µM) of aurantiamide acetate. Aurantiamide acetate greatly decreased the cell viability in a dose- and time-dependent manner. It induced moderate mitochondrial fragmentation and the loss of mitochondrial membrane potential. No significant difference was found in the alternation of other intracellular organelles, although F-actin structure was slightly disturbed. Apparent ultrastructure alternation with increased autophagosome and autolysosome accumulation was observed in aurantiamide acetate-treated cells. The expression of LC3-II was greatly up-regulated in cells exposed to aurantiamide acetate (P < 0.05 compared with control). The cytoplasmic accumulation of autophagosomes and autolysosomes induced by aurantiamide acetate treatment was confirmed by fluorescent reporter protein labelling. Administration of chloroquine (CQ), which inhibits the fusion step of autophagosomes, further increased the accumulation of autophagosomes in the cytoplasm of U87 cells. Autophagy inhibition by 3-methyladenine, Bafilomycin A1 or CQ had no influence on aurantiamide acetate-induced cytotoxicity, whereas autophagy stimulator rapamycin significantly suppressed aurantiamide acetate-induced cell death. The anti-tumour effects of aurantiamide acetate were further evaluated in tumour-bearing nude mice. Intratumoural injection of aurantiamide acetate obviously suppressed tumour growth, and increased number of autophagic vacuoles was observed in tumour tissues of animals receiving aurantiamide acetate. Our findings suggest that aurantiamide acetate may suppress the growth of malignant gliomas by blocking autophagic flux.
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Autofagia/efectos de los fármacos , Neoplasias Encefálicas/prevención & control , Proliferación Celular/efectos de los fármacos , Clematis/química , Dipéptidos/farmacología , Glioma/prevención & control , Animales , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Dipéptidos/química , Dipéptidos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Glioma/metabolismo , Glioma/patología , Células Hep G2 , Humanos , Ratones Desnudos , Microscopía Confocal , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Estructura Molecular , Células PC12 , Fagosomas/efectos de los fármacos , Fagosomas/metabolismo , Fagosomas/ultraestructura , Fitoterapia , Componentes Aéreos de las Plantas/química , Ratas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: The glucagon-like peptide-1 (GLP-1) has been shown to exert cardioprotective effects in animals and patients. This study tests the hypothesis that preservation of GLP-1 by the GLP-1 receptor agonist liraglutide or the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin is associated with a reduction of angiotensin (Ang) II-induced cardiac fibrosis. METHODS AND RESULTS: Sprague-Dawley rats were subjected to Ang II (500 ng/kg/min) infusion using osmotic minipumps for 4 weeks. Liraglutide (0.3 mg/kg) was subcutaneously injected twice daily or linagliptin (8 mg/kg) was administered via oral gavage daily during Ang II infusion. Relative to the control, liraglutide, but not linagliptin decreased MAP (124 ± 4 vs. 200 ± 7 mmHg in control, p < 0.003). Liraglutide and linagliptin comparatively reduced the protein level of the Ang II AT1 receptor and up-regulated the AT2 receptor as identified by a reduced AT1/AT2 ratio (0.4 ± 0.02 and 0.7 ± 0.01 vs. 1.4 ± 0.2 in control, p < 0.05), coincident with the less locally-expressed AT1 receptor and enhanced AT2 receptor in the myocardium and peri-coronary vessels. Both drugs significantly reduced the populations of macrophages (16 ± 6 and 19 ± 7 vs. 61 ± 29 number/HPF in control, p < 0.05) and α-SMA expressing myofibroblasts (17 ± 7 and 13 ± 4 vs. 66 ± 29 number/HPF in control, p < 0.05), consistent with the reduction in expression of TGFß1 and phospho-Smad2/3, and up-regulation of Smad7. Furthermore, ACE2 activity (334 ± 43 and 417 ± 51 vs. 288 ± 19 RFU/min/µg protein in control, p < 0.05) and GLP-1 receptor expression were significantly up-regulated. Along with these modulations, the synthesis of collagen I and tissue fibrosis were inhibited as determined by the smaller collagen-rich area and more viable myocardium. CONCLUSION: These results demonstrate for the first time that preservation of GLP-1 using liraglutide or linagliptin is effective in inhibiting Ang II-induced cardiac fibrosis, suggesting that these drugs could be selected as an adjunctive therapy to improve clinical outcomes in the fibrosis-derived heart failure patients with or without diabetes.
