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Stroke is the second leading cause of death worldwide and a leading cause of disability. The innate immune response occurs immediately after cerebral ischemia, resulting in adaptive immunity. More and more experimental evidence has proved that the immune response caused by cerebral ischemia plays an important role in early brain injury and later the recovery of brain injury. Innate immune cells and adaptive cells promote the occurrence of cerebral ischemic injury but also protect brain cells. A large number of studies have shown that cytokines and immune-related substances also have dual functions of promoting injury, reducing injury, or promoting injury recovery in the later stage of cerebral ischemia. They can be an important target for treating cerebral ischemic recovery. Therefore, this study discussed the immune cells, cytokines, and immune-related substances with dual roles in cerebral ischemia and summarized the therapeutic targets of cerebral ischemia. To explore more effective methods to treat cerebral ischemia, promote the recovery of brain function, and improve the prognosis of patients.
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Lesões Encefálicas , Isquemia Encefálica , Citocinas , Humanos , Isquemia Encefálica/imunologia , Isquemia Encefálica/terapia , Animais , Citocinas/metabolismo , Lesões Encefálicas/imunologia , Lesões Encefálicas/terapia , Imunidade Inata , Imunidade AdaptativaRESUMO
Field-effect transistors (FETs) based on semiconductor nanowires (NWs) have been extensively investigated and used for constructing novel nanoelectronic and optoelectronic devices in the past two decades. High electric field transport characteristics in FETs are of significance in both physics and applications. However, some specific physics phenomena at high electric field, such as drift velocity saturation, have rarely been reported in semiconductor NW FETs. In this work, the high electric field transport characteristics in FETs based on CdSe NWs were investigated. In the output characteristic curves, the current saturation phenomenon at high electric field caused by drift velocity saturation was observed. Typical values of saturation drift velocity and low electric field mobility in CdSe NW FETs were obtained. The low electric field mobility is in the range of 265.2 to 388.0 cm2 V-1 s-1. The saturation drift velocity is in the range of 5.1 × 105 to 7.0 × 105 cm s-1 and decreases monotonically with the increase of charge density, indicating that the electron-phonon scattering mechanism dominates at high electric field. Saturation drift velocity is an important figure-of-merit which characterizes the high electric field transport performance in FETs. As far as we know, this is the first experimental report on saturation drift velocity in CdSe NW FETs, which may provide valuable guidance for the design of nanoelectronic and optoelectronic devices based on CdSe NWs in the future.
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Differential evolution of apoptosis, programmed necrosis, and autophagy, parthanatos is a form of cell death mediated by poly(ADP-ribose) polymerase 1 (PARP1), which is caused by DNA damage. PARP1 hyper-activation stimulates apoptosis-inducing factor (AIF) nucleus translocation, and accelerates nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP) depletion, leading to DNA fragmentation. The mechanisms of parthanatos mainly include DNA damage, PARP1 hyper-activation, PAR accumulation, NAD+ and ATP depletion, and AIF nucleus translocation. Now, it is reported that parthanatos widely exists in different diseases (tumors, retinal diseases, neurological diseases, diabetes, renal diseases, cardiovascular diseases, ischemia-reperfusion injury...). Excessive or defective parthanatos contributes to pathological cell damage; therefore, parthanatos is critical in the therapy and prevention of many diseases. In this work, the hallmarks and molecular mechanisms of parthanatos and its related disorders are summarized. The questions raised by the recent findings are also presented. Further understanding of parthanatos will provide a new treatment option for associated conditions.
