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Myocardial ischemia-reperfusion injury (MIRI) is an injury to cardiomyocytes due to restoration of blood flow after myocardial infarction (MI). It has recently gained much attention in clinical research with special emphasis on the roles of mitochondrial autophagy and inflammation. A mild inflammatory response promotes recovery of post-ischemic cardiomyocyte function and vascular regeneration, but a severe inflammatory response can cause irreversible and substantial cellular damage. Similarly, moderate mitochondrial autophagy can help inhibit excessive inflammation and protect cardiomyocytes. However, MIRI is aggravated when mitochondrial function is disrupted, such as inadequate clearance of damaged mitochondria or excessive activation of mitophagy. How to moderately control mitochondrial autophagy while promoting its balance with nucleotide-binding oligomerization structural domain receptor protein 3 (NLRP3) inflammasome activation is critical. In this paper, we reviewed the molecular mechanisms of mitochondrial autophagy and NLRP3 inflammasome, described the interaction between NLRP3 inflammasome and mitochondrial autophagy, and the effects of different signaling pathways and molecular proteins on MIRI, to provide a reference for future research.
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The environment surrounding proteins is tightly linked to its dynamics, which can significantly influence the conformation of proteins. This study focused on the effect of pH conditions on the ultrastructure of Immunoglobulin E (IgE) molecules. Herein, the morphology, height, and area of IgE molecules incubated at different pH were imaged by atomic force microscopy (AFM), and the law of IgE changes induced by pH value was explored. The experiment results indicated that the morphology, height and area of IgE molecules are pH dependent and highly sensitive. In particular, IgE molecules were more likely to present small-sized ellipsoids under acidic conditions, while IgE molecules tend to aggregate into large-sized flower-like structures under alkaline conditions. In addition, it was found that the height of IgE first decreased and then increased with the increase of pH, while the area of IgE increased with the increase of pH. This work provides valuable information for further study of IgE, and the methodological approach used in this study is expected to developed into AFM to investigate the changes of IgE molecules mediated by other physical and chemical factors. RESEARCH HIGHLIGHTS: The ultrastructure of IgE molecules is pH dependent and highly sensitive. IgE molecules were tend to present small-sized ellipsoids under acidic pH. Alkaline pH drives IgE self-assembly into flower-like aggregates.
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For chronic wounds, frequent replacement of bandages not only increases the likelihood of secondary damage and the risk of cross infection but also wastes medication. Therefore, in situ real-time monitoring of the concentrations of residual drugs in bandages is crucial. Here, we propose a novel strategy that combines a triboelectric nanogenerator (TENG) with medical bandages to develop a smart bandage based on zeolite imidazolate framework TENG. During the process of wound healing, the electrical output of TENG changes with the continuous release of drugs. Based on the correlation between the electrical signal of TENG and drug concentration, the concentration of residual drugs in the bandage can be monitored in real-time in situ, guiding medical staff to replace the bandage at the most appropriate time. The smart bandage based on TENG provides a new strategy for in situ real-time monitoring of drug concentration and also provides an ideal and feasible solution for the field of biomedical drug sensing.
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Bandagens , Zeolitas/química , Animais , Cicatrização/efeitos dos fármacos , Humanos , Nanotecnologia/instrumentação , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/métodos , Estruturas Metalorgânicas/químicaRESUMO
Aging causes degenerative changes in organs, leading to a decline in physical function. Over the past two decades, researchers have made significant progress in understanding the rejuvenating effects of young blood on aging organs, benefiting from heterochronic parabiosis models that connect the blood circulation of aged and young rodents. It has been discovered that young blood can partially rejuvenate organs in old animals by regulating important aging-related signaling pathways. Clinical trials have also shown the effectiveness of young blood in treating aging-related diseases. However, the limited availability of young blood poses a challenge to implementing anti-aging therapies on a large scale for older individuals. As a promising alternative, scientists have identified some specific anti-aging circulating factors in young blood that have been shown to promote organ regeneration, reduce inflammation, and alleviate fibrosis associated with aging in animal experiments. While previous reviews have focused primarily on the effects and mechanisms of circulating factors on aging, it is important to acknowledge that studying the rejuvenating effects and mechanisms of young blood has been a significant source of inspiration in this field, and it will continue to be in the future. In recent years, new findings have emerged, further expanding our knowledge in this area. This review aims to summarize the rejuvenating effects and mechanisms of young blood and circulating factors, discussing their similarities and connections, addressing discrepancies in previous studies, outlining future research directions, and highlighting the potential for clinical translation in anti-aging interventions.
