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Surgery of jawbones has a high potential risk of causing complications associated with temporomandibular joint disorder (TMD). The objective of this study was to investigate the effects of two drive modeling methods on the biomechanical behavior of the temporomandibular joint (TMJ) including articular disc during mandibular movements. A finite element (FE) model from a healthy human computed tomography was used to evaluate TMJ dynamic using two methods, namely, a conventional spatial-oriented method (displacement-driven) and a compliant muscle-initiated method (masticatory muscle-driven). The same virtual FE model was 3D printed and a custom designed experimental platform was established to validate the accuracy of experimental and theoretical results of the TMJ biomechanics during mandibular movements. The results show that stress distributed to TMJ and articular disc from mandibular movements provided better representation from the muscle-driving approach than those of the displacement-driven modeling. The simulation and experimental data exhibited significant strong correlations during opening, protrusion, and laterotrusion (with canonical correlation coefficients of 0.994, 0.993, and 0.932, respectively). The use of muscle-driven modeling holds promise for more accurate forecasting of stress analysis of TMJ and articular disc during mandibular movements. The compliant approach to analyze TMJ dynamics would potentially contribute to clinic diagnosis and prediction of TMD resulting from occlusal disease and jawbone surgery such as orthognathic surgery or tumor resection.
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Proteolysis targeting chimeras (PROTAC) are bifunctional chimeric molecules capable of directly degrading binding proteins through the ubiquitin-proteasome pathway. PROTACs have demonstrated significant potential in overcoming drug resistance and targeting previously untreatable targets. However, several limitations still need to be addressed, including their high molecular weight resulting in poor membrane permeability and bioavailability. In this study, we proposed that cancer-targeted penetrating peptides could enhance the cell permeability of PROTACs. We developed 26 novel targeted penetrating peptides for leukemia and lymphoma cells, among which C9C-f(3Bta) and Cyclo-C9C-R exhibited superior membrane permeability, targetability, and stability. By combining C9C-f(3Bta) and Cyclo-C9C-R with IMA-PROTAC, we effectively enhanced the anti-proliferative activity of IMA-PROTAC, facilitated degradation of Bcr-Abl protein in K562 cells, and reduced downstream STAT5 phosphorylation. Furthermore, the combined application promoted cell apoptosis while blocking G1 phase progression. HPLC-MRM-MS revealed that the combination of C9C-f(3Bta) or Cyclo-C9C-R with IMA-PROTAC significantly enhanced intracellular IMA-PROTAC content. In summary, our proof-of-concept study validated the hypothesis that combining PROTACs with targeted penetrating peptides can improve protein degradation efficiency as well as anti-proliferative capabilities.
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Xylem-associated fungus can secrete many secondary metabolites to help Aquilaria trees resist various stresses and play a crucial role in facilitating agarwood formation. However, the dynamics of endophytic fungi in Aquilaria sinensis xylem after artificial induction have not been fully elaborated. Endophytic fungi communities and xylem physio-biochemical properties were examined before and after induction with an inorganic salt solution, including four different times (pre-induction (0M), the third (3M), sixth (6M) and ninth (9M) month after induction treatment). The relationships between fungal diversity and physio-biochemical indices were evaluated. The results showed that superoxide dismutase (SOD) and peroxidase (POD) activities, malondialdehyde (MDA) and soluble sugar content first increased and then decreased with induction time, while starch was heavily consumed after induction treatment. Endophytic fungal diversity was significantly lower after induction treatment than before, but the species richness was promoted. Fungal ß-diversity was also clustered into four groups according to different times. Core species shifted from rare to dominant taxa with induction time, and growing species interactions in the network indicate a gradual complication of fungal community structure. Endophytic fungi diversity and potential functions were closely related to physicochemical indices that had less effect on the relative abundance of the dominant species. These findings help assess the regulatory mechanisms of microorganisms that expedite agarwood formation after artificial induction.
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The phenomenon of the experiences of mutual support of co-morbid couples of recurrent older stroke survivors during hospitalization is receiving increased interest from nursing scholars. However, little is known about how they support each other. The aim of this study was to explore the experiences of co-morbid couples of older stroke survivors with recurrent stroke who support each other during hospitalization. A descriptive phenomenology study was employed. 21 co-morbid couples with recurrent older stroke survivors were recruited. The interviews were analyzed with Colaizzi's descriptive analysis framework. Three themes emerged from the data analysis: (1) maintaining the couple's relationship through mutual support, (2) mutual support so as not to drag the children down, and (3) providing support while struggling between ideals and reality. It is crucial to provide them with individualized, tailored support and interventions that can help these couples achieve a more optimal balance in their mutual support.