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Angiotensina II/efectos adversos , Fibrosis/patología , Expresión Génica/efectos de los fármacos , Péptido 1 Similar al Glucagón/metabolismo , Miocardio/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Receptor de Angiotensina Tipo 1/biosíntesis , Receptor de Angiotensina Tipo 2/biosíntesis , Enzima Convertidora de Angiotensina 2 , Animales , Presión Sanguínea/efectos de los fármacos , Colágeno/metabolismo , Fibrosis/inducido químicamente , Fibrosis/tratamiento farmacológico , Fibrosis/metabolismo , Linagliptina/farmacología , Linagliptina/uso terapéutico , Liraglutida/farmacología , Liraglutida/uso terapéutico , Masculino , Miocardio/enzimología , Miocardio/patología , Ratas , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/biosíntesisRESUMEN
AIM: To investigate the roles of cysteinyl leukotriene receptors CysLT1R and CysLT2R in leukotriene D4 (LTD4)-induced activation of microglial cells in vitro. METHODS: Mouse microglial cell line BV2 was transfected with pcDNA3.1(+)-hCysLT1R or pcDNA3.1(+)-hCysLT2R. The expression of relevant mRNAs and proteins in the cells was detected using RT-PCR and Western blotting, respectively. Phagocytosis was determined with flow cytometry analysis. The release of interleukin-1ß (IL-1ß) from the cells was measured using an ELISA assay. RESULTS: The expression of CysLT1R or CysLT2R was considerably increased in the transfected BV2 cells, and the receptors were mainly distributed in the plasma membrane and cytosol. Treatment of the cells expressing CysLT1R or CysLT2R with CysLT receptor agonist LTD4 (0.1-100 nmol/L) concentration-dependently enhanced the phagocytosis, and increased mRNA expression and release of IL-1ß. Moreover, the responses of hCysLT1R-BV2 cells to LTD4 were significantly larger than those of hCysLT2R-BV2 or WT-BV2 cells. Pretreatment of hCysLT1R-BV2 cells with the selective CysLT1R antagonist montelukast (1 µmol/L) significantly blocked LTD4-induced phagocytosis as well as the mRNA expression and release of IL-1ß, whereas the selective CysLT2R antagonist HAMI 3379 (1 µmol/L) had no such effects. CONCLUSION: CysLT1R mediates LTD4-induced activation of BV2 cells, suggesting that CysLT1R antagonists may exert anti-inflammatory activity in brain diseases.
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Leucotrieno D4/farmacología , Microglía/efectos de los fármacos , Microglía/metabolismo , Receptores de Leucotrienos/agonistas , Receptores de Leucotrienos/fisiología , Animales , Línea Celular , Relación Dosis-Respuesta a Droga , Humanos , RatonesRESUMEN
OBJECTIVE: To examine the effect of a selective inhibitor of 5-lipoxygenase (5-LOX) zileuton on microglia-mediated rotenone neurotoxicity. METHODS: The supernatant from different concentrations of rotenone-stimulated mouse microglia BV2 cells was used as the conditioned media (CM) for PC12 cells. The viability of PC12 cells was determined by MTT assay and lactate dehydrogenase (LDH) release. Cell death was observed by LDH release and double fluorescence staining with Hoechst/propidiumiodide (PI). The effect of zileuton on microglia-mediated rotenone toxicity was evaluated by the above methods. RESULTS: Rotenone at 1-10 nmol/L was nontoxic to PC12 cells directly. However, the CM from BV2 cells that were treated with rotenone (1-10 nmol/L) resulted in toxicity of PC12 cells. The BV2 CM which stimulated with rotenone (1-10 nmol/L) induced morphological changes, reduced cell viability, and increased LDH release and cell necrosis in PC12 cells. Pretreatment of BV2 cells with the 5-LOX inhibitor zileuton (0.01-1 µmol/L) protected PC12 cells from the microglia-mediated rotenone toxicity. CONCLUSION: The 5-LOX inhibitor zileuton effectively attenuates microglia-mediated rotenone toxicity in PC12 cells. These results suggest that 5-LOX pathway may be involved in neuronal death induced by microglial inflammation.
