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The clinical advantage staging and underlying mechanisms of Wangbi Tablets against knee osteoarthritis(KOA) were studied based on the "disease-formula" interaction network. Firstly, the clinical symptoms and related genes corresponding to Wangbi Tablets and KOA in the acute, remission, and recovery phases were collected from clinical guidelines/consensus and SoFDA database, and the putative targets of Wangbi Tablets were obtained from ETCM 2.0. Then, Jaccard similarity and cosine similarity were employed to assess the similarities of clinical symptoms, genes, and enriched pathways between Wangbi Tablets and KOA in different phases. The "disease-formula" interaction network of the drug targets and disease genes was constructed, and the key targets were screened by topological feature calculation. KEGG and Reactome database were used for the functional enrichment of the key targets, on the basis of which the functional characteristics of Wangbi Tablets against KOA in the acute, remission, and recovery phases were predicted. Finally, the SW1353 cells exposed to lipopolysaccharide were used to decipher the mechanism of Wangbi Tablets against KOA. The results showed that 92/3 921, 138/3 708, 139/3 800, and 196/3 946 clinical symptoms and the related genes corresponded to KOA in the acute, remission, and recovery phases and Wangbi Tablets were collected from SoFDA, and 260 putative targets of Wangbi Tablets were obtained from ETCM 2.0. Wangbi Tablets had highest similarity of clinical symptoms, genes, and enriched pathways with KOA in the remission phase and the secondary highest similarity with KOA in the recovery phase. The key targets of Wangbi Tablets mainly participated in the regulation of immunity-inflammation imbalance and exerted pain-relieving and bone-protecting effects to alleviate symptoms such as knee joint pain, joint swelling, soreness, fatigue, and dysfunction. Intriguingly, the key targets of Wangbi Tablets possessed antioxidant effects during KOA in the acute and remission phases, while they maintained material and energy metabolism homeostasis and protected vessels during KOA in the recovery phase. The cell experiment indicated that Wangbi Tablets down-regulated the expression of interleukin(IL)-6, IL-1ß, tumor necrosis factor-α(TNF-α), and Bcl-2-associated X protein(Bax)/B-cell lymphoma 2(Bcl-2) via regulating the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt) signaling pathway. The findings lay a theoretical foundation for further clarifying the clinical advantage stage and precise clinical application of Wangbi Tablets in treating KOA.
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Medicamentos Herbarios Chinos , Osteoartritis de la Rodilla , Comprimidos , Humanos , Medicamentos Herbarios Chinos/farmacología , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/metabolismoRESUMEN
Bolometers based on graphene have demonstrated outstanding performance with high sensitivity and short response time. In situ adjustment of bolometers is very important in various applications, but it is still difficult to implement in many systems. Here we propose a gate-tunable bolometer based on two strongly coupled graphene nanomechanical resonators. Both resonators are exposed to the same light field, and we can measure the properties of one bolometer by directly tracking the resonance frequency shifts, and indirectly measure the other bolometer through mechanical coupling. We find that the sensitivity and the response bandwidth of both bolometers can be independently adjusted by tuning the corresponding gate voltages. Moreover, the properties of the indirectly measured bolometer show a dependence on the coupling between the two resonators, with other parameters being fixed. Our method has the potential to optimize the design of large-scale bolometer arrays, and open new horizons in infrared/terahertz astronomy and communication systems.
