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Under shock loading, the spall strength of nanocrystals exhibits intricate grain-size effects due to the presence of abundant grain boundary and dislocation activities. However, the influence of size on spall toughness and void evolution has been largely overlooked. This study employs molecular dynamics simulations to investigate the damage accumulation characteristics of nanocrystalline aluminum across various grain sizes. Unlike the trade-off observed in quasi-static loading conditions, our study reveals a consistency in which grain size governs both nanovoid nucleation and coalescence, yielding a novel spall strength-toughness synergy. These insights highlight grain sizes that are particularly susceptible to spall fracture, offering a crucial understanding of nanocrystal failure mechanisms in extreme environments.
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The transformation of public consumption patterns has become a burning question, but there are few studies on public consumption patterns. Therefore, evaluating the impact of Information consumption city (ICC) policy on carbon emission efficiency holds significant implications. This study settles on 104 pilot cities in China from 2006 to 2020 to assess the impact and the response mechanism of ICC policy on carbon emission efficiency through the time-vary Difference-in-Difference (DID) model. The result shows that: (1) ICC policy significantly promotes the local carbon emission efficiency, which remains robust after a battery of sensitivity tests. (2) It improves carbon emission efficiency through production factors agglomeration effect, industrial structural changing effect, innovation promotion effect, and environmental attention effect; (3) The direct impact of ICC policy on carbon emission efficiency varies across regions with different information consumption and carbon emission base. (4) ICC can improve carbon emission efficiency through the joint implementation of smart city (SC), new urbanization (NU), ecological civilization city construction (EC), Belt and Road Initiative (BR), Broadband China (BC), low-carbon city pilot policy (LCC), and air quality standards (AQS) policy.
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Cidades , China , Carbono/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , Política Ambiental , Poluentes Atmosféricos/análise , Urbanização , Monitoramento Ambiental/métodosRESUMO
BACKGROUND: Areas with saline soils are sparsely populated and have fragile ecosystems, which severely restricts the sustainable development of local economies. Zoysia grasses are recognized as excellent warm-season turfgrasses worldwide, with high salt tolerance and superior growth in saline-alkali soils. However, the mechanism underlying the salt tolerance of Zoysia species remains unknown. RESULTS: The phenotypic and physiological responses of two contrasting materials, Zoysia japonica Steud. Z004 (salt sensitive) and Z011 (salt tolerant) in response to salt stress were studied. The results show that Z011 was more salt tolerant than was Z004, with the former presenting greater K+/Na+ ratios in both its leaves and roots. To study the molecular mechanisms underlying salt tolerance further, we compared the transcriptomes of the two materials at different time points (0 h, 1 h, 24 h, and 72 h) and from different tissues (leaves and roots) under salt treatment. The 24-h time point and the roots might make significant contributions to the salt tolerance. Moreover, GO and KEGG analyses of different comparisons revealed that the key DEGs participating in the salt-stress response belonged to the hormone pathway, various TF families and the DUF family. CONCLUSIONS: Zoysia salt treatment transcriptome shows the 24-h and roots may make significant contributions to the salt tolerance. The auxin signal transduction family, ABA signal transduction family, WRKY TF family and bHLH TF family may be the most important families in Zoysia salt-stress regulation.
