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With the rapid development of electronic industry, it's pressing to develop multifunctional electromagnetic interference (EMI) shielding materials to ensure the stable operation of electronic devices. Herein, multilayered flexible PEG@PAN/MXene (Ti3C2Tx)/PVDF@SiO2 (PMF) composite film has been constructed from the level of microstructure design via coaxial electrospinning, coating spraying, and uniaxial electrospinning strategies. Benefiting from the effective encapsulation for PEG and high conductivity of MXene coating, PEG@PAN/MXene composite film with MXene coating loading density of 0.70 mg cm-2 exhibits high thermal energy storage density of 120.77 J g-1 and great EMI shielding performance (EMI SE of 34.409 dB and SSE of 49.086 dB cm3 g-1) in X-band (8-12 GHz). Therefore, this advanced composite film can not only help electronic devices prevent the influence of electromagnetic pollution in the X-band but also play an important role in electronic device thermal management. Additionally, the deposition of nano PVDF@SiO2 fibers (289 ± 128 nm) endowed the PMF composite film with great hydrophobic properties (water contact angle of 126.5°) to ensure the stable working of hydrophilic MXene coating, thereby breaks the limitation of humid application environments. The finding paves a new way for the development of novel multifunctional EMI shielding composite films for electronic devices.
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Transarterial radioembolization (TARE) is a highly effective localized radionuclide therapy that has been successfully used to treat hepatocellular carcinoma (HCC). Extensive research has been conducted on the use of radioactive microspheres (MSs) in TARE, and the development of ideal radioactive MSs is crucial for clinical trials and patient treatment. This study presents the development of a radioactive MS for TARE of HCC. These MSs, referred to as 177Lu-MS@PLGA, consist of poly(lactic-co-glycolic acid) (PLGA) copolymer and radioactive silica MSs, labeled with 177Lu and then coated with PLGA. It has an extremely high level of radiostability. Cellular experiments have shown that it can cause DNA double-strand breaks, leading to cell death. In vivo radiostability of 177Lu-MS@PLGA is demonstrated by microSPECT/CT imaging. In addition, the antitumor study has shown that TARE of 177Lu-MS@PLGA can effectively restrain tumor growth without harmful side effects. Thus, 177Lu-MS@PLGA exhibits significant potential as a radioactive MS for the treatment of HCC.
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Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Lutécio , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Radioisótopos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/radioterapia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Humanos , Camundongos , Lutécio/química , Radioisótopos/química , Radioisótopos/administração & dosagem , Embolização Terapêutica/métodos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Camundongos Nus , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Introduction: Pruritus ani lotion combined with a Chinese medicine formula named Huajiao (Pericarpium Zanthoxyli Bungeani)-Gancao (Radix Glycyrrhizae)-Bingpian (Borneol) is effective in treating pruritus ani. Aim: To investigate the mechanism of traditional Chinese medicine (TCM) in pruritus ani via network pharmacology and molecular dynamics (MD). Material and methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was utilised to screen active ingredients and their corresponding targets. Genes associated with pruritus ani were collected through GeneCards. Protein-protein interaction (PPI) network between target genes of the active ingredients of this formula and genes associated with pruritus ani was established through the STRING database. A drug-active ingredient-gene interaction network was constructed using Cytoscape with the top 50 genes in affinity coefficients. Molecular docking and MD simulation analysis were performed. Results: Epidermal growth factor receptor (EGFR) and Signal Transducer and Activator of Transcription 3 (STAT3) were core genes. Direct targeting of EGFR by the active ingredients (quercetin and luteolin) and direct targeting of STAT3 by the active ingredient (licochalcone A) may be key molecular mechanisms for the treatment of pruritus ani. Simulated trajectories of structural nuclear motion by MD also revealed that the binding of two pairs of molecules was relatively stable. Conclusions: This study unravels potential targets, active ingredients, and mechanisms of pruritus ani lotion combined with Huajiao-Gancao-Bingpian oil in the treatment of pruritus ani, providing a reference for future treatment.
