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This paper aimed to study the chemical constituents from Clitocybe clavipes. Silica gel, ODS, Sephadex LH-20, and semi-p reparative HPLC were employed to separate the ethanol extract of C. clavipes. Six compounds were identified by ~1H-NMR, ~(13)CNMR,and ESI-MS as clavilactone L(1), clavilactone A(2), clavilactone B(3), clavilactone E(4), clavilactone H(5), and clav ilactone I(6). Among them, compound 1 was a new meroterpenoid with a 10-membered carbocycle connected to a hydroquinone. Theantitumor activities of compounds 1-6 were determined by the methyl thiazolyl tetrazolium(MTT) ass ay. The results showed that compounds 1-6 exerted inhibitory effects on the proliferation of human gastric cancer cells(MGC-803),human non-small cell lung cancer cells(A549), and cervical cancer cells(HeLa). Compound 1 exhibited significant inhibitory activity against MGC-803 cells, with the half maximal inhibitory concentration(IC_(50)) of 11. 76 µmol·L~(-1).
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Proliferação de Células , Humanos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Estrutura Molecular , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/químicaRESUMO
Ischemic stroke is one of the main causes of disability and death. However, recanalization of occluded cerebral arteries is effective only within a very narrow time window. Therefore, it is particularly important to find neuroprotective biological targets for cerebral artery recanalization. Here, gene expression profiles of datasets GSE160500 and GSE97537 were downloaded from the GEO database, which were related to ischemic stroke in rats. Olfactory receptor 78 (Olfr78) was screened, and which highly associated with Calcium signalling pathway and MAPK pathway. Interacting protein of Olfr78, Prkaca, was predicted by STRING, and their interaction was validated by Co-IP analysis. Then, a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) and a neuronal cell model stimulated by oxygen-glucose deprivation/reoxygenation (OGD/R) were constructed, and the results showed that expression of Olfr78 and Prkaca was downregulated in MCAO rats and OGD/R-stimulated neurons. Overexpression of Olfr78 or Prkaca inhibited the secretion of inflammatory factors, Ca2+ overload, and OGD/R-induced neuronal apoptosis. Moreover, Overexpression of Prkaca increased protein levels of cAMP, PKA and phosphorylated p38 in OGD/R-stimulated neurons, while SB203580, a p38 inhibitor, treatment inhibited activation of the cAMP/PKA-MAPK pathway and counteracted the effect of Olfr78 overexpression on improvement of neuronal functions. Meanwhile, overexpression of Olfr78 or Prkaca markedly inhibited neuronal apoptosis and improved brain injury in MCAO/R rats. In conclusion, overexpression of Olfr78 inhibited Ca2+ overload and reduced neuronal apoptosis in MCAO/R rats by promoting Prkaca-mediated activation of the cAMP/PKA-MAPK pathway, thereby improving brain injury in cerebral ischaemia-reperfusion.
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Apoptose , AMP Cíclico , Ratos Sprague-Dawley , Receptores Odorantes , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/genética , Ratos , Masculino , AMP Cíclico/metabolismo , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Neurônios/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Transdução de SinaisRESUMO
Electrohydrodynamic (EHD) direct-writing has recently gained attention as a highly promising additive manufacturing strategy for fabricating intricate micro/nanoscale architectures. This technique is particularly well-suited for mimicking the extracellular matrix (ECM) present in biological tissue, which serves a vital function in facilitating cell colonization, migration, and growth. The integration of EHD direct-writing with other techniques has been employed to enhance the biological performance of scaffolds, and significant advancements have been made in the development of tailored scaffold architectures and constituents to meet the specific requirements of various biomedical applications. Here, a comprehensive overview of EHD direct-writing is provided, including its underlying principles, demonstrated materials systems, and biomedical applications. A brief chronology of EHD direct-writing is provided, along with an examination of the observed phenomena that occur during the printing process. The impact of biomaterial selection and architectural topographic cues on biological performance is also highlighted. Finally, the major limitations associated with EHD direct-writing are discussed.
