RESUMO
A series of fluorescent molecules with 1,1-dimethylnaphthalene-2(1H)-one as the core were synthesized to overcome aggregation quenching and emit bright green fluorescence. The low molecular weight of these molecules led to them to smoothly pass through the cell membrane and penetrate deep into the nucleus to emit the corresponding fluorescence. Among them, NC-4-Br and NC-5-3O have good optical and in vitro properties and showed potential for use as fluorescent probes.
RESUMO
Polyurea has gained significant attention in recent years as a functional polymer material, specifically regarding blast and impact protection. The molecular structure of polyurea is characterized by the rapid reaction between isocyanate and the terminal amine component, and forms an elastomeric copolymer that enhances substrate protection against blast impact and fragmentation penetration. At the nanoscale, a phase-separated microstructure emerges, with dispersed hard segment microregions within a continuous matrix of soft segments. This unique microstructure contributes to the remarkable mechanical properties of polyurea. To maximize these properties, it is crucial to analyze the molecular structure and explore methods like formulation optimization and the incorporation of reinforcing materials or fibers. Current research efforts in polyurea applications for protective purposes primarily concentrate on construction, infrastructure, military, transportation and industrial products and facilities. Future research directions should encompass deliberate formulation design and modification, systematic exploration of factors influencing protective performance across various applications and the integration of numerical simulations and experiments to reveal the protective mechanisms of polyurea. This paper provides an extensive literature review that specifically examines the utilization of polyurea for blast and impact protection. It encompasses discussions on material optimization, protective mechanisms and its applications in blast and impact protection.
RESUMO
Numerous natural bioactive compounds extracted from Chinese medicines have been proved to be promising and potent agents in the treatment of ischemic stroke. Hydroxysafflor yellow A (HSYA), separated from Carthamus tinctorius, has increasingly attracted attention for its broad spectrum of pharmacological effects, especially of its neuroprotective action. Our previous studies revealed that HSYA plays significant beneficial roles in a dose-dependent manner in rats with focal cerebral ischemia. However, treatment with higher doses of HSYA appeared to bring about adverse reactions in the rats. In present study, we adopted tenuigenin (TEN), extracted from the Polygala tenuifolia root, in combination with HSYA to optimize the therapeutic strategy against ischemic stroke, and further explored the underlying mechanisms of action of the combination in vivo and in vitro. We firstly confirmed the pharmacological efficacies of co-treatment of HSYA and TEN in middle cerebral ischemia occlusion (MCAO) rats and observed the synergistic improvement of infarct volume, cerebral edema, and morphology of neuron cell body. Behavioral experiments indicated that combination of HSYA and TEN could synergistically improve motor and cognitive function in MCAO rats. We also observed increased viability and suppressed cell apoptosis after HSYA and TEN co-treatments in the oxygen-glucose deprivation/reperfusion (OGD/R) SH-SY5Y cells. Furthermore, JAK2/STAT3 and SOCS3 signaling interaction was demonstrated to be a critical responsor to the co-treatment of HSYA and TEN. In the subsequent experiments with silencing SOCS3 in OGD/R-exposed cells, we found that HSYA and TEN might suppress JAK2/STAT3 pathway through different regulatory mechanisms targeting SOCS3-negative feedback signaling. HSYA seemed to impose excessive activation of JAK2/STAT3 to trigger SOCS3-negative feedback signaling, while TEN appeared to provoke SOCS3 inhibitory feedback role directly to further attenuate JAK2-mediated signaling. Collectively, HSYA and TEN might modulate the crosstalk between JAK2/STAT3 and SOCS3 signaling pathways in different manners that eventually contributed to their synergistic therapeutic effects against cerebral ischemic stroke.