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Proteínas de Plantas/genética , Poaceae/fisiologia , Tolerância ao Sal/fisiologia , Proteínas de Plantas/metabolismo , Poaceae/genética , Tolerância ao Sal/genética , TranscriptomaRESUMO
The aim of this paper was to investigate the effect of Schizonepetae Herba and Saposhnikoviae Radix(wind medicine) on the expression of AQP4 and AQP8 in colonic mucosa in rats with ulcerative colitis(UC). A total of 35 healthy SD male rats were randomly divided into normal group(gavaged with normal saline), DSS model group, as well as low, middle, and high dose wind medicine groups(Schizonepeta and Saposhnikovia 1â¶1, gavaged at dosages of 6, 12, and 24 g·kg~(-1)·d~(-1)), with 7 in each group. UC rat model was established by free drinking of 3% dextran sulphate sodium(DSS) solution for 10 days. At the end of the 10 th day after the treatment, mice were put to death to collect colonic mucosa. The length of colon was measured; the colonic mucosal injury index(CMDI) and pathological changes of colon were observed. ELISA method was used for measuring the content of serum IL-1, IL-8, and immunohistochemical method was used to measure AQP4, AQP8 protein expressions in colon mucosa. The expressions of AQP4, AQP8 mRNA were measured by Real-time PCR. As compared with the normal group, the length of colon tissue was significantly reduced(P<0.01), CMDI scores and pathological scores were significantly increased(P<0.01), the levels of serum IL-1 and IL-8 were significantly increased(P<0.05) in model group; the immunohistochemical results showed that the protein expressions of AQP4, AQP8 were lower; the color was light yellow or brown; AQP4, AQP8 mRNA expressions in colon mucosa were significantly decreased in model group(P<0.01). CMDI scores, pathological scores, and the levels of serum IL-1, IL-8 in high, middle, low dose wind medicine groups were obvious lower than those in the model group(P<0.01 or P<0.05); the protein expressions of AQP4, AQP8 were higher; the color was chocolate brown or dark brown; the length of colon tissue, and the expressions of AQP4, AQP8 mRNA were obvious higher in wind medicine groups(P<0.01 or P<0.05). Schizonepetae Herba and Saposhnikoviae Radix could significantly improve the symptoms and histopathology of UC model rats and accelerate the intestinal mucosal healing. The mechanism may be related with up-regulating the expression level of AQP4 and AQP8 in colonic mucosa.
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Apiaceae , Colite Ulcerativa , Animais , Aquaporina 4 , Colo , Mucosa Intestinal , Masculino , Camundongos , Raízes de Plantas , RatosRESUMO
The aim of this paper was to screen the active targets of Schizonepetae Herba and Saposhnikoviae Radix in the treatment of ulcerative colitis by means of network pharmacology,and to investigate their mechanism of action. The effective components of Schizonepetae Herba and Saposhnikoviae Radix were screened out by traditional Chinese medicine systematic pharmacological( TCMSP)database,with oral bioavilability( OB) ≥30% and drug-like( DL) ≥18% selected as the thresholds. Target PPI network was built between the main components and their corresponding targets. One hundred and eighty-two human genes corresponding to the medicine target sites were obtained from Uniprot database; 3 874 genes corresponding to ulcerative colitis were obtained from Genecard database.A total of 115 intersection genes were screened from disease genes and medicine genes,and the PPI interaction analysis was conducted by using String tool. Disease-target PPI network was drawn by using Cytoscape software,and component-target-disease network was constructed. One hundred and eight nodes and 1 882 connections were found,and then Cytoscape software was used to merge the networks and filter the core network for gene GO function analysis and KEGG pathway enrichment analysis. The mechanism of Schizonepetae Herba and Saposhnikoviae Radix was then verified by animal experiment. Gene GO functional analysis suggested that biological process,molecular functions and cell components were involved,and it was found that ulcerative colitis might be related to transcription factor activity,and cytokine receptor binding,etc. Gene KEGG pathway enrichment analysis showed that the mechanism of ulcerative colitis might be associated with TNF and Toll-like receptors( TLRs) signaling pathway-mediated cytoinflammatory factors interleukin-1( IL-1) and interleukin-6( IL6). The possible mechanism of the effective components of Schizonepetae Herba and Saposhnikoviae Radix in treating ulcerative colitis might be related to intervening the cytokine receptor binding of TNF and TLRs signaling pathways,reducing the transcription of nuclear factor-kappaB( NF-κB),and inhibiting the secretion of intestinal inflammatory factors IL-1 and IL-6.
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Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Mapeamento de Interação de Proteínas , Animais , Apiaceae/química , Bases de Dados Genéticas , Humanos , Interleucinas/metabolismo , Lamiaceae/química , Medicina Tradicional Chinesa , Fitoterapia , Raízes de Plantas/química , Transdução de Sinais , Software , Receptores Toll-Like/metabolismoRESUMO
The purpose of this pilot study was to determine whether blood-borne microvesicles from newly diagnosed glioblastoma patients could be used as biomarkers. We collected 2.8 mL blood from 16 post-operative patients at the time that they were being simulated for chemoradiation therapy (radiation with concurrent temozolomide). Two additional samples were collected during chemoradiation therapy and a final sample was collected at the end of chemoradiation therapy. Patients continued with the therapy suggested by their physicians, based on tumor conference consensus and were followed for recurrence and overall survival. Microvesicles were isolated using serial centrifugation and stained for surface markers (Annexin V for phosphotidyl serine, CD41 for platelets, anti-EGFR for tumor cells, and CD235 for red blood cells). Flow cytometry analysis was performed. Our findings provide initial evidence that increases in Annexin V positive microvesicle levels during chemoradiation therapy are associated with earlier recurrence and shorter overall survival in newly diagnosed glioblastoma patients. The effect is dramatic, with over a four-fold increase in the hazard ratio for an individual at the 75th versus the 25th percentile. Moreover the pattern of Annexin V positive microvesicles remain significant after adjustment for confounding clinical variables that have previously been shown to be prognostic for recurrence and survival. Inclusion of neutrophil levels at the start of chemoradiation therapy in the model yielded the largest attenuation of the observed association. Further studies will be needed to verify and further investigate the association between these two entities.