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Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1ß(IL-1ß). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1ß signaling pathway-mediated microglia p38/IL-1ß inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
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Metaloproteinasa 9 de la Matriz , Neuralgia , Ratas , Ratones , Animales , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Ratas Sprague-Dawley , Enfermedades Neuroinflamatorias , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Médula Espinal/metabolismo , Transducción de Señal , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismoRESUMEN
The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
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Dolor Crónico , Medicamentos Herbarios Chinos , Ratas , Ratones , Animales , Dolor Crónico/complicaciones , Dolor Crónico/metabolismo , Ratas Sprague-Dawley , Ganglios Espinales/metabolismo , Ligandos , Transducción de Señal , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/etiología , Hiperalgesia/metabolismoRESUMEN
High-carbohydrate diet could achieve cost-sparing effect in aquafeed, but it may cause adverse effects on the growth condition or health status of fish. In order to reduce the adverse effects caused by high carbohydrate diet, mannan oligosaccharides (MOS), a commonly used prebiotics, was used as the feed additive to feed juvenile Nile tilapia (Oreochromis niloticus) (1.19 ± 0.01g) for ten weeks. Three treatments including CON (35% carbohydrate diet), HC (45% carbohydrate diet) and HM (45% carbohydrate supplemented diet with 5 g/kg MOS) were involved. The results showed that MOS supplementation increased the weight gain and body length of juvenile Nile tilapia compared with the HC group. Addition of MOS decreased serum glucose and liver glycogen by increasing enzymes activity related to glycolysis. Furthermore, supplementation of MOS decreased the high carbohydrate diet induced triglycerides accumulation in liver by reducing the expression level of genes related to TG synthesis. Dietary MOS also down-regulated the gene expression level of inflammation factors in liver. Intestinal bacterial composition analyses showed that supplementation of MOS in high carbohydrate diet altered the gut microbial composition and enriched pathways related to the glucose metabolism based on KEGG analyses. In general, our results demonstrated that MOS supplementation in high carbohydrate diet could regulate glucose and lipid homeostasis which may be related to the alteration of gut microbiota. These findings shed light on the application of prebiotics to increase the growth performance, alleviate the metabolic disorders and regulate inflammatory response in aquaculture.
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Cíclidos , Microbioma Gastrointestinal , Alimentación Animal/análisis , Animales , Cíclidos/genética , Dieta/veterinaria , Suplementos Dietéticos/análisis , Glucosa/farmacología , Lípidos , Glucógeno Hepático/farmacología , Mananos/farmacología , Oligosacáridos/farmacología , Prebióticos/análisis , TriglicéridosRESUMEN
Chronic inflammatory pain is mainly manifested by peripheral sensitization. Baimai Ointment(BMO), a classical Tibetan medicine for external use, has good clinical efficacy in the treatment of chronic inflammatory pain, while its pharmacodynamics and mechanism for relieving peripheral sensitization remain unclear. This study established an animal model of chronic inflammatory pain induced by complete Freund's adjuvant to explore the mechanism of BMO in the treatment of chronic inflammatory pain by behavioral test, side effect assessment, network analysis, and experimental verification. The pharmacodynamics experiment showed that BMO increased the thresholds of mechanical pain sensitivity and thermal radiation pain sensitivity of chronic inflammatory pain mice in a dose-dependent manner, and had inhibitory effect on foot swelling, inflammatory mediator, and the expression of transient receptor potential vanilloid-1(TRPV1) and transient receptor potential A1(TRPA1). The results of body weight monitoring, pain sensitivity threshold detection in normal mice, rotarod performance test, and forced swimming test showed that BMO had no obvious toxic or side effect. The network analysis of 51 candidate active molecules selected according to the efficacy of BMO, content of main components, and ADME parameters showed that the inhibitory effect of BMO on chronic inflammatory pain was associated with the core regulatory elements of tumor necrosis factor(TNF) and T cell receptor signaling pathways. BMO down-regulated the protein levels of mitogen-activated protein kinase 14(MAPK14), MAPK1, and prostaglandin-endoperoxide synthase 2(PTGS2), and up-regulated the phosphorylation le-vel of glycogen synthase kinase 3 beta(GSK3 B) in the plantar tissue of mice. In conclusion, BMO can effectively relieve peripheral sensitization of chronic inflammatory pain without inducing tolerance and obvious toxic and side effects. The relevant mechanism may be related to the regulation of BMO on core regulatory elements of TNF and T cell receptor signaling pathways in surrounding tissues.
