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Spatiotemporal optical vortex (STOV) pulses, possessing inherent transverse orbital angular momentum (OAM) and exhibiting phase singularity and intensity null in the spatiotemporal (ST) domain, have received increasing attention in recent years. Here, we investigate theoretically the third harmonic generation and evolution properties of STOV pulses via the interaction of 800-nm-STOV pulses with air-plasma filaments. We show that beautiful third harmonic STOV pulses are generated at a propagation distance of several millimeters. During further propagation, the ST intensity profiles of the third harmonics undergo variations in a periodic way, leading to the distortion and subsequent restoration to the initial ring pattern. The periodic evolution is a result of the interference effects between the third harmonics generated with different phases. Consequently, the evolution period is roughly twice the dephasing length of the third harmonics. Meanwhile, additional singularities emerge in the intensity patterns due to destructive interference occurring at specific dephasing lengths for the specific frequency components. The high-frequency components experience destructive interference earlier than the low-frequency components during each evolution period because the dephasing length decreases with frequency. This results in the sequentially appearance of the additional singularities from top to bottom in the ST intensity patterns. The proposed scheme demonstrates a way for higher-order STOV generation and manipulation in air-plasma filaments, which can be of interest for experiments related to vortex light science.
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We propose a scheme to manipulate the local orbital angular momentum (OAM) of the ultra-broadband (0.1-30 THz) terahertz (THz) waves from the laser-induced short air filament via chirping the few-cycle vortex laser pump. The simulation results show that either the THz vortex pulses with linear azimuth-dependent phases or the THz angular accelerating vortex beams (AAVBs) with nonlinear azimuth-dependent phases can be produced by tuning the chirp parameter of the pump. Thus, the dominant physical mechanism for THz generation can be determined. The THz temporal and transverse spatial distributions can be also controlled by the chirp parameter. Furthermore, their local OAM density distributions present very complex structures because most of the modulated azimuthal intensity and the corresponding local angular helicity distributions are not able to cancel out completely. Via analyzing the simulated THz results at the different pump intensities, we classify the initial pump intensity into three cases. For the low intensity case, the Kerr effect comes into prominence, so the generated THz radiation shall be vortex pulses. While for the high intensity case, the leading plasma effect dominates. In contrast, when the pump intensity is at the medium level, the Kerr nonlinearity and the plasma effect may be comparable and competitive. Basically, THz AAVBs are generated for both high and medium intensity cases. Our study will provide the possibility for studying the optically induced rotation technology more intuitively from the perspective of angular momentum transfer.
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Electron beam longitudinal polarization during the interaction with counterpropagating circularly polarized ultraintense laser pulses is investigated, while accounting for the anomalous magnetic moment of the electron. Although it is known that the helicity transfer from the laser photons to the electron beam is suppressed in linear and nonlinear Compton scattering processes, we show that the helicity transfer nevertheless can happen via an intermediate step of the electron radiative transverse polarization, phase matched with the driving field, followed up by spin rotation into the longitudinal direction as induced by the anomalous magnetic moment of the electron. With spin-resolved QED Monte Carlo simulations, we demonstrate the consequent helicity transfer from laser photons to the electron beam with a degree up to 10%, along with an electron radial polarization up to 65% after multiple photon emissions in a femtosecond timescale. This effect is detectable with currently achievable laser facilities, evidencing the role of the leading QED vertex correction to the electron anomalous magnetic moment in the polarization dynamics in ultrastrong laser fields.