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Hidroxiurea/análogos & derivados , Microglía/citología , Rotenona/toxicidad , Animales , Muerte Celular/efectos de los fármacos , Células Cultivadas , Hidroxiurea/farmacología , Inhibidores de la Lipooxigenasa/farmacología , Ratones , Células PC12 , RatasRESUMEN
OBJECTIVE: To investigate the antioxidative effects of two cysteinyl leukotriene receptors antagonists (CysLT1R and CysLT2R) montelukast and HAMI 3379 on ischemic injury of rat cortical neurons in vitro. METHODS: Cultured rat cortical neurons were pretreated with CysLT1R antagonist montelukast and CysLT2R antagonist HAMI 3379, and then exposed to oxygen-glucose deprivation/recovery (OGD/Rï¼or H2O2. Reactive oxygen species (ROS) mitochondrial membrane potential (MMP) depolarization, neuronal viability and lactate dehydrogenase (LDH) release were determined. Meanwhile, RNA interference was used to inhibit the expression of CysLT1R and CysLT2Rï¼and the effects were observed. RESULTS: ROS production in neurons was significantly increased after 1 h OGD, which reached the peak at 30 min and lasted for 1.5 h after recovery. Montelukast and HAMI 3379 at 0.01-1µmol/L moderately decreased OGD/R-induced ROS production (P<0.05). Montelukast mildly attenuated OGD/R-induced MMP depolarization (P<0.05)ï¼but HAMI 3379 had no effect. H2O2 reduced neuronal viability and increased LDH release, namely inducing neuronal injury. Montelukast and HAMI 3379 at 0.1-1µmol/L moderately attenuated H2O2-induced neuronal injury (P<0.05). However, both CysLT1R siRNA and CysLT2R shRNA did not significantly affect the responses mentioned above. CONCLUSION: In ischemic neuronal injury, montelukast and HAMI 3379 exert a moderate antioxidative effect, and this effect may be receptor-independent.
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Acetatos/farmacología , Antioxidantes/farmacología , Ácidos Ciclohexanocarboxílicos/farmacología , Neuronas/efectos de los fármacos , Ácidos Ftálicos/farmacología , Quinolinas/farmacología , Animales , Hipoxia de la Célula/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Corteza Cerebral/citología , Ciclopropanos , Antagonistas de Leucotrieno/farmacología , Neuronas/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , SulfurosRESUMEN
It is necessary for the further development of sludge degradative solvent extraction (DSE) to significantly increase the bio-oil yield and adjust its composition. In this study, the effects of MCM-41, HZSM-5, and SSZ-13 on the physical properties, yield, and composition of bio-oil were compared. Results show that all three catalysts effectively promote the conversion of volatiles in the residue to the heavy component (heavy-s). The addition of MCM-41 improved the yieldof both the light component (light-s) and heavy-s. Their yields increased from 8.11% and 20.47% to 14.39% and 29.18%, respectively. Its all-silicon structure and weak acidity have no significant effect on the composition of the bio-oil. HZSM-5 addition increases the light-s yield to 25.58%. Its MFI structure and proper acidity are beneficial to the formation of aromatic hydrocarbons and olefins, while effectively reducing oxygenates. SSZ-13 increases the heavy-s yield to 27.89%, and promoted the formation of nitrogen-containing compounds significantly.
RESUMEN
Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.
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Aprendizaje Profundo , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Lesiones Precancerosas , Humanos , Persona de Mediana Edad , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Estudios Prospectivos , Lesiones Precancerosas/patologíaRESUMEN
The cysteinyl leukotrienes (CysLTs) are inflammatory mediators closely associated with neuronal injury after brain ischemia through the activation of their receptors, CysLT1R and CysLT2R. Here we investigated the involvement of both receptors in oxygen-glucose deprivation/recovery (OGD/R)-induced ischemic neuronal injury and the effect of the novel CysLT2R antagonist HAMI 3379 [3-({[(1S,3S)-3- carboxycyclohexyl]amino}carbonyl)-4-(3-{4-[4-(cyclo-hexyloxy)butoxy]phenyl}propoxy)benzoic acid] in comparison with the CysLT1R antagonist montelukast. In primary neurons, neither the nonselective agonist leukotriene D4 (LTD4) nor the CysLT2R agonist N-methyl-leukotriene C4 (NMLTC4) induced neuronal injury, and HAMI 3379 did not affect OGD/R-induced neuronal injury. However, in addition to OGD/R, LTD4 and NMLTC4 induced cell injury and neuronal loss in mixed cultures of cortical cells, and neuronal loss and necrosis in neuron-microglial cocultures. Moreover, they induced phagocytosis and cytokine release (interleukin-1ß and tumor necrosis factor-α) from primary microglia, and conditioned medium from the treated microglia induced neuronal necrosis. HAMI 3379 inhibited all of these responses, and its effects were the same as those of CysLT2R interference by CysLT2R short hairpin RNA, indicating CysLT2R dependence. In comparison, montelukast moderately inhibited OGD/R-induced primary neuronal injury and most OGD/R- and LTD4-induced (but not NMLTC4-induced) responses in mixed cultures, cocultures, and microglia. The effects of montelukast were both dependent and independent of CysLT1Rs because interference by CysLT1R small interfering RNA had limited effects on neuronal injury in neuron-microglial cocultures and on cytokine release from microglia. Our findings indicated that HAMI 3379 effectively blocked CysLT2R-mediated microglial activation, thereby indirectly attenuating ischemic neuronal injury. Therefore, CysLT2R antagonists may represent a new type of therapeutic agent in the treatment of ischemic stroke.