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Glucógeno Sintasa Quinasa 3 , Hiperalgesia , Ratones , Animales , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Glucógeno Sintasa Quinasa 3/efectos adversos , Glucógeno Sintasa Quinasa 3/metabolismo , Dolor/tratamiento farmacológico , Dolor/inducido químicamente , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Canales Catiónicos TRPV/efectos adversosRESUMEN
Asthma is a chronic inflammatory disease of the lungs that poses a considerable health and socioeconomic burden. Several risk factors work synergistically to affect the progression of asthma. Lipid metabolism, especially in distinct cells such as T cells, macrophages, granulocytes, and non-immune cells, plays an essential role in the pathogenesis of asthma, as lipids are potent signaling molecules that regulate a multitude of cellular response. In this review, we focused on the metabolic pathways of lipid molecules, especially fatty acids and their derivatives, and summarized their roles in various cells during the pathogenesis of asthma along with the current pharmacological agents targeting lipid metabolism.
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Asma/metabolismo , Granulocitos/inmunología , Metabolismo de los Lípidos/inmunología , Macrófagos/inmunología , Linfocitos T/inmunología , Animales , Asma/tratamiento farmacológico , Asma/epidemiología , Ácidos Grasos/metabolismo , Humanos , Inmunidad Celular , Terapia Molecular Dirigida , Factores de Riesgo , Transducción de SeñalRESUMEN
Graphene has been considered as one of the best materials to implement mechanical resonators due to their excellent properties such as low mass, high quality factors and tunable resonant frequencies. Here we report the observation of phonon lasing induced by the photonthermal pressure in a few-layer graphene resonator at room temperature, where the graphene resonator and the silicon substrate form an optical cavity. A marked threshold in the oscillation amplitude and a narrowing linewidth of the vibration mode are observed, which confirms a phonon lasing process in the graphene resonator. Our findings will stimulate the studies on phononic phenomena, help to establish new functional devices based on graphene mechanical resonators, and might find potential applications in classical and quantum sensing fields, as well as in information processing.
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Prussian blue analogues (PBAs, A2 T[M(CN)6 ], A = Li, K, Na; T = Fe, Co, Ni, Mn, Cu, etc.; M = Fe, Mn, Co, etc.) are a large family of materials with an open framework structure. In recent years, they have been intensively investigated as active materials in the field of energy conversion and storage, such as for alkaline-ion batteries (lithium-ion, LIBs; sodium-ion, NIB; and potassium-ion, KIBs), and as electrochemical catalysts. Nevertheless, few review papers have focused on the intrinsic chemical and structural properties of Prussian blue (PB) and its analogues. In this Review, a comprehensive insight into the PBAs in terms of their structural and chemical properties, and the effects of these properties on their materials synthesis and corresponding performance is provided.
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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Current therapies present significant limitations. Triptolide (TP) is highly effective against multiple cancers including HCC. However, high toxicity, low water solubility, and unknown therapeutic targets limit its clinical application. Herein, we designed galactosylated-chitosan-TP-nanoparticles (GC-TP-NPs) with high drug loading capacities for targeted delivery to HCC. In addition to a sustained release pattern, an efficient asialoglycoprotein receptor mediated cellular uptake in vitro, and high liver tumor accumulation in vivo, GC-TP-NPs showed lower systemic and male reproductive toxicities than free TP. Importantly, GC-TP-NPs retained the anti-cancer activities of the free TP, exerting the same pro-apoptotic and anti-proliferative effects on HCC cells in vitro, and displayed higher efficacies in reducing tumor sizes in vivo. Further investigation revealed that GC-TP-NPs induced cancer cell apoptosis via blocking TNF/NF-κB/BCL2 signaling. Collectively, GC-TP-NP represents a promising candidate in halting liver cancer progression while minimizing systemic toxicity.
