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In this study, Cu-Cu2O/PtPd nanocomposites were synthesized and characterized for their peroxidase-like enzyme activity. X-ray diffraction and energy dispersive X-ray spectroscopy analyses confirmed the successful synthesis of the nanocomposites, which exhibited a flower-like morphology and a more uniform dispersion than Cu-Cu2O. The catalytic activity of Cu-Cu2O/PtPd was evaluated using the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB), finding that Cu-Cu2O/PtPd outperformed Cu-Cu2O. The optimal temperature and pH for the catalytic activity of Cu-Cu2O/PtPd were determined to be 40 °C and pH 4.0, respectively. A kinetic analysis revealed that Cu-Cu2O/PtPd followed Michaelis-Menten kinetics and exhibited a higher affinity toward TMB than the horseradish peroxidase enzyme. The catalytic mechanism of Cu-Cu2O/PtPd involved the generation of hydroxyl radicals, which facilitated the oxidation of TMB. Furthermore, the Cu-Cu2O/PtPd nanocomposite was successfully applied for the colorimetric detection of glucose, demonstrating a linear range of 8-90 µM, a detection limit of 2.389 µM, and high selectivity for glucose over other sugars.
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Colorimetria , Glucose , Colorimetria/métodos , Cinética , Glucose/análise , Peroxidase/química , Peroxidases/metabolismo , Peróxido de Hidrogênio/química , CatáliseRESUMO
Cobalt oxyhydroxide (CoOOH) is a promising catalytic material for oxygen evolution reaction (OER). In the traditional CoOOH structure, Co3+ exhibits a low-spin state configuration ([Formula: see text]), with electron transfer occurring in face-to-face [Formula: see text] orbitals. In this work, we report the successful synthesis of high-spin state Co3+ CoOOH structure, by introducing coordinatively unsaturated Co atoms. As compared to the low-spin state CoOOH, electron transfer in the high-spin state CoOOH occurs in apex-to-apex [Formula: see text] orbitals, which exhibits faster electron transfer ability. As a result, the high-spin state CoOOH performs superior OER activity with an overpotential of 226 mV at 10 mA cm-2, which is 148 mV lower than that of the low-spin state CoOOH. This work emphasizes the effect of the spin state of Co3+ on OER activity of CoOOH based electrocatalysts for water splitting, and thus provides a new strategy for designing highly efficient electrocatalysts.
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Seasonal influenza still greatly threatens public health worldwide, leading to significant morbidity and mortality. Antiviral medications for influenza treatment are limited and accompanied by increased drug resistance. In severe influenza virus infection, hyperinflammation and hypoxia may be the significant threats associated with mortality, so the development of effective therapeutic methods to alleviate excessive inflammation while reducing viral damage is highly pursued. Here, a multifunctional MOF-based nanohybrid of CuâTCPP@Mn3 O4 as a novel drug against influenza A virus infection (MOF = metal-organic framework; TCPP = tetrakis (4-carboxyphenyl) porphyrin) is designed. CuâTCPP@Mn3 O4 exhibits potent inhibitory capability against influenza A virus infection in vitro and in vivo. The mechanism study reveals that CuâTCPP@Mn3 O4 inhibits the virus entry by binding to the HA2 subunit of influenza A virus hemagglutinin. In addition, the nanoparticles of Mn3 O4 in CuâTCPP@Mn3 O4 can scavenge intracellular ROS with O2 generation to downregulate inflammatory factors and effectively inhibit cytokines production. By reconstructing the antioxidant microenvironment, CuâTCPP@Mn3 O4 features as a promising nanomedicine with anti-inflammatory and anti-viral synergistic effects.
