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The poor reversibility and stability of Zn metal anode (ZMA) caused by uncontrolled Zn deposition behaviors and serious side reactions severely impeded the practical application of aqueous Zn metal battery. Herein, a liquid-dynamic and self-adaptive protective layer (LSPL) was constructed on the ZMA surface for inhibiting dendrites and by-products formation. Interestingly, the outer LSPL consists of liquid perfluoropolyether (PFPE), which can dynamically adapt volume change during repeat cycling and inhibit side reactions. Moreover, it can also decrease the de-solvation energy barrier of Zn2+ by strong interaction between C-F bond and foreign Zn2+ , improving Zn2+ transport kinetics. For the LSPL inner region, in-situ formed ZnF2 through the spontaneous chemical reaction between metallic Zn and part PFPE can establish an unimpeded Zn2+ migration pathway for accelerating ion transfer, thereby restricting Zn dendrites formation. Consequently, the LSPL-modified ZMA enables reversible Zn deposition/dissolution up to 2000 h at 1 mA cm-2 and high coulombic efficiency of 99.8% at 4 mA cm-2 . Meanwhile, LSPL@Zn||NH4 V4 O10 full cells deliver an ultralong cycling lifespan of 100 00 cycles with 0.0056% per cycle decay rate at 10 A g-1 . This self-adaptive layer provides a new strategy to improve the interface stability for next-generation aqueous Zn battery.
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FeS/SnS@N-C composites were successfully synthesized through the combination of nucleation self-assembly, N-doped carbon coating, and in situ vulcanization. The experimental results show that the discharge capacitance of FeS/SnS@N-C in the lithium storage process is 796.90 mAh g-1 at 0.5 A g-1 after 200 cycles, and more importantly, the discharge capacitance can maintain 278.84 mAh g-1 at 5 A g-1 after 2000 cycles. FeS in FeS/SnS@N-C plays a key role in the electrochemical performance, which is due to the certain electronic density of states (DOS) near the Fermi level. In short, our research expands the application of transition metal sulfide composites in lithium-ion batteries.
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Uncontrolled dendrites growth and serious parasitic reactions in aqueous electrolytes, greatly hinder the practical application of aqueous zinc-ion battery. On the basis of in situ-chemical construction and performance-improving mechanism, multifunctional fluoroethylene carbonate (FEC) is introduced into aqueous electrolyte to construct a high-quality and ZnF2 -riched inorganic/organic hybrid SEI (ZHS) layer on Zn metal anode (ZMA) surface. Notably, FEC additive can regulate the solvated structure of Zn2+ to reduce H2 O molecules reactivity. Additionally, the ZHS layer with strong Zn2+ affinity can avoid dendrites formation and hinder the direct contact between the electrolyte and anode. Therefore, the dendrites growth, Zn corrosion, and H2 evolution reaction on ZMA in FEC-included ZnSO4 electrolyte are highly suppressed. Thus, ZMA in such electrolyte realize a long cycle life over 1000â h and deliver a stable coulombic efficiency of 99.1 % after 500â cycles.
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Osteosarcoma (OS) is the most common bone tumor that occurs predominantly in children and teenagers. Although many genes, such as p53 and Rb1, have been shown to be mutated, deregulation of the canonical Wnt/ß-catenin signaling pathway is frequently observed in OS. We recently demonstrated that heat shock protein 90 (HSP90) is involved in the regulation of runt-related transcription factor 2 via the AKT/GSK-3ß/ß-catenin signaling pathway in OS. However, the precise role of T cell factors/lymphoid enhancer-binding factor (TCFs/LEF) family members, which are the major binding complex of ß-catenin, in OS is poorly understood. In the present study, we first demonstrated that TCF-1 is overexpressed in OS compared with other bone tumors. Knockdown of TCF-1 significantly induced cell cycle arrest, severe DNA damage, and subsequent caspase-3-dependent apoptosis. Interestingly, coexpression of HSP90 and TCF-1 was observed in OS, and mechanistically, we demonstrated that TCF-1 expression is regulated by HSP90 either through a ß-catenin-dependent mechanism or a direct degradation of the proteasome. We also found that overexpression of TCF-1 partially abolishes the apoptosis induced by HSP90 inhibition. Furthermore, we provided evidence that p53, but not miR-34a, plays a crucial role in the HSP90-regulated TCF-1 expression and subsequent apoptosis. Given the diverse combination regimens of HSP90 inhibition with some other treatments, we propose that the p53 status and the expression level of TCF-1 should be taken into consideration to enhance the therapeutic efficacy of HSP90 inhibition.