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Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/patologia , Micropartículas Derivadas de Células/patologia , Glioblastoma/patologia , Recidiva Local de Neoplasia/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Feminino , Seguimentos , Glioblastoma/diagnóstico , Glioblastoma/mortalidade , Glioblastoma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
Using matched data from China Stock Market and Accounting Research (CSMAR) and Wind databases, this paper explores the impact of exports on the green technology innovation (GTI) of small- and medium-sized enterprises (SMEs). The mechanisms are analyzed through a two-way fixed effects model. First, exports contribute significantly to GTI of SMEs. Second, exports mainly contribute to GTI of SMEs by attracting government subsidies and increasing firms' environmental awareness. Third, from the perspective of heterogeneity, exports significantly positively impact GTI of SMEs especially in medium- and low-technology industries and in eastern China. The impact of exports on GTI is also examined by replacing core variables, modifying the sample for robustness testing, and utilizing both urban river density and distance from the center of the city to the nearest port as instrumental variables for endogeneity test. With the continuous development of international import and export trade, enterprises increase GTI research and development by attracting government subsidies, improving the quality of disclosed information, and increasing environmental awareness.
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In this paper, a quasi-natural experiment of national innovative city pilot policy (NICPP) is carried out to investigate the impact of the NICPP on green technology innovation (GTI) and its intrinsic mechanism with the method of difference-in-differences. It is found that the NICPP significantly enhances GTI, and there is a certain lag and persistence in this effect. Heterogeneity analysis shows that the higher the administrative level and the more the geographical advantages of NICPP, the more obvious the driving effect of GTI. The mechanism test shows that the NICPP has an effect on the GTI through three channels: innovation factor input, agglomeration effect of science and technology talent, and entrepreneurial vitality empowerment. The findings of this study provide policy insights for further optimizing the construction of innovative cities and then promoting GTI development, ultimately realizing green dynamics transformation and high-quality development of China's economy.
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This paper uses the environmental information announcement system as a quasi-natural experiment, cleaning China's Industrial Enterprise Pollution Database, a unique and comprehensive firm-level database, and merges it with China's Industrial Enterprise Database. Then, we use the difference-in-differences model to test the effect of environmental information announcements on firm pollution emissions and the transmission mechanism. The empirical results found that environmental information announcement has a significant environmental performance improvement effect. That is, environmental information announcements can significantly reduce pollution emissions. Moreover, the effects of environmental information announcement differ significantly under different regions, city levels, and environmental regulatory intensities. Specifically, in the eastern region, first-class cities, and regions with higher environmental regulations, the emission reduction effects of enterprises are more obvious. Further transmission mechanism test results show that environmental information disclosure has a dual emission reduction mechanism of internal driving and external pressure. Front-end of technological innovation and end-of-end environmental governance are important manifestations in internal driving. Under external pressure, companies will reduce production so as to achieve the goal of reducing pollution emissions.