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Atomic force microscope enables ultra-precision imaging of living cells. However, atomic force microscope imaging is a complex and time-consuming process. The obtained images of living cells usually have low resolution and are easily influenced by noise leading to unsatisfactory imaging quality, obstructing the research and analysis based on cell images. Herein, an adaptive attention image reconstruction network based on residual encoder-decoder was proposed, through the combination of deep learning technology and atomic force microscope imaging supporting high-quality cell image acquisition. Compared with other learning-based methods, the proposed network showed higher peak signal-to-noise ratio, higher structural similarity and better image reconstruction performances. In addition, the cell images reconstructed by each method were used for cell recognition, and the cell images reconstructed by the proposed network had the highest cell recognition rate. The proposed network has brought insights into the atomic force microscope-based imaging of living cells and cell image reconstruction, which is of great significance in biological and medical research.
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Intelligent technology can assist in the diagnosis and treatment of disease, which would pave the way towards precision medicine in the coming decade. As a key focus of medical research, the diagnosis and prognosis of cancer play an important role in the future survival of patients. In this work, a diagnostic method based on nano-resolution imaging was proposed to meet the demand for precise detection methods in medicine and scientific research. The cell images scanned by AFM were recognized by cell feature engineering and machine learning classifiers. A feature ranking method based on the importance of features to responses was used to screen features closely related to categorization and optimization of feature combinations, which helps to understand the feature differences between cell types at the micro level. The results showed that the Bayesian optimized back propagation neural network has accuracy rates of 90.37% and 92.68% on two cell datasets (HL-7702 & SMMC-7721 and GES-1 & SGC-7901), respectively. This provides an automatic analysis method for identifying cancer cells or abnormal cells, which can help to reduce the burden of medical or scientific research, decrease misjudgment and promote precise medical care for the whole society.
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Teorema de Bayes , Aprendizado de Máquina , Microscopia de Força Atômica , Redes Neurais de Computação , Humanos , Microscopia de Força Atômica/métodos , Linhagem Celular Tumoral , Algoritmos , Neoplasias/diagnóstico por imagemRESUMO
Enhancing immune response activation through the synergy of effective antigen delivery and immune enhancement using natural, biodegradable materials with immune-adjuvant capabilities is challenging. Here, we present NAPSL.p that can activate the Toll-like receptor 4 (TLR4) pathway, an amphiphilic exopolysaccharide, as a potential self-assembly adjuvant delivery platform. Its molecular structure and unique properties exhibited remarkable self-assembly, forming a homogeneous nanovaccine with ovalbumin (OVA) as the model antigen. When used as an adjuvant, NAPSL.p significantly increased OVA uptake by dendritic cells. In vivo imaging revealed prolonged pharmacokinetics of NAPSL. p-delivered OVA compared to OVA alone. Notably, NAPSL.p induced elevated levels of specific serum IgG and isotype titers, enhancing rejection of B16-OVA melanoma xenografts in vaccinated mice. Additionally, NAPSL.p formulation improved therapeutic effects, inhibiting tumor growth, and increasing animal survival rates. The nanovaccine elicited CD4+ and CD8+ T cell-based immune responses, demonstrating the potential for melanoma prevention. Furthermore, NAPSL.p-based vaccination showed stronger protective effects against influenza compared to Al (OH)3 adjuvant. Our findings suggest NAPSL.p as a promising, natural self-adjuvanting delivery platform to enhance vaccine design across applications.