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Colorectal cancer (CRC) is a prevalent and aggressive malignancy characterized by a complex tumor microenvironment (TME). Given the variations in the level of adipocyte infiltration in TME, the prognosis may differ among CRC patients. Thus, there is an urgent need to establish a reliable method for identifying adipocyte subtypes in CRC in order to elucidate the impact of adipocyte infiltration on CRC treatment and prognosis. Herein, 144 adipocyte-infiltration-related genes (AIRGs) were identified as predictive markers for the immune-associated features and prognosis of CRC patients. Based on the 144 genes, the unsupervised clustering algorithm identified two distinct clusters of CRC patients with variations in molecular and signaling pathways, clinicopathological characteristics and responses to CRC chemotherapy and immunotherapy. Furthermore, an AIRG prognostic signature was constructed and validated in independent datasets. Overall, this study developed a prognostic signature based on AIRGs in CRC, which may contribute to the development of personalized treatment strategies and enhance prognostic prediction for CRC patients.
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BACKGROUND: Lung ischemia reperfusion injury (IRI) is the principal cause of primary graft dysfunction (PGD) after lung transplantation, affecting short-term and long-term mortality post-transplantation. PANoptosis, a newly identified form of regulated cell death involving apoptosis, necroptosis, and pyroptosis, is now considered a possible cause of organ damage and IRI. However, the specific role of PANoptosis to the development of lung IRI following lung transplantation is still not fully understood. METHODS: In this study, we identified differentially expressed genes (DEGs) by analyzing the gene expression data from the GEO database related to lung IRI following lung transplantation. PANoptosis-IRI DEGs were determined based on the intersection of PANoptosis-related genes and screened DEGs. Hub genes associated with lung IRI were further screened using Lasso regression and the SVM-RFE algorithm. Additionally, the Cibersort algorithm was employed to assess immune cell infiltration and investigate the interaction between immune cells and hub genes. The upstream miRNAs that may regulate hub genes and compounds that may interact with hub genes were also analyzed. Moreover, an external dataset was utilized to validate the differential expression analysis of hub genes. Finally, the expressions of hub genes were ultimately confirmed using quantitative real-time PCR, western blotting, and immunohistochemistry in both animal models of lung IRI and lung transplant patients. RESULTS: PANoptosis-related genes, specifically interferon regulatory factor 1 (IRF1) and interleukin 1 alpha (IL1A), have been identified as potential biomarkers for lung IRI following lung transplantation. In mouse models of lung IRI, both the mRNA and protein expression levels of IRF1 and IL1A were significantly elevated in lung tissues of the IRI group compared to the control group. Moreover, lung transplant recipients exhibited significantly higher protein levels of IRF1 and IL1A in PBMCs when compared to healthy controls. Patients who experienced PGD showed elevated levels of IRF1 and IL1A proteins in their blood samples. Furthermore, in patients undergoing lung transplantation, the protein levels of IRF1 and IL1A were notably increased in peripheral blood mononuclear cells (PBMCs) compared to healthy controls. In addition, patients who developed primary graft dysfunction (PGD) exhibited even higher protein levels of IRF1 and IL1A than those without PGD. Furthermore, PANoptosis was observed in the lung tissues of mouse models of lung IRI and in the PBMCs of patients who underwent lung transplantation. CONCLUSIONS: Our research identified IRF1 and IL1A as biomarkers associated with PANoptosis in lung IRI, suggesting their potential utility as targets for diagnosing and therapeutically intervening in lung IRI and PGD following lung transplantation.