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OBJECTIVE: Previous clinical studies and meta-analyses have shown controversial results on the association between C3435T polymorphism of the ABCB1 gene and anti-epileptic drug (AED) resistance. Based on the fact that sample size and confounding factors could contribute to the inconsistency, we performed an updated meta-analysis by including the most recent studies, and subgroup analysis was conducted to evaluate the effect of confounding factors on the association. MATERIALS AND METHODS: We searched articles in 6 electronic databases including PubMed, Medline, Embase, Web of science, Cochrane Library, CNKI (China National Knowledge Infrastructure) for relevant articles up to June 2020. RESULTS: The current analysis showed that the C allele of C3435T variant was a risk factor for drug resistance in the overall populations (C allele vs. T allele, OR: 1.13; 95% CI: 1.02 - 1.25; p = 0.02) and in the Caucasians (C allele vs. T allele, OR: 1.09; 95% CI: 1.09 - 1.43; p = 0.002), while no association was observed in Asians and Indians. Particularly, our study reported for the first time that the 3435T allele was more common in epilepsy patients with drug resistance in the Tunisian population (C allele vs. T allele, OR: 0.31; 95% CI: 0.15 - 0.65; p = 0.002). In addition, our present analysis suggested an association between C3435T and AED resistance in cryptogenic, symptomatic, but not in idiopathic patients. Subgroup studies based on age and gender showed no association. CONCLUSION: AED resistance in Caucasian and Tunisian populations may benefit from ABCB1 C3435T genotyping. We recommend that more details, such as gender and etiology of epilepsy, should be taken into account to draw a reliable conclusion in future studies.
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Anticonvulsivantes , Epilepsia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Anticonvulsivantes/efeitos adversos , Povo Asiático/genética , Resistência a Medicamentos/genética , Epilepsia/tratamento farmacológico , Epilepsia/genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The production of a highly polarized positron beam via nonlinear Breit-Wheeler processes during the interaction of an ultraintense circularly polarized laser pulse with a longitudinally spin-polarized ultrarelativistic electron beam is investigated theoretically. A new Monte Carlo method employing fully spin-resolved quantum probabilities is developed under the local constant field approximation to include three-dimensional polarization effects in strong laser fields. The produced positrons are longitudinally polarized through polarization transferred from the polarized electrons by the medium of high-energy photons. The polarization transfer efficiency can approach 100% for the energetic positrons moving at smaller deflection angles. This method simplifies the postselection procedure to generate high-quality positron beams in further applications. In a feasible scenario, a highly polarized (40%-65%), intense (10^{5}-10^{6}/bunch), collimated (5-70 mrad) positron beam can be obtained in a femtosecond timescale. The longitudinally polarized positron sources are desirable for applications in high-energy physics and material science.
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Generation of circularly polarized (CP) and linearly polarized (LP) γ rays via the single-shot interaction of an ultraintense laser pulse with a spin-polarized counterpropagating ultrarelativistic electron beam has been investigated in nonlinear Compton scattering in the quantum radiation-dominated regime. For the process simulation, a Monte Carlo method is developed which employs the electron-spin-resolved probabilities for polarized photon emissions. We show efficient ways for the transfer of the electron polarization to the high-energy photon polarization. In particular, multi-GeV CP (LP) γ rays with polarization of up to about 95% can be generated by a longitudinally (transversely) spin-polarized electron beam, with a photon flux meeting the requirements of recent proposals for the vacuum birefringence measurement in ultrastrong laser fields. Such high-energy, high-brilliance, high-polarization γ rays are also beneficial for other applications in high-energy physics, and laboratory astrophysics.
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The generation of ultrarelativistic polarized positrons during the interaction of an ultrarelativistic electron beam with a counterpropagating two-color petawatt laser pulse is investigated theoretically. Our Monte Carlo simulation, based on a semiclassical model, incorporates photon emissions and pair productions, using spin-resolved quantum probabilities in the local constant field approximation, and describes the polarization of electrons and positrons for the pair production and photon emission processes, as well as the classical spin precession in between. The main reason for the polarization is shown to be the spin asymmetry of the pair production process in strong external fields, combined with the asymmetry of the two-color laser field. Employing a feasible scenario, we show that highly polarized positron beams, with a polarization degree of ζ≈60%, can be produced in a femtosecond timescale, with a small angular divergence, â¼74 mrad, and high density, â¼10^{14} cm^{-3}. The laser-driven polarized positron source raises hope for providing an alternative for high-energy physics studies.