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Adjuvantes Imunológicos , Melanoma Experimental , Camundongos Endogâmicos C57BL , Ovalbumina , Probióticos , Animais , Ovalbumina/imunologia , Ovalbumina/química , Camundongos , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Probióticos/farmacologia , Melanoma Experimental/imunologia , Feminino , Células Dendríticas/imunologia , Receptor 4 Toll-Like/metabolismo , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/química , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Humanos , Nanopartículas/química , Linfócitos T CD4-Positivos/imunologiaRESUMO
INTRODUCTION: Zhilong Huoxue Tongyu Capsule (ZL) is a Chinese medicine used for the treatment of cardio-cerebral diseases. However, the pharmacological mechanisms underlying its regulation of myocardial ischemia/reperfusion injury (MI/RI) remain unclear. PURPOSE: This study aims to investigate the effects and mechanisms of ZL on MI/RI in mice. MATERIALS AND METHODS: C57BL/6J mice were randomly assigned to four groups: Sham group, I/R group, ZL group, and ZLY group. The MI/RI mouse model was established by ligation of the left anterior descending coronary artery for 30 minutes, followed by reperfusion for 120 minutes to restore blood perfusion. Cardiac function was evaluated using cardiac ultrasound. Histopathological changes and myocardial infarction area were assessed using Hematoxylin and eosin (H&E) staining and triphenyltetrazolium chloride (TTC) staining. The changes in oxidative stress- and ferroptosis-related markers were detected. RT-qPCR, Western blot, and ELISA were conducted to further explore the mechanism of ZL in improving MI/RI. RESULTS: Our findings demonstrated that ZL exerted a protective effect against MI/RI by inhibiting ferroptosis, evidenced by the upregulation of antioxidant enzymes such as GSH and GPX4, coupled with the downregulation of ACSL4, a pro-ferroptosis factor. Furthermore, ZL positively impacted the PI3K/AKT/Nrf2 pathway by promoting ATPase activities and enhancing the relative protein expression of its components. Notably, the administration of a PI3K/AKT inhibitor reversed the antioxidant and anti-ferroptosis effects of ZL to some extent, suggesting a potential role for this pathway in mediating ZL's protective effects. CONCLUSIONS: ZL protects against MI/RI-induced ferroptosis by modulating the PI3K/AKT signaling pathway, leading to increased Nrf2 expression and activation of the HO-1/GPX4 pathway. These findings shed light on the potential therapeutic mechanisms of ZL in the context of cardiovascular diseases.
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Medicamentos de Ervas Chinesas , Ferroptose , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica , Fator 2 Relacionado a NF-E2 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Camundongos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Ferroptose/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Globally, alcohol-associated liver disease (ALD) has become an increased burden for society. Disulfirams, Benzodiazepines (BZDs), and corticosteroids are commonly used to treat ALD. However, the occurrence of side effects such as hepatotoxicity and dependence, impedes the achievement of desirable and optimal therapeutic efficacy. Therefore, there is an urgent need for more effective and safer treatments. Hovenia dulcis is an herbal medicine promoting alcohol removal clearance, lipid-lowering, anti-inflammatory, and hepatoprotective properties. Hovenia dulcis has a variety of chemical components such as dihydromyricetin, quercetin and beta-sitosterol, which can affect ALD through multiple pathways, including ethanol metabolism, immune response, hepatic fibrosis, oxidative stress, autophagy, lipid metabolism, and intestinal barrier, suggesting its promising role in the treatment of ALD. Thus, this work aims to comprehensively review the chemical composition of Hovenia dulcis and the molecular mechanisms involved in the process of ALD treatment.
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To address the issues of tractors using too much fuel and not being energy efficient, a predictive control strategy based on Pontryagin's minimum principle integrating working condition prediction is proposed for agricultural hybrid tractors. The Dongfanghong 1804 tractor is being used for research. Firstly, the main parameters of the hybrid drive system are determined and modeled. Secondly, based on the adaptive cubic exponential forecasting method, the working condition information for a period of time in the future is predicted through historical working condition information. Furthermore, combining the predicted working conditions information, the goal is to minimize the total energy consumption cost of the entire machine. Motor power and diesel engine power are control variables. The battery state of charge is a state variable. Subsequently, a predictive control strategy based on Pontryagin's minimum principle integrating working condition prediction is proposed. Finally, the simulation test is carried out based on the MATLAB simulation platform. Research indicates: under plowing conditions, compared with the power following control strategy, the proposed predictive control strategy can effectively manage the performance of the diesel engine and motor, ensuring they operate at their most efficient level. The total energy consumption costs of the power following control and predictive control strategies are 37.17 China Yuan (CNY) and 33.67 CNY, respectively. The cost of energy used is decreased by 9. 42%, which helps make tractor field plowing more efficient and economical.