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Fator Regulador 1 de Interferon , Interleucina-1alfa , Transplante de Pulmão , Pulmão , Traumatismo por Reperfusão , Transplante de Pulmão/efeitos adversos , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Animais , Fator Regulador 1 de Interferon/genética , Fator Regulador 1 de Interferon/metabolismo , Humanos , Camundongos , Pulmão/patologia , Pulmão/imunologia , Masculino , Interleucina-1alfa/genética , Interleucina-1alfa/metabolismo , Necroptose , Camundongos Endogâmicos C57BL , Piroptose , Modelos Animais de Doenças , Disfunção Primária do Enxerto/genética , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/imunologia , Disfunção Primária do Enxerto/diagnósticoRESUMO
Three new sesquiterpenes, 4S-1-(3-hydroxybutyl)-7-(11-hydroxypropyl)-10-methyl- cyclohepta-7,5,10-trien-8-one (1), 8R-hydroxy-7-(4S-4,10-dimethyl-5-oxooct-1-en-7-yl)-11- methylfuran-12-one (2), (1S,5R,7S,10R)-1-hydroxy-7-(11-hydroxypropyl)-10-methyl-4- methyleneoctahydronaphthalen-8-one (3), along with 30 known terpenoids (4-33) were obtained from the rhizomes of Curcuma kwangsiensis S.G. Lee et C.F. Ling. Through comprehensive analysis of chemical evidence and spectral data including UV, ECD, IR, 1D and 2D NMR and HR-ESI-MS, as well as quantum chemical calculation, the structures of these novel compounds were successfully determined. Additionally, the inhibitory effects of compounds 1-2, 4-33 on NO production were evaluated in lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, compound 33 exhibited the most significant inhibitory effect with an IC50 value of 3.55 ± 0.55 µM.
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In this study, a low field nuclear magnetic resonance (LF-NMR) homogeneous sensor was constructed for detection of Escherichia coli (E. coli) based on the copper metabolism of E. coli triggered click reaction. When live E. coli was present, a large amount of Cu2+ ions were transformed into Cu+ via copper metabolism, which then catalyzed a Cu+-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between two materials, azide group modified gadolinium oxide nanorods (Gd2O3-Az) and PA-GO@Fe3O4 i.e., graphene oxide (GO) loaded with large amounts of alkynyl (PA) groups and Fe3O4 nanoparticles simultaneously. After magnetic separation, unbound Gd2O3-Az was dissolved by added hydrochloric acid (HCl) to generate homogeneous Gd3+ solution, enabling homogeneous detection of E. coli. Triple signal amplification was achieved through the CuAAC reaction induced by E. coli copper metabolism, functional nanomaterials, and HCl assisted homogeneous detection. Under the optimal experimental conditions, the linear range and limit of detection (LOD) for E. coli were 10-1.0 × 107 CFU/mL and 3.5 CFU/mL, respectively, and the relative standard deviations (RSDs) were all less than 2.8 %. In addition, the sensor has satisfactory selectivity, stability and practical sample application capability, providing a new approach for the LF-NMR detection of food-borne pathogenic bacteria.
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Alcinos , Azidas , Química Click , Cobre , Escherichia coli , Grafite , Escherichia coli/isolamento & purificação , Cobre/química , Azidas/química , Grafite/química , Alcinos/química , Espectroscopia de Ressonância Magnética , Reação de Cicloadição , Gadolínio/química , Limite de Detecção , Nanotubos/químicaRESUMO
Transcatheter arterial chemoembolization (TACE) is the first-line therapy for hepatocellular carcinoma (HCC). However, the exacerbated hypoxia microenvironment induces tumor relapse and metastasis post-TACE. Here, temperature-sensitive block polymer complexed with polyphosphate-cisplatin (Pt-P@PND) was prepared for the enhancement of tumor artery embolization by coagulation activation. After supra-selective infusion into the tumor vessels, Pt-P@PND nanogels performed efficient embolization of tumor arteries by sol-gel transition at body temperature. Meanwhile, coagulation cascade was evoked to form blood clots in the peripheral arteries inaccessible to the nanogels by released PolyP. The blood clots-filled hydrogel networks composed of gel and clots showed a denser structure and higher modulus, thereby achieving long-term embolization of all levels of tumor arteries. Pt-P@PND nanogels efficiently inhibited tumor growth and reduced the expression of HIF-1α, VEGF, CD31, and MMP-9 on VX2 tumor-bearing rabbit model. The released Nitro-Pt stimulated the immunogenic cell death of tumor cells, thus enhancing the antitumor immune response to suppress tumor relapse and metastasis post-TACE. It is hoped that Pt-P@PND nanogels can be developed as a promising embolic agent with procoagulant activity for enhancing the antitumor immune response through a combination of embolism, coagulation, and chemotherapy. STATEMENT OF SIGNIFICANCE: Clinical embolic agents, such as Lipiodol and polyvinyl alcohol (PVA) microspheres, are limited by their rapid elimination or larger size, thus lead to incomplete embolization of trans-catheter arterial chemoembolization (TACE). Herein, temperature-sensitive Pt-P@PND nanogels were developed to achieve long-term embolization of all levels of tumor arteries by gel/clot generation. The released Nitro-Pt induced immunogenic cell death in tumor cells, which improved the antitumor immune microenvironment by the maturation of DCs and lymphocytic infiltration. Pt-P@PND nanogels successfully inhibited tumor growth and activated an antitumor immune response to curb the recurrence and metastasis of residual tumor cells both in VX2 tumor-bearing rabbit model and 4T1 tumor-bearing mouse model. These findings suggested that Pt-P@PND could be developed as an ideal embolic agent for clinical TACE treatment.