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Circular RNAs (circRNAs) may be involved in tumorigenesis. Recently, the role of circRNAs in hepatocellular carcinoma (HCC) has drawn wide attention. Herein, we aimed to explore the regulation and function of hsa_circ_0005239 in the malignant biological behavior and angiogenesis of HCC, as well as the link between hsa_circ_0005239 and programmed cell death ligand 1 (PD-L1) in HCC. Quantitative real-time polymerase chain reaction (qRT-PCR) assays revealed that hsa_circ_0005239 was upregulated in HCC tumor samples and cell lines. Furthermore, a series of in vitro and in vivo assays explored the effects of hsa_circ_0005239 on biological processes involved in the development of HCC. Knockdown of hsa_circ_0005239 significantly inhibited cell migration, cell invasion, and angiogenesis in HCC, while overexpression showed the opposite effect. In the in vivo assays, hsa_circ_0005239 downregulation suppressed the growth of xenograft tumors in nude mice, which supported that hsa_circ_0005239 is a tumor promoter in HCC. Mechanistically, hsa_circ_0005239 binds to miR-34a-5p and functions as a competing endogenous RNA to modulate the expression of PD-L1. Further experiments revealed that the hsa_circ_0005239/PD-L1 axis regulates the malignant phenotypes of HCC cells through the phosphoinositide-3 kinase/protein kinase B (PI3K/Akt) signaling pathway. These results revealed the role of hsa_circ_0005239 and the hsa_circ_0005239/miR-34a-5p/PD-L1 axis in HCC, providing a potential diagnostic biomarker and therapeutic target for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Animais , Camundongos , Humanos , RNA Circular/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , MicroRNAs/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão GênicaRESUMO
The mitochondrion is the core site of cell signaling, energy metabolism and biosynthesis. Here, taking advantage of activity-based probes, we synthesized two photocontrollable probes (YGH-1 and YGH-2), composed of a mitochondrial localization moiety "triphenylphosphonium", a photo-triggered group to achieve spatially and temporally controlled protein capture, and an alkyne group to enrich the labeled protein. Proteomic validation was further carried out to facilitate identification of the mitochondrial proteome in HeLa cells. The results show that half of the identified protein hits (â¼300) labeled by YGH-1 and YGH-2 belong to mitochondria, and are mostly localized in the mitochondrial matrix and inner mitochondrial membrane. Our results provide a new tool for spatial and temporal analysis of subcellular proteomes.
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Mitocôndrias , Proteômica , Células HeLa , Humanos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteoma/metabolismo , Proteômica/métodosRESUMO
BACKGROUND: Epithelial-mesenchymal transition (EMT) has been associated with wound healing, tumorigenesis, and metastasis. Circular RNAs (circRNAs) are functional non-coding RNAs involved in multiple human cancers. However, whether and how circRNAs contribute to the EMT in hepatocellular carcinomas (HCC) remains to be deciphered. In this study, we investigated the regulation and function of hsa_circ_0003288 on programmed death-1 ligand 1 (PD-L1) during EMT and HCC invasiveness. METHODS: Hsa_circ_0003288 expression was measured by real-time quantitative reverse transcriptase PCR (qRT-PCR). Luciferase reporter assays, RNA pull-down assay and fluorescence in situ hybridization (FISH) were used to determine the correlation between hsa_circ_0003288 and miR-145 and between miR-145 and PD-L1. Furthermore, ectopic overexpression and siRNA-mediated downregulation of hsa_circ_0003288, transwell assays, and in vivo studies were used to determine the function of hsa_circ_0003288 on the EMT and invasiveness of L02 and HCC cells. RESULTS: miR-145 directly targeted the PD-L1 3'-untranslated region (UTR) region, and hsa_circ_0003288 acted as a miR-145 sponge to regulate PD-L1 expression. Overexpression of hsa_circ_0003288 increased PD-L1 levels and promoted EMT, migration, and invasiveness of L02 cells. These observations were reversed after knockdown of hsa_circ_0003288 in HepG2 and Huh7 cells. Overexpression of PD-L1 rescued EMT, migration, and invasiveness of HepG2 and Huh7 cells after knockdown of hsa_circ_0003288. Furthermore, hsa_circ_0003288 knockdown reduced EMT in in vivo studies. Hsa_circ_0003288/PD-L1 axis was found to mediate the metastatic phenotypes via the PI3K/Akt pathway in HCC. Additionally, expression levels of hsa_circ_0003288 were increased and positively correlated with PD-L1 expression in HCC tissues. CONCLUSION: Our findings demonstrated that hsa_circ_0003288 promoted EMT and invasion of HCC via the hsa_circ_0003288/miR-145/PD-L1 axis through the PI3K/Akt pathway. Targeting hsa_circ_0003288 may be a therapeutic strategy for the treatment of HCC.