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Parthanatos , Trifosfato de Adenosina , Fator de Indução de Apoptose/genética , Fator de Indução de Apoptose/metabolismo , Morte Celular/fisiologia , NAD/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismoRESUMO
Water contamination by mercury ions (Hg2+) causes irreversible and serious effect on the ambient environment, ecological systems, and human health, necessitating further improvement of Hg2+ monitoring at low concentrations. Here, we proposed a novel surface plasmon resonance (SPR) sensor for Hg2+ detection with desirable advantages of high sensitivity, simple operation, label-free, and low cost, in which the chitosan/poly (vinyl alcohol)/SnO2 composite film was modified on sensing surface as the active layer for sensitivity enhancement. Benefiting from the relatively high refractive index of SnO2 nanoparticles, the evanescent field generated at the metal-solution interface can be significantly enhanced, which results in a 5 times improvement of sensitivity. Through appropriate optimization in the aspects of componential constitutions, the sensor exhibits excellent sensitivity of 25.713 nm/µg/L and ultra-low calculated detection limit of 6.61 ng/L(32.95 pM). Such detection limit is strikingly lower than the limitation (10 nM) in drinking water set by the US Environmental Protection Agency. In addition, the as-prepared sensor presents relatively high selectivity for Hg2+, attributing to plenty of binding sites for specific adsorption produced by functionalized chitosan/poly (vinyl alcohol) composites, which have been furtherly verified by characterization of FTIR and XPS spectra. The proposed sensor also exhibits great repeatability and good time stability for 15 days. This work provides a promising strategy for developing high-performance SPR sensor for Hg2+ detection and a prospective application in environmental monitoring.
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In this paper, the optimization of the extraction/purification process of multiple components was performed by the entropy weight method (EWM) combined with Plackett-Burman design (PBD) and central composite design (CCD). We took the macroporous resin purification of Astragalus saponins as an example to discuss the practicability of this method. Firstly, the weight of each component was given by EWM and the sum of the product between the componential content and its weight was defined as the comprehensive score, which was taken as the evaluation index. Then, the single factor method was adopted for determining the value range of each factor. PBD was applied for screening the significant factors. Important variables were further optimized by CCD to determine the optimal process parameters. After the combination of EWM, PBD and CCD, the resulting optimal purification conditions were as follows: pH value of 6.0, the extraction solvent concentration of 0.15 g/mL, and the ethanol volume fraction of 75%. Under the optimal conditions, the practical comprehensive score of recoveries of saponins was close to the predicted value (n = 3). Therefore, the present study provided a convenient and efficient method for extraction and purification optimization technology of multiple components from natural products.
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Produtos Biológicos , Entropia , Flavonoides , Resinas VegetaisRESUMO
Photoelectrochemical (PEC) cells offer a promising approach for developing low-cost solar energy conversion systems. However, the lack of stable and cost-effective electrodes remains a bottleneck that hampers their practical applications. Here, we propose a kind of integrated all-in-one three-dimensional (3D) carbon nanowall (CNW) electrode without sensitized semiconductors for stable all-carbon PEC cells. The all-in-one CNW electrodes were fabricated by directly growing CNW on both sides of the SiO2/Si/SiO2 wafer employing the radio frequency plasmon enhanced chemical vapor deposition method. Benefitting from the interconnected 3D textured structure, the CNW can effectively absorb the incident light and provide a large electrochemical reaction interface at the CNW surface that promotes the separation of photogenerated charge carriers, which makes it a superior electrode material. Experimental results show that the all-in-one CNW electrodes possess excellent PEC performance with a photocurrent density of 830 µA cm-2. Moreover, the CNW electrodes exhibit excellent photoresponses over a wide waveband and superior stability with a maintained photocurrent response, even after 60 d, which outperforms the electrodes using the other two-dimensional layered materials or semiconductor sensitized electrodes. Such an all-in-one electrode with impressive photovoltaic properties provides a promising platform for PEC applications that is eco-friendly with high efficiency, excellent stability and low cost.
