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Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.
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Epilepsia del Lóbulo Temporal , Serpinas , Animales , Ratones , Astrocitos/metabolismo , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/metabolismo , Hipocampo/metabolismo , Ácido Kaínico/toxicidad , Enfermedades Neuroinflamatorias , FN-kappa B/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Convulsiones/inducido químicamente , Convulsiones/metabolismo , Transducción de Señal , Serpinas/metabolismoRESUMEN
Sodium-ion batteries capable of operating at rate and temperature extremes are highly desirable, but elusive due to the dynamics and thermodynamics limitations. Herein, a strategy of electrode-electrolyte interfacial chemistry modulation is proposed. The commercial hard carbon demonstrates superior rate performance with 212â mAh g-1 at an ultra-high current density of 5â A g-1 in the electrolyte with weak ion solvation/desolvation, which is much higher than those in common electrolytes (nearly no capacity in carbonate-based electrolytes). Even at -20 °C, a high capacity of 175â mAh g-1 (74 % of its room-temperature capacity) can be maintained at 2â A g-1 . Such an electrode retains 90 % of its initial capacity after 1000 cycles. As proven, weak ion solvation/desolvation of tetrahydrofuran greatly facilitates fast-ion diffusion at the SEI/electrolyte interface and homogeneous SEI with well-distributed NaF and organic components ensures fast Na+ diffusion through the SEI layer and a stable interface.
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Seven long-chain amides, including five previously undescribed bacillamidins Aâ»E (1â»5) and two previously reported synthetic analogs, bacillamidins F (6) and G (7), were isolated from extracts of the marine-derived Bacillus pumilus strain RJA1515. The structures of the new compounds were established by extensive analysis of 1D and 2D nuclear magnetic resonance (NMR) data as well as high resolution mass spectrometry (HRMS), and the absolute configurations of the stereogenic carbons of 1â»4 were established by comparison of the calculated and the experimental electronic circular dichroism (ECD) spectra. The cytotoxic and antimicrobial activities of 1â»7 were evaluated.
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Amidas/farmacología , Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Organismos Acuáticos/química , Bacillus pumilus/química , Amidas/química , Amidas/aislamiento & purificación , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Bacterias/efectos de los fármacos , Línea Celular Tumoral , Dicroismo Circular , Humanos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
Two new long-chain unsaturated compounds, (2E, 6E)-10-methoxy-3,7-dimethyl-10-oxodeca-2,6-dienoic acid (1) and (2E, 6E)-3,7,11-trimethyldodeca-2,6-dienedioic acid (2), together with seven known compounds were isolated from a marine-derived Streptomyces sp. Their structures were determined by spectroscopic methods, including 2D NMR techniques. Compounds 1 and 2 were investigated for their antibacterial activities.
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Antibacterianos/aislamiento & purificación , Ácidos Grasos Insaturados/aislamiento & purificación , Streptomyces/química , Antibacterianos/química , Antibacterianos/farmacología , Ácidos Grasos Insaturados/química , Ácidos Grasos Insaturados/farmacología , Biología Marina , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Phytochemical investigation on the stems of Kadsura renchangiana led to the isolation of two new sesquiterpenoids, renchangianins F and G (1 and 2). Their structures were elucidated by spectroscopic methods, including 2D NMR techniques. The in vitro cytotoxic activities of the isolates were studied against HepG2, A549, and LN229 cancer cell lines.
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Antineoplásicos Fitogénicos/aislamiento & purificación , Kadsura/química , Sesquiterpenos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Tallos de la Planta/química , Sesquiterpenos/química , Sesquiterpenos/farmacologíaRESUMEN
A new isocoumarin, chamerilactone A(1) was isolated from the ethanol extract of Chamerion angustifolium with normal phase silica column chromatography, Sephadex LH-20, MCI CHP-20 and semi- preparative HPLC methods. Its structure and stereochemistry were elucidated by spectroscopic methods, including 2D-NMR and optical rotation techniques.
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Isocumarinas/aislamiento & purificación , Onagraceae/química , Cromatografía Líquida de Alta Presión , Estructura MolecularRESUMEN
A new dibenzocyclooctadiene lignan, renchangianin E (1) was isolated from the stems of Kadsura renchangiana. Its structure and stereochemistry were elucidated by spectroscopic methods, including 2D-NMR techniques.