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Influenza Humana , Nanopartículas , Humanos , Espécies Reativas de Oxigênio , Inflamação/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêuticoRESUMO
Trifolium pratense is an important legume forage grass and a key component of sustainable livestock development. Serving as an essential component, the WRKY gene family, a crucial group of regulatory transcription factors in plants, holds significant importance in their response to abiotic stresses. However, there has been no systematic analysis conducted on the WRKY gene family in Trifolium pratense. This study conducted a comprehensive genomic characterization of the WRKY gene family in Trifolium pratense, utilizing the latest genomic data, resulting in the identification of 59 TpWRKY genes. Based on their structural features, phylogenetic characteristics, and conserved motif composition, the WRKY proteins were classified into three groups, with group II further subdivided into five subgroups (II-a, II-b, II-c, II-d, and II-e). The majority of the TpWRKYs in a group share a similar structure and motif composition. Intra-group syntenic analysis revealed eight pairs of duplicate segments. The expression patterns of 59 TpWRKY genes in roots, stems, leaves, and flowers were examined by analyzing RNA-seq data. The expression of 12 TpWRKY genes under drought, low-temperature (4°C), methyl jasmonate (MeJA) and abscisic acid (ABA) stresses was analyzed by RT-qPCR. The findings indicated that TpWRKY46 was highly induced by drought stress, and TpWRKY26 and TpWRKY41 were significantly induced by low temperature stress. In addition, TpWRKY29 and TpWRKY36 were greatly induced by MeJA stress treatment, and TpWRKY17 was significantly upregulated by ABA stress treatment. In this research, we identified and comprehensively analyzed the structural features of the WRKY gene family in T.pratense, along with determined the possible roles of WRKY candidate genes in abiotic stress. These discoveries deepen our understandings of how WRKY transcription factors contribute to species evolution and functional divergence, laying a solid molecular foundation for future exploration and study of stress resistance mechanisms in T.pratense.
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Vacuolar sugar transporters transport sugar across the tonoplast, are major players in maintaining sugar homeostasis, and therefore play vital roles in plant growth, development, and biomass yield. In this study, we analyzed the physiological roles of the tonoplast monosaccharide transporter 2 (TMT2) in Arabidopsis. In contrast to the wild type (WT) that produced uniform seedlings, the tmt2 mutant produced three types of offspring: un-germinated seeds (UnG), seedlings that cannot form true leaves (tmt2-S), and seedlings that develop normally (tmt2-L). Sucrose, glucose, and fructose can substantially, but not completely, rescue the abnormal phenotypes of the tmt2 mutant. Abnormal cotyledon development, arrested true leaf development, and abnormal development of shoot apical meristem (SAM) were observed in tmt2-S seedlings. Cotyledons from the WT and tmt2-L seedlings restored the growth of tmt2-S seedlings through micrografting. Moreover, exogenous sugar sustained normal growth of tmt2-S seedlings with cotyledon removed. Finally, we found that the TMT2 deficiency resulted in growth defects, most likely via changing auxin signaling, target of rapamycin (TOR) pathways, and cellular nutrients. This study unveiled the essential functions of TMT2 for seed germination and initial seedling development, ensuring cotyledon function and mobilizing sugars from cotyledons to seedlings. It also expanded the current knowledge on sugar metabolism and signaling. These findings have fundamental implications for enhancing plant biomass production or seed yield in future agriculture.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Carboidratos , Germinação , Glucose/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Plântula/metabolismoRESUMO
Rechargeable aqueous zinc batteries (RAZBs) represent a sustainable, environmentally benign, cost-efficient energy storage solution for the scaled renewable power system. However, the cycling endurance and temperature adaptability of RAZBs are hindered by practical technological barriers such as the subzero freezing point of aqueous electrolyte, severe cation dissolution of the cathode, and dendrite growth on the Zn anode. Herein, we optimize the hybrid electrolyte formulation of 8 M ZnCl2 in the ethylene glycol-water mixed solvent to reconfigure the hydrogen bonding and [Zn(H2O)1.80(EG)0.23]2+ solvation sheath, which well balances the ionic conductivity and the antifreezing property until -125 °C. As monitored by operando X-ray diffraction, meanwhile, the structural dissolution of the V2O5 cathode upon the dynamic cycling and static idling storage at elevated temperature are effectively restrained. At the anode side, the thermally induced substitution between the Ag2Se overcoating and Zn foil in situ constructs the site-selective, mosaic interface layer, in which the solvophilic ZnSe facilitates the desolvation, while the Ag species provide zincophilic nucleation sites for high-throughput Zn deposition. The synergistic coupling of the antifreezing electrolyte and anode interfacial design enables the wide-temperature-range adaptability of the RAZB prototype (10 µm Zn foil and 1 mAh cm-2 V2O5 cathode), which balances the cycling endurance (92.5% capacity retention rate for 1000 cycles), 84.7% mitigation of the self-discharge rate at 55 °C, as well as the secured cyclability even at -40 °C.