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Glicogênio Sintase Quinase 3 beta/genética , Proteínas de Choque Térmico HSP90/genética , Osteossarcoma/genética , Fator 1 de Transcrição de Linfócitos T/genética , Proteína Supressora de Tumor p53/genética , Apoptose/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes/genética , Humanos , MicroRNAs/genética , Proteína Oncogênica v-akt/genética , Osteossarcoma/patologia , Fatores de Transcrição TCF/genética , Transcrição Gênica/genética , beta Catenina/genéticaRESUMO
Chemical composition in fingermarks could provide useful information for forensic studies and applications. Here, we evaluate the feasibility of analysis and imaging of fingermarks via elements by synchrotron radiation X-ray fluorescence (SRXRF) and commercial X-ray fluorescence (XRF). As a proof of concept, we chose four brands of sunscreens to make fingermarks on different substrates, including plastic film, glass, paper, and silicon wafer. We obtained an evident image of fingermarks via zinc and titanium by XRF methods. In addition, the ratios of element concentrations in sunscreen fingermarks were obtained, which were in accordance with the results obtained by acid digestion and ICP-OES analysis. In comparison, commercial XRF offers the most advantages in terms of non-destructive detection, easy accessibility, fast element images, and broad applicability. The possibility to acquire fingermark images simultaneously with element information opens up new avenues for forensic science. Graphical abstract.
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Protetores Solares/química , Estudo de Prova de Conceito , Espectrometria por Raios X , Titânio/análise , Zinco/análiseRESUMO
Chondrosarcoma is the second most malignant bone tumor with poor prognosis and limited treatment options. Thus, development of more effective treatments has become urgent. Recently, natural compounds derived from medicinal plants have emerged as promising therapeutic options via targeting multiple key cellular molecules. Andrographolide (Andro) is such a compound, which has previously been shown to induce cell cycle arrest and apoptosis in several human cancers. However, the molecular mechanism through which Andro exerts its anti-cancer effect on chondrosarcoma remains to be elucidated. In the present study, we showed that Andro-induced G2/M cell cycle arrest of chondrosarcoma by fine-tuning the expressions of several cell cycle regulators such as p21, p27, and Cyclins, and that prolonged treatment of cells with Andro caused pronounced cell apoptosis. Remarkably, we found that SOX9 was highly expressed in poor-differentiated chondrosarcoma, and that knockdown of SOX9 suppressed chondrosarcoma cell growth. Further, our results showed that Andro dose-dependently down-regulated SOX9 expression in chondrosarcoma cells. Concomitantly, an inhibition of T cell factor 1 (TCF-1) mRNA expression and an enhancement of TCF-1 protein degradation by Andro were observed. In contrast, the expression and subcellular localization of ß-catenin were not altered upon the treatment of Andro, suggesting that ß-catenin might not function as the primary target of Andro. Additionally, we provided evidence that there was a mutual regulation between TCF-1 and SOX9 in chondrosarcoma cells. In conclusion, these results highlight the potential therapeutic effects of Andro in treatment of chondrosarcoma via targeting the TCF-1/SOX9 axis. J. Cell. Biochem. 118: 4575-4586, 2017. © 2017 Wiley Periodicals, Inc.