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The mitochondrion is one of the most important organelles in the eukaryotic cell. Characterization of the mitochondrial proteome is a prerequisite for understanding its cellular functions at the molecular level. Here we report a proteomics method based on mitochondrion-targeting groups and click chemistry. In our strategy, three different mitochondrion-targeting moieties were each augmented with a clickable handle and a cysteine-reactive group. Fluorescence-based bioimaging and fractionation experiments clearly showed that most signals arising from the labels were localized in the mitochondria of cells, as a result of covalent attachment between probe and target proteins. The three probes had distinct profiling characteristics. Furthermore, we successfully identified more than two hundred mitochondrial proteins. The results showed that different mitochondrion-targeting groups targeted distinct proteins with partial overlap. Most of the labeled proteins were localized in the mitochondrial matrix and inner mitochondrial membrane. Our results provide a tool for chemoproteomic analysis of mitochondrion-related proteins.
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Mitocôndrias/química , Proteínas Mitocondriais/análise , Sondas Moleculares/química , Proteoma/análise , Alcinos/síntese química , Alcinos/química , Cromatografia Líquida , Química Click , Corantes Fluorescentes/química , Células HeLa , Humanos , Proteínas Mitocondriais/química , Sondas Moleculares/síntese química , Oligopeptídeos/síntese química , Oligopeptídeos/química , Proteoma/química , Proteômica/métodos , Rodaminas/química , Espectrometria de Massas em TandemRESUMO
Monoamine oxidase (MAO) is a membrane-bound mitochondrial enzyme that plays an important role by catalyzing oxidative deamination to maintain the homeostasis of neurotransmitters and other biogenic amines in living systems. MAO activity is critical for the brain and central nervous system. Its dysfunction is closely related with many neurological and psychiatric disorders. Fluorescent probes provide a useful approach to accurately detect MAO activity and assist to better elucidate their biological functions. Herein, in this Minireview, we summarize the recent advances in reaction based MAO type fluorescent probes and their imaging applications in living systems.
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Corantes Fluorescentes/química , Monoaminoxidase/análise , Animais , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , OxirreduçãoRESUMO
In the presence of cesium carbonate, an efficient synthesis of aryl methyl sulfides by the reactions of aryl halides with commercially available S-methylisothiourea sulfate is developed. This odourless and highly crystalline solid can be used as the substitute for malodorous methanethiol. The gram-scale reaction also proceeds smoothly without the use of column chromatography separation. Similarly, 2-(dimethylamino)ethylthio and cyclopropylmethylthio groups can be easily introduced into the aromatic rings from the corresponding S-[2-(dimethylamino)ethyl]isothiourea dihydrochloride and S-cyclopropylmethylisothiourea hydrobromide. The possible reaction mechanism is proposed. It is believed that this route to aryl alkyl sulfides is well competitive with currently known methods due to its wide substrate scope, excellent yields, easy operation and transition-metal-free conditions.