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As the structural basis of connective and load-bearing tissues, collagen fibers with orientation play an important role in the mechanical properties and physiological and biochemical functions of the tissues, but viable methods for preparing scaffolds with highly oriented collagenous structure still need to be further studied. In this study, pure collagen was used as printing ink to 3D printing. Harnessing oriented collagen fiber structure by 3D printing for promoting mechanical and osteogenic properties of scaffolds. The scaffolds with different printed angles and thicknesses were prepared to fit the bone defect site and realize personalized customization. The orientation assembly of collagen fibers was promoted by shear force action of 3D printing, the regular arrangement of collagen fibers and stabilization of fiber structure were promoted by pH adjustment and glutaraldehyde cross-linking, and the collagen fibers were mineralized by cyclic mineralization method. The microscopic morphology of fiber arrangement in the scaffolds were investigated by scanning electron microscopy. Results demonstrated that collagen fibers were changed from non-oriented to oriented after 3D printing. And the tensile modulus of the scaffolds with oriented collagen fibers was nine times higher than that of the scaffolds with non-oriented fibers. Moreover, the effects of oriented collagen fibers on the proliferation, differentiation and mineralization of MC3T3-E1 cells were studied by CCK-8 assay, live/dead cell staining, alkaline phosphatase activity test, and Alizarin red staining. The results indicated that cell proliferation, differentiation and mineralization were significantly promoted by oriented collagen fibers, and the cells proliferated directionally in the direction of the fibers. Taken together, mineralized collagen fiber scaffolds with oriented collagen fibers have great potential in bone tissue engineering applications.
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Diferenciação Celular , Proliferação de Células , Colágeno , Osteoblastos , Osteogênese , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Alicerces Teciduais/química , Camundongos , Animais , Colágeno/química , Engenharia Tecidual/métodos , Osteoblastos/citologia , Teste de Materiais , Resistência à Tração , Materiais Biocompatíveis/química , Linhagem Celular , Microscopia Eletrônica de Varredura , Calcificação Fisiológica , Células 3T3 , Estresse MecânicoRESUMO
The ability to finely tune/balance the structure and rigidity of enzymes to realize both high enzymatic activity and long-term stability is highly desired but highly challenging. Herein, we propose the concept of the "silicazyme", where solid inorganic silica undergoes controlled hybridization with the fragile enzyme under moderate conditions at the single-enzyme level, thus enabling simultaneous structure augmentation, long-term stability, and high enzymatic activity preservation. A multivariate silicification approach was utilized and occurred around individual enzymes to allow conformal coating. To realize a high activity-stability trade-off the structure flexibility/rigidity of the silicazyme was optimized by a component adjustment ternary (CAT) plot method. Moreover, the multivariate organosilica frameworks bring great advantages, including surface microenvironment adjustability, reversible modification capability, and functional extensibility through the rich chemistry of silica. Overall silicazymes represent a new class of enzymes with promise for catalysis, separations, and nanomedicine.
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Dióxido de Silício , Dióxido de Silício/química , Estabilidade Enzimática , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismoRESUMO
INTRODUCTION: Parkinson's disease (PD) is the most common neurodegenerative disease worldwide. Studies have shown that insulin-like growth factor-binding protein 5 (IGFBP5) may contribute to methamphetamine-induced neurotoxicity and neuronal apoptosis in PC-12 cells and rat striatum. Here, we studied the expression and role of IGFBP5 in the 6-OHDA-toxicant model of PD. METHODS: PC-12 and SH-SY5Y cells were exposed to 50 µ
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Apoptose , Proteínas Hedgehog , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina , Oxidopamina , Doença de Parkinson , Transdução de Sinais , Animais , Proteínas Hedgehog/metabolismo , Ratos , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Humanos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Modelos Animais de Doenças , Masculino , Células PC12 , Ratos Sprague-DawleyRESUMO
White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI.