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Apoptose/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Condrossarcoma/tratamento farmacológico , Diterpenos/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição SOX9/metabolismo , Fator 1 de Transcrição de Linfócitos T/metabolismo , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Condrossarcoma/genética , Condrossarcoma/metabolismo , Condrossarcoma/patologia , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/genética , Proteínas de Neoplasias/genética , Fatores de Transcrição SOX9/genética , Fator 1 de Transcrição de Linfócitos T/genéticaRESUMO
Chondrosarcoma, the second-most frequent primary bone malignancy, is generally more resistant to conventional chemotherapy and radiotherapy. Therefore, the development of an effective adjuvant therapy is necessary. Recently, targeting the epigenetic regulator such as bromodomain and extraterminal domain (BET) proteins has achieved great success. For instance, the bromodomain inhibitor JQ1 has been shown to inhibit the growth of several cancer cells both in vitro and in vivo. Herein, we demonstrated that JQ1 significantly inhibited chondrosarcoma cell growth and colony formation. JQ1 also induced marked G1-phase cell cycle arrest coincided with the up-regulation of p21WAF1/CIP1 , p27Kip1 , and Cyclin D1 expression, and the down-regulation of Cyclin E2 expression. Moreover, JQ1 induced the premature senescence of SW 1353 cells, and that prolong treatment of JQ1 caused cell apoptosis. Mechanistically, the JQ1-induced cell growth inhibition was correlated with the suppression of c-Myc and Bcl-xL, which are the prime genes for cell cycle control and anti-apoptosis. Furthermore, we demonstrated that p21 negatively regulated the expression of c-Myc and Bcl-xL upon JQ1 treatment, and that the growth inhibition of SW 1353 and Hs 819.T cells and induction of p21 were predominantly regulated by the LATS1/YAP signaling but not through a p53-dependent manner. In conclusion, we disclosed a novel mechanism that JQ1 inhibits cell proliferation, induces cell senescence and apoptosis of chondrosarcoma cells through the regulation of the YAP/p21/c-Myc/Bcl-xL signaling axis. J. Cell. Biochem. 118: 2182-2192, 2017. © 2017 Wiley Periodicals, Inc.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Azepinas/farmacologia , Condrossarcoma/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fosfoproteínas/metabolismo , Proteínas/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/metabolismo , Triazóis/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Senescência Celular/efeitos dos fármacos , Senescência Celular/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Immunoblotting , Fosfoproteínas/genética , Proteínas Proto-Oncogênicas c-myc/genética , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Fatores de Transcrição , Proteínas de Sinalização YAPRESUMO
Ultrafast and high capacity all-carbon supercapacitors with 3D porous aerogel electrode are realized by combining carbon nanostructures of various dimensionalities, including 0D carbon onions, 1D carbon nanotubes, and 2D graphene oxide. The synergistic effects from the different forms of nanocarbons render this hybrid outstanding capacitance with excellent stability, even at ultrafast charge-discharge rates.
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Although a breakthrough in the fabrication of green laser diodes has occurred, the high costs associated with the difficulty of manufacture still present a great obstacle for its practical application. Another approach for producing a green laser, by combining a laser device and a nonlinear crystal, entails the fabrication of complex structures and exhibits unstable performance due to interface contact defects, thus limiting its application. In this work, we report the fabrication by domain engineering of high quality periodically poled LiNbO3, co-doped with Nd³âº and Mg²âº, which combines a laser medium and a high efficiency second harmonic conversion crystal into a single system that is designed to overcome the above problems. An 80 mW self-frequency doubling green laser was constructed for the first time from a periodically poled Nd:Mg:LiNbO3 crystal of 16 mm in length. This crystal can be used for developing compact, stable, highly efficient mini-solid-state-lasers, which promise to have many applications in portable laser-based spectroscopy, photo-communications, terahertz wave generation, and laser displays.
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Intervertebral disc degeneration (IVDD) contributes largely to low back pain. Recent studies have highlighted the exacerbating role of diabetes mellitus (DM) in IVDD, mainly due to the influence of hyperglycemia (HG) or the accumulation of advanced glycation end products (AGEs). Vascular endothelial growth factor A (VEGFA) newly assumed a distinct impact in nonvascular tissues through mitophagy regulation. However, the combined actions of HG and AGEs on IVDD and the involved role of VEGFA remain unclear. We confirmed the potential relation between VEGFA and DM through bioinformatics and biological specimen detection. Then we observed that AGEs induced nucleus pulposus (NP) cell degeneration by upregulating cellular reactive oxygen species (ROS), and HG further aggravated ROS level through breaking AGEs-induced protective mitophagy. Furthermore, this adverse effect could be strengthened by VEGFA knockdown. Importantly, we identified that the regulation of VEGFA and mitophagy were vital mechanisms in AGEs-HG-induced NP cell degeneration through Parkin/Akt/mTOR and AMPK/mTOR pathway. Additionally, VEGFA overexpression through local injection with lentivirus carrying VEGFA plasmids significantly alleviated NP degeneration and IVDD in STZ-induced diabetes and puncture rat models. In conclusion, the findings first confirmed that VEGFA protects against AGEs-HG-induced IVDD, which may represent a therapeutic strategy for DM-related IVDD.