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Agricultura , Motivação , Fenômenos Físicos , China , Simulação por ComputadorRESUMO
The rpl1001 gene encodes 60S ribosomal protein L10, which is involved in intracellular protein synthesis and cell growth. However, it is not yet known whether it is involved in the regulation of cell mitosis dynamics. This study focuses on the growth, spore production, cell morphology, the dynamics of microtubules, chromosomes, actin, myosin, and mitochondria of fission yeast (Schizosaccharomyces pombe) to investigate the impact of rpl1001 deletion on cell mitosis. RNA-Seq and bioinformatics analyses were also used to reveal key genes, such as hsp16, mfm1 and isp3, and proteasome pathways. The results showed that rpl1001 deletion resulted in slow cell growth, abnormal spore production, altered cell morphology, and abnormal microtubule number and length during interphase. The cell dynamics of the rpl1001Δ strain showed that the formation of a monopolar spindle leads to abnormal chromosome segregation with increased rate of spindle elongation in anaphase of mitosis, decreased total time of division, prolonged formation time of actin and myosin loops, and increased expression of mitochondrial proteins. Analysis of the RNA-Seq sequencing results showed that the proteasome pathway, up-regulation of isp3, and down-regulation of mfm1 and mfm2 in the rpl1001Δ strain were the main factors underpinning the increased number of spore production. Also, in the rpl1001Δ strain, down-regulation of dis1 caused the abnormal microtubule and chromosome dynamics, and down-regulation of hsp16 and pgk1 were the key genes affecting the delay of actin ring and myosin ring formation. This study reveals the effect and molecular mechanism of rpl1001 gene deletion on cell division, which provides the scientific basis for further clarifying the function of the Rpl1001 protein in cell division.
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Context: Cardiomyocyte hypertrophy due to hemodynamic overload eventually leads to heart failure. Hirudin has been widely used in the treatment of cardiovascular diseases and NLRP3 inflammasome was proven to induce cardiomyocyte pyroptosis. However, the mechanism by which it inhibits cardiomyocyte hypertrophy remains unclear. Objective: To explore the mechanism of hirudin inhibiting cardiomyocyte hypertrophy based on NLRP3 inflammasome activation and mitophagy. Materials & methods: 1 µM AngII was used for cardiac hypertrophy modeling in H9C2 cells, and cell viability was quantified by CCK-8 assay to screen the appropriate action concentrations of hirudin. After that, we cultured AngII induced-H9C2 cells for 24 h with 0, 0.3, 0.6, and 1.2 mM hirudin, respectively. Next, we marked H9C2 cells with phalloidine and observed them using fluorescence microscope. IL-1ß, IL-18, IL-6, TNF-α, ANP, BNP, ß-MHC, and mtDNA were analyzed by qRT-PCR; ROS were quantified by Flow cytometry; SOD, MDA, and GSH-Px were detected by ELISA; and proteins including NLRP3, ASC, caspase-1, pro-caspase-1, IL-1ß, IL-18, PINK-1, Parkin, beclin-1, LC3-â , LC3-â ¡, p62, were quantified by western blotting. Results: It was discovered that hirudin reduced the superficial area of AngII-induced H9C2 cells and inhibited the AngII-induced up-regulation of ANP, BNP, and ß-MHC. Besides, hirudin down-regulated the expressions of NLRP3 inflammasome-related cytokines, containing IL-1ß, IL-18, IL-6, TNF-α. It also down-regulated the expression of mtDNA and ROS, decreased the expression levels of NLRP3 inflammasome activation related proteins, including NLRP3, ASC, caspase-1, pro-caspase-1, IL-1ß, IL-18; and increased the expressions of PINK-1, Parkin, beclin-1, LC3-â ¡/LC3-â , p62 in AngII-induced H9C2 cells. Discussion: Hirudin promoted the process of mitophagy, inhibited the development of inflammation and oxidative stress, and inhibited the activation of the NLRP3 inflammasome and the PINK-1/Parkin pathway. Conclusion: Hirudin has the activity to suppress cardiac hypertrophy may benefit from the inhibition of NLRP3 inflammasome and activating of PINK-1/Parkin related-mitophagy.