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OBJECTIVE: To investigate the incidence of early postpartum urinary incontinence in parturients from Chengdu, and to find out the high-risk factors for reference for clinical diagnosis and treatment. METHODS: A total of 9 918 parturient women who gave delivery at the West China Second University Hospital of Sichuan University from January 2014 to January 2018 were enrolled and reviewed 6 weeks after delivery. The prevalence of urinary incontinence at 6 weeks postpartum was investigated by questionnaire. χ2 test and multivariate logistic regression analysis were used to analyze the risk factors affecting the prevalence. RESULTS: 9 550 parturient women were actually investigated. The prevalence of urinary incontinence was 15.53% (1 483/9 550) at 6 weeks postpartum in Chengdu, among which stress urinary incontinence was the most common (73.03%, 1 083/1 483). Univariate analysis showed that age, pelvic surgery history, prenatal body mass index (BMI), urinary incontinence during pregnancy, neonatal body mass, the number of parturition, delivery mode, lateral perineal incision, perineal laceration and prolonged second stage of labor were all correlated with the occurrence of urinary incontinence at 6 weeks postpartum (P < 0.05). Multivariate logistic regression analysis showed that cesarean section can reduce the risk of urinary incontinence compared with vaginal delivery ãodds ratio (OR)=0.373, P < 0.001ã. Age≥35 yr. (OR=1.803, P=0.001), pelvic surgery history (OR=1.260, P=0.003), BMI≥28 kg/m2 during pregnancy (OR=1.694, P=0.025), urinary incontinence during pregnancy (OR=2.605, P < 0.001), neonatal body mass ≥4 kg (OR=2.307, P=0.040), multipara (OR=1.284, P=0.023) and perineal laceration (OR=1.372, P=0.035) were independent risk factors for urinary incontinence at 6 weeks postpartum. CONCLUSIONS: Urinary incontinence at 6 weeks postpartum is not rare in Chengdu, and stress urinary incontinence is more frequent. Eutocia, elderly parturient, multipara, pelvic surgery history, prenatal obesity, urinary incontinence during pregnancy, large neonatal body mass and perineal laceration are the main risk factors for urinary incontinence at 6 weeks postpartum.
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Período Pós-Parto , Incontinência Urinária/diagnóstico , Cesárea , China/epidemiologia , Feminino , Humanos , Gravidez , Fatores de Risco , Incontinência Urinária/epidemiologiaRESUMO
Gamma-ray beams with a large angular momentum may affect astrophysical phenomena, which calls for appropriate earth-based experimental investigations. For this purpose, we investigate the generation of well-collimated γ-ray beams with a very large orbital angular momentum using nonlinear Compton scattering of a strong laser pulse of twisted photons at ultrarelativistic electrons. Angular momentum conservation among absorbed laser photons, quantum radiation, and electrons is numerically demonstrated in the quantum radiation-dominated regime. We point out that the angular momentum of the absorbed laser photons is not solely transferred to the emitted γ photons, but due to radiation reaction shared between the γ photons and interacting electrons. The efficiency of the angular momentum transfer is optimized with respect to the laser and electron beam parameters. The accompanying process of electron-positron pair production is furthermore shown to enhance the orbital angular momentum gained by the γ-ray beam.
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The impact of the carrier-envelope phase (CEP) of an intense multicycle laser pulse on the radiation of an electron beam during nonlinear Compton scattering is investigated. We have identified a CEP effect specific to the ultrarelativistic regime. When the electron beam counterpropagates with the laser pulse, pronounced high-energy x-ray double peaks emerge near the backward direction relative to the initial electron motion. This is achieved in the relativistic interaction domain, where both the electron energy is required to be lower than for the electron reflection condition at the laser peak and the stochasticity effects in the photon emission need to be weak. The asymmetry parameter of the double peaks in the angular radiation distribution is shown to serve as a sensitive measure for the CEP of up to 10-cycle long laser pulses and can be applied for the characterization of extremely strong laser pulses in present and near future laser facilities.