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An evaluation of the ultrasonic extraction process and the antioxidant activities of hydroxysafflor yellow A (HSYA) and anhydrosafflor yellow B (AHSYB) from safflower are presented herein. Using response surface methodology (RSM), based on a four-factor-three-level Box-Behnken design (BBD), the extraction parameters, namely, temperature, extraction time, solvent-to-material ratio, and extraction power, were optimized for maximizing the yields of HSYA and AHSYB. The maximum yield was obtained at a temperature of 66 °C with an extraction time of 36 min, solvent-to-material ratio of 16 mL/g, and the extraction power of 150 W, which was adjusted according to the actual conditions. The HSYA and AHSYB contents were determined using high performance liquid chromatography (HPLC). The yield and the comprehensive evaluation value of HSYA and AHSYB were calculated. The antioxidant activities of the extracts were determined using a ferric reducing antioxidant power (FRAP) kit and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. The results suggested that the safflower extracts possessed obvious ferric reducing and DPPH radical scavenging activities. The antioxidant activity increased with increasing concentration. The results suggested that optimizing the conditions of ultrasonic extraction using RSM can significantly increase the yields of HSYA and AHSYB from safflower. The safflower extracts showed better antioxidant activity. This study can encourage future research on cardiovascular and cerebrovascular diseases.
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Antioxidantes/isolamento & purificação , Carthamus tinctorius/química , Chalcona/análogos & derivados , Pigmentos Biológicos/isolamento & purificação , Quinonas/isolamento & purificação , Antioxidantes/química , Compostos de Bifenilo/química , Chalcona/química , Chalcona/isolamento & purificação , Fracionamento Químico , Cromatografia Líquida de Alta Pressão , Sequestradores de Radicais Livres/química , Fenóis/química , Picratos/química , Pigmentos Biológicos/química , Extratos Vegetais/química , Quinonas/química , UltrassomRESUMO
A combinational approach of back propagation neural network (BPNN) and genetic algorithm (GA) was proposed in the present study to optimize the extraction technology of tetramethylpyrazine (TMP) in Ligusticum wallichii Franchat. Based on the single factor test, the orthogonal experiment design method of four factors and three levels was adopted, and the concentration of TMP was measured by high performance liquid chromatography (HPLC). Subsequently, BPNN model was trained for a predictive computational model of the performance indices via experimental data, and GA was exploited to find the optimization con ditions for extraction technology of TMP. Meanwhile, both the model and algorithm were implemented in R language. Ethanol concentration of 80%, extraction time of 1.5h, extraction temperature of 55â and liquid-solid ratio of 8:1 were derived as optimal conditions with a maximum content of TMP of 2.04 mg/g, which was confirmed with the relative error 2.63% through the validation of the experiments. This mathematical model could be used to analyze and predict the extraction technology of TMP in Ligusticum wallichii Franchat and provide a new reference for screening optimization of Chinese medicine effective parts and components.
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Algoritmos , Medicamentos de Ervas Chinesas/química , Ligusticum/química , Redes Neurais de Computação , Pirazinas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Modelos TeóricosRESUMO
Schottky junctions based on one-dimensional semiconductor nanomaterials, such as nanowires (NWs) and nanobelts (NBs), have been widely used in building high-performance nano-electric and nano-optoelectric devices during the past 15 years. Meanwhile, with considerable development in diverse application fields, more and more interests are turning to the investigation of the fundamental physics inside the junctions. The inhomogeneity of the interface between semiconductor NWs/NBs and metal electrodes has significant influence on the electrical transport mechanism of Schottky junctions. However, few researchers are involved in such studies and the physical mechanism here is far from fully understood. In this work, we fabricated Schottky junctions based on single CdSe NWs, in which Au was used as a Schottky contact with CdSe NW. The temperature dependence of the electrical transport characteristics of typical CdSe NW/Au Schottky junctions were characterized. The ideality factor was found to decrease and the zero-bias Schottky barrier height (SBH) increased monotonously as the temperature was increased from 140 to 320 K, and this relationship was ascribed to SBH inhomogeneity. The electrical transport mechanism was analyzed quantitatively with a spatial potential fluctuation model, in which SBHs obey the Gaussian distribution. The standard deviation of the SBH distribution was determined to be as high as 13.54% and 13.94% of the zero-bias mean SBH in the temperature ranges 140-200 K and 200-320 K, respectively. Our work revealed the barrier inhomogeneity at CdSe NW/Au interfaces and its influence on the electrical transport mechanism of NW-based Schottky junctions.