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Background: Due to the immunosuppressive tumor microenvironment (TME), radiation therapy (RT)-mediated immune response is far from satisfactory. How to improve the efficacy of immunogenic RT by priming strong immunogenic cell death (ICD) is an interesting and urgent challenge. Methods: A polyacrylic acid-coated core-shell UiO@Mn3O4 (denoted as UMP) nanocomposite is constructed for immunogenic RT via multiple strategies. Results: Reshaping the TME via Mn3O4-mediated integration of O2 production, GSH depletion, ROS generation and cell cycle arrest, accompanied by Hf-based UiO-mediated radiation absorption, eventually amplifies UMP-mediated RT to induce intense ICD. With the potent ICD induction and reprogrammed tumor-associated macrophages, this synergetic strategy can promote dendritic cells maturation and CD8+ T cells infiltration, and potentiate anti-tumor immunity against primary, distant, and metastatic tumors. Conclusion: This work is expected to shed light on the immunosuppressive TME-reshaping via multiple strategies to reinforce the immunogenic RT outcome and facilitate the development of effective cancer nanomedicine.
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Morte Celular , Nanomedicina , Nanoestruturas , Neoplasias , Animais , Humanos , Camundongos , Linfócitos T CD8-Positivos/imunologia , Pontos de Checagem do Ciclo Celular , Morte Celular/imunologia , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Glutationa/metabolismo , Camundongos Endogâmicos BALB C , Nanomedicina/métodos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Metástase Neoplásica/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/radioterapia , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral , Macrófagos Associados a Tumor/imunologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The low X-ray attenuation coefficient of tumor soft tissue and the hypoxic tumor microenvironment (TME) during radiation therapy (RT) of breast cancer result in RT resistance and thus reduced therapeutic efficacy. In addition, immunosuppression induced by the TME severely limits the antitumor immunity of radiation therapy. In this paper, we propose a PCN-224@IrNCs/D-Arg nanoplatform for the synergistic radiosensitization, photodynamic, and NO therapy of breast cancer that also boosts antitumor immunity (PCN = porous coordination network, IrNCs = iridium nanocrystals, D-Arg = D-arginine). The local tumors can be selectively ablated via reprogramming the tumor microenvironment (TME), photodynamic therapy (PDT) and NO therapy, and the presence of the high-Z element Ir that sensitizes radiotherapy. The synergistic execution of these treatment modalities also resulted in adapted antitumor immune response. The intrinsic immunomodulatory effects of the nanoplatform also repolarize macrophages toward the M1 phenotype and induce dendritic cell maturation, activating antitumor T cells to induce immunogenic cell death as demonstrated in vitro and in vivo. The nanocomposite design reported herein represents a new regimen for the treatment of breast cancer through TME reprogramming to exert a synergistic effect for effective cancer therapy and antitumor immunity.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Microambiente Tumoral , Neoplasias/tratamento farmacológico , Nanopartículas/uso terapêutico , Nanopartículas/química , Terapia de Imunossupressão , Linhagem Celular TumoralRESUMO
Background Data regarding the impact of successful chronic total occlusion treated with percutaneous coronary intervention (CTO-PCI) on symptoms and quality of life (QOL) in elderly patients (≥75 years) are unknown. This prospective study aimed to assess whether successful CTO-PCI could improve the symptoms and QOL in elderly patients (≥75 years). Methods and Results Consecutive patients who underwent elective CTO-PCI were prospectively enrolled and subdivided into 3 groups based on age: age<65 years, 65 years≤age<75 years, and age≥75 years. The primary outcomes included symptoms, as assessed with the New York Heart Association functional class and Seattle Angina Questionnaire, and QOL, as assessed with the 12-Item Short-Form Health Survey questionnaire, at baseline, 1 month, and 1 year after successful CTO-PCI. Of 1076 patients with CTO, 101 were age≥75 years (9.39%). Hemoglobin, estimated glomerular filtration rate, and left ventricular ejection fraction levels all decreased with increasing age, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) increased. The proportion of dyspnea and coronary lesions, including multivessel disease, multi-CTO lesion, and calcification were higher in elderly patients. Procedural success rate, intraprocedural complications, and in-hospital major adverse cardiac events were not statistically different in the 3 groups. Importantly, symptoms, including dyspnea and angina, were markedly improved regardless of age at 1-month and 1-year follow-up (P<0.05). Likewise, successful CTO-PCI significantly improved QOL at 1-month and 1-year follow-up (P<0.01). Additionally, the incidence of major adverse cardiac events and all-cause mortality at 1-month and 1-year follow-up was not statistically different in the 3 groups. Conclusions Successful PCI was beneficial and feasible to improve symptoms and QOL in patients ≥75 years of age with CTO.