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Degeneração do Disco Intervertebral , Núcleo Pulposo , Fator A de Crescimento do Endotélio Vascular , Animais , Ratos , Apoptose , Regulação para Baixo , Glucose/metabolismo , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Mitofagia/fisiologia , Núcleo Pulposo/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Produtos Finais de Glicação Avançada/metabolismoRESUMO
The electronic circular dichroism (ECD) and UV-visible absorption (UV-vis) spectra of Strandberg-type polyoxometalates (POMs) (R, R)-[(R*PO3)2M5O15](2-) (R* = CH3CH(NH3), (M = Mo, W)) have been explored using the time-dependent density functional theory (TDDFT) method. It demonstrates that the absolute configurations of chiral systems can be determined by chiroptical spectroscopic methods combined with DFT calculations. The calculated ECD spectra of the Strandberg-type molybdate were produced over the range of 3.3-6.5 eV, which are generally in agreement with the experimental spectra. In addition, the ECD spectra of (R, R)-[(R*PO3)2W5O15](2-) (R* = CH3CH(NH3)) were produced over the range of 4.5-8.5 eV. The Becke's half-and-half hybrid exchange-correlation functional (BHandHLYP) with the HF exchange fraction to 55% hybrid functional was found to well predict the excitation energies of studied systems. The origins of the ECD bands of two systems are mainly ascribed to charge-transfer (CT) transitions from oxygen atoms to metal atoms in polyanion. The results suggest that the polyanion are chiroptical chromophores. The polyanion plays a role as an optically active chromophore and contribute to the absorptions of ECD spectra. The difference of the UV-vis/ECD spectra between two systems shows that the transition metal atom significantly influences on the chiroptical properties of the studied Strandberg-type POMs.
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A tuberculosis (TB) epidemic model with Beddington-DeAngelis incidence and distributed delay is proposed to characterize the interaction between latent period, endogenous reactivation, treatment of latent TB infection, as well as relapse. The basic reproduction number R 0 is defined, and the globally asymptotic stability of disease-free equilibrium is shown when R 0 < 1 , while if R 0 > 1 the globally asymptotic stability of endemic equilibrium is also acquired. Theoretical results are validated through performing numerical simulations, wherein we detect that TB dynamic behavior between models with discrete and distributed delays could be same and opposite, and TB is more persistent in the model with distributed delay. Besides, increasing the protection level of susceptible and infectious individuals is crucial for the control of TB.
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Knee osteoarthritis (KOA) is one of the most commonly encountered degenerative diseases of the joints in people over 45 years of age. Currently, there are not any effective therapeutics for KOA,and the only end-point strategy is total knee arthroplasty (TKA); therefore, KOA is associated with economic burdens and societal costs. The immune inflammatory response is involved in the occurrence and development of KOA. We previously established a mouse model of KOA using type II collagen. Hyperplasia of the synovial tissue was present in the model, alongside a large number of infiltrated inflammatory cells. Silver nanoparticles have substantial anti-inflammatory effects and have been widely used in tumor therapy and surgical drug delivery. Therefore, we evaluated the therapeutic effects of silver nanoparticles in a collagenase II-induced KOA model. The experimental results showed that silver nanoparticles significantly reduced synovial hyperplasia and the infiltration of neutrophils in the synovial tissue. Hence, this work demonstrates the identification of a novel strategy for OA and provides a theoretical basis for preventing the progress of KOA.
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Nanopartículas Metálicas , Osteoartrite do Joelho , Camundongos , Animais , Prata , Hiperplasia , Osteoartrite do Joelho/terapia , Membrana SinovialRESUMO
The UV/CD spectra of tin-bearing acetonyl-substituted Wells-Dawson polyoxotungstates α(1)- and α(2)-[P(2)W(17)O(61){SnCH(2)CH(2)C(âO)}](6-) were systematically investigated using the time-dependent density functional theory (TDDFT) method. The electronic circular dichroism (ECD) spectra were produced over the range of 3.3-5.8 eV. The calculated ECD spectra of the α(1)-R isomer were generally in agreement with the experimental spectra. The CAM-B3LYP hybrid functional was found to predict the excitation energies of tin-containing polyoxotungstates well. The fact that the UV/ECD spectra of α(1)-isomers are different from those of α(2)-isomers demonstrates the effect of the tin substitution site on the chiroptical properties of the studied isomers. The origins of the ECD bands are mainly ascribed to charge-transfer (CT) transitions from oxygen atoms to W atoms, from organic fragments to W atoms, or from the combination of two CT transitions. The results suggest that the organic fragment and polyoxometalate (POM) cage are chiroptical chromophores.