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Conservação dos Recursos Naturais , Revelação , China , Política Ambiental , Poluição AmbientalRESUMO
OBJECTIVE: This study aimed to investigate the possible mechanism of the Zhishi and Baizhu herb pair in the treatment of gastric cancer by means of network pharmacology and molecular docking and to provide a theoretical basis for experiments and clinical application of traditional Chinese medicine for treating gastric cancer. METHODS: The main active chemical components of Zhishi and Baizhu were screened through Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and selected by using the thresholds of oral bioavailability ≥30% and drug-likeness ≥18%. The targets of Zhishi and Baizhu were obtained from TCMSP, Therapeutic Targets Database (TTD), and the DrugBank database. The corresponding genes of the targets were retrieved from the UniProt database, and the gastric cancer targets were obtained from the GeneCards database and TTD. Subsequently, the networks were built between the main drug components, drug targets, and gastric cancer targets. Then, the enrichment analyses of GO and KEGG were applied to predict the potential roles of gastric cancer pathogenesis via the R package clusterProfiler. Finally, molecular docking was used to determine the affinity between the targets and components. RESULTS: Twenty-seven main active components were predicted from the Zhishi-Baizhu herb pair, and a total of 120 intersection genes were screened from 303 potential medicine genes and 1,839 disease genes. The enrichment included the PI3K-Akt and IL-17 signaling pathways, and the network analysis showed that the Zhishi-Baizhu herb pair acted on seven key targets, namely, AKT1, MMP9, IL-6, CCND1, BCL2, MTOR, and MDM2 (where they played a role in treating gastric cancer). Molecular docking showed that luteolin and naringenin could stably bind to the targets. CONCLUSION: The possible mechanisms of the components of the Zhishi-Baizhu herb pair in treating gastric cancer might be related to luteolin and naringenin, which intervened with the targets AKT1, MMP9, IL-6, CCND1, BCL2, MTOR, and MDM2, and are linked with the PI3K-Akt and IL-17 signaling pathways. This knowledge will lay a solid foundation for further experimental and clinical studies.
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Diagnostic and prognostic indicators are key components to achieve the goal of personalized cancer therapy. Two distinct approaches to this goal include predicting response by genetic analysis and direct testing of possible therapies using cultures derived from biopsy specimens. Optimally, the latter method requires a rapid assessment, but growing xenograft tumors or developing patient-derived cell lines can involve a great deal of time and expense. Furthermore, tumor cells have much different responses when grown in 2D versus 3D tissue environments. Using a modification of existing methods, we show that it is possible to make tumor-fragment (TF) spheroids in only 2-3 days. TF spheroids appear to closely model characteristics of the original tumor and may be used to assess critical therapy-modulating features of the microenvironment such as hypoxia. A similar method allows the reproducible development of spheroids from mixed tumor cells and fibroblasts (mixed-cell spheroids). Prior literature reports have shown highly variable development and properties of mixed-cell spheroids and this has hampered the detailed study of how individual tumor-cell components interact. In this study, we illustrate this approach and describe similarities and differences using two tumor models (U87 glioma and SQ20B squamous-cell carcinoma) with supporting data from additional cell lines. We show that U87 and SQ20B spheroids predict a key microenvironmental factor in tumors (hypoxia) and that SQ20B cells and spheroids generate similar numbers of microvesicles. We also present pilot data for miRNA expression under conditions of cells, tumors, and TF spheroids.
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Neoplasias/genética , Neoplasias/patologia , Esferoides Celulares , Biomarcadores , Linhagem Celular Tumoral , Fibroblastos , Humanos , MicroRNAs , Neovascularização Patológica , Células Estromais , Células Tumorais Cultivadas , Microambiente TumoralRESUMO
PURPOSE: RNA interference mediated by small interfering RNAs (siRNAs) is a powerful technology allowing the silencing of mamalian genes with great specificity and potency. The purpose of this study was to demonstrate the feasibility of RNA interference mediated by siRNA in retinal cells in vitro and in the murine retina in vivo. METHODS: siRNAs specific for enhanced green fluorescent protein (EGFP) and murine and human vascular endothelial growth factor (VEGF) were designed. In vitro studies in human cell lines entailed modulation of endogenous VEGF levels through chemically induced hypoxia. Effects of siRNA treatment on these levels were measured by ELISA. In vivo studies evaluating effects of siRNA on levels of EGFP and VEGF were performed by co-injecting recombinant viruses carrying EGFP or hVEGF cDNAs along with the appropriate siRNAs subretinally in mice. Additional studies aimed at blocking production of endogenous mVEGF were performed using laser-induced choroidal neovascularization (CNV) in mice. Effects of in vivo treatments were evaluated ophthalmoscopically. Retinal/choroidal flat mounts were evaluated after perfusion with dextran-fluorescein. Alternatively, retinas were evaluated in histological sections or VEGF levels were measured in intact eyes using ELISA. RESULTS: Successful delivery of siRNA to the subretinal space was confirmed by observing significantly reduced levels of EGFP in eyes treated with Ad.CMV.EGFP plus EGFP-directed siRNA. siRNAs directed against hVEGF effectively and specifically inhibit hypoxia-induced VEGF levels in human cell lines and after adenoviral induced hVEGF transgene expression in vivo. In addition, subretinal delivery of siRNA directed against murine Vegf significantly inhibited CNV after laser photocoagulation. CONCLUSIONS: Delivery of siRNA can be used in vitro and in vivo to target specific RNAs and to reduce the levels of the specific protein product in the targeted cells. This work suggests that RNA interference has potential for application to studies of retinal biology and for the treatment of a variety of retinal diseases, including those involving abnormal blood vessel growth.