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Carcinoma Hepatocelular/prevención & control , Quitosano/química , Diterpenos/administración & dosificación , Galactosa/química , Neoplasias Hepáticas/prevención & control , Nanopartículas/administración & dosificación , Fenantrenos/administración & dosificación , Reproducción , Animales , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/farmacocinética , Apoptosis , Carcinoma Hepatocelular/patología , Proliferación Celular , Diterpenos/química , Diterpenos/farmacocinética , Compuestos Epoxi/administración & dosificación , Compuestos Epoxi/química , Compuestos Epoxi/farmacocinética , Humanos , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Desnudos , Nanopartículas/química , Fenantrenos/química , Fenantrenos/farmacocinética , Transducción de Señal , Distribución Tisular , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
DNA barcode molecular biological technique is used to identify the species of 23 unknown Li minority medicinal plants.DNA was extracted from 23 unknown medicines using the Plant Genomic DNA Extraction kit. The ITS2 and psbA-trnH regions were amplified and sequenced bi-directionally. The Codon Code Aligner V 7. 0. 1 was used to proofread and assemble the contigs and generated consensus sequences. All the sequences were submitted to Traditional Chinese Medicine DNA Barcode Database and NCBI Gen Bank to get information of the species identifications. If the maximum similarity of the identification result is ≥ 97%,exact species can be known. If it is between 97% and 90%,samples' genus can be confirmed; If it is <90%,then we can only confirm its family. Finally there are 17 samples can be identified to species level,5 can be identified to genus level and 1 can be identified to family level. This shows that DNA barcoding used in medicinal plants molecular identification,can identify unknown species rapidly and accurately.
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Código de Barras del ADN Taxonómico , Plantas Medicinales/clasificación , ADN de Plantas/genética , Medicina Tradicional China , Análisis de Secuencia de ADNRESUMEN
Growing clinical evidence shows that a partial rheumatoid arthritis( RA) patient treated with Tripterygium Glycosides Tablets( TGT) may fail to achieve clinical improvement. It is of great clinical significance to predict the therapeutic effect of TGT in RA. Therefore,the aim of the current study was to identify potential biomarkers for TGT treatment in RA. Affymetrix EG1.0 arrays were applied to detect gene expression in peripheral blood mononuclear cells obtained from 6 RA patients( 3 responders and 3 non-responders) treated with TGT. By integrating differential expression data analysis and biomolecular network analysis,360 mRNAs( 185 up-regulated and 175 down-regulated) and 24 miRNAs( 7 up-regulated and 17 down-regulated) which were differentially expressed between TGT responder and non-responder groups were identified. A total of 206 candidate target genes for the differentially expressed miRNAs were obtained based on miRanada and Target Scan databases,and then the miRNA target gene coexpression network and miRNA-mediated gene signal transduction network were constructed. Following the network analyses,three candidate miRNAs biomarkers( hsa-miR-4720-5 p,hsa-miR-374 b-5 p,hsa-miR-185-3 p) were identified as candidate biomarkers predicting individual response to TGT. Partialleast-squares( PLS) was applied to construct a model for predicting response to TGT based on the expression levels of the candidate gene biomarkers in RA patients. The five-fold cross-validation showed that the prediction accuracy( ACC) of this PLS-based model efficacy was 100.00%,100.00%,100.00%,66.67% and 66.67% respectively,and all the area under the receiver operating characteristic curve( AUC) were 1.00,indicating the highly predictive efficiency of this PLS-based model. In conclusion,the integrating transcription data mining and biomolecular network investigation show that hsa-mir-4720-5 p,hsa-mir-374 b-5 p and hsa-mir-185-3 p may be candidate biomarkers predicting individual response to TGT. In addition,the PLS model based on the expression levels of these candidate biomarkers may be helpful for the clinical screen of RA patients,which potentially benefit individualized therapy of RA in a daily clinical setting.