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BACKGROUND: Protocatechuic aldehyde (PAL) and hydroxysafflor yellow A (HSYA) are 2 effective ingredients of Danhong Injection, which is extensively used for the clinical treatment of cardio-cerebrovascular diseases. This study aims to investigate the pharmacokinetic differences between single and combined medication of PAL and HSYA and analyze the interaction of the above effective components in hyperlipidemia rats. METHODS: Thirty male SD rats were randomly divided into the control group (n = 6) and the model group (n = 24). The hyperlipidemia model was established by feeding with superfatted forage. The successful model rats were then randomly divided into the PAL group (16 mg/kg), the HSYA group (10 mg/kg), and the combination group (16 mg/kg + 10 mg/kg). Administration through tail-vein, and orbital blood was sampled at different time points. The mass concentration of PAL and HSYA was determined by high performance liquid chromatography (HPLC-DAD). Analysis of pharmacokinetic parameters was conducted by using DAS 3.2.6 software and SPSS 19.0 statistical analysis software. RESULTS: According to the parameters of statistical moment of non-compartmental model, there was a significant difference in plasma clearance (CL) between the PAL group and the drug combination group (p < 0.01), as well as in the area under the first moment of the plasma concentration-time curve and the elimination half-life (t1/2) between the HSYA group and the drug combination group (p < 0.01) but no obvious differences about the blood concentration time curve area, the average dwell time (MRT), and the peak concentration (Cmax; p > 0.05). CONCLUSION: The combined medication of PAL and HSYA could increase the plasma CL significantly and have a great influence on the absorption of HSYA in rats with hyperlipidemia.
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Benzaldeídos/farmacocinética , Catecóis/farmacocinética , Chalcona/análogos & derivados , Hiperlipidemias/metabolismo , Quinonas/farmacocinética , Animais , Anticoagulantes/sangue , Anticoagulantes/farmacocinética , Benzaldeídos/sangue , Cardiotônicos/farmacocinética , Catecóis/sangue , Chalcona/sangue , Chalcona/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Hiperlipidemias/sangue , Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , Masculino , Quinonas/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
The ultrasonic-assisted extraction process and antioxidant activity of flavonoids from Sophora flavescens were investigated in this study. In order to optimize the extraction of flavonoids from Sophora flavescens, the influence of extraction time, methanol concentration, ultrasonic temperature, and solvent-to-material ratio was analyzed. Results showed that the extraction yields reached a maximum with the extraction time of 30 min, methanol concentration of 80%, temperature of 80 °C, and solvent-to-material ratio of 26 mL/g. The flavonoids were determined by HPLC, and the mean yields of trifolirhizin, formononetin, isoxanthohumol, maackiain, and kurarinone under the optimal conditions were 2.570, 0.213, 0.534, 0.797, and 3.091 mg/g, respectively. The evaluation of vitro antioxidant activity exhibited Sophora flavescens flavonoids had a strong 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging ability with IC50 of 0.984 and 1.084 mg/g, respectively. These results indicate that ultrasonic-assisted extraction is an efficient approach for the selective extraction of flavonoids, and response surface methodology further optimized the extraction.
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Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Sophora/química , Análise de Variância , Antioxidantes/química , Fracionamento Químico/métodos , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Estrutura Molecular , Extratos Vegetais/química , Temperatura , Fatores de Tempo , Ondas UltrassônicasRESUMO
Graphene is a favorable candidate for electrodes of organic light emitting diodes (OLEDs). Graphene has quite a high work function of â¼4.5 eV, and has been extensively studied when used as anodes of OLEDs. In order to use graphene as a cathode, the electron injection barrier between the graphene cathode and the electron transport layer has to be low enough. Using 4,7-diphenyl-1,10-phenanthroline (Bphen):Cs2CO3 to n-dope graphene is a very good method, but the electron injection barrier between the n-doped graphene and Bphen:Cs2CO3 is still too high to be â¼1.0 eV. In this work, in order to further reduce the electron injection barrier, a novel method is suggested. On the graphene cathode, a Sm layer with a lot of nano-hollows, and subsequently a layer of Bphen:Cs2CO3, are deposited. The Bphen:Cs2CO3 can n-dope graphene in the nano-hollows, and the Fermi level of the graphene rises. The nano Sm layer is very easily oxidized. Oxygen adsorbed on the surface of graphene may react with Sm to form an O--Sm+ dipole layer. On the areas of the Sm oxide dipole layer without nano-hollows, the electron injection barrier can be further lowered by the dipole layer. Electrons tend to mainly inject through the lower electron barrier where the dipole layer exists. Based on this idea, an effective inverted small molecular OLED with the structure of graphene/1 nm Sm layer with a lot of nano-hollows/Bphen:Cs2CO3/Alq3:C545T/NPB/MoO3/Al is presented. The maximum current efficiency and maximum power efficiency of the OLED with a 1 nm Sm layer are about two and three times of those of the reference OLED without any Sm layer, respectively.