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Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Idoso , Lactente , Qualidade de Vida , Volume Sistólico , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Prospectivos , Oclusão Coronária/diagnóstico , Oclusão Coronária/cirurgia , Função Ventricular Esquerda , Dispneia/etiologia , Doença Crônica , Resultado do Tratamento , Fatores de Risco , Sistema de RegistrosRESUMO
The delivery of biocompatible reagents into cancer cells can elicit an anticancer effect by taking advantage of the unique characteristics of the tumor microenvironment (TME). In this work, we report that nanoscale two-dimensional FeII- and CoII-based metal-organic frameworks (NMOFs) of porphyrin ligand meso-tetrakis (6-(hydroxymethyl) pyridin-3-yl) porphyrin (THPP) can catalyze the generation of hydroxyl radicals (â¢OH) and O2 in the presence of H2O2 that is overexpressed in the TME. Photodynamic therapy consumes the generated O2 to produce a singlet oxygen (1O2). Both â¢OH and 1O2 are reactive oxygen species (ROS) that inhibit cancer cell proliferation. The FeII- and CoII-based NMOFs were non-toxic in the dark but cytotoxic when irradiated with 660 nm light. This preliminary work points to the potential of porphyrin-based ligands of transition metals as anticancer drugs by synergizing different therapeutic modalities.
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Antineoplásicos , Neoplasias da Mama , Estruturas Metalorgânicas , Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Feminino , Estruturas Metalorgânicas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Porfirinas/farmacologia , Peróxido de Hidrogênio/farmacologia , Ligantes , Fotoquimioterapia/métodos , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Compostos Ferrosos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Microambiente TumoralRESUMO
A temperature-controlled electrochemical sensor was constructed based on a composite membrane composed of temperature-sensitive polymer poly (N-isopropylacrylamide) (PNIPAM) and carboxylated multi-walled carbon nanotubes (MWCNTs-COOH). The sensor has good temperature sensitivity and reversibility in detecting Dopamine (DA). At low temperatures, the polymer is stretched to bury the electrically active sites of carbon nanocomposites. Dopamine cannot exchange electrons through the polymer, representing an "OFF" state. On the contrary, in a high-temperature environment, the polymer shrinks to expose electrically active sites and increases the background current. Dopamine can normally carry out redox reactions and generate response currents, indicating the "ON" state. In addition, the sensor has a wide detection range (from 0.5 µM to 150 µM) and low LOD (193 nM). This switch-type sensor provides new avenues for the application of thermosensitive polymers.
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The current synthesis methods of high-entropy alloy (HEA) thin-film coatings face huge challenges in facile preparation, precise thickness control, conformal integration, and affordability. These challenges are more specific and noteworthy for noble metal-based HEA thin films where the conventional sputtering methods encounter thickness control and high-cost issues (high-purity noble metal targets required). Herein, for the first time, we report a facile and controllable synthesis process of quinary HEA coatings consisting of noble metals (Rh, Ru, Pt, Pd, and Ir), by sequential atomic layer deposition (ALD) coupled with electrical Joule heating for post-alloying. Furthermore, the resulting quinary HEA thin film with a thickness of â¼50 nm and an atomic ratio of 20:15:21:18:27 shows promising potential as a platform for catalysis, exhibiting enhanced electrocatalytic hydrogen evolution reaction (HER) performances with lower overpotentials (e.g., from 85 to 58 mV in 0.5 M H2SO4) and higher stability (by retaining more than 92% of the initial current after 20 h with a current density of 10 mA/cm2 in 0.5 M H2SO4) than other noble metal-based structure counterparts in this work. The enhanced material properties and device performances are attributed to the efficient electron transfer of HEA with the increased number of active sites. This work not only presents RhRuPtPdIr HEA thin films as promising HER catalysts but also sheds light on controllable fabrication of conformal HEA-coated complex structures toward a broad range of applications.