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Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Glicósidos/uso terapéutico , MicroARNs/genética , Tripterygium/química , Biomarcadores , Minería de Datos , Humanos , Leucocitos Mononucleares , ComprimidosRESUMEN
BACKGROUND The formation of new blood vessels, known as angiogenesis, is critical for recovery from ischemic heart disease, and estrogen is considered an important factor in this process. Here, we investigated the effects of 17ß-estradiol (17ß-E2) on proliferation and migration of cardiac microvascular endothelial cells (CMECs) in vitro. MATERIAL AND METHODS Rat CMECs were isolated and cultured with 17ß-E2 (0.001-1 µmol/l) in the absence or presence of the estrogen antagonist tamoxifen. Then, the expression level of estrogen receptor alpha was evaluated by using immunofluorescence assay, RT-PCR, and Western blot. Cell proliferation was detected by methyl thiazolyl tetrazolium analysis and the cell migration was verified by a scraping assay and quantified by a Transwell chamber assay. CMEC differentiation was examined using a tube formation assay. Vascular endothelial growth factor (VEGF) secretion was detected by enzyme-linked immunosorbent assay. RESULTS CMECs exhibited homogenous, polygonal, exhibited contact inhibition, and had characteristically ovoid nuclei with 1 or 2 nucleoli, and the cytoplasm exhibited red fluorescence after staining for von Willebrand factor. 17ß-E2 treatment upregulated estrogen receptor alpha expression in CMECs. 17ß-E2 treatment significantly promoted the proliferation, migration, tubular structure formation, and VEGF secretion in CMECs. The maximal proliferation occurred in the presence of 0.01 µmol/l 17ß-E2. Furthermore, estrogen and VEGF were found to synergistically stimulate angiogenesis. CONCLUSIONS Our data show that 17ß-E2 promotes angiogenesis in vitro and suggests that estrogen treatment as a novel therapeutic modality in the management of arterial insufficiency.
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Células Endoteliales/efectos de los fármacos , Estradiol/farmacología , Inductores de la Angiogénesis , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Endoteliales/citología , Células Endoteliales/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Corazón/efectos de los fármacos , Masculino , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patología , Miocardio/citología , Miocardio/patología , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Cultivo Primario de Células , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
An effective method has been employed as a tool for screening active components in Kudiezi injection by using cell chromatography and sensitive UHPLC-HR-MSn method. The potential bioactive components in Kudiezi injection could be selectively bound to the HUVECs target cells first. After cell target desensitization and inactivation, the chemical constituents with cell target affinity were identified by LC-MS, so as to screen the possible active components in Kudiezi injection. Based on the accurate mass measurements and the retention time, in total, 9 compounds were tentatively identified and characterized, including 4 sesquiterpene lactones, 3 phenolic acids and 2 flavonoids. HUVECs biospecific extraction coupled with UHPLC-LTQ-Orbitrap analysis could provide a rapid and efficient method for the identification of potential bioactive components in Kudiezi injection, and provide the reference for further research on its effective materials basis.
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Medicamentos Herbarios Chinos/química , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Fitoquímicos/análisis , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Endotelio Vascular , Flavonoides/análisis , Humanos , Hidroxibenzoatos/análisis , Espectrometría de Masas , Sesquiterpenos/análisisRESUMEN
Graphite-nanoplate-coated Bi2 S3 composite (Bi2 S3 @C) has been prepared by a simple, scalable, and energy-efficient precipitation method combined with ball milling. The Bi2 S3 @C composite was used as the cathode material for sodium-sulfide batteries. It delivered an initial capacity of 550â mAh g(-1) and high stable specific energy in the range of 275-300â Wh kg(-1) at 0.1â C, with an enhanced capacity retention of 69 % over 100â cycles. The unique structure demonstrates superior cycling stability, with a capacity drop of 0.3 % per cycle over 100â cycles, compared with that of bare Bi2 S3 . The sodium storage mechanism of Bi2 S3 was investigated based on ex situ X-ray diffraction and scanning transmission electron microscopy.