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Bainha de Mielina , Neovascularização Fisiológica , Pericitos , Animais , Pericitos/metabolismo , Pericitos/efeitos dos fármacos , Camundongos , Bainha de Mielina/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/fisiologia , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/farmacologia , Animais Recém-Nascidos , Hipóxia/metabolismo , Diferenciação Celular/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Células Precursoras de Oligodendrócitos/metabolismo , Células Precursoras de Oligodendrócitos/efeitos dos fármacos , Receptores da Somatotropina/metabolismo , Receptores da Somatotropina/genética , AngiogêneseRESUMO
Therapeutic approaches for triple-negative breast cancer (TNBC) have been continuously advancing, but inadequate control over release behavior, insufficient tumor selectivity, and limited drug availability continue to impede therapeutic outcomes in nanodrug systems. In this study, we propose a general hydrophobic antineoplastic delivery system, termed spatiotemporally-controlled hydrophobic antineoplastic delivery system (SCHADS) for enhanced TNBC treatment. The key feature of SCHADS is the formation of metastable photosensitive-antineoplastic complexes (PACs) through the self-assembly of hydrophobic drugs driven by photosensitive molecules. With the further decoration of tumor-targeting peptides coupled with the EPR effect, the PACs tend to accumulate in the tumor site tremendously, promoting drug delivery efficiency. Meanwhile, the disassembly behavior of the metastable PACs could be driven by light on demand to achieve in situ drug release, thus promoting chemotherapeutics availability. Furthermore, the abundant ROS generated by the photosensitizer could effectively kill tumor cells, ultimately realizing an effective combination of photodynamic and chemotherapeutic therapy. As an exemplary presentation, chlorin e6 has been chosen to drive the formation of PACs with the system xc- inhibitor sorafenib. Compared with pure drug treatment, the PACs with the above-described preponderances exhibit superior therapeutic effects both in vitro and in vivo and circumvent the side effects due to off-target. By manipulating the laser irradiation, the PACs-treated cell death mechanism could be dynamically regulated, thus providing the potential to remedy intrinsic/acquired resistance of tumor. Collectively, this SCHADS achieves spatio-temporal control of the drug that greatly enhances the availability of anticarcinogen and realizes synergistic antitumor effect in TNBC treatment, even ultimately being extended to the treatment of other types of tumors.
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Antineoplásicos , Sistemas de Liberação de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Fármacos Fotossensibilizantes , Porfirinas , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Feminino , Animais , Humanos , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Porfirinas/administração & dosagem , Porfirinas/química , Clorofilídeos , Camundongos Nus , Camundongos Endogâmicos BALB C , Fotoquimioterapia/métodos , Sorafenibe/administração & dosagem , Sorafenibe/farmacologia , Sorafenibe/química , Liberação Controlada de FármacosRESUMO
Cerebral ischaemia-reperfusion (CIR) injury occurs in stroke patients after the restoration of cerebral perfusion. Sinigrin, a phytochemical found in cruciferous vegetables, exhibits strong antioxidant activity. This study investigated the role of sinigrin in oxidative stress using a CIR injury model. The effects of sinigrin were studied in middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-injured SH-SY5Y cells. Sinigrin treatment improved brain injury and neurological deficits induced by MCAO surgery in rats. Sinigrin inhibited apoptosis in brain tissues and SH-SY5Y cells following OGD/R induction. Additionally, sinigrin elevated the levels of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) while reducing malondialdehyde (MDA) levels. Furthermore, sinigrin inhibited the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signalling pathway. The anti-apoptotic and antioxidant activities of sinigrin in OGD/R-injured SH-SY5Y cells were reversed by TLR4 overexpression. In conclusion, sinigrin inhibits oxidative stress in CIR injury by suppressing the TLR4/MyD88 signalling pathway.
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Isquemia Encefálica , Glucosinolatos , Neuroblastoma , Traumatismo por Reperfusão , Humanos , Ratos , Animais , Receptor 4 Toll-Like/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Glutationa/metabolismo , Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , ApoptoseRESUMO
Monolepta is one of the diverse genera in the subfamily Galerucinae, including 708 species and 6 sub-species worldwide. To explore the information on the mitogenome characteristics and phylogeny of the section "Monoleptites", especially the genus Monolepta, we obtained the newly completed mitochondrial genomes (mitogenomes) of four Monolepta species using high-throughput sequencing technology. The lengths of these four new mitochondrial genomes are 16,672 bp, 16,965 bp, 16,012 bp, and 15,866 bp in size, respectively. All four mitochondrial genomes include 22 transfer RNA genes (tRNAs), 13 protein-coding genes (PCGs), 2 ribosomal RNA genes (rRNAs), and one control region, which is consistent with other Coleoptera. The results of the nonsynonymous with synonymous substitution rates showed that ND6 had the highest evolution rate, while COI displayed the lowest evolution rate. The substitution saturation of three datasets (13 PCGs_codon1, 13 PCGs_codon2, 13 PCGs_codon3) showed that there was no saturation across all datasets. Phylogenetic analyses based on three datasets (ND1, 15 genes of mitogenomes, and 13 PCGs_AA) were carried out using maximum likelihood (ML) and Bayesian inference (BI) methods. The results showed that mitogenomes had a greater capacity to resolve the main clades than the ND1 gene at the suprageneric and species levels. The section "Monoleptites" was proven to be a monophyletic group, while Monolepta was a non-monophyletic group. Based on ND1 data, the newly sequenced species whose antennal segment 2 was shorter than 3 were split into several clades, while, based on the mitogenomic dataset, the four newly sequenced species had close relationships with Paleosepharia. The species whose antennal segment 2 was as long as 3 were split into two clades, which indicated that the characteristic of "antennal segment 2 as long as 3" of the true "Monolepta" evolved multiple times in several subgroups. Therefore, to explore the relationships among the true Monolepta, the most important thing is to perform a thorough revision of Monolepta and related genera in the future.