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Nanomedicine exhibits emerging potentials to deliver advanced therapeutic strategies in the fight against triple-negative breast cancer (TNBC). Nevertheless, it is still difficult to develop a precise codelivery system that integrates highly effective photosensitizers, low toxicity, and hydrophobicity. In this study, PCN-224 is selected as the carrier to enable effective cancer therapy through light-activated reactive oxygen species (ROS) formation, and the PCN-224@Mn3 O4 @HA is created in a simple one-step process by coating Mn3 O4 nanoshells on the PCN-224 template, which can then be used as an "ROS activator" to exert catalase- and glutathione peroxidase-like activities to alleviate tumor hypoxia while reducing tumor reducibility, leading to improved photodynamic therapeutic (PDT) effect of PCN-224. Meanwhile, Mn2+ produced cytotoxic hydroxyl radicals (âOH) via the Fenton-like reaction, thus producing a promising spontaneous chemodynamic therapeutic (CDT) effect. Importantly, by remodeling the tumor microenvironment (TME), Mn3 O4 nanoshells downregulated hypoxia-inducible factor 1α expression, inhibiting tumor growth and preventing tumor revival. Thus, the developed nanoshells, via light-controlled ROS formation and multimodality imaging abilities, can effectively inhibit tumor proliferation through synergistic PDT/CDT, and prevent tumor resurgence by remodeling TME.
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Estruturas Metalorgânicas , Nanoconchas , Neoplasias , Fotoquimioterapia , Humanos , Estruturas Metalorgânicas/farmacologia , Espécies Reativas de Oxigênio , Linhagem Celular Tumoral , Microambiente Tumoral , Peróxido de HidrogênioRESUMO
TUBA1C is correlated with an unfavourable prognosis and the infiltration of immune cells in several cancers. However, its function as a significant biomarker for the prognosis of immunotherapy in pan-cancer remains unclear. This study aims at assessing the role of TUBA1C in pan-cancer at multiple levels, including mutations, gene expression, methylation, m6A methylation, and immune cell infiltration levels. Data retrieved from major public databases, such as TCGA, GEO, GTEx, GSCA, CancerSEA, HPA, and RNAactDrugs, revealed that TUBA1C expression was high in 33 cancer types. Survival analysis revealed that TUBA1C was a poor prognostic factor for 12 tumour types, and mutations, CNVs, and methylation affected the prognosis of some cancer types. Furthermore, TUBA1C was found to be related to immune-related genes, immune cell infiltration, and the immune microenvironment. In addition, the sensitivity of 10 anticancer drugs was associated with high TUBA1C expression. Therefore, TUBA1C may serve as a viable prognostic biomarker for immunotherapy of pan-cancer.
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Neoplasias , Humanos , Prognóstico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Imunoterapia , Mutação , Processamento de Proteína Pós-Traducional , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Diabetes was commonly seen in chronic total occlusion (CTO) patients but data regarding the impact of successful percutaneous coronary intervention (PCI) on clinical outcome of CTO patients with diabetes was controversial. And importantly, no studies have compared quality of life (QOL) after CTO-PCI in patients with and without diabetes. METHODS: Consecutive patients undergoing elective CTO-PCI were prospectively enrolled from Apr. 2018 to May 2021. Patients were subdivided into 2 groups: Diabetes and No Diabetes. Detailed baseline characteristics, assessment of symptoms and QOL, angiographic and procedural details, in-hospital complications, and 1 month and 1 year follow-up data were collected. These data were analyzed accordingly for risk predictors of clinical outcome in patients who have diabetes and received successful CTO-PCI. RESULTS: A total of 1076 patients underwent CTO-PCI attempts. Diabetes was present in 374 (34.76%) patients, who had more hypertension, previous PCI and stroke. Regarding the coronary lesions, diabetic patients suffered more LCX lesion, multivessel disease, number of lesions per patient, blunt stump, calcification and higher J-CTO score (p < 0.05). In-hospital major adverse cardiac event (MACE) (4.13% vs. 5.35%; p = 0.362) was similar in the two groups. At 1 month and 1 year follow-up after successful CTO-PCI, the incidence of MACE and all-cause mortality were also similar in the two groups (p > 0.05). Number of lesions per patient was an independent risk factor of MACE and all-cause mortality (p < 0.001) 1 year after successful CTO-PCI. Symptom and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up, and importantly, patients with diabetes showed similar degrees of improvement to those without diabetes (P > 0.05). CONCLUSIONS: Successful CTO-PCI could represent an effective strategy improving clinical outcome, symptoms and QOL in CTO patients with diabetes.