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Neovascularização de Coroide/prevenção & controle , Fatores de Crescimento Endotelial/genética , Inativação Gênica , Marcação de Genes , Peptídeos e Proteínas de Sinalização Intercelular/genética , Linfocinas/genética , RNA Interferente Pequeno/genética , Adenovírus Humanos/genética , Animais , Corioide/irrigação sanguínea , Corioide/cirurgia , Neovascularização de Coroide/metabolismo , Vírus Defeituosos , Modelos Animais de Doenças , Regulação para Baixo , Fatores de Crescimento Endotelial/metabolismo , Ensaio de Imunoadsorção Enzimática , Proteínas de Fluorescência Verde , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fotocoagulação a Laser , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Linfocinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Epitélio Pigmentado Ocular/metabolismo , Epitélio Pigmentado Ocular/virologia , Transfecção , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
UNLABELLED: The standard of care for glioblastoma (GB) is surgery followed by concurrent radiation therapy (RT) and temozolomide (TMZ) and then adjuvant TMZ. This regime is associated with increased survival but also increased occurrence of equivocal imaging findings, e.g., tumor progression (TP) versus treatment effect (TE), which is also referred to as pseudoprogression (PsP). Equivocal findings make decisions regarding further treatment difficult and often delayed. Because none of the current imaging assays have proven sensitive and specific for differentiation of TP versus TE/PsP, we investigated whether blood-derived microvesicles (MVs) would be a relevant assay. METHODS: 2.8 ml of citrated blood was collected from patients with GB at the time of their RT simulation, at the end of chemoradiation therapy (CRT), and multiple times following treatment. MVs were collected following multiple centrifugations (300g, 2500g, and 15,000g). The pellet from the final spin was analyzed using flow cytometry. A diameter of approximately 300 nm or greater and Pacific Blue-labeled Annexin V positivity were used to identify the MVs reported herein. RESULTS: We analyzed 19 blood samples from 11 patients with GB. MV counts in the patients with stable disease or TE/PsP were significantly lower than patients who developed TP (P = .014). CONCLUSION: These preliminary data suggest that blood analysis for MVs from GB patients receiving CRT may be useful to distinguish TE/PsP from TP. MVs may add clarity to standard imaging for decision making in patients with equivocal imaging findings.
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Traditional anticancer chemotherapy often displays toxic side effects, poor bioavailability, and a low therapeutic index. Targeting and controlled release of a chemotherapeutic agent can increase drug bioavailability, mitigate undesirable side effects, and increase the therapeutic index. Here we report a polymersome-based system to deliver gemcitabine to Panc-1 cells in vitro. The polymersomes were self-assembled from a biocompatible and completely biodegradable polymer, poly(ethylene oxide)-poly(caprolactone), PEO-PCL. We showed that we can encapsulate gemcitabine within stable 200 nm vesicles with a 10% loading efficiency. These vesicles displayed a controlled release of gemcitabine with 60% release after 2 days at physiological pH. Upon treatment of Panc-1 cells in vitro, vesicles were internalized as verified with fluorescently labeled polymersomes. Clonogenic assays to determine cell survival were performed by treating Panc-1 cells with varying concentrations of unencapsulated gemcitabine (FreeGem) and polymersome-encapsulated gemcitabine (PolyGem) for 48 hours. 1 µM PolyGem was equivalent in tumor cell toxicity to 1 µM FreeGem, with a one log cell kill observed. These studies suggest that further investigation on polymersome-based drug formulations is warranted for chemotherapy of pancreatic cancer.