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In order to strengthen the overall planning and coordination of urban construction and ecological space in Baishan City, we should formulate a scientific land type planning of Production-Living-Ecological Space (PLES). In this paper, land use dynamic attitude model, land use transfer matrix, land use function center of gravity transfer model, eco-environmental quality index(EEQI) and geographic detector model are used to discuss the spatio-temporal evolution of PLES in Baishan City from 2000 to 2020. Spatio-temporal evolution of EEQI and its influencing factors. The results show that: (1) During the study period, Baishan City showed the characteristics that the production space first increased and then decreased, the ecological space decreased, and the living space continued to increase. Among them, the ecological space is the dominant space of Baishan City, covering an area of more than 80%. From the perspective of the transformation of PLES, from 2000 to 2020, Baishan City is mainly characterized by the transformation of ecological space into production space and living space. In the second type of space, green ecological space, forestry ecological space and other ecological space have decreased, while other types of space have increased in varying degrees. (2) During the study period, the overall EEQI of Baishan City remained in good condition, and the ecological environment quality(EEQ) of the three periods were 0.6571, 0.6412 and 0.6562 respectively. The higher EEQI is distributed in Changbai County and Linjiang City, while the areas with lower EEQI are concentrated in the north-central part of Hunjiang City, the middle part of Jiangyuan District and the northwest of Fusong County. (3) According to the analysis of the influencing factors of EEQ, the influence of the factors of spatial differentiation of EEQI in Baishan City changed significantly from 2000 to 2020, and the average annual rainfall was the core factor affecting the spatial differentiation of EEQ in Baishan City, the second is the urbanization rate and the distance from the county government, and the interaction between the average annual rainfall and the distance from the county government has a strong influence on the spatial differentiation of EEQ in Baishan City. This study reveals the evolution of spatial types and EEQ of PLES in Baishan City, and provides a scientific reference for the effective management and utilization of land resources in Baishan City.
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Throughout the history of coal mining in all countries of the world, large areas of goaf have been left behind, and sudden collapses and surface subsidence of large areas of goaf may occur, especially for mining areas with long mining cycles. The northern new district of the Liaoyuan mining area has been subjected to nearly half a century of mining activities, accompanied by a gradual accumulation of disasters, which have occurred frequently in recent years. In order to assess the stability of the goaf in the study area, this paper proposes a hybrid decision-making multi-factor integrated evaluation method. The distribution of underground goafs was determined using geophysical exploration techniques (seismic survey and transient electromagnetic method) and geological drilling exploration. First, an evaluation index system was established based on the specifications of the goaf, the ecological and geological environment, and the mining conditions; the system included 14 indicators. Two weight calculation methods, AHP-EWM, were employed to determine the comprehensive weight of each indicator by combining subjective and objective weights on the basis of improved game theory. Subsequently, the fuzzy comprehensive evaluation method was utilised to complete the stability rating of each block in the study area, and MapGIS and ArcGIS were employed to complete the drawing of the stability zoning map of the northern new district goaf. The study area was divided into three zones of stability, basic stability and instability, according to the critical value. These zones accounted for 23.03%, 36.45% and 40.52% of the total area of the study area, respectively. The comprehensive on-site investigation revealed a decrease in the size and number of collapse pits and the rate of damage to the houses from the unstable zone to the stable zone. This indicates that the results of the division are consistent with the actual situation. The classification results are consistent with the actual ground disaster situation, thus verifying the rationality and validity of the evaluation method. The results indicate that the stability of the study area is generally at the lower middle level.
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The broad learning system (BLS) featuring lightweight, incremental extension, and strong generalization capabilities has been successful in its applications. Despite these advantages, BLS struggles in multitask learning (MTL) scenarios with its limited ability to simultaneously unravel multiple complex tasks where existing BLS models cannot adequately capture and leverage essential information across tasks, decreasing their effectiveness and efficacy in MTL scenarios. To address these limitations, we proposed an innovative MTL framework explicitly designed for BLS, named group sparse regularization for broad multitask learning system using related task-wise (BMtLS-RG). This framework combines a task-related BLS learning mechanism with a group sparse optimization strategy, significantly boosting BLS's ability to generalize in MTL environments. The task-related learning component harnesses task correlations to enable shared learning and optimize parameters efficiently. Meanwhile, the group sparse optimization approach helps minimize the effects of irrelevant or noisy data, thus enhancing the robustness and stability of BLS in navigating complex learning scenarios. To address the varied requirements of MTL challenges, we presented two additional variants of BMtLS-RG: BMtLS-RG with sharing parameters of feature mapped nodes (BMtLS-RGf), which integrates a shared feature mapping layer, and BMtLS-RGf and enhanced nodes (BMtLS-RGfe), which further includes an enhanced node layer atop the shared feature mapping structure. These adaptations provide customized solutions tailored to the diverse landscape of MTL problems. We compared BMtLS-RG with state-of-the-art (SOTA) MTL and BLS algorithms through comprehensive experimental evaluation across multiple practical MTL and UCI datasets. BMtLS-RG outperformed SOTA methods in 97.81% of classification tasks and achieved optimal performance in 96.00% of regression tasks, demonstrating its superior accuracy and robustness. Furthermore, BMtLS-RG exhibited satisfactory training efficiency, outperforming existing MTL algorithms by 8.04-42.85 times.