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Hyperuricemia, caused by an imbalance between the rates of production and excretion of uric acid (UA), may greatly increase the mortality rates in patients with cardiovascular and cerebrovascular diseases. Herein, for fast-acting and long-lasting hyperuricemia treatment, armored red blood cell (RBC) biohybrids, integrated RBCs with proximal, cascaded-enzymes of urate oxidase (UOX) and catalase (CAT) encapsulated within ZIF-8 framework-based nanoparticles, have been fabricated based on a super-assembly approach. Each component is crucial for hyperuricemia treatment: 1) RBCs significantly increase the circulation time of nanoparticles; 2) ZIF-8 nanoparticles-based superstructure greatly enhances RBCs resistance against external stressors while preserving native RBC properties (such as oxygen carrying capability); 3) the ZIF-8 scaffold protects the encapsulated enzymes from enzymatic degradation; 4) no physical barrier exists for urate diffusion, and thus allow fast degradation of UA in blood and neutralizes the toxic by-product H2 O2 . In vivo results demonstrate that the biohybrids can effectively normalize the UA level of an acute hyperuricemia mouse model within 2 h and possess a longer elimination half-life (49.7 ± 4.9 h). They anticipate that their simple and general method that combines functional nanomaterials with living cell carriers will be a starting point for the development of innovative drug delivery systems.
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Hiperuricemia , Estruturas Metalorgânicas , Humanos , Animais , Camundongos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Modelos Animais de Doenças , Ácido Úrico , Eritrócitos/metabolismoRESUMO
Conversion-type electrodes offer a promising multielectron transfer alternative to intercalation hosts with potentially high-capacity release in batteries. However, the poor cycle stability severely hinders their application, especially in aqueous multivalence-ion systems, which can fundamentally impute to anisotropic ion diffusion channel collapse in pristine crystals and irreversible bond fracture during repeated conversion. Here, an amorphous bismuth sulfide (a-BS) formed in situ with unprecedentedly self-controlled moderate conversion Cu2+ storage is proposed to comprehensively regulate the isotropic ion diffusion channels and highly reversible bond evolution. Operando synchrotron X-ray diffraction and substantive verification tests reveal that the total destruction of the BiâS bond and unsustainable deep alloying are fully restrained. The amorphous structure with robust ion diffusion channels, unique self-controlled moderate conversion, and high electrical conductivity discharge products synergistically boosts the capacity (326.7 mAh g-1 at 1 A g-1 ), rate performance (194.5 mAh g-1 at 10 A g-1 ), and long-lifespan stability (over 8000 cycles with a decay rate of only 0.02 per cycle). Moreover, the a-BS Cu2+ âZn2+ hybrid ion battery can well supply a stable energy density of 238.6 Wh kg-1 at 9760 W kg-1 . The intrinsically high-stability conversion mechanism explored on amorphous electrodes provides a new opportunity for advanced aqueous storage.