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OBJECTIVES: To investigate the effects and mechanisms of Nardostachys chinensis (NC) on spontaneous ventricular arrhythmias in rats with hyper-acute myocardial infarction (AMI). METHODS: Seventy-two rats were randomly divided into the control group (n = 24), metoprolol group (n = 24), and the NC group (n = 24). Premature ventricular contractions (PVCs), ventricular tachycardias (VTs), ventricular fibrillations (VFs), and blood pressure were monitored for 4 hours after coronary artery ligation. The connexin 43 (Cx43) expression in ventricular myocardium was measured by immunohistochemistry, Western blot, and real-time RT-PCR. RESULTS: Compared with the control, metoprolol and NC decreased the VF incidence (50% vs. 4.2%, P < 0.001, and 50% vs. 12.5%, P = 0.005, respectively). There was a steady decrease in the cumulative number of PVCs and VTs within 4 hours from ligating in 3 groups. Compared with the control, metoprolol and NC reduced the cumulative number of VTs and PVCs. Compared with control, metoprolol and NC decreased the infarct size of the left ventricular tissue (55.98% ± 6.20% vs. 39.13% ± 4.53%, P < 0.001, and 55.98% ± 6.20% vs. 42.39% ± 3.44%, P < 0.001, respectively). The results from immunohistochemistry, Western blot, and real-time RT-PCR showed that the protein expression of Cx43 in the control group was significantly lower than that in the metoprolol and NC groups in the infarcted zone. CONCLUSIONS: NC decreased the incidence of spontaneous ventricular arrhythmias (especially VF), reduced Cx43 degradation, and improved Cx43 redistribution in myocardial infarcted zone in rats with hyper-AMI. The data of the present study indicated that NC may be a promising drug in the future to prevent patients with AMI from lethal ventricular arrhythmias in prehospital setting.
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Antiarrítmicos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Nardostachys/química , Taquicardia Ventricular/prevención & control , Fibrilación Ventricular/prevención & control , Complejos Prematuros Ventriculares/prevención & control , Animales , Antiarrítmicos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Western Blotting , Conexina 43/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Electrocardiografía , Femenino , Inmunohistoquímica , Masculino , Metoprolol/administración & dosificación , Metoprolol/uso terapéutico , Infarto del Miocardio/complicaciones , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Rizoma/química , Taquicardia Ventricular/etiología , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/patología , Fibrilación Ventricular/etiología , Fibrilación Ventricular/metabolismo , Fibrilación Ventricular/patología , Complejos Prematuros Ventriculares/etiología , Complejos Prematuros Ventriculares/metabolismo , Complejos Prematuros Ventriculares/patologíaRESUMEN
Recently, sodium ion batteries (SIBs) have been given intense attention because they are the most promising alternative to lithium ion batteries for application in renewable power stations and smart grid, owing to their low cost, their abundant natural resources, and the similar chemistry of sodium and lithium. Elemental phosphorus (P) is the most promising anode materials for SIBs with the highest theoretical capacity of 2596 mA h g(-1), but the commercially available red phosphorus cannot react with Na reversibly. Here, we report that simply hand-grinding commercial microsized red phosphorus and carbon nanotubes (CNTs) can deliver a reversible capacity of 1675 mA h g(-1) for sodium ion batteries (SIBs), with capacity retention of 76.6% over 10 cycles. Our results suggest that the simply mixed commercial red phosphorus and CNTs would be a promising anode candidate for SIBs with a high capacity and low cost.
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Nanocompuestos/química , Nanotubos de Carbono/química , Fósforo/química , Suministros de Energía Eléctrica , Electrodos , Iones/química , Litio/química , Sodio/químicaRESUMEN
Background: The Scn3b gene encodes for Navß3, a pivotal regulatory subunit of the fast sodium channel in cardiomyocytes. However, its mutation status in the Chinese population suffering from Brugada Syndrome (BrS) has not been characterized, and the contributory pathophysiological mechanisms to disease pathology remain undefined. Methods and Results: A Scn3b (c.260C>T, p.P87l) mutation was identified in a patient with BrS of Chinese descent. Functional analyses demonstrated that sodium channel activation for the wild type, mutant samples, and co-expression of both commenced at -55â mv and peaked at -25â mv. The mutant group exhibited a notable reduction, approximately 60%, in peak sodium channel activation current (INa) at -25â mv. The parameters for half-maximal activation voltages (V1/2) and slope factors (k) showed no significant differences when comparing wild type, mutant, and combined expression groups (P = 0.98 and P = 0.65, respectively). Additionally, no significant disparities were evident in terms of the steady-state sodium channel inactivation parameters V1/2 and k (with P-values of 0.85 and 0.25, respectively), nor were there significant differences in the activation time constant τ (P = 0.59) and late sodium current density (P = 0.23) across the wild-type, mutant, and co-expressed groups. Confocal imaging and Western blot analysis demonstrated decreased plasma membrane localization of SCN3B and SCN5A in the P87l group. Computational simulations of cardiac action potentials suggested that SCN3B P87l can alter the morphology of the action potentials within the endocardium and epicardium while reducing the peak of depolarization. Conclusions: The pathogenic impact of the Scn3b P87l mutation predominantly originates from a reduction in peak INa activation current coupled with decreased cell surface expression of Nav1.5 and Navß3. These alterations may influence cardiac action potential configurations and contribute to the risk of ventricular arrhythmias in individuals with BrS.