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Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high-risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol-O-methyltransferase (COMT) genes, and paranoid and motor-impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor-impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor-impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high-risk psychotic symptoms in MAUD patients.
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Metanfetamina , Polimorfismo de Nucleotídeo Único , Humanos , Catecol O-Metiltransferase/genética , Dopamina , Metanfetamina/efeitos adversos , Genótipo , MetilaçãoRESUMO
BACKGROUND: Detecting and identifying of clots and fibrins in serum is an important process in the analysis stage before laboratory analysis. Currently, visual examination is commonly employed in clinical laboratories for this purpose. However, this method is not only time-consuming but also highly subjective and may result in misjudgments. METHOD: A serum image blood clot and fibrin segmentation method based on improved UNeXt was proposed. The improved UNeXt segmentation network was used to train the self-built serum dataset, and the trained model was used for blood clot and fibrin segmentation in serum images. Whether the serum images contained blood clots and fibrins was identified according to the segmentation results. RESULTS: The average Dice coefficient of the serum image segmentation network output was 0.8707, which realized more accurate segmentation of blood clots and fibrins in serum images. In 13,230 clinical serum samples, the sensitivity, specificity, and accuracy of blood clot and fibrins segmentation in serum images were 95.74%, 98.11% and 97.93%, respectively, which meet clinical test requirements. CONCLUSIONS: The improved UNeXt segmentation network rapidly and accurately segmented and recognized blood clots and fibrins in serum images, which provided an accurate basis for the sampling height of the sampling needle in the automated biochemical and immunological assembly line.
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Aprendizado Profundo , Trombose , Humanos , Fibrina , Processamento de Imagem Assistida por Computador/métodosRESUMO
Objective: Zhilong Huoxue Tongyu capsule (ZL) is a Chinese patent medicine for treating cardio-cerebral diseases. However, the pharmacological mechanism by which it regulates blood lipids and treats atherosclerosis (AS) is unclear. Therefore, the purpose of this study is to explore the mechanism of ZL inhibiting hyperlipidemia and treating AS through NF-κB/NLRP3 signaling pathway. Methods: Fifty New Zealand white rabbits were divided into control, model, model + ZL (3.12 g/kg/d, i.g.), model + atorvastatin (0.51 mg/kg/d, i.g.), and model + ZL + atorvastatin groups. Except for the control group, all other groups underwent carotid intima air drying and received a high-fat diet for 28 days to establish hyperlipidemia AS model, and drug treatment was given for the same period of time after modeling. Pathological changes and blood lipids were detected, NF-κB/NLRP3-related protein or gene expression levels were analyzed in carotid tissue. Results: ZL significantly reduced blood lipids and delayed the progression of AS. TC, TG, and LDL-C were decreased while HDL-C was increased in blood, IMT thickening and plaque formation of carotid arteries were inhibited, VRI was alleviated, and pathological features were improved. NF-κB, NLRP3 and IL-1ß in the carotid artery were significantly down-regulated after intervention with ZL. RT-PCR and western blot analysis showed that NF-κB (p-NF-κB), NLRP3, caspase-1, IL-1ß and IL-18 were significantly downregulated by ZL. Conclusions: ZL can be used effectively as adjuvant therapy for hyperlipidemia and AS, combining it with atorvastatin yielded more optimized efficacy, but its anti-inflammatory and pharmacological mechanisms of inhibiting pyroptosis should be studied further.