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The blood-brain barrier (BBB) plays a crucial role in the central nervous system by tightly regulating the influx and efflux of biological substances between the brain parenchyma and peripheral circulation. Its restrictive nature acts as an obstacle to protect the brain from potentially noxious substances such as blood-borne toxins, immune cells, and pathogens. Thus, the maintenance of its structural and functional integrity is vital in the preservation of neuronal function and cellular homeostasis in the brain microenvironment. However, the barrier's foundation can become compromised during neurological or pathological conditions, which can result in dysregulated ionic homeostasis, impaired transport of nutrients, and accumulation of neurotoxins that eventually lead to irreversible neuronal loss. Initially, the BBB is thought to remain intact during neurodegenerative diseases, but accumulating evidence as of late has suggested the possible association of BBB dysfunction with Parkinson's disease (PD) pathology. The neurodegeneration occurring in PD is believed to stem from a myriad of pathogenic mechanisms, including tight junction alterations, abnormal angiogenesis, and dysfunctional BBB transporter mechanism, which ultimately causes altered BBB permeability. In this review, the major elements of the neurovascular unit (NVU) comprising the BBB are discussed, along with their role in the maintenance of barrier integrity and PD pathogenesis. We also elaborated on how the neuroendocrine system can influence the regulation of BBB function and PD pathogenesis. Several novel therapeutic approaches targeting the NVU components are explored to provide a fresh outlook on treatment options for PD.
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Barreira Hematoencefálica , Doença de Parkinson , Humanos , Barreira Hematoencefálica/fisiologia , Doença de Parkinson/patologia , Encéfalo/patologia , Sistema Nervoso Central , Transporte Biológico/fisiologiaRESUMO
As the world grapples with the challenges of energy transition and industrial decarbonization, the development of carbon capture technologies presents a promising solution. The Scalable Modeling, Artificial Intelligence (AI), and Rapid Theoretical calculations, referred as SMART here, is an interdisciplinary approach that combines high-throughput calculation and data-driven modeling with expertise from chemical, materials, environmental, computer and data science and engineering, leading to the development of advanced capabilities in simulating and optimizing carbon capture processes. This perspective discusses the state-of-the-art material discovery research enabled by high-throughput calculation and data-driven modeling. Further, we propose a framework for material discovery, and illustrate the synergies among deep learning models, pretrained models, and comprehensive data sets, emerging as a robust framework for data-driven design and development in carbon capture. In essence, the adoption of the SMART approach promises a revolutionary impact on efforts in energy transition and industrial decarbonization.
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Inteligência Artificial , Aprendizado de Máquina , Tecnologia , Carbono , IndústriasRESUMO
BACKGROUND: Cardiovascular disease and cancer are the main causes of morbidity and mortality worldwide. Studies have shown that these two diseases may have some common risk factors. Atorvastatin is mainly used for the treatment of atherosclerosis in clinic. A large number of studies show that atorvastatin may produce anti-tumor activities. This study aimed to predict the common targets of atorvastatin against atherosclerosis and non-small cell lung cancer (NSCLC) based on network pharmacology. METHODS: The target genes of atherosclerosis and NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The disease-target-component model map and the core network were obtained using Cytoscape 3.7.1. The MTS and wound healing assay were used to detect the effect of atorvastatin on cell viability and migration of A549 cells. The expression of potential common target genes of atorvastatin against atherosclerosis and NSCLC were confirmed in A549 cells and lung cancer tissues of patients. RESULTS: We identified 15 identical pathogenic genes, and four of which (MMP9, MMP12, CD36, and FABP4) were considered as the key target genes of atorvastatin in anti-atherosclerosis and NSCLC. The MTS and wound healing assays revealed that atorvastatin decreased A549 cells migration significantly. Atorvastatin markedly decreased the expression of MMP9, MMP12, CD36, and FABP4 in A549 cells and patients were treated with atorvastatin. CONCLUSIONS: This study demonstrated 15 common pathogenic genes in both atherosclerosis and NSCLC. And verified that MMP 9, MMP 12, CD 36 and FABP 4 might be the common target genes of atorvastatin in anti-atherosclerosis and NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/uso terapêutico , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Metaloproteinase 12 da Matriz/uso terapêuticoRESUMO