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To study the pharmacokinetics-pharmacodynamics correlation of protocatechuic aldehyde and hydroxysafflor yellow A alone or their combination use in rats with hyperlipidemia. In this study, the hyperlipidemia model was established by intravenous injection of protocatechuic aldehyde (20 mgâ¢kg⻹) and hydroxysafflor yellow A (12 mgâ¢kg⻹). The HPLC-DAD method was applied to determine the plasma concentration of protocatechuic aldehyde and hydroxysafflor yellow A at different time points and draw the drug effect-time curve. Meanwhile, the platelet activating factors (PAF) and plasma a granule membrane protein (GMP-140) contents were determined at different time points to draw the time-effect curve. Then DAS 3.2.6 software was used to process the data, analyze their correlation, and compare the difference of pharmacokinetics and pharmacodynamics of protocatechuic aldehyde and hydroxysafflor yellow A in hyperlipidemia rats after alone or their combined application, so as to evaluate the effect of protocatechuic aldehyde and hydroxysafflor yellow A on hyperlipidemia rats. According to the result, the pharmacokinetics and pharmacodynamics process of protocatechuic aldehyde and hydroxysafflor yellow A in hyperlipidemia rats after alone or their combination were consistent to the three-compartment model. In model group, the plasma PAF and GMP-140 were significantly increased, and the PAF and GMP-140 in vivo contents were decreased in a certain time after treatment. The effects of protocatechuic aldehyde and hydroxysafflor yellow A against the pharmacodynamic action may be related with their level in vivo, and their plasma concentration was positively related to the PAF and GMP-140 contents. The pharmacodynamic indexes were better after the combined use of protocatechuic aldehyde and hydroxysafflor yellow A, with certain influence on each other in hyperlipidemia rats; at the same time, it also reflected the rationality of protocatechuic aldehyde and hydroxysafflor yellow A combined application.
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Benzaldeídos/farmacocinética , Catecóis/farmacocinética , Chalcona/análogos & derivados , Hiperlipidemias/tratamento farmacológico , Quinonas/farmacocinética , Animais , Chalcona/farmacocinética , RatosRESUMO
To efficiently promote the phase retrieval in quantitative phase imaging, a new approach of quantitative phase extraction is proposed based on two intensities with dual wavelength after filtering the corresponding dc terms for each wavelength, in which a special phase shift is used. In this approach, only the combination of the phase-shifting technique and subtraction procedures is needed, and no additional algorithms are required. The thickness of the phase object can be achieved from the phase image, which is related to the synthetic beat wavelength. The feasibility of this method is verified by the simulated experiments of the optically transparent objects.
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The spatial version of evolutionary prisoner's dilemma on infinitely large regular lattice with purely deterministic strategies and no memories among players is investigated in this paper. Based on the statistical inferences, it is pertinent to confirm that the frequency of cooperation for characterizing its macroscopic behaviors is very sensitive to the initial conditions, which is the most practically significant property of chaos. Its intrinsic complexity is then justified on firm ground from the theory of symbolic dynamics; that is, this game is topologically mixing and possesses positive topological entropy on its subsystems. It is demonstrated therefore that its frequency of cooperation could not be adopted by simply averaging over several steps after the game reaches the equilibrium state. Furthermore, the chaotically changing spatial patterns via empirical observations can be defined and justified in view of symbolic dynamics. It is worth mentioning that the procedure proposed in this work is also applicable to other deterministic spatial evolutionary games therein.