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Promoting ecological conservation and high-quality development in the Yellow River basin is an important objective in China's 14th Five-Year Plan. Understanding the spatio-temporal evolution of and factors affecting the resources and environmental carrying capacity (RECC) of the urban agglomerations is critical for boosting high-quality green-oriented development. We first combined the Driver-Pressure-State-Impact-Response (DPSIR) framework and the improved Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) model to evaluate the RECC of Shandong Peninsula urban agglomeration in 2000, 2010 and 2020; we then used trend analysis and spatial autocorrelation analysis to understand the spatio-temporal evolution and distribution pattern of RECC. Furthermore, we employed Geodetector to detect the influencing factors and classified the urban agglomeration into six zones based on the weighted Voronoi diagram of RECC as well as specific conditions of the study area. The results show that the RECC of Shandong Peninsula urban agglomeration increased consistently over time, from 0.3887 in 2000 to 0.4952 in 2010 and 0.6097 in 2020, respectively. Geographically, RECC decreased gradually from the northeast coast to the southwest inland. Globally, only in 2010 the RECC presented a significant spatial positive correlation, and that in the other years were not significant. The high-high cluster was mainly located in Weifang, while the low-low cluster in Jining. Furthermore, our study reveals three key factors-advancement of industrial structure, resident consumption level, and water consumption per ten thousand yuan of industrial added value-that affected the distribution of RECC. Other factors, including the interactions between residents' consumption level and environmental regulation, residents' consumption level and advancement of industrial structure, as well as between the proportion of R&D expenditure in GDP and resident consumption level also played important roles resulting in the variation of RECC among different cities within the urban agglomeration. Accordingly, we proposed suggestions for achieving high-quality development for different zones.
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Conservação dos Recursos Naturais , Desenvolvimento Econômico , Cidades , Análise Espacial , Indústrias , China , Rios , UrbanizaçãoRESUMO
ICPC-a was from the Imperata cylindrica with a molecular weight of 45 kDa, which was composed of α-D-1,3-Glcp and α-D-1,6-Glcp. The ICPC-a showed thermal stability, maintaining its structural integrity up to 220°C. X-ray diffraction analysis confirmed its amorphous nature, while scanning electron microscopy revealed a layered morphology. ICPC-a significantly ameliorated uric acid stimulation-induced HK-2 cell injury and apoptosis and reduced uric acid levels in mice with hyperuricemic nephropathy. ICPC-a protected against renal injury by inhibiting lipid peroxidation levels, increasing antioxidant damage and defense levels, inhibiting secretion of pro-inflammatory factors, regulating purine metabolism, PI3K-Akt signaling pathway, NF-κB signaling pathway, inflammatory bowel disease, mTOR signaling pathway, and MAPK signaling pathway. These findings indicate that ICPC-a is a promising natural substance with multiple targets, multiple pathways of action, and without toxicity, making it a valuable subject for further research and development.
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Dextranos , Ácido Úrico , Camundongos , Animais , Dextranos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Poaceae/metabolismo , Rim/metabolismo , NF-kappa B/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used clinically to treat inflammatory diseases clinically. However, the adverse effects of NSAIDs cannot be ignored. Therefore, it is critical for us to find alternative anti-inflammatory drugs that can reduce adverse reactions to herbal medicine, such as Iris tectorum Maxim., which has therapeutic effects and can treat inflammatory diseases and liver-related diseases. AIM OF THE STUDY: This study aimed to isolate active compounds from I. tectorum and investigate their anti-inflammatory effects and action mechanisms. MATERIALS AND METHODS: Fourteen compounds were isolated from I. tectorum using silica gel column chromatography, Sephadex LH-20, ODS and high performance liquid chromatography, and their structures were identified by examining physicochemical properties, ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. Classical inflammatory cell models were established using lipopolysaccharide (LPS)-stimulated RAW264.7 cells and rat primary peritoneal macrophages to examine the effect of these compounds. To examine the action mechanisms, the nitric oxide (NO) levels were measured by Griess reagent and the levels of inflammatory cytokines in the supernatant were measured by ELISA; The expressions of major proteins in prostaglandin E2 (PGE2) synthesis and the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were examined by Western blotting, and the mRNA expression levels were measured by quantitative real-time polymerase chain reaction; and the nuclear translocation of p65 was examined by high content imaging. Molecular docking was used to predict the binding of active compound to target protein. RESULTS: Our findings revealed that Iristectorigenin C (IT24) significantly inhibited the levels of NO and PGE2 without affecting cyclooxygenase (COX)-1/COX-2 expression in LPS-induced RAW264.7 cells and rat peritoneal macrophages. Furthermore, IT24 was shown to decrease the expression of microsomal prostaglandin synthetase-1 (mPGES-1) in LPS-induced rat peritoneal macrophages. IT24 did not suppress the phosphorylation and nuclear translocation of proteins in the NF-κB pathway, but it inhibited the phosphorylation of p38/JNK in LPS-stimulated RAW264.7 cells. Additionally, molecular docking analysis indicated that IT24 may directly bind to the mPGES-1 protein. CONCLUSION: IT24 might inhibit mPGES-1 and the p38/JNK pathway to exert its anti-inflammatory effects and could be also developed as an inhibitor of mPGES-1 to prevent and treat mPGES-1-related diseases, such as inflammatory diseases, and holds promise for further research and drug development.