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Hepatocellular carcinoma (HCC) is a common tumor. Our group has previously reported that sorcin (SRI) plays an important role in the progression and prognosis of HCC. This study aims to explore the mechanism of SRI inhibiting the mitochondrial apoptosis. Bioinformatics analysis, co-IP and immunofluorescence were used to analyze the relationship between SRI and STAT3. MMP and Hoechst staining were performed to detect the effect of SRI on cell apoptosis. The expression of apoptosis-related proteins and NF-κB signaling pathway were examined by Western blot and immunohistochemistry when SRI overexpression or underexpression in vivo and in vitro were found. Moreover, inhibitors were used to further explore the molecular mechanism. Overexpression of SRI inhibited cell apoptosis, which was attenuated by SRI knockdown in vitro and in vivo. Moreover, we identified that STAT3 is an SRI-interacting protein. Mechanistically, SRI interacts with STAT3 and then activates the NF-κB signaling pathway in vitro and in vivo. SRI interacting with STAT3 inhibits apoptosis by the NF-κB pathway and further contributes to the proliferation in HCC, which offers a novel clue and a new potential therapeutic target for HCC.
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Apoptose , Carcinoma Hepatocelular , Neoplasias Hepáticas , Mitocôndrias , NF-kappa B , Fator de Transcrição STAT3 , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Humanos , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Animais , Camundongos , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Nus , Masculino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Based on first-principles calculations in the density functional theory, we systematically investigated the possible interface structure, magnetism, and electronic properties of the all-Heusler alloy Co2MnGe/CoTiMnGe(100) heterojunction. The calculation indicated that the Co2MnGe Heusler alloy is a half-metal with a magnetic moment of 4.97 µB. CoTiMnGe is a narrow-band gap semiconductor and may act as an ultra-sensitive photocatalyst. We cannot find an "ideal" spin-polarization of 100% in CoCo termination and MnGe termination. Due to the interface interaction, the direct magnetic hybridization or indirect RKKY exchange will be weakened, leading to an increase in the atomic magnetic moment of the interfacial layer. For eight possible heterojunction structures, the half-metallic gaps in the Co2MnGe bulk have been destroyed by the inevitable interface states. The spin-polarization value of 94.31% in the CoCo-TiGe-B heterojunction revealed that it is the most stable structure. It is feasible to search for high-performance magnetic tunnel junction by artificially constructing suitable all-Heusler alloy heterojunctions.
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In this work, graphene oxide (GO)/polymer hybrid microcapsule-loaded self-healing agents were prepared via the combination of the emulsion template method and photopolymerization technology. The incorporation of GO in the microcapsule shell not only improved the impermeability, mechanical property, and solvent resistance property of the microcapsules significantly but also endowed the microcapsules with photothermal conversion property. By incorporating GO/polymer hybrid microcapsules in water-borne epoxy resin, a novel kind of anticorrosion coating with a double self-healing property was successfully fabricated. When the coating was scratched, the linseed oil (LO) encapsulated in the microcapsules could fill the crack, and the photothermal conversion property of GO could promote the molecular chain movement of the damaged area under near-infrared (NIR) irradiation to realize the close of the crack. Based on the filling of LO and photothermal conversion-induced scratch narrowing, the "filling" and "close" double self-healing effect can be realized under temporal NIR irradiation, which could lead to the complete recovery of the scratched coating. The |Z|f=0.1Hz value of the damaged coating with GO/polymer microcapsules after double healing was comparable to that of the intact coating, which was about 4 orders of magnitude higher than that of the scratched blank coating and single self-healing coating. As to the neutral salt spray test, the scratched blank coating failed in protection after 100 h, while the healed composite coating did not show any corrosion after 300 h.