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Ácidos Ciclohexanocarboxílicos/farmacología , Antagonistas de Leucotrieno/farmacología , Microglía/efectos de los fármacos , Neuronas/efectos de los fármacos , Ácidos Ftálicos/farmacología , Receptores de Leucotrienos/metabolismo , Acetatos/farmacología , Animales , Animales Recién Nacidos , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/patología , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Hipoxia de la Célula , Células Cultivadas , Corteza Cerebral/citología , Técnicas de Cocultivo , Ciclopropanos , Citocinas/metabolismo , Femenino , Glucosa/metabolismo , Masculino , Microglía/metabolismo , Microglía/patología , Necrosis , Neuronas/metabolismo , Neuronas/patología , Oxígeno/metabolismo , Fagocitosis , Cultivo Primario de Células , Quinolinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Leucotrienos/agonistas , SulfurosRESUMEN
Autophagy is a principal degradation pathway for the turnover of intracellular proteins or cytoplasmic organelles in response to starvation. During autophagic activation, autophagosomes fuse with lysosomes to form autolysosomes where incorporated materials are degraded. However, the dynamics of autolysosomes in neurites of live cells was still poorly known. In this study, various subsets of microscope were applied to analyse the autophagy induction and highly dynamic transport of autolysosomes in rat PC12 neurites. Beading formation was found in degenerating PC12 neurites under phase contrast light microscope after serum deprivation. The monomeric red fluorescence protein-green fluorescence protein-light chain 3-labelled autolysosomes accumulated throughout PC12 neurites after 18 h of serum deprivation as revealed by fluorescence microscope analysis. The single-membrane autolysosomes were also visualized in PC12 cells under transmission electron microscope. Moreover, fluorescence recovery after photobleaching experiment, which was conducted by confocal laser scanning microscope, demonstrated that autolysosomes were motile vesicles and moved along PC12 neurites during starvation. The directional transport of monomeric red fluorescence protein -labelled autolysosomes in neurites was further monitored by a motorized video microscope. Both anterograde and retrograde transport of autolysosomes were observed. In addition, the autolysosomes were precisely mapped by using 2D Gaussian fitting and then their highly dynamic movement was robustly tracked by using multidimensional assignment. Collectively, by using different microscopical techniques, our results confirmed the dynamic transport of autolysosomes in starved PC12 neurites and may provide valuable insight into understanding the biophysical characteristics of autolysosomes in neurites under physiological and pathological conditions.
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Lisosomas/metabolismo , Lisosomas/ultraestructura , Neuritas/fisiología , Neuritas/ultraestructura , Fagosomas/metabolismo , Fagosomas/ultraestructura , Animales , Línea Celular , Microscopía Confocal/métodos , Microscopía Electrónica de Transmisión/métodos , Microscopía Fluorescente/métodos , Microscopía de Contraste de Fase/métodos , Neuritas/metabolismo , RatasRESUMEN
Due to the complexity of metabolic and regulatory networks in microorganisms, it is difficult to obtain robust phenotypes through artificial rational design and genetic perturbation. Adaptive laboratory evolution (ALE) engineering plays an important role in the construction of stable microbial cell factories by simulating the natural evolution process and rapidly obtaining strains with stable traits through screening. This review summarizes the application of ALE technology in microbial breeding, describes the commonly used methods for ALE, and highlights the important applications of ALE technology in the production of lipids and terpenoids in yeast and microalgae. Overall, ALE technology provides a powerful tool for the construction of microbial cell factories, and it has been widely used in improving the level of target product synthesis, expanding the range of substrate utilization, and enhancing the tolerance of chassis cells. In addition, in order to improve the production of target compounds, ALE also employs environmental or nutritional stress strategies corresponding to the characteristics of different terpenoids, lipids, and strains.