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Ciclooctanos/química , Kadsura/química , Lignanos/química , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
BACKGROUND: Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs. METHODS: In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity. RESULTS: GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913-0.999, P = .05), Intestinibacter (OR = 0.908, 95% CI:0.831-0.993, P = .03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841-0.973, P = .007), Turicibacter (OR = 0.904, 95% CI: 0.838-0.976, P = .01), Holdemania (OR, 0.898; 95% CI: 0.810-0.995, P = .04) and Odoribacter (OR, 0.835; 95% CI: 0.710-0.993, P = .04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas. CONCLUSION: Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice.
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OBJECTIVE: To explore the influence of compound whole grain complex antioxidant chain on oxidative stress to the hyperlipidemia population. METHODS: From March 2008 to March 2009, 418 hyperlipemia residents (45 to 75 years of age) of Han group were screened from 3 main districts in Nanjing, according to the community, blood lipids and oxidative indicators, stratified into intervention and control group by quasi-experimental design. The intervention group (212 individuals) were provided with compound whole grain and health education while only health education was provided for the control group (206 individuals). Body mass index (BMI), waist-to-hip ratio (WHR), total cholesterol (TC), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) and oxidative indicators (including T-AOC, MDA, SOD, GSH-Px) were measured before and after the one-year intervention period. Analyses of the correlation between posture, biochemical markers and oxidative stress indicators before and after intervention were carried out. RESULTS: After intervention, BMI ((25.53 ± 2.77) kg/m(2)), WHR (0.82 ± 0.03), TC ((4.60 ± 0.98) mmol/L), TG ((1.26 ± 0.88) mmol/L) in the intervention group were decreased significantly compared to the levels of BMI ((26.60 ± 3.18) kg/m(2)), WHR (0.93 ± 0.05), TC ((4.97 ± 1.02) mmol/L), TG ((1.98 ± 1.11) mmol/L) in the control group (all P values < 0.05); while HDL-C ((1.34 ± 0.26) mmol/L) in the intervention group was increased significantly compared to the level of HDL-C ((1.18 ± 0.17) mmol/L) in the control group (P < 0.05); After intervention, levels of T-AOC (19.52 ± 0.81), SOD ((85.42 ± 21.65) U/ml) and GSH-Px ((128.26 ± 33.65) µmol/L) were increased significantly compared to the levels of T-AOC (11.11 ± 1.30), SOD ((78.68 ± 30.48) U/ml) and GSH-Px ((118.48 ± 24.19) µmol/L) in the control group (all P values < 0.05); while MDA ((1.78 ± 1.16) nmol/ml) decreased significantly compared to the level of MDA ((2.12 ± 1.37) nmol/ml in the control group (P < 0.05); Pearson product moment correlation analysis showed that: T-AOC with TC, TG, BMI showed a negative correlation (r values were -0.258, -0.266, -0.230, respectively, all P values < 0.05), while with HDL-C was a positive correlation (r values was 0.194, P < 0.05); SOD with TC, TG, BMI showed a negative correlation (r values were -0.282, -0.311, -0.217, respectively, all P values < 0.05), while with HDL-C was a positive correlation (r values was 0.169, P < 0.05). CONCLUSION: Compound whole grain could improve lipid metabolism to the hyperlipidemia population. There was a correlation between common human metabolism and the levels of oxidative stress.
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Dieta , Grano Comestible , Educación en Salud , Hiperlipidemias/metabolismo , Estrés Oxidativo , Anciano , Anciano de 80 o más Años , Antioxidantes , China/epidemiología , Encuestas sobre Dietas , Femenino , Humanos , Hiperlipidemias/epidemiología , Hiperlipidemias/prevención & control , Metabolismo de los Lípidos , Masculino , Persona de Mediana EdadRESUMEN
With 8-(methyltosylaminoethynyl)-1-naphthyl (MTAEN) glycoside as donors, a novel and efficient glycosylation protocol has been established. The MTAEN glycosylation protocol exhibits the merits of shelf-stable donors, mild catalytic promotion conditions, considerably extended substrate scope encompassing both free alcohols, silylated alcohols, nucleobases, primary amides, and C-type nucleophile acceptors, and applicability to various one-pot strategies for highly efficient synthesis of oligosaccharides, such as orthogonal one-pot, single-catalyst one-pot, and acceptor reactivity-controlled one-pot strategies.