Assuntos
Isquemia Encefálica , Chalcona , Janus Quinase 2 , Fármacos Neuroprotetores , Quinonas , Ratos Sprague-Dawley , Fator de Transcrição STAT3 , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas , Animais , Janus Quinase 2/metabolismo , Chalcona/análogos & derivados , Chalcona/farmacologia , Chalcona/uso terapêutico , Quinonas/farmacologia , Quinonas/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Masculino , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/complicações , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Apoptose/efeitos dos fármacosRESUMO
In contemporary times, electromagnetic radiation poses a significant threat to both human health and the normal functioning of electronic devices. Developing composites as adsorption materials possess exceptional electromagnetic wave absorption performances can efficient address this critical issue. Herein, hollow core-shell NiCo2O4@polypyrrole nanofibers/reduced graphene oxide (NiCo-HFPR) composites are fabricated by the combination of electrostatic spinning, air calcination, in-situ polymerization, freeze-drying and hydrazine vapor reduction. As anticipated, NiCo-HFPR-0.2 exhibits noteworthy properties, with the minimum reflection loss (RLmin) of -61.20 dB at 14.26 GHz and 1.56 mm, as well as the effective absorption bandwidth (EAB) of 4.90 GHz at 1.57 mm. Additionally, the simulation procedure is employed to determine the radar cross-section (RCS) attenuation. In comparison to a singular perfect electrically conductive (PEC) layer, the PEC layer coated with NiCo-HFPR-0.2 consistently yields an RCS value below -10 dB m2 within the range of -60° < θ < 60°. The RCS attenuation value of the NiCo-HFPR-0.2 coating achieves an outstanding 31.0 dB m2 at θ = 0°, strongly affirming the ability to effectively attenuate electromagnetic wave in real-world applications. The employed experimental methodology, the meticulously crafted composite, and the simulation outcomes presented in this study bear great promise for the progressive advancement of both theoretical investigations and practical applications within the domain of electromagnetic wave absorption.
RESUMO
Objective: To compare the effectiveness of lower extremity axial distractor (LEAD) and traction table assisted closed reduction and intramedullary nail fixation in treatment of femoral subtrochanteric fracture. Methods: The clinical data of 117 patients with subtrochanteric fracture of femur treated by closed reduction and intramedullary nail fixation between May 2012 and May 2022 who met the selection criteria were retrospectively analyzed. According to the auxiliary reduction tools used during operation, the patients were divided into LEAD group (62 cases with LEAD reduction) and traction table group (55 cases with traction table reduction). There was no significant difference in baseline data, such as gender, age, injured side, cause of injury, fracture Seinsheimer classification, time from injury to operation, and preoperative visual analogue scale (VAS) score, between the two groups ( P>0.05). Total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, closed reduction rate, fracture reduction quality, fracture healing time, weight-bearing activity time, and incidence of complications, as well as hip flexion and extension range of motion (ROM), Harris score, and VAS score at 1 month and 6 months after operation and last follow-up were recorded and compared between the two groups. Results: There were 14 cases in the LEAD group from closed reduction to limited open reduction, and 43 cases in the traction table group. The incisions in the LEAD group healed by first intention, and no complication such as nerve and vascular injury occurred during operation. In the traction table group, 3 cases had perineal crush injury, which recovered spontaneously in 1 week. The total incision length, operation time, intraoperative blood loss, fluoroscopy frequency, and closed reduction rate in the LEAD group were significantly better than those in the traction table group ( P<0.05). There was no significant difference in the quality of fracture reduction between the two groups ( P>0.05). Patients in both groups were followed up 12-44 months, with an average of 15.8 months. In the LEAD group, 1 patient had delayed fracture union at 6 months after operation, 1 patient had nonunion at 3 years after operation, and 1 patient had incision sinus pus flow at 10 months after operation. In the traction table group, there was 1 patient with fracture nonunion at 15 months after operation. X-ray films of the other patients in the two groups showed that the internal fixator was fixed firmly without loosening and the fractures healed. There was no significant difference in fracture healing time, weight bearing activity time, incidence of complications, and postoperative hip flexion and extension ROM, Harris score, and VAS score at different time points between the two groups ( P>0.05). Conclusion: For femoral subtrochanteric fracture treated by close reduction and intramedullary nail fixation, compared with traction table, LEAD assisted fracture reduction can significantly shorten the operation time, reduce intraoperative blood loss and fluoroscopy frequency, reduce incision length, effectively improve the success rate of closed reduction, and avoid complications related to traction table reduction. It provides a new method for good reduction of femoral subtrochanteric fracture.
Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas do Quadril , Ferida Cirúrgica , Humanos , Pinos Ortopédicos , Tração , Perda Sanguínea Cirúrgica/prevenção & controle , Estudos Retrospectivos , Resultado do Tratamento , Fraturas do Quadril/cirurgia , Extremidade Inferior , Fixação Interna de FraturasRESUMO
The unique layered structure and high conductivity of MXene materials make them highly promising for microwave absorption. However, the finite loss mechanism and severe agglomeration present challenging obstacles for ideal microwave absorbers, which could be effectively improved by constructing a three-dimensional (3D) porous structure. This study reports a 3D honeycomb MXene using a straightforward template method. The 3D MXene framework offers ample cavities to anchor the Prussian blue microcubes and their derivatives including Fe microboxes and Fe clusters by a simple annealing process. Based on the superiority of the 3D honeycomb architecture and magnetic-dielectric synergistic effects, the Fe/MXene absorbers demonstrate outstanding microwave absorption capabilities with the optimum reflection loss value of -40.3 dB at 2.00 mm in the low-frequency range from 4.2 to 5.6 GHz. The absorber also manifests superior radar wave attenuation by finite element analysis and exhibits great potential to be a flexible and thermal insulation material in a wide range of temperatures. This work proposes a useful reference for the design of 3D MXene-based porous architectures, and the synergistic magnetic-dielectric strategy further expands the potential of MXene-based absorbers, enabling them to be used as flexible and highly efficient microwave absorbers.
RESUMO
A series of CoNi/C nanocomposite fibers with different Co and Ni ratios were successfully prepared by electrospinning and carbonization techniques for the study of electromagnetic microwave (EMW) absorbing materials. We systematically studied the influence of Co and Ni content on the microstructure, chemical composition, magnetic properties, and EMW absorption characteristics of the samples. The results showed that CoNi/C nanocomposite fibers obtained excellent EMW absorption ability through the reasonable design of the composition, and the Co/Ni ratio significantly affected the microstructure and EMW absorption performance. When the Co/Ni ratio was 1/3, the minimum reflection loss (RLmin) is -71.2 dB (2.4 mm, 13.4 GHz), and the maximum effective absorption bandwidth (EAB, RLï¼-10 dB) is up to 5.9 GHz (2.2 mm, 12.1-18 GHz), covering almost the entire Ku band. This study demonstrated the enormous potential of one-dimensional structure in the field of EMW absorption. In addition, the CoNi/C nanocomposite fiber synthesized using a straightforward and low-cost method not only has excellent EMW absorption performance but also has the potential for practical application. The results of this study provide a simple and effective approach for designing high-performance EMW absorbing materials.
RESUMO
Composite materials that combine magnetic and dielectric losses offer a potential solution to enhance impedance match and significantly improve microwave absorption. In this study, Co3O4/ZnCo2O4 and ZnCo2O4/ZnO with varying metal oxide compositions are successfully synthesized, which are achieved by modifying the ratios of Co2+ and Zn2+ ions in the CoZn bimetallic metal-organic framework (MOF) precursor, followed by a high-temperature oxidative calcination process. Subsequently, a layer of polypyrrole (PPy) is coated onto the composite surfaces, resulting in the formation of core-shell structures known as Co3O4/ZnCo2O4@PPy (CZCP) and ZnCo2O4/ZnO@PPy (ZCZP) composites. The proposed method allows for rapid adjustments to the metal oxide composition within the inner shell, enabling the creation of composites with varying degrees of magnetic losses. The inclusion of PPy in the outer shell serves to enhance the bonding strength of the entire composite structure while contributing to conductive and dielectric losses. In specific experimental conditions, when the loading is set at 50 wt%, the CZCP composite exhibits an effective absorption bandwidth (EAB) of 5.58 GHz (12.42 GHz-18 GHz) at a thickness of 1.53 mm. Meanwhile, the ZCZP composite demonstrates an impressive minimum reflection loss (RLmin) of -71.2 dB at 13.04 GHz, with