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Partial multilabel learning (PML) addresses the issue of noisy supervision, which contains an overcomplete set of candidate labels for each instance with only a valid subset of training data. Using label enhancement techniques, researchers have computed the probability of a label being ground truth. However, enhancing labels in the noisy label space makes it impossible for the existing partial multilabel label enhancement methods to achieve satisfactory results. Besides, few methods simultaneously involve the ambiguity problem, the feature space's redundancy, and the model's efficiency in PML. To address these issues, this article presents a novel joint partial multilabel framework using broad learning systems (namely BLS-PML) with three innovative mechanisms: 1) a trustworthy label space is reconstructed through a novel label enhancement method to avoid the bias caused by noisy labels; 2) a low-dimensional feature space is obtained by a confidence-based dimensionality reduction method to reduce the effect of redundancy in the feature space; and 3) a noise-tolerant BLS is proposed by adding a dimensionality reduction layer and a trustworthy label layer to deal with PML problem. We evaluated it on six real-world and seven synthetic datasets, using eight state-of-the-art partial multilabel algorithms as baselines and six evaluation metrics. Out of 144 experimental scenarios, our method significantly outperforms the baselines by about 80%, demonstrating its robustness and effectiveness in handling partial multilabel tasks.
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Natural small molecular organic matter (NSOM), ubiquitous in natural waters and distinct from humic acid or fulvic acid, is a special type of dissolved organic matter (DOM) which is characterized as strong photosensitivity and simple molecular structure. However, little study had been directed on the role of NSOM in eliminating emerging contaminants in advanced reduction process (ARP). This study took three small molecular isomeric organic acids (p-hydroxybenzoic acid, pHBA; salicylic acid, SA; m-hydroxybenzoic acid, mHBA) as the representative substances of NSOM to explore these mechanisms on promoting Ribavirin (RBV, an anti COVID-19 medicine) degradation in ultraviolet activated sulfite (UV/Sulfite) process. The results demonstrated that the observed degradation rate constant of RBV (kobs-RBV) was 7.56 × 10-6 s-1 in UV/Sulfite process, indicating that hydrated electron (eaq-) from UV/Sulfite process could not effectively degrade RBV, while it increased by 178 and 38 times when pHBA and SA were introduced into UV/Sulfite process respectively, suggesting that pHBA and SA strongly promoted RBV degradation while mHBA had no promotion on RBV abatement in UV/Sulfite process. Transient absorption spectra and reactive intermediates scavenging experiment indicated that the triplet excited state pHBA and SA (3pHBA* and 3SA*) contributed to the degradation of RBV through non-radical process. Notably, eaq- played the role of key initiator in transforming pHBA and SA into their triplet states. The difference of kobs-RBV in UV/Sulfite/pHBA and UV/Sulfite/SA process was attributed to different generation pathways of 3pHBA* and 3SA* (high molar absorptivity at the wavelength of 254 nm and photosensitive cycle, respectively) and their second order rate constants towards RBV (kRBV-3pHBA* = 8.60 × 108 M-1 s-1 and kRBV-3SA* = 6.81 × 107 M-1 s-1). mHBA could not degrade RBV for its lack of intramolecular hydrogen bond and low molar absorptivity at 254 nm to abundantly transform into its triplet state. kobs-RBV increased as pH increased from 5.0 to 11.0 in UV/Sulfite/SA process, due to the high yield of eaq- in alkaline condition which promoted the generation of 3SA* and the stable of the absorbance of SA at 254 nm. By contrast, kobs-RBV underwent a process of first increasing and then decreasing in UV/Sulfite/pHBA process as the increase of pH, and its highest value achieved in a neutral condition. This lied in the exposure of eaq- increased as the increase of pH which promoted the generation of 3pHBA*, while the molar absorptivity of pHBA at 254 nm decreased as the increase of pH in an alkaline condition which inhibited the yield of 3pHBA*. The RBV degradation pathways and products toxicity assessment indicated that UV/Sulfite/pHBA had better detoxification performance on RBV than UV/Sulfite/SA process. This study disclosed a novel mechanism of emerging contaminants abatement through non-radical process in NSOM mediated ARP, and provide a wide insight into positive profile of DOM in water treatment process, instead of only taking DOM as a quencher of reactive intermediates.