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The abnormal expression and regulation of circular RNA (circRNA) is involved in the occurrence and development of a variety of tumors. The current study aimed to determine the role of circRNA_141539 in esophageal squamous cell carcinoma (ESCC). CircRNA_141539 expression in ESCC was detected via circRNA chip analysis and verified via reverse transcription-quantitative PCR. Associations between circRNA_141539, patient clinicopathological characteristics and prognosis were also statistically analyzed. Additionally, the effects of circRNA_141539 on ESCC cell proliferation and invasion were assessed. A dual-luciferase assay was performed to analyze the interaction between circRNAs, microRNAs (miRs) and mRNAs. The results revealed that circRNA_141539 was significantly up-regulated in patients with ESCC. Furthermore, high circRNA_141539 expressions were significantly associated with TNM stage, differentiation and poor prognosis, revealing high diagnostic value (P<0.05). Furthermore, circRNA_141539 overexpression promoted cell proliferation and invasion, while circRNA_141539 silencing inhibited cell proliferation and invasion (P<0.05). The dual-luciferase reporter assay identified that circRNA_141539 directly binds to miR-4469 and also revealed that cyclin-dependent kinase-3 (CDK3) was negatively regulated by miR-4469. The results indicated that circRNA_141539 served as an oncogenic factor in ESCC by sponging miR-4469 and activating CDK3 expression. circRNA_141539 may present as a novel diagnostic and prognostic biomarker and a therapeutic target for patients with ESCC.
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Quinasa 3 Dependiente de Ciclina/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , MicroARNs/metabolismo , ARN Circular/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , Carcinogénesis/genética , Proliferación Celular/genética , Mucosa Esofágica/patología , Mucosa Esofágica/cirugía , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , PronósticoRESUMEN
With the continuous development of China's society and economy, the breadth and depth of cultivated land resources development and utilization have been continuously expanded, while the production efficiency and scale of cultivated land gradually have been improved. There were rapidly increases of carbon emission induced from cultivated land management, such as the agricultural inputs and energy consumptions. Taking carbon emission from cultivated land utilization in Northeast China as the research object, we determined the carbon emission accounting framework system according to the life cycle method. Based on estimation results of carbon emissions from 1979 to 2015 in Northeast China, the driver factor system affecting agricultural carbon emissions was constructed using logarithmic mean Divisia index model and the influence mechanism of cultivated land carbon emissions in Northeast China was deeply explored. The results showed that total carbon emission from cultivated land utilization in 2015 was 21.9% higher than that in 1979 and carbon emission intensity in 2015 was 1.54 t·hm-2 lower than that in 1979. Soil management and agricultural inputs were the main sources of carbon emissions from cultivated land accounting for 83.6% of the total carbon emissions. The increases of land productivity and science and technology fund allocation rate were found to be the driving factors of carbon emission from cultivated land utilization. On the contrary, the reduction of input/output ratio, cultivated land area per capita and intensity of science and technology investment decreased carbon emission from cultivated land utilization.
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Agricultura , Carbono , Carbono/análisis , Dióxido de Carbono/análisis , China , SueloRESUMEN
Virus infection can alter immune regulatory activity, and thus may be involved in the occurrence of autoimmune diseases. Recently, the pandemic of COVID-19 has posed a huge threat to public health and emerging evidence suggests that coronavirus may be implicated in the development and pathogenesis of autoimmune diseases. However, how coronavirus infection impacts the risk of autoimmune disease remains largely unknown. In this review, we focused on the association between coronavirus and autoimmunity, and elucidated the molecular mechanisms linking coronavirus exposure to autoimmunity. Additionally, we briefly introduced the role that coronavirus plays in several autoimmune diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and idiopathicthrombocytopenic purpura (ITP).
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Enfermedades Autoinmunes , COVID-19 , Lupus Eritematoso Sistémico , Autoinmunidad , Humanos , SARS-CoV-2RESUMEN
The 2,2-dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) group was introduced to synthetic carbohydrate chemistry as a protecting group (PG) for the first time. Benefiting from a unique chemical structure and novel deprotection conditions, the DMNPA group can be cleaved rapidly and mutually orthogonal to other PGs. Orchestrated application of the DMNPA group with other PGs led to the highly efficient synthesis of the glycan of thornasterside A.