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Introduction: Restless legs syndrome is a common and severe complication in patients undergoing peritoneal dialysis (PD), which seriously affects the life quality and prognosis of patients undergoing PD. Unfortunately, there are still no effective prevention and treatment measures. Serum hepcidin was demonstrated to be related to primary restless legs syndrome (RLS), whereas there are no studies on the relationship between serum hepcidin and RLS in patients undergoing PD. We aimed to evaluate the role and function of serum hepcidin in patients undergoing PD with RLS. Methods: A total of 51 patients undergoing PD with RLS and 102 age-and gender-matched patients undergoing PD without RLS were included. We collected the clinical data including serum hepcidin of those patients undergoing PD. We scored the severity of RLS according to the International restless leg Syndrome Research Group rating scale (IRLS). We compared the clinical characteristics of the two groups and evaluated the determinant factors of RLS by Logistic regression analysis. In addition, we evaluated the diagnostic value of serum hepcidin in patients undergoing PD with RLS by receiver operating characteristic (ROC) curve. We also analyzed the influencing factors of IRLS by multivariate linear regression analysis. Results: The duration of PD, serum hepcidin, and calcium were found to be significantly higher in patients undergoing PD with RLS than those patients undergoing PD without RLS (P < 0.001, P < 0.001, and P = 0.002, respectively). The level of hemoglobin, albumin, and RKF were significantly lower in patients undergoing PD with RLS (P = 0.002, P = 0.042, and P < 0.001, respectively). The duration of PD [odds ratio (OR) 1.038, 95% CI: 1.017, 1.060, P < 0.001], hemoglobulin level (OR 0.969, 95% CI: 0.944, 0.995, P = 0.019), calcium level (OR 9.224, 95% CI: 1.261, 67.450, P = 0.029), albumin level (OR 0.835, 95% CI: 0.757, 0.921, P < 0.001), hepcidin level (OR 1.023, 95% CI: 1.009, 1.038, P = 0.001), and RKF (OR 0.65, 95% CI: 0.495, 0.856, P = 0.002) are independent determinant factors of RLS in patients undergoing PD. Multivariate linear regression analysis revealed that, in addition to albumin, they were also independently associated with the severity of RLS. Conclusion: A significant relation was detected between serum hepcidin level and RLS in patients undergoing PD.
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AIMS: The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration. METHODS: IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively. RESULTS: DT plus 30 ng/ml of IL4 (DT + 30 IL4) from day 3 to day 7 significantly (p < 0.01) enhanced macrophage type 2 polarization and BMMSC osteogenesis compared with the other groups. Local injection of IL4 enhanced new bone formation surrounding the DT. CONCLUSION: DT + 30 IL4 may switch macrophage polarization at the appropriate timepoints to promote bone regeneration. Cite this article: Bone Joint Res 2021;10(7):411-424.
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Chondrosarcoma (CHS) is the second most common bone malignancy with limited therapeutic approaches. Our previous study has found that Yes associated protein 1 (YAP1) is downregulated in CHS cells treated with bromodomain and extraterminal domain (BET) inhibitor JQ1. However, the precise role of YAP1 in CHS is largely unknown. Herein, we found that YAP1 expression was upregulated in CHS tissues, and positively correlated with its grading score. Loss of YAP1 inhibited CHS proliferation and induced cellular senescence, while expression of YAP1 mutants revealed YAP1/TEA domain family member (TEAD)-dependent negative regulation of p21 and subsequent cellular senescence. These results were validated by in vivo experiments using stable shYAP1 cell lines. Mechanistically, negative regulation of p21 by YAP1 occurred post-transcriptionally via Dicer-regulated miRNA networks, specifically, the miR-17 family. Furthermore, we demonstrated that sequential targeting of YAP1 and p21 enhanced the elimination of JQ1-induced senescent cells in a Bcl-2-like 1 (Bcl-XL)/Caspase-3 dependent manner. Altogether, we unveil a novel role of YAP1 signaling in mediating CHS cell senescence and propose a one-two punch approach that sequentially targets the YAP1/p21 axis to eliminate senescent cells.