The discovery and identification of mushroom toxins has long been an important area in the fields of toxicology and food safety. Mushrooms are widely favored for their culinary and medicinal value; however, the presence of potentially lethal toxins in some species poses a substantial challenge in ensuring their safe consumption. Therefore, the development of a robust and sensitive analytical method is necessary for accurately identifying the risks associated with mushroom consumption. The study of mushroom toxins, which are characterized by their diversity and substantial variations in chemical structures, present a considerable challenge for achieving precise and high-throughput analysis. To address this issue, the present study employed a robust approach combining a solid-phase extraction (SPE) purification technique with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to establish an analytical method for the detection and quantification of five amatoxins and two tryptamines (psilocybin and bufotenine) present in some mushrooms. Several optimization procedures were undertaken, including optimizing the chromatographic conditions, mass spectrometric parameters, and sample extraction and purification. The procedure involved the extraction of dry mushroom powder with methanol containing 0.3% formic acid, followed by purification using a strong cation exchange cartridge (SCX). The analytes were separated on a T3 chromatographic column (100 mm×2.1 mm, 1.8 µm) using mobile phases of acetonitrile and 5 mmol/L ammonium acetate solution containing 0.1% formic acid. The multiple reaction monitoring (MRM) mode was employed for data acquisition. Amatoxins were quantified using matrix-matched standard calibration curves, whereas isotopic internal standards were used to quantify tryptamine. The results showed that all seven toxins exhibited good linearities (r2>0.99) within the optimized concentration range. The limits of detection (LODs) for bufotenine, psilocybin, and amatoxins were determined as 2.0, 5.0, and 10 µg/kg, respectively, while the limits of quantification (LOQs) were determined as 5.0, 10, and 20 µg/kg, respectively. The LOD and LOQ values further underscore the ability of the method to detect minute quantities of toxins, making it particularly well suited for screening food samples for potential contamination. Using dried shiitake mushroom powder as the matrix, the recoveries of the two tryptamines ranged from 80.6% to 117%, with relative standard deviations (RSDs) ranging from 1.73% to 5.98%, while the recoveries of amatoxins ranged from 71.8% to 115%, with RSDs varying from 2.14% to 9.92% at the three concentration levels. The consistent and satisfactory recoveries of amatoxins and tryptamines demonstrated the ability of this method to accurately quantify the target analytes even in a complex matrix. Comparison with the results of supplementary test method recognized by State Administration for Market Regulation for food (BJS 202008) demonstrated comparable results, indicating no significant differences (p>0.05) in amatoxin contents. The newly developed method is rapid, accurate, precise, meets the required standards, and is suitable for the detection of seven toxins in wild mushrooms. As part of the application of this method, a comprehensive investigation of the distribution of toxins in wild mushrooms from Fujian Province was undertaken. In this study, 59 wild mushroom samples from nine cities were collected in the Fujian province. Species identification was conducted using rDNA-internal transcribed space (rDNA-ITS) molecular barcode technology, which revealed the presence of toxins in the two samples. Notably, one specimen named Amanita fuligineoides contained α-amanitin, ß-amanitin, and phalloidin in quantities of 607, 377, and 69.0 mg/kg, respectively. Additionally, another sample, identified as Tricholomataceae, had a psilocybin concentration of 12.6 mg/kg.
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Amanita , Micotoxinas , Cromatografia Líquida de Alta Pressão , Amanita/química , Espectrometria de Massas em Tandem , Psilocibina , Bufotenina , Pós , Triptaminas , DNA RibossômicoRESUMO
Electronic structure defines the conductivity and ion absorption characteristics of a functional electrode, significantly affecting the charge transfer capability in batteries, while it is rarely thought to be involved in mesoscopic volume and diffusion kinetics of the host lattice for promoting ion storage. Here, we first correlate the evolution in electronic structure of the Mo6S8 cathode with the ability to bound volume expansion and accelerate diffusion kinetics for high-performance aqueous Cu2+ storage. Operando synchrotron energy-dispersive X-ray absorption spectroscopy reveals that accumulative delocalized Mo 4d electrons enhance the Mo-Mo interaction with distinctly contracting and uniformizing Mo6 clusters during the reduction of Mo6S8, which potently restrain lattice expansion and release space to promote Cu2+ diffusion kinetics. Operando synchrotron X-ray diffraction and comprehensive characterizations further validate the structural and electrochemical properties induced by the Cu2+ intercalation electronic structure, endowing the Mo6S8 cathode a high specific capacity with small volume expansion, fast ions diffusion, and long-term cycling stability.