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The 2,2-dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) group permits, via robust neighboring group participation (NGP) or long distance participation (LDP) effects, the stereocontrolled 1,2-trans, 1,2-cis, as well as ß-2,6-dideoxy glycosidic bond generation, while suppressing the undesired orthoester byproduct formation. The robust stereocontrol capability of the DMNPA is due to the dual-participation effect from both the ester functionality and the nitro group, verified by control reactions and DFT calculations and further corroborated by X-ray spectroscopy.
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Hidrocarburos Aromáticos/química , Glicosilación , EstereoisomerismoRESUMEN
A new isoflavanone compound, ficustikounone A (1), together with 22 known flavones, was isolated from Ficus tikoua Bur. The structures of these isolates were determined by UV, ECD, HRESIMS, 1D and 2D spectral analyses.
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Ficus/química , Isoflavonas/aislamiento & purificación , Células A549 , Línea Celular Tumoral , Flavonas , Células Hep G2 , Humanos , Isoflavonas/química , Estructura Molecular , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Plantas Medicinales/químicaRESUMEN
The aerial parts of Epilobium plants are widely used as folk medicine and food around the world. The present study was aimed to investigate the antioxidant activities and active chemical constituents from Epilobium angustifolium L. The results revealed that the EtOAc extract, rich in phenolic compounds and flavonoids (16.81 ± 0.67 g GAE/100 g extract and 4.95 ± 0.21 g QE/100 g extract, respectively), possessed significantly antioxidant activities in reducing power, DPPH radical scavenging activity, ABTS radical scavenging activity and highly in inhibiting lipid peroxidation activity. Simultaneously, active fractions F to H from EtOAc extracts showing potent in vitro antioxidant activities also contained high content of total phenolic and flavonoid. Twenty-eight compounds were identified as phenolic compounds and flavonoids by LC-MS/MS. The results illustrate that the E. angustifolium L., which is rich in phenolics, could be used as a natural resource of antioxidant ingredient.
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Antioxidantes/farmacología , Epilobium/química , Fenoles/análisis , Extractos Vegetales/farmacología , Antioxidantes/química , Cromatografía Líquida de Alta Presión/métodos , Flavonoides/análisis , Flavonoides/química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Peroxidación de Lípido/efectos de los fármacos , Fenoles/química , Componentes Aéreos de las Plantas/química , Extractos Vegetales/análisis , Extractos Vegetales/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
One new compound, himalain A (1), together with 12 known compounds were isolated from Mirabilis himalaica. Their structures were determined by spectroscopic methods, including 2D NMR techniques, and the absolute configuration of the 1,2-diol moiety in 1 was defined through Riguera's method. All isolated compounds were tested for their cytotoxic and antibacterial activities.
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Mirabilis/química , Éteres Fenílicos/aislamiento & purificación , Antibacterianos/farmacología , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Humanos , Éteres Fenílicos/química , Éteres Fenílicos/farmacologíaRESUMEN
BACKGROUND AND OBJECTIVES: Patients with previous gastrectomy have an increased incidence of gallstones and gallbladder morbidity requiring surgery. We investigated the possible risk factors that contribute to severe gallbladder disease in patients with previous gastrectomy and the role of laparoscopic cholecystectomy (LC) in the treatment of these patients. METHODS: In this retrospective study, we reviewed a database of patients who underwent LC in our hospital during the period January 1, 2010, through May 1, 2015. RESULTS: The average operation time in patients with previous gastrectomy was longer (P < .05), but the operation times of patients with a long interval (>5 years) between gastrectomy and LC showed no statistical difference from those of patients without a history of gastrectomy (P > .05). The conversion rate did not differ between the 2 groups (P > .05), but in patients with previous gastrectomy, the conversion rate was significantly reduced after we adopted a comprehensive preoperative evaluation procedure (P < .05). The frequency of cholecystitis attacks, rate of combination with gallbladder polyps, and rate of combination with pancreatitis were higher and gallstone formation time shorter, in the patients with malignant tumor, those undergoing Billroth II gastroenterostomy or esophagojejunostomy, and those with accompanying diabetes mellitus or hypercholesterolemia (P < .05). CONCLUSION: LC plays an important role in the treatment of benign gallbladder diseases in patients with a history of gastrectomy, and a comprehensive preoperative evaluation and accomplished surgical technique are necessary for successful outcomes. Previously identified clinical features may represent a risk factor for severe cholecystic morbidity in these patients.