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Antivirais , Antivirais/química , Raios Ultravioleta , Sulfitos/químicaRESUMO
This study successfully utilized a straightforward approach, choosing liquid-liquid phase separation to build a porous structure and synthesize composite absorbers based on polyimide-based porous carbon/Fe3C (PIC/Fe3C-1, PIC/Fe3C-2) nanoparticles and porous carbon/FeCo alloy nanoparticles (PIC/FeCo). The specially designed network structure pore structures contributed multiple reflection, conduction loss and strong interfacial polarization. After characterization, PIC/Fe3C-2 obtained minimum RL of -35.37 dB at 17.04 GHz with 1.55 mm thickness and effective absorption bandwidth of 4.95 GHz with 1.66 mm thickness. Furthermore, PIC/FeCo, with a thickness of 1.63 mm, exhibits the most robust electromagnetic wave loss ability at 15.6 GHz, with a minimum RL of -56.32 dB and an effective absorption bandwidth of 4.88 GHz. Thus, the design strategy presented in this study could serve as a model for synthesizing other high-performance absorbers, effectively mitigating electromagnetic wave-induced pollution.
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This study successfully utilized a straightforward approach, choosing liquid-liquid phase separation to build a porous structure and synthesize composite absorbers based on polyimide-based porous carbon and cobalt nanoparticles (designated as PPC/Co-700 and PPC/Co-800). A fine porous structure was achieved as a result of the excellent heat resistance of polyimide resulting in an excellent electromagnetic wave absorption ability of PPC/Co composites. The results obtained clearly indicated that PPC/Co-700 and PPC/Co-800 exhibit a porous structure with coral-like pores, enhancing both impedance matching properties and microwave attenuation abilities. This improvement in impedance matching conditions and dissipation capability is attributed to the synergistic effect of dielectric loss induced by carbon and magnetic loss induced by Co nanoparticles. PPC/Co-700 showed the strongest absorption performance with a minimum reflection loss of -59.85 dB (30 wt% loading, thickness of 3.42 mm) and an effective absorption bandwidth (EABW, RL ≤ -10 dB) of 6.24 GHz (30 wt% loading, thickness of 2.78 mm). Therefore, this work provides a facile strategy for the development of a promising absorbing material with outstanding electromagnetic wave absorption performance.
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Organic-contaminated shallow aquifers have become a global concern of groundwater contamination, yet little is known about the coupled effects of hydrodynamic-thermal-chemical-microbial (HTCM) multi-field on organic contaminant transport and transformation over a short time in aquifers. Therefore, this study proposed a quick and efficient field experimental method for the transport-transformation of contaminants under multi-field coupling to explore the relationship between organic contaminants (total petroleum hydrocarbon (TPH), polycyclic aromatic hydrocarbons (PAHs), benzene-toluene-ethylbenzene-xylene (BTEX) and phthalates acid esters (PAEs)) and multi-field factors. The results showed that hydrodynamics (affecting pH, p < 0.001) and temperature (affecting dissolved oxygen, pH and HCO3-, p < 0.05) mainly affected the organic contaminants indirectly by influencing the hydrochemistry to regulate redox conditions in the aquifer. The main degradation reactions of the petroleum hydrocarbons (TPH, PAHs and BTEX) and PAEs in the aquifer were sulfate reduction and nitrate reduction, respectively. Furthermore, the organic contamination was directly influenced by microbial communities, whose spatial patterns were shaped by the combined effects of the spatial pattern of hydrochemistry (induced by the organic contamination pressure) and other multi-field factors. Overall, our findings imply that the spatiotemporal patterns of organic contaminants are synergistically regulated by HTCM, with distinct mechanisms for petroleum hydrocarbons and PAEs.