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Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Azepinas/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Condrossarcoma/tratamento farmacológico , Inibidor de Quinase Dependente de Ciclina p21/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Triazóis/farmacologia , Proteínas rho de Ligação ao GTP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Condrossarcoma/genética , Condrossarcoma/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Terapia de Alvo Molecular , Proteínas/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Sinalização YAPRESUMO
Osteosarcoma (OS) is the most common bone malignancy in adolescents and has poor clinical outcomes. Protein arginine methyltransferase 5 (PRMT5) has recently been shown to be aberrantly expressed in various cancers, yet its role in OS remains elusive. Here, we found that PRMT5 was overexpressed in OS and its overexpression predicted poor clinical outcomes. PRMT5 knockdown significantly triggered pronounced senescence in OS cells, as evidenced by the increase in senescence-associated ß-galactosidase (SA-ß-gal)-stained cells, induction of p21 expression, and upregulation of senescence-associated secretory phenotype (SASP) gene expression. In addition, we found that PRMT5 plays a key role in regulating DNA damaging agents-induced OS cell senescence, possibly, via affecting the repair of DNA damage. Furthermore, we found that TXNIP acts as a key factor mediating PRMT5 depletion-induced DNA damage and cellular senescence. Mechanistically, TRIM21, which interacts with PRMT5, was essential for the regulation of TXNIP/p21 expression. In summary, we propose a model in which PRMT5, by interaction with TRIM21, plays a key role in regulating the TXNIP/p21 axis during senescence in OS cells. The present findings suggest that PRMT5 overexpression in OS cells might confer resistance to chemotherapy and that targeting the PRMT5/TRIM21/TXNIP signaling may enhance the therapeutic efficacy in OS.
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Neoplasias Ósseas/patologia , Senescência Celular/fisiologia , Osteossarcoma/patologia , Proteína-Arginina N-Metiltransferases/metabolismo , Ribonucleoproteínas/metabolismo , Adolescente , Adulto , Proteínas de Transporte/metabolismo , Criança , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Feminino , Humanos , Masculino , Transdução de Sinais/fisiologiaRESUMO
Here we demonstrate a ternary Cu2NiZn alloy substrate for controllably synthesizing monolayer graphene using a liquid carbon precursor cyclohexane via a facile CVD route. In contrast with elemental metal or bimetal substrates, the alloy-induced synergistic effects that provide an ideal metallic platform for much easier dehydrogenation of hydrocarbon molecules, more reasonable strength of adsorption energy of carbon monomer on surface and lower formation energies of carbon chains, largely renders the success growth of monolayer graphene with higher electrical mobility and lower defects. The growth mechanism is systemically investigated by our DFT calculations. This study provides a selective route for realizing high-quality graphene monolayer via a scalable synthetic method by using economic liquid carbon supplies and multialloy metal substrates.
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The combined effect of Oroxylum indicum seed extracts (OISE) or major flavonoids from OISE and acarbose on reducing postprandial blood glucose (PBG) levels was investigated in vitro and in vivo. In vitro, the IC50 values of OISE and baicalein against α-glucosidase were 43.4±0.731µgmL-1 and 25.9±0.412µgmL-1 respectively. A combination of acarbose with OISE or baicalein synergistically inhibited rat intestinal α-glucosidase. The combination index (CI) values for acarbose with OISE ranged from 0.33 to 0.75, suggesting a synergistic but not additive effect. OISE was determined to be a non-competitive inhibitor of maltose-hydrolyzing activity. In vivo, OISE were administered to normoglycemic and diabetic mice, either alone or in combination with acarbose. At doses between 50 and 200mgkg-1, OISE enhanced the efficacy of acarbose by up to 5-fold. These results demonstrated that OISE enhances the efficacy of acarbose in vivo, and that the combination of OISE and acarbose displayed a synergistic effect in vitro. Therefore, OISE can be used to design dietary supplements to treat diabetes.