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INTRODUCTION: According to the American Heart Association guideline for coronary artery bypass grafting (CABG), female patients undergoing on-pump CABG (ONCAB) are at higher risk of short-term adverse outcomes than male patients. However, whether off-pump CABG (OPCAB) can improve the short-term outcome of female patients compared to ONCAB remains unclear. METHODS: We conducted a meta-analysis to study the effect of the female sex on short-term outcomes of OPCAB vs. ONCAB. A total of 31,115 patients were enrolled in 12 studies, including 20,245 females who underwent ONCAB and 10,910 females who underwent OPCAB. RESULTS: The in-hospital mortality in female patients who underwent OPCAB was significantly lower than in those in the ONCAB group with (2.7% vs. 3.4%; odds ratio [OR] 0.76; 95% confidence interval [CI] 0.65-0.89) and without (OR 0.68; 95% CI 0.52-0.89) adjustment for cardiovascular risk factor. The incidence of postoperative stroke in female patients who underwent OPCAB was lower than in those in the ONCAB group (1.2% vs. 2.1%; OR 0.59; 95% CI 0.48-0.73) before cardiovascular risk factor adjustment but was not significant (OR 0.87; 95% CI 0,66-1.16) after adjustment. There was no significant difference in the incidence of postoperative myocardial infarction between women who underwent OPCAB and those in the ONCAB group (1.3% vs. 2.3%; OR 0.88; 95% CI 0.54-1.43). CONCLUSION: In contrast to the American Heart Association CABG guideline, female patients who had OPCAB don't have unfavorable outcomes compared with the ONCAB group.
Asunto(s)
Puente de Arteria Coronaria Off-Pump , Infarto del Miocardio , Humanos , Masculino , Femenino , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria Off-Pump/efectos adversos , Infarto del Miocardio/complicaciones , Complicaciones Posoperatorias/etiología , Mortalidad Hospitalaria , Resultado del TratamientoRESUMEN
This study investigated the effects of yellow mealworm meal (YM) replacing soybean meal (SBM) at different proportions (0%, 15%, 30% and 45%, referred as YM0, YM15, YM30 and YM45, respectively) on the flesh quality of Nile tilapia. A total of 360 fish (70.0 ± 0.12 g) were randomly divided into 4 groups (3 tanks per group). Fish were fed the experimental diet twice daily for 10 wk. The results showed that muscle protein content significantly decreased in YM30 and YM45, while the lipid content significantly decreased in YM45 (P < 0.05). The essential amino acids and flavor amino acids of the muscle were not affected by the YM substitution, while saturated fatty acid content decreased in YM30 and YM45 compared with YM0 (P < 0.05). Fillets in YM45 had higher hardness, gumminess, and a higher proportion of thin myofibers (≤100 µm, P < 0.05) than those in other groups. Further analysis revealed that apoptosis and atrophy related genes were up-regulated, while the muscle antioxidant capacity decreased significantly in YM45 (P < 0.05), which may be related to the high acid value in YM45 diet. Our findings indicated that YM could replace up to 30% SBM without substantially altering the flesh quality. When the replacement ratio increased to 45%, the flesh quality would change. Special attention should be paid to avoid feed rancidity which may affect the flesh quality of fish.