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Oclusão Coronária , Diabetes Mellitus , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Qualidade de Vida , Angiografia Coronária , Resultado do Tratamento , Fatores de Risco , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Doença Crônica , Sistema de RegistrosRESUMO
Background: IQGAP3 has important function in cancer progression and has become a potential therapeutic target as a transmembrane protein. But its role in tumor immunity and pan-cancer was not systematically investigated. This study evaluated the potential role of IQGAP3 and clinical significance in pan-cancer through combined multiomics analysis. Methods: From Genotype Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases, transcriptomic datasets were first obtained, and from Gene Expression Omnibus (GEO), expression profiling microarray data were acquired and integrated to systematically assess the expression differences and prognostic relevance of IQGAP3 in pancreatic cancer. Immunohistochemical data were obtained from Human Protein Atlas (HPA) to assess IQGAP3 protein expression differences, and exome data from TCGA were used to analyze IQGAP3 expression in relation to tumor mutational burden (TMB), microsatellite instability (MSI), and mutation. Additionally, we also analyzed the relationship between IQGAP3 expression and immune checkpoints, mismatch repair (MMR), and IQGAP3 relationship with methylation and copy number variation based on expression profiles. Results: Microsatellite instability (MSI), immune checkpoints, mismatch repair (MMR), and tumor mutational burden (TMB) all closely interacted with IQGAP3 mRNA. In addition, detailed relationships between the immune microenvironment and IQGAP3 mRNA as well as immune cell CD4+ Th2 and myeloid-derived suppressor cells (MDSCs) were determined. Mechanistically, IQGAP3 was involved in cytoskeleton formation, T cell receptor signaling pathways, DNA damage, cell cycle, P53 pathway, Fc gamma R-mediated phagocytosis, and apoptosis. Conclusion: IQGAP3 could serve as an effective prognostic biomarker for pan-cancer immune-related therapy.
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Instabilidade de Microssatélites , Neoplasias , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Variações do Número de Cópias de DNA , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Proteínas Ativadoras de GTPase/uso terapêutico , Humanos , Neoplasias/patologia , Prognóstico , RNA Mensageiro , Receptores de Antígenos de Linfócitos T/genética , Microambiente Tumoral/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Background: The onset and progression of many cancers, including gastric cancer (GC), are strongly influenced by cell senescence. Numerous studies have demonstrated that long non-coding RNA (lncRNA) impacts cell senescence, thus affecting cancer progression. However, it is not possible to develop a relevant predictive model for GC owing to the absence of a cell senescence-linked lncRNA. Since lncRNAs are linked to cellular senescence, the goal of this work was to create a prognostic signature for stomach adenocarcinoma (STAD) patients utilizing these lncRNAs. Methods: Through the Pearson correlation, variance, and univariate Cox regression analyses, the cellular senescence lncRNAs that were related to the disease prognosis could be successfully identified. Using the least absolute shrinkage and selection operator (LASSO) regression algorithm, a predictive model that utilized the 11 cellular senescence-linked lncRNAs was constructed. Kaplan-Meier (KM) survival and the receiver operating characteristic (ROC) curve analyses, were employed for assessing the prognostic performance of the proposed model. In addition, ESTIMATE analysis of the low- and high-risk subtypes for the infiltration of various immune cells was carried out. Additionally, the CIBERSORT algorithm was utilized for investigating the infiltration status of numerous immune cells in both groups, while the expression of the immune checkpoint genes in the two groups, was also determined. Results: In this study, a new prognostic model was constructed using 11 cellular senescence-related lncRNAs. The findings revealed that the OS status of the patients in the low-risk group (category) was significantly higher compared to the high-risk category (P<0.001). The 1-year ROC-area under the curve (AUC) values for the risk score in the training group was 0.714, while the AUC value for the test and comprehensive groups were recorded to be 0.666 and 0.695, respectively, which were obviously due to stage, grade, age, etc. And based on univariate [hazard ratio (HR): 1.435; P<0.001; 95% confidence interval (CI): 1.295-1.589] and multivariate analyses (P<0.001; 95% CI: HR: 1.387; 1.247-1.543), it was noted that risk scores were effectively employed as a patient-independent prognostic factor. Conclusions: Taken together, these results suggest that cellular senescence-related lncRNAs are likely to be valuable prognostic markers for GC. They also reflect the situation of the STAD immune microenvironment and may provide direction for future GC treatment.