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Objective To evaluate the efficacy and safety of Liujin Runzao Concentrated Decoction (LRCD) for the treatment of primary Sjögren's syndrome (pSS). Methods Forty pSS patients with fluid depletion and distribution obstacles syndrome (FDDOS) were randomly assigned to the experimen- tal group and the control group according to 1:1 proportion. All patients received standard therapy: Radix Paeoniae alba total glycosides 600 mg, twice per day. Patients in the experimental group additionally took LRCD, 30 mL each time, twice per day. The therapeutic course for all was 4 weeks, and two courses for all. The improvement of dry mouth and dry eyes were comprehensively evaluated. Each outcome of composite index constitutions (integrals of dry eyes and dry mouth, salivary flow rate, Schirmer test) was respectively reported. Schirmer test and salivary flow rate were determined as well. Score of TCM syndrome, blood sedimentation,'immunoglobulin, and adverse drug reactions were observed. Results The effective rate of comprehensive effect for dry eyes and dry mouth improvement at the end of 8 weeks was 80% in the experimental group and 35% in the control group, with statistical difference (X² =8. 286, P <0. 05). As for the composition of comprehensive effect for dry eyes and dry mouth improvement: The score for dry eyes and dry mouth decreased in the two groups more after treatment than before treatment. The difference in pre-post treatment score for dry eyes and dry mouth at week 8 was higher in the experimental group than in the control group. The difference in pre-post treatment score at week 8 was 1. 71 (95% Cl: -0. 37 -3. 78) between the two groups (P <0. 05). The difference in pre-post treatment Schirmer test and salivary flow rate at week 8 was higher in the experimental group than in the control group, but with on statistical difference (P >0. 05). The difference in pre-post treatment Schirmer test and salivary flow rate at week 8 was 2. 74 mL/15 min (95% Cl: 0. 49 -4.98) and 0. 13 mm/5 min (95% Cl: 0. 92 -1. 23) between the two groups (P <0. 05). The score of TCM syndrome decreased more in the two groups, as compared with before treatment. The difference in pre-post treatment score of TCM syn- drome at week 8 was 1. 71 (95% CI: -1. 40 -4. 81) between the two groups (P >0. 05). One case of uri- nary tract infections occurred in the control group, while no obvious adverse event occurred in the exper- imental group. Conclusion Standard treatment combined LRCD showed better comprehensive effect for dry eyes and dry mouth in pSS patients with FDDOS, and was more safe.
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Medicamentos de Ervas Chinesas , Síndrome de Sjogren , Sedimentação Sanguínea , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Síndrome de Sjogren/terapiaRESUMO
We numerically study the propagation of a few-cycle pulse carrying orbital angular momentum (OAM) through a dense atomic system. Nonlinear precursors consisting of high-order vortex harmonics are generated in the transmitted field due to carrier effects associated with ultrafast Bloch oscillation. The nonlinear precursors survive to propagation effects and are well separated with the main pulse, which provides a straightforward way to measure precursors. By virtue of carrying high-order OAM, the obtained vortex precursors as information carriers have potential applications in optical information and communication fields where controllable loss, large information-carrying capacity, and high speed communication are required.
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This numerical study demonstrates that Doppler redshift exists in the reflected spectrum of a few-cycle pulse, propagating through a dense medium. It manifests itself in two different forms, a sharp low-frequency spike (LFS) located at the red edge of the reflected spectrum and a relatively broader redshift near the carrier frequency. With the variation of the laser and medium parameters, the dominant reflection mechanism changes between bulk generation of backwards propagation waves and nonlinear reflection near the front face. This leads to the manifestation of Doppler effect changing accordingly between the two different forms. This study unifies the physical mechanism behind the LFS and dynamic nonlinear optical skin effect, which enriches the theoretical explanation of the spectral redshift of few-cycle pulse propagation beyond the intrapulse four-wave mixing.
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The hippocampus is one of the most commonly studied brain regions in the context of depression. The volume of the hippocampus is significantly reduced in patients with depression, which severely disrupts hippocampal neuroplasticity. However, antidepressant therapies that target hippocampal neuroplasticity have not been identified as yet. Chinese medicine (CM) can slow the progression of depression, potentially by modulating hippocampal neuroplasticity. Xiaoyaosan (XYS) is a CM formula that has been clinically used for the treatment of depression. It is known to protect Gan (Liver) and Pi (Spleen) function, and may exert its antidepressant effects by regulating hippocampal neuroplasticity. In this review, we have summarized the association between depression and aberrant hippocampal neuroplasticity. Furthermore, we have discussed the researches published in the last 30 years on the effects of XYS on hippocampal neuroplasticity in order to elucidate the possible mechanisms underlying its therapeutic action against depression. The results of this review can aid future research on XYS for the treatment of depression.