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Multimetal phosphides derived from metal-organic frameworks (MOFs) have garnered significant interest owing to their distinct electronic configurations and abundant active sites. However, developing robust and efficient catalysts based on metal phosphides for overall water splitting (OWS) remains challenging. Herein, we present an approach for synthesizing a self-supporting hollow porous cubic FeNiP-CoP@NC catalyst on a nickel foam (NF) substrate. Through ion exchange, the reconstruction chemistry transforms the FeNi-MOF nanospheres into intricate hollow porous FeNi-MOF-Co nanocubes. After phosphorization, numerous N, P co-doped carbon-coated FeNiP-CoP nanoparticles were tightly embedded within a two-dimensional (2D) carbon matrix. The NF/FeNiP-CoP@NC heterostructure retained a porous configuration, numerous heterogeneous interfaces, distinct defects, and a rich composition of active sites. Moreover, incorporating Co and the resulting structural evolution facilitated the electron transfer in FeNiP-CoP@NC, enhancing the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) processes. Consequently, the NF/FeNiP-CoP@NC catalyst demonstrated very low overpotentials of 78 mV for OER and 254 mV for HER in an alkaline medium. It also exhibited excellent long-term stability at various potentials (@10 mA cm-2, @20 mA cm-2, and @50 mA cm-2). As an overall water splitting cell, it required only 1.478 V to drive a current density of 50 mA cm-2 and demonstrated long-term stability. Density functional theory (DFT) calculations revealed a synergistic effect between multimetal phosphides, enhancing the intrinsic OER and HER activities of FeNiP-CoP@NC. This work not only elucidates the role of heteroatom induction in structural reconstruction but also highlights the importance of electronic structure modulation.
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Uncontrollable dendrite growth and corrosion induced by reactive water molecules and sulfate ions (SO42-) seriously hindered the practical application of aqueous zinc ion batteries (AZIBs). Here we construct artificial solid electrolyte interfaces (SEIs) realized by sodium and calcium bentonite with a layered structure anchored to anodes (NB@Zn and CB@Zn). This artificial SEI layer functioning as a protective coating to isolate activated water molecules, provides high-speed transport channels for Zn2+, and serves as an ionic sieve to repel negatively charged anions while attracting positively charged cations. The theoretical results show that the bentonite electrodes exhibit a higher binding energy for Zn2+. This demonstrates that the bentonite protective layer enhances the Zn-ion deposition kinetics. Consequently, the NB@Zn//MnO2 and CB@Zn//MnO2 full-battery capacities are 96.7 and 70.4 mAh g-1 at 2.0 A g-1 after 1000 cycles, respectively. This study aims to stabilize Zn anodes and improve the electrochemical performance of AZIBs by ion-selection sieving.
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MAIN CONCLUSION: In this study, six ZaBZRs were identified in Zanthoxylum armatum DC, and all the ZaBZRs were upregulated by abscisic acid (ABA) and drought. Overexpression of ZaBZR1 enhanced the drought tolerance of transgenic Nicotiana benthamian. Brassinosteroids (BRs) are a pivotal class of sterol hormones in plants that play a crucial role in plant growth and development. BZR (brassinazole resistant) is a crucial transcription factor in the signal transduction pathway of BRs. However, the BZR gene family members have not yet been identified in Zanthoxylum armatum DC. In this study, six members of the ZaBZR family were identified by bioinformatic methods. All six ZaBZRs exhibited multiple phosphorylation sites. Phylogenetic and collinearity analyses revealed a closest relationship between ZaBZRs and ZbBZRs located on the B subgenomes. Expression analysis revealed tissue-specific expression patterns of ZaBZRs in Z. armatum, and their promoter regions contained cis-acting elements associated with hormone response and stress induction. Additionally, all six ZaBZRs showed upregulation upon treatment after abscisic acid (ABA) and polyethylene glycol (PEG), indicating their participation in drought response. Subsequently, we conducted an extensive investigation of ZaBZR1. ZaBZR1 showed the highest expression in the root, followed by the stem and terminal bud. Subcellular localization analysis revealed that ZaBZR1 is present in the cytoplasm and nucleus. Overexpression of ZaBZR1 in transgenic Nicotiana benthamiana improved seed germination rate and root growth under drought conditions, reducing water loss rates compared to wild-type plants. Furthermore, ZaBZR1 increased proline content (PRO) and decreased malondialdehyde content (MDA), indicating improved tolerance to drought-induced oxidative stress. The transgenic plants also showed a reduced accumulation of reactive oxygen species. Importantly, ZaBZR1 up-regulated the expression of drought-related genes such as NbP5CS1, NbDREB2A, and NbWRKY44. These findings highlight the potential of ZaBZR1 as a candidate gene for enhancing drought resistance in transgenic N. benthamiana and provide insight into the function of ZaBZRs in Z. armatum.