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Rheumatoid arthritis (RA) is an inflammatory type of arthritis that causes joint pain and damage. The inflammatory cell infiltration (e.g., M1 macrophages), the poor O2 supply at the joint, and the excess reactive oxygen species (ROS)-induced oxidative injury are the main causes of RA. We herein report a polydopamine (PDA)-coated CeO2-dopped zeolitic imidazolate framework-8 (ZIF-8) nanocomposite CeO2-ZIF-8@PDA (denoted as CZP) that can synergistically treat RA. Under near-infrared (NIR) light irradiation, PDA efficiently scavenges ROS and results in an increased temperature in the inflamed area because of its good light-to-heat conversion efficiency. The rise of temperature serves to obliterate hyper-proliferative inflammatory cells accumulated in the diseased area while vastly promoting the collapse of the acidic-responsive skeleton of ZIF-8 to release the encapsulated CeO2. The released CeO2 exerts its catalase-like activity to relieve hypoxia by generating oxygen via the decomposition of H2O2 highly expressed in the inflammatory sites. Thus, the constructed CZP composite can treat RA through NIR-photothermal/ROS-scavenging/oxygen-enriched combinative therapy and show good regression of pro-inflammatory cytokines and hypoxia-inducible factor-1α (HIF-1α) in vitro and promising therapeutic effect on RA in rat models. The multimodal nano-platform reported herein is expected to shed light on the design of synergistic therapeutic nanomedicine for effective RA therapy.
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Artrite Reumatoide , Zeolitas , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/terapia , Peróxido de Hidrogênio/efeitos adversos , Concentração de Íons de Hidrogênio , Indóis , Oxigênio/efeitos adversos , Polímeros , Ratos , Espécies Reativas de Oxigênio/efeitos adversosRESUMO
Featured with an exposed active facet, favorable ion diffusion pathway, and tailorable interfacial properties, low-dimensional structures are extensively explored as alternative electroactive materials with game-changing redox properties. Through a stepwise "proton exchange-insertion-exfoliation" procedure, in this article, we develop Na2Ti6-xMoxO13 (NTMO) nanosheets with weakened out-of-plane bonding and in-plane Mo6+ doping of the tunnel structure. Real-time phase tracking of the laminated NTMO structures upon the lithiation/delithiation process suggests mitigated lattice variation; meanwhile, the kinetics simulation shows a mitigated Li-ion diffusion barrier along the [010] orientation. At an industrial-level areal capacity loading (2.5 mAh cm-2), the NTMO electrode maintains robust cycling endurance (91% capacity retention for 2000 cycles) even at 40 C, as well as the high energy/power densities in the as-constructed NTMO||LiFePO4 full cell prototype. The dimensional and lattice modifications presented in this study thus encourage further exploration of the tailored cation diffusion pathway for the construction of fast-charging batteries.
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A multifunctional nanoplatform with core-shell structure was constructed in one-pot for the synergistic photothermal, photodynamic, and chemotherapy against breast cancer. In the presence of gambogic acid (GA) as the heat-shock protein 90 (HSP90) inhibitor and the gold nanostars (AuNS) as the photothermal reagent, the assembly of Zr4+ with tetrakis (4-carboxyphenyl) porphyrin (TCPP) gave rise to the nanocomposite AuNS@ZrTCPP-GA (AZG), which in turn, further coated with PEGylated liposome (LP) to enhance the stability and biocompatibility, and consequently the antitumor effect of the particle. Upon cellular uptake, the nanoscale metal - organic framework (NMOF) of ZrTCPP in the resulted AuNS@ZrTCPP-GA@LP (AZGL) could be slowly degraded in the weak acidic tumor microenvironment to release AuNS, Zr4+, TCPP, and GA to exert the synergistic treatment of tumors via the combination of AuNS-mediated mild photothermal therapy (PTT) and TCPP-mediated photodynamic therapy (PDT). The introduction of GA serves to reduce the thermal resistance of the cell to re-sensitize PTT and the constructed nanoplatform demonstrated remarkable anti-tumor activity in vitro and in vivo. Our work highlights a facile strategy to prepare a pH-dissociable nanoplatform for the effective synergistic treatment of breast cancer.