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Antidepressivos , Medicamentos de Ervas Chinesas , Hipocampo , Plasticidade Neuronal , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Plasticidade Neuronal/efeitos dos fármacos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Animais , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Medicina Tradicional ChinesaRESUMO
PURPOSE: The role of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is not fully understood. METHODS: In this retrospective analysis, we included 316 HCC patients who underwent hepatectomy and preoperative CTC detection. We selected 41 pairs of matched HCC patients with and without PVTT using propensity score matching (PSM) analysis. We compared the preoperative CTC counts in patients from both the full cohort and the PSM model. We also analyzed their associations with disease-free survival (DFS) and overall survival (OS). RESULTS: Before and after PSM analysis, the preoperative CTC counts in the HCC with PVTT group were substantially higher than in the HCC without PVTT group. In both the full cohort of patients and the PSM model, patients with CTC ≥ 2 had significantly shorter OS and DFS than patients with CTC < 2. The outcomes of HCC patients with PVTT could be well differentiated by preoperative CTC levels. HCC patients with CTC ≥ 2 had noticeably shorter OS (9.9 months vs. 24.6 months, P = 0.0003) and DFS (6.0 months vs. 12.3 months, P = 0.0041) than those with CTC < 2. Moreover, preoperative CTC ≥ 2 remained an independent predictor in all groups' multivariate analysis. CONCLUSION: We discovered a link between preoperative CTC counts and the occurrence of PVTT and confirmed the prognostic significance of preoperative CTC in HCC patients with PVTT. These findings suggest that preoperative CTC counts have the potential to assist in identifying patients with HCC and PVTT who may benefit from surgery.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Células Neoplásicas Circulantes , Trombose Venosa , Humanos , Carcinoma Hepatocelular/patologia , Prognóstico , Neoplasias Hepáticas/patologia , Veia Porta/patologia , Estudos Retrospectivos , Pontuação de Propensão , Células Neoplásicas Circulantes/patologia , Trombose Venosa/patologia , Resultado do TratamentoRESUMO
OBJECTIVES: To explore the key genes involved in the occurrence and development of glioblastoma (GBM) by analyzing whole-transcriptome sequencing and biologic data from GBM and normal cerebral cortex tissues and to search for important noncoding RNA (ncRNA) molecular markers based on the competitive endogenous RNA (ceRNA) network. METHODS: Ten GBM and normal cerebral cortex tissues were collected for full transcriptome sequencing, screened for differentially expressed (DE) mRNAs, miRNAs, lncRNAs, and circRNAs, and subjected to bioinformatic analysis. We constructed a Protein-Protein Interaction (PPI) network and a circRNA/lncRNA-miRNA-mRNA regulatory network and identified them using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Finally, The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were used to validate and conduct a survival analysis of the target genes. RESULTS: A total of 5341 DEmRNAs, 259 DEmiRNAs, 3122 DElncRNAs, and 2135 DEcircRNAs were identified. Enrichment analysis showed that target genes regulated by DEmiRNA, DElncRNA, and DEcircRNA were closely related to chemical synaptic transmission and ion transmembrane transport. A PPI network analysis screened 10 hub genes that directly participate in tumor cell mitosis regulation. In addition, the ceRNA composite network showed that hsa-miR-296-5p and hsa-miR-874-5p were the central nodes of the network, and the reliability of relevant key molecules was successfully verified through RT-qPCR identification and the TCGA database. The CGGA database survival analysis produced 8 DEmRNAs closely related to GBM patient survival prognosis. CONCLUSIONS: This study revealed the important regulatory functions and molecular mechanisms of ncRNA molecules and identified hsa-miR-296-5p and hsa-miR-874-5p as key molecules in the ceRNA network. They may play an important role in GBM pathogenesis, treatment, and prognosis.