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Secas , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas , Plantas Geneticamente Modificadas , Zanthoxylum , Plantas Geneticamente Modificadas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Zanthoxylum/genética , Zanthoxylum/fisiologia , Zanthoxylum/metabolismo , Nicotiana/genética , Nicotiana/fisiologia , Nicotiana/efeitos dos fármacos , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Família Multigênica , Brassinosteroides/metabolismo , Brassinosteroides/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estresse Fisiológico/genética , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Resistência à SecaRESUMO
The misregulation of protein phosphatases is a key factor in the development of many human diseases, notably cancers. Here, based on a 100 MHz quartz crystal microbalance (QCM) biosensing platform, the dephosphorylation process of phosphopeptide (P-peptide) caused by protein tyrosine phosphatase 1B (PTP1B) was monitored in real time for the first time and PTP1B activity was assayed rapidly and sensitively. The QCM chip, coated with a gold (Au) film, was used to immobilized thiol-labeled single-stranded 5'-phosphate-DNAs (P-DNA) through Au-S bond. The P-peptide, specific to PTP1B, was then connected to the P-DNA via chelation between Zr4+ and phosphate groups. When PTP1B was injected into the QCM flow cell where the P-peptide/Zr4+/MCH/P-DNA/Au chip was placed, the P-peptide was dephosphorylated and released from the Au chip surface, resulting in an increase in the frequency of the QCM Au chip. This allowed the real-time monitoring of the P-peptide dephosphorylation process and sensitive detection of PTP1B activity within 6 min with a linear detection range of 0.01-100 pM and a detection limit of 0.008 pM. In addition, the maximum inhibitory ratios of inhibitors were evaluated using this proposed 100 MHz QCM biosensor. The developed 100 MHz QCM biosensing platform shows immense potential for early diagnosis of diseases related to protein phosphatases and the development of drugs targeting protein phosphatases.
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Técnicas Biossensoriais , Fosfopeptídeos , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Técnicas de Microbalança de Cristal de Quartzo , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/análise , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Técnicas de Microbalança de Cristal de Quartzo/métodos , Fosfopeptídeos/análise , Técnicas Biossensoriais/métodos , Fosforilação , Humanos , Zircônio/química , Fatores de Tempo , Ouro/química , Ensaios Enzimáticos/métodosRESUMO
Sodium-ion batteries (SIBs) have garnered significant interest as one of the most promising energy suppliers for power grid energy storage. However, the poor electrode/electrolyte interfacial stability leads to continual electrolyte decomposition and transition metal dissolution, resulting in rapid performance degradation of SIBs. In this work, we propose a strategy integrating multiple functional bonds to regulate electrode/electrolyte interphase by triple-coupling of succinonitrile (SN), sodium hexafluorophosphate (NaPF6) and fluorinated ethylene carbonate (FEC). Theoretical calculation and experiment results show that the solvation structure of Na+ and ClO4 - is effectively reconfigured by the solvated FEC, SN and PF6 - in PC-based carbonate electrolyte. The newly developed electrolyte demonstrates increased Na+-FEC coordination, weakened interaction of Na+-PC and participation of SN and PF6 - anions in solvation, resulting in the formation of a conformal interfacial layer comprising of sodium oxynitrides (NaNxOy), sodium fluoride (NaF) and phosphorus oxide compounds (NaPxOy). Consequently, a 3â Ah pouch full cell of hard carbon//NaNi1/3Fe1/3Mn1/3O2 exhibits an excellent capacity retention of 90.4 % after 1000â cycles. Detailed postmortem analysis of interface chemistry is further illustrated by multiple characterization methods. This study provides a new avenue for developing electrolyte formulations with multiple functional bonds integrated interphases to significantly improve the long-term cycling stability of SIBs.