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Modelos Teóricos , Dilema do PrisioneiroRESUMO
Spintronic devices rely on the spin degree of freedom (DOF), and spin orbit coupling (SOC) is the key to manipulate spin DOF. Quasi-one-dimensional structures, possessing marked anisotropy gives more choice for the manipulation of the spin DOF since the concrete SOC form varies along with crystallographic directions. The anisotropy of the Dresselhaus SOC in cadmium selenide (CdSe) nanobelt and nanowire was studied by circular photogalvanic effect. It was demonstrated that the Dresselhaus SOC parameter is zero along the [0001] crystallographic direction, which suppresses the spin relaxation and increases the spin diffusion length, and thus is beneficial to the spin manipulation. To achieve a device structure with Rashba SOC presence and Dresselhaus SOC absence for manipulating the spin DOF, an ionic liquid gate was produced on a nanowire grown along the [0001] crystallographic direction, and the Rashba SOC was induced by gating, as expected.
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Compostos de Cádmio/química , Líquidos Iônicos/química , Nanofios , Compostos de Selênio/química , Cristalografia , Microscopia Eletrônica de TransmissãoRESUMO
OBJECTIVE: To optimize the prescription dose of Mahuang decoction in a multi-target manner, in order to provide reference for the quantitative optimization of the prescription dose of the traditional Chinese medicine compound. METHOD: The number of diaphoretic spots in rats, the tracheal antispasmodic rate in guinea pigs and the writhing times by acetic acid in mice were taken as the indexes for evaluating the diaphoretic, antispasmodic and analgesic effects. According to the experimental results of the 16 orthogonal combination prescriptions, a mathematical dose-effect model was built by support vector regression (SVR) and quadratic response surface regression (RSR) respectively. The multi-target optimization was achieved by elitist non-dominated sorting genetic algorithm (NSGA-II) and entropy weight TOPSIS method. RESULT: The optimal dose of Mahuang decoction after being optimized by SVR modeling contained 17.71 g of Ephedrae Herba, 9.57 g of Cinnamomi Ramulus, 11.75 g of Armeniacae Semen Amarum and 4.39 g of Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle. The optimized result by RSR modeling contained 13.37 g of Ephedrae Herba, 11.61 g of Cinnamomi Ramulus, 11.98 g of Armeniacae Semen Amarum and 5.67 g of Glycyrrhizae Radix et Rhizoma Praeparate Cum Melle. SVR was superior to RSR in both of the forecast capacity and optimization results. CONCLUSION: SVR-NSGA-II-TOPSIS method could be adopted for the multi-target optimization for the dose of Mahuang decoction and other traditional Chinese medicine compounds. It is proved to be the optimal prescription with the best efficacy, and could provide scientific quantitative basis for determining the dose of traditional Chinese medicine compound prescriptions and developing new traditional Chinese medicines.
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Cinnamomum/química , Composição de Medicamentos/métodos , Ephedra sinica/química , Ephedra/química , Glycyrrhiza/química , Animais , Cálculos da Dosagem de Medicamento , Prescrições de Medicamentos , Cobaias , Camundongos , RatosRESUMO
In China, with the "Double Carbon" goal within reach, Micro, Small and Medium-sized Enterprises (MSMEs) emerge as pivotal contributors to economic advancement. However, they are now confronted with the imperative of transitioning towards green and low-carbon practices. To facilitate the attainment of peak carbon dioxide emissions and carbon neutrality, a refined approach is imperative. This entails precise capital allocation, enhanced financial services, streamlined management, and robust risk mitigation strategies. Consequently, conducting thorough credit risk assessments for MSMEs becomes a crucial endeavor. However, obtaining substantial loans for them proves challenging due to their elusive credit ratings and potential defaults. To address this issue, this study leverages machine learning and intelligent optimization algorithms to construct a classification model for default and credit ratings of MSMEs, utilizing their daily invoice data. Specifically, twelve indicators pertaining to default and credit ratings are extracted. Subsequently, Principal Component Analysis is employed to reduce dimensionality and synthesize all pertinent information. Following this, the Genetic Algorithm-based Back Propagation Neural Network (GA-BPNN) is utilized to delineate the relationship between indicators and default, as well as credit rating, respectively. The results indicate a prediction accuracy of 0.92 for default risk and 0.86 for credit rating. This underscores the efficacy of GA-BPNN in effectively classifying the underlying default risk and credit ratings of MSMEs, offering a promising approach for decision-making.