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OBJECTIVES: To estimate the safety and effectiveness of emergent transjugular intrahepatic portosystemic shunt (TIPS) creation for acute variceal bleeding (AVB) in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Data of thirty-three patients with AVB and HCC undergoing emergent TIPS creation from January 2016 to January 2022 were enrolled and were retrospectively analyzed. The primary outcomes were the safety of emergent TIPS creation, the bleeding control rate, and the rebleeding rate. The secondary outcomes included overall survival (OS), liver function, overt hepatic encephalopathy (HE), and shunt dysfunction. RESULTS: Emergent TIPS creation was technically successful in 33 patients (100%) and one (3.0%) patient suffered a major procedure-related adverse event. The control rate of bleeding (within 5 days) was 100%. During a median follow-up period of 26.3 months, rebleeding occurred in 6 (18.2%) patients. The median OS was 20.0 months. The 6-week and 1-year survival rates were 87% and 65%, respectively. Laboratory tests showed no significant impairment of liver function following TIPS creation. The incidences of overt HE and shunt dysfunction were 24.2% and 6.1%, respectively. CONCLUSION: Emergent TIPS creation is feasible and effective for treatment of AVB in cirrhotic patients with HCC.
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Carcinoma Hepatocelular , Varizes Esofágicas e Gástricas , Neoplasias Hepáticas , Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/cirurgia , Hemorragia Gastrointestinal/complicações , Estudos Retrospectivos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia , Cirrose Hepática/complicações , Resultado do TratamentoRESUMO
Intratumor heterogeneity is one of the major features of cancers, leading to aggressive disease and treatment failure. Cancer stem-like cells (CSCs) are believed to give rise to the heterogeneous cell types within tumors. Hence, understanding the regulatory mechanism underlying the recurrence process of heterogeneous tumor by CSCs could facilitate the development of CSC-targeted therapies. Here, utilizing single-cell transcriptomics, we present the molecular profile of osteosarcoma CSCs-derived heterogeneous tumors consisting of CSC clusters, osteoprogenitor and differentiated cell types, such as pre-osteoblasts, osteoblasts and chondroblasts. Furthermore, by constructing the comprehensive map of modulated genes during CSCs self-renewal and differentiation, we identify RAN exhibiting specific peak expression in osteosarcoma CSCs clusters which is transcriptionally up-regulated by MYBL2. Functionality, MYBL2-RAN pathway promotes the CSCs self-renewal by enhancing the nuclear accumulation of MYC protein, which in turn boosts the overexpression of RAN as a positive feedback. Importantly, blockage of MYBL2-RAN pathway sensitizes CSCs to cisplatin treatment and synergistically enhanced the cisplatin-induced cytotoxicity. Both MYBL2 and RAN are highly expressed in clinical osteosarcoma tissues which indicate poor prognosis. Collectively, our study provides advanced insights into the regeneration process of heterogeneous tumor originating from CSCs and highlights the MYBL2-RAN pathway as a promising target for CSC-based therapy in osteosarcoma.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Neoplasias Ósseas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Células-Tronco Neoplásicas/metabolismo , Osteossarcoma/tratamento farmacológico , Transativadores/metabolismo , Regulação para CimaRESUMO
Cuproptosis is a novel discovered mode of programmed cell death. To identify the molecular regulatory patterns related to cuproptosis, this study was designed for exploring the correlation between cuproptosis-related genes (CRGs) and the prognosis, metabolism, and treatment of hepatocellular carcinoma (HCC). Cancer Genome Atlas (TCGA) database was used to screen 363 HCC samples, which were categorized into 2 clusters based on the expression of CRGs. Survival analysis demonstrated that overall survival (OS) was better in Cluster 1 than Cluster 2 which might to be relevant to differences in metabolic based on functional analysis. With LASSO regression analysis and univariate COX regression, 8 prognosis-related genes were screened, a differently expressed genes (DEGs) were then constructed (HCC patients' DEGs)-based signature. The signature's stability was also validated in the 2 independent cohorts and test cohorts (GSE14520, HCC dataset in PCAWG). The 1-year, 3-year, and 5-year area under the curve (AUC) were 0.756, 0.706, and 0.722, respectively. The signature could also well predict the response to chemotherapy, targeted and transcatheter arterial chemoembolization (TACE) by providing a risk score. Moreover, the correlation was uncovered by the research between the metabolism and risk score. In conclusion, a unique cuproptosis-related signature that be capable of predicting patients' prognosis with HCC, and offered valuable insights into chemotherapy, TACE and targeted therapies for these patients has been developed.