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The abnormal expression of protein tyrosine phosphatase 1B (PTP1B) is highly related to several serious human diseases. Therefore, an accurate PTP1B activity assay is beneficial to the diagnosis and treatment of these diseases. In this study, a dual-mode biosensing platform that enabled the sensitive and accurate assay of PTP1B activity was constructed based on the high-frequency (100 MHz) quartz crystal microbalance (QCM) and dual-signaling electrochemical (EC) ratiometric strategy. Covalent-organic framework@gold nanoparticles@ferrocene@single-strand DNA (COF@Au@Fc-S0) was introduced onto the QCM Au chip via the chelation between Zr4+ and phosphate groups (phosphate group of the phosphopeptide (P-peptide) on the QCM Au chip and the phosphate group of thiol-labeled single-stranded DNA (S0) on COF@Au@Fc-S0) and used as a signal reporter. When PTP1B was present, the dephosphorylation of the P-peptide led to the release of COF@Au@Fc-S0 from the QCM Au chip, resulting in an increase in the frequency of the QCM. Meanwhile, the released COF@Au@Fc-S0 hybridized with thiol/methylene blue (MB)-labeled hairpin DNA (S1-MB) on the Au NPs-modified indium-tin oxide (ITO) electrode. This caused MB to be far away from the electrode surface and Fc to be close to the electrode, leading to a decrease in the oxidation peak current of MB and an increase in the oxidation peak current of Fc. Thus, PTP1B-induced dephosphorylation of the P-peptide was monitored in real time by QCM, and PTP1B activity was detected sensitively and reliably using this innovative QCM-EC dual-mode sensing platform with an ultralow detection limit. This platform is anticipated to serve as a robust tool for the analysis of protein phosphatase activity and the discovery of drugs targeting protein phosphatase.
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Técnicas Eletroquímicas , Compostos Ferrosos , Ouro , Estruturas Metalorgânicas , Metalocenos , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Técnicas de Microbalança de Cristal de Quartzo , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/análise , Ouro/química , Humanos , Estruturas Metalorgânicas/química , Compostos Ferrosos/química , Metalocenos/química , DNA de Cadeia Simples/química , DNA de Cadeia Simples/metabolismo , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Zircônio/química , Ensaios Enzimáticos/métodosRESUMO
Histone Deacetylase 6 (HDAC6) is an essential regulator of histone acetylation processes, exerting influence on a multitude of cellular functions such as cell motility, endocytosis, autophagy, apoptosis, and protein trafficking through its deacetylation activity. The significant implications of HDAC6 in diseases such as cancer, neurodegenerative disorders, and immune disorders have motivated extensive investigation into the development of specific inhibitors targeting this enzyme for therapeutic purposes. Single targeting drugs carry the risk of inducing drug resistance, thus prompting exploration of dual targeting therapy which offers the potential to impact multiple signaling pathways simultaneously, thereby lowering the likelihood of resistance development. While pharmacological studies have exhibited promise in combined therapy involving HDAC6, challenges related to potential drug interactions exist. In response to these challenges, researchers are investigating HDAC6 hybrid molecules which enable the concomitant targeting of HDAC6 and other key proteins, thus enhancing treatment efficacy while mitigating side effects and reducing the risk of resistance compared to traditional combination therapies. The published design strategies for dual targeting inhibitors of HDAC6 are summarized and discussed in this review. This will provide some valuable insights into more novel HDAC6 dual targeting inhibitors to meet the urgent need for innovative therapies in oncology and other related fields.
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Antineoplásicos , Desacetilase 6 de Histona , Inibidores de Histona Desacetilases , Neoplasias , Desacetilase 6 de Histona/antagonistas & inibidores , Desacetilase 6 de Histona/metabolismo , Humanos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/síntese química , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/química , Estrutura Molecular , AnimaisRESUMO
Organophosphorus-fluorine compounds are of significant utility across biology, pharmacy, and chemical synthesis. Here, we introduce a photocatalyzed oxidative-fluorination approach employing SF6 as a formal electrophilic fluorinating reagent. It offers an innovative pathway to forge P(O)-F bonds. Notably, sulfur hexafluoride plays a dual role as both the oxidant and the fluorinating reagent under mild conditions in this transformation. Meanwhile, this method contributes to environmental sustainability by consuming a notorious greenhouse gas, underscoring the ecological benefits of our approach.