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Lipopolissacarídeos , Sistema de Sinalização das MAP Quinases , Ratos , Animais , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Simulação de Acoplamento Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Macrófagos Peritoneais , Ciclo-Oxigenase 2/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismoRESUMO
Aiming at the unreasonable determination of the power coupling device speed ratio and the power battery capacity in the initial design stage of the dual-motor electric tractor, a dual-motor drive system is designed, and a parameter optimization method based on driving cycles (POMBDC) is proposed. By analyzing the driving characteristics requirements and actual working conditions of the tractor, the dynamic model of the dual-motor drive system under different working modes is established, and the parameters of the dual-motor, transmission and maximum service mass are designed. On this basis, based on the driving cycles and aiming at the lowest power consumption, the POMBDC is formed, this method can collaboratively optimize the power coupling device speed ratio and the power battery capacity. In order to verify the rationality of the POMBDC, the instantaneous optimization-constant speed ratio design method (IO-CSRDM), rule-optimization speed ratio design method (R-OSRDM) and rule-constant speed ratio design method (R-CSRDM) are developed as comparison methods, and simulation experiments are carried out. Under plowing conditions, the power battery capacity of the POMBDC is 3.08%, 5.71%, and 8.73% lower than those of the IO-CSRDM, R-OSRDM, and R-CSRDM, respectively. The power consumption resulting from the POMBDC is reduced by 3.11%, 5.74%, and 8.8%, compared with those of the IO-CSRDM, R-OSRDM and R-CSRDM, respectively. Under rotary tillage conditions, the power battery capacity of the POMBDC is 6%, 8.64%, and 11.11% lower than those of the IO-CSRDM, R-OSRDM, and R-CSRDM, respectively. The power consumption resulting from the POMBDC is reduced by 6.05%, 8.66%, and 11.13%, compared with those of the IO-CSRDM, R-OSRDM and R-CSRDM, respectively. The POMBDC can effectively increase the operating mileage of pure electric tractors and reduce costs.
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Agricultura , Eletricidade , Simulação por Computador , Fontes de Energia ElétricaRESUMO
Laboratory nanocomputed tomography (nano-CT), which can provide a spatial resolution of up to 100 nm, has been widely used due to its volume advantage. However, the drift of the x-ray source focal spot and the thermal expansion of the mechanical system can cause projection drift during long-time scanning. The three-dimensional result reconstructed from the drifted projections contains severe drift artifacts, which reduce the spatial resolution of nano-CT. Registering the drifted projections using rapidly acquired sparse projections is one of the mainstream correction methods, but the high noise and contrast differences of projections in nano-CT affect the correction effectiveness of existing methods. Herein, we propose a rough-to-refined projection registration method, which fully combines the information of the features in the gray and frequency domains of the projections. Simulation data show that the drift estimation accuracy of the proposed method is improved by 5× and 16× compared with the mainstream random sample consensus and locality preserving matching based on features. The proposed method can effectively improve the imaging quality of nano-CT.