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Microalgas , Terpenos , Terpenos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Microalgas/genética , Lípidos/genética , Ingeniería Metabólica/métodosRESUMEN
OBJECTIVES: Traditional preoperative reminding services have been applied to enhance the quality of bowel preparation for colonoscopy. In this study we aimed to evaluate the effectiveness of an automated electronic reminder system (E-reminder) on improving bowel preparation and the quality of preoperative education before colonoscopy. METHODS: From August 2021 to March 2022, 833 outpatients aged 50-75 years who underwent colonoscopy were included and randomly assigned to the E-reminder group and the control group. While the control group received routine preoperative education. The E-reminder group received automatic phone call, text message reminders and web services regarding the details of bowel preparation before the colonoscopic examination. The quality of bowel preparation was evaluated by the Boston Bowel Preparation Scale (BBPS) score and the previously validated objective evaluation scale of automatic BBPS (e-BBPS). RESULTS: In manual assessment, the rate of adequate bowel preparation was improved in the E-reminder group of intention-to-treat population using BBPS (60.7% vs 54.5%, P = 0.01). The percentage of objective evaluated adequate bowel preparation using e-BBPS in the E-reminder group of per-protocol population was significantly higher than that in the control group (76.9% vs 69.2%, P = 0.02). CONCLUSIONS: E-reminder was an effective tool to improve the quality of bowel preparation and compliance with medical instructions. It may be regarded as an efficient and convenient education tool, improving the quality of medical service.
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Catárticos , Sistemas Recordatorios , Humanos , Colonoscopía/métodos , Cuidados Preoperatorios/métodos , Estudios ProspectivosRESUMEN
The push-pull effect (PPE) has been recognized as a deleterious contributor to fatal flight accidents. The purpose of the study was to establish a push-pull manoeuvre (PPM) simulation with a tri-axes centrifuge, studying the effect of this PPM on the +Gz tolerance, and to make this simulation suitable for pilot centrifuge training. The PPM was realized through pre-programmed acceleration profiles consisting of -1 Gz for 5 s followed by a +Gz plateau for 10 s. Relaxed +Gz tolerance recordings were obtained from 20 healthy male fighter aircraft pilots and 6 healthy male volunteers through exposure to pre-programmed profiles with and without previous -1 Gz exposure. A statistically significant decrease in +Gz tolerance was seen in all subjects after -1 Gz for 5 s exposure, 0.87 ± 0.13 G in the volunteer group and 0.95 ± 0.25 G in the pilot group. The ear opacity pulse as a +Gz tolerance endpoint criterion was sometimes found to be unreliable during the PPM experiments. The simulated PPM in this study elicited a PPE, which was obvious from the significant reduction in +Gz tolerance. The PPM profile appears useful to be included in centrifuge training.
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Aceleración , Adaptación Fisiológica/fisiología , Mano/fisiología , Hipergravedad , Movimiento/fisiología , Análisis y Desempeño de Tareas , Aeronaves , Centrifugación , Ecosistema , Humanos , Masculino , Adulto JovenRESUMEN
OBJECTIVE: To investigate whether cysteinyl leukotriene receptor 1 (CysLT1 receptor) is involved in rotenone-induced injury of PC12 cells. METHODS: After 24 h treatment with rotenone or with rotenone and the CysLT1 receptor antagonist montelukast, PC12 cell viability was determined by the colorimetric MTT reduction assay. After PC12 cells were treated with various concentrations of rotenone for 24 h or with 3 µmol/L rotenone for various durations, the expression of CysLT(1) receptor was determined by Western blotting, and its intracellular distribution was detected by immunocytochemistry. RESULTS: Rotenone (0.3-30 µmol/L) induced PC12 cell injury; this injury was significantly attenuated by montelukast at 1 and 5 µmol/L.The expression of CysLT(1) receptor increased after rotenone treatment at 1-10 µmol/L, or at 3 µmol/L for 3 and 24 h. Rotenone caused concentration-and time-dependent translocation of CysLT1 receptor from the nucleus to the cytosol. CONCLUSION: Cysteinyl leukotriene receptor 1 is involved in rotenone-induced injury of PC12 cells.