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AIMS: We aimed to evaluate the effect of periplocin on inhibiting hepatocellular carcinoma (HCC) and further determine its mechanisms. MAIN METHODS: Cytotoxic activity of periplocin against HCC cells was tested by CCK-8 and colony formation assays. The antitumor effects of periplocin were evaluated in human HCC SK-HEP-1 xenograft and murine HCC Hepa 1-6 allograft mouse models. Flow cytometry was used to measure cell cycle distribution, apopotosis, and the number of myeloid-derived suppressor cells (MDSCs). Hoechst 33258 dye was applied to observe the nuclear morphology. Network pharmacology was performed to predict possible signaling pathways. Drug affinity responsive target stability assay (DARTS) was used to evaluate AKT binding of periplocin. Western blotting, immunohistochemistry, and immunofluorescence were used to examine the protein expression levels. KEY FINDING: Periplocin inhibited cell viability with IC50 values from 50 nM to 300 nM in human HCC cells. Periplocin disrupted cell cycle distribution and promoted cell apoptosis. Moreover, AKT was predicted as the target of periplocin by network pharmacology, which was confirmed by that AKT/NF-κB signaling was inhibited in periplocin-treated HCC cells. Periplocin also inhibited the expression of CXCL1 and CXCL3, leading to decreased accumulation of MDSCs in HCC tumors. SIGNIFICANCE: These findings reveal the function of periplocin in inhibiting HCC progression by G2/M arrest, apoptosis and suppression of MDSCs accumulation through blockade of the AKT/NF-κB pathway. Our study further suggests that periplocin has the potential to be developed as an effective therapeutic agent for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Células Supressoras Mieloides , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/patologia , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Hepáticas/patologia , Células Supressoras Mieloides/metabolismo , Proliferação de Células , Apoptose , Linhagem Celular TumoralRESUMO
The activation of oxygen (O2) under room condition is important for the utilization of air to perform oxidation. Here, we report a porous carbon-encapsulated MnO (MnO@C) derived from Mn metal-organic framework (MOF)grown in-situ on a graphite felt (GF) support. The MnO@C exhibits superior catalytic activity in an electric field-assisted catalytic oxidation system for the degradation of organic pollutants under room condition. The catalytic oxidation reaction applies a surface reaction pathway in which the surface-bound chemisorbed oxygen species are electro-oxidized and then involved in the oxidation of co-adsorbed organic pollutants. The abundant oxygen vacancies and oxygenated functional groups in MnO@C provide active sites for the chemisorption of O2, and its conductive mesoporous structure allows facile electrons and mass transfer. As a result, the MnO@C/GF catalyst displays quite high turnover frequency (TOF) value as 0.038 mg-TOC mg-MnO-1 min-1, which is 6.66 times higher than that of the MnO/GF catalyst prepared by impregnation method as a comparison. With the aid of + 1.0 V of positive electric field, the catalytic oxidation system exhibits extensive effectiveness in mineralizing a variety of dyes, pharmaceuticals, personal care products, and phenolic compounds under room condition with significantly enhanced biodegradability.
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Poluentes Ambientais , Grafite , Estruturas Metalorgânicas , Poluentes Químicos da Água , Catálise , Grafite/química , Oxirredução , Oxigênio/químicaRESUMO
UGT1A1 is the main enzyme that catalyzes the metabolic elimination and detoxification of SN-38, the active form of the drug irinotecan. Milk thistle products have been used widely to protect the liver from injury associated with the use of chemotherapeutic agents. To evaluate whether SN-38 metabolism can be affected by milk thistle products, the inhibitory effects of silybins on UGT1A1*1 and UGT1A1*6 were evaluated in the present investigation. Both silybin A and silybin B potently inhibited SN-38 glucuronidation catalyzed by UGT1A1*1 or UGT1A1*6. It was noteworthy that silybin A and silybin B showed synergistic effect in UGT1A1*1 microsomes at concentration around IC50, while additive effect in UGT1A1*6. According to the predicted AUCi/AUC ratios (the ratio of the area under the plasma concentration-time curve of SN-38 in the presence and absence of silybins), the coadministration of irinotecan and several milk thistle products, including silybin-phosphatidylcholine complex, two Legalon capsules, four Silymarin tablets or four Liverman capsules, may lead to clinically significant herb-drug interactions (HDI) via UGT1A1 inhibition. Meanwhile, Rgut values were much higher than 11 in all the groups, indicating potential HDI due to intestinal UGT1A1 inhibition.
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Glucuronosiltransferase , Silybum marianum , Irinotecano/metabolismo , Silibina/metabolismo , Silibina/farmacologia , Glucuronosiltransferase/metabolismo , Microssomos Hepáticos/metabolismo , Catálise , CamptotecinaRESUMO
OBJECTIVE: Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear. METHODS: An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins. RESULTS: XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons. CONCLUSION: Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.