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Cerebral ischemia (CI) is the main cause of stroke morbidity and disability. This study aims to identify the early molecular regulation responsible for the therapeutic effectiveness of the Herb pair Danshen-Honghua (DH) for CI. The major targets of DH were identified by searching the public database of traditional Chinese medicine (TCM). In addition, GeneCards, Disgenet, and GeneMap databases in OMIM were used to determine the disease targets of CI. A total of 88 common targets of DH and CI were selected, a protein-protein interaction (PPI) network was established by Cytoscape, and 19 core targets were screened. These genes were primarily enriched in biological processes including wound healing, reaction to oxidative stress, and response to peptides, lipid and atherosclerosis, Age-rage signaling pathway, and TNF signaling pathway by KEGG and GO enrichments. The effective components of DH had stable binding to these key targets by molecular docking. Finally, it was verified that the mechanism of DH on CI treatment may be related to the activation of the TNF-α/JNK signaling pathway by establishing the middle cerebral artery occlusion (MCAO) rat model.
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Carthamus tinctorius , Medicamentos de Ervas Chinesas , Traumatismo por Reperfusão , Salvia miltiorrhiza , Animais , Ratos , Simulação de Acoplamento Molecular , Infarto Cerebral , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológicoRESUMO
BACKGROUND: The combination of Astragalus membranaceus and Carthamus tinctorius (AC) exhibits significant therapeutic effects in cerebral ischemia/reperfusion injury (CIRI). Understanding the metabolic characteristics of brain microregions and disturbances in tissues and systemic circulation is crucial for elucidating the mechanisms of CIRI and the therapeutic benefits of AC. However, in situ metabolic regulation of the complex brain structure has not been adequately studied, and the therapeutic mechanism of AC requires immediate clarification. PURPOSE: The present study aimed to unveil the specific metabolic reprogramming of CIRI at systemic and microregional levels, identify key metabolic pathways and metabolites, and elucidate the therapeutic mechanisms of AC. METHODS: Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), a newly developed technique, was used to investigate metabolites in brain microregions. Hematoxylin-eosin, Nissl, and immunofluorescence staining were performed to visualize the microscopic changes associated with spatial metabolism. A comprehensive metabolomics study was conducted on serum, brain tissue, and microregions, along with neurological assessments, cerebral infarction measurements, and Evans blue experiments, to assess the systemic and local metabolic effects of AC treatment for CIRI. RESULTS: AC significantly reduced neurological damage, minimized infarct size, and repaired blood-brain barrier damage in CIRI rats. AFADESI-MSI demonstrated that the metabolic imbalance caused by CIRI primarily occurs in the cerebral cortex, hippocampus, caudate putamen, thalamus, cerebellar cortex, and fiber tract regions. Significant changes in 16 metabolites were observed in these regions, corresponding to neuron damage, glial cell activation, and neural repair. 20 metabolites from serum and 4 from brain tissue varied significantly with the sham group. Comprehensive metabolomics analysis indicated a close relationship among serum, tissue, and microregional metabolism. CIRI-induced systemic and localized metabolic disorders involve 14 metabolic pathways. AC conferred therapeutic benefits in CIRI by reversing various metabolic imbalances. CONCLUSION: AFADESI-MSI efficiently visualized brain microregion metabolism. Comprehensive metabolomics analysis revealed detailed insights into the specific metabolic reprogramming in CIRI and the therapeutic impacts of AC. AC demonstrated significant clinical potential as an adjunct therapy to existing CIRI treatments.