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Titanium selenide (TiSe2 ), a model transition metal chalcogenide material, typically relies on topotactic ion intercalation/deintercalation to achieve stable ion storage with minimal disruption of the transport pathways but has restricted capacity (<130 mAh g-1 ). Developing novel energy storage mechanisms beyond conventional intercalation to break capacity limits in TiSe2 cathodes is essential yet challenging. Herein, the ion storage properties of TiSe2 are revisited and an unusual thermodynamically stable twin topotactic/nontopotactic Cu2+ accommodation mechanism for aqueous batteries is unraveled. In situ synchrotron X-ray diffraction and ex situ microscopy jointly demonstrated that topotactic intercalation sustained the ion transport framework, nontopotactic conversion involved localized multielectron reactions, and these two parallel reactions are miraculously intertwined in nanoscale space. Comprehensive experimental and theoretical results suggested that the twin-reaction mechanism significantly improved the electron transfer ability, and the reserved intercalated TiSe2 structure anchored the reduced titanium monomers with high affinity and promoted efficient charge transfer to synergistically enhance the capacity and reversibility. Consequently, TiSe2 nanoflake cathodes delivered a never-before-achieved capacity of 275.9 mAh g-1 at 0.1 A g-1 , 93.5% capacity retention over 1000 cycles, and endow hybrid batteries (TiSe2 -Cu||Zn) with a stable energy supply of 181.34 Wh kg-1 at 2339.81 W kg-1 , offering a promising model for aqueous ion storage.
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High-energy metal anodes for large-scale reversible batteries with inexpensive and nonflammable aqueous electrolytes promise the capability of supporting higher current density, satisfactory lifetime, nontoxicity, and low-cost commercial manufacturing, yet remain out of reach due to the lack of reliable electrode-electrolyte interphase engineering. Herein, in situ formed robust interphase on copper metal electrodes (CMEs) induced by a trace amount of potassium dihydrogen phosphate (0.05 m in 1 m CuSO4 -H2 O electrolyte) to fulfill all aforementioned requirements is demonstrated. Impressively, an unprecedented ultrahigh-speed copper plating/stripping capability is achieved at 100 mA cm-2 for over 12 000 cycles, corresponding to an accumulative areal capacity up to tens of times higher than previously reported CMEs. The use of solid-electrolyte interface-protection strategy brings at least an order of magnitude improvement in cycling stability for symmetric cells (Cu||Cu, 2800 h) and full batteries with CMEs using either sulfur cathodes (S||Cu, 1000 cycles without capacity decay) or zinc anodes (Cu||Zn with all-metal electrodes, discharge voltage ≈1.02 V). The comprehensive analysis reveals that the hydrophilic phosphate-rich interphase nanostructures homogenize copper-ion deposition and suppress nucleation overpotential, enabling dendrite-free CMEs with sustainability and ability to tolerate unusual-high power densities. The findings represent an elegant forerunner toward the promising goal of metal electrode applications.
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BACKGROUND: BRCA1 associated protein (BRAP) participates in the regulation of myocardial infarction and atherosclerosis. But the function of BRAP in cerebral ischemia-reperfusion (CIR) injury has not been elucidated yet. METHODS: BRAP expression in PC12 cells in response to oxygen-glucose deprivation/reoxygenation (OGD/R) treatment was examined with Western blot assay. PC12 cells underwent OGD/R-treatment and were subsequently transfected with pcDNA-BRAP or sh-BRAP, followed by determination of viability, lactate dehydrogenase (LDH) production, apoptosis, inflammatory cytokine secretion, and oxidative stress marker protein levels. Paraoxonase 1 (PON1) promoter methylation was evaluated with methylation-specific PCR assay. the effect of BRAP/PON1 axis on CIR injury was investigated by rescue experiments. Additionally, sh-BRAP was injected into a middle cerebral artery occlusion (MCAO) rat model, and the changes of neurological damage were evaluated. RESULTS: BRAP overexpression exacerbated OGD/R-induced viability reduction, LDH production, apoptosis, inflammatory cytokine secretion and oxidative stress in PC12 neuronal cells. In contrast, BRAP silencing showed the opposite results. Mechanistically, BRAP reduced PON1 expression by promoting DNA methyl transferase1 (DNMT1)-mediated PON1 promoter methylation. PON1 silencing reversed BRAP-mediated neuroprotection. Additionally, BRAP silencing alleviated CIR-induced neurological damage in MCAO rats. CONCLUSION: BRAP silencing suppressed OGD/R-induced neuronal apoptosis, inflammation, and oxidative stress, and alleviated CIR-induced neurological damage in MCAO rats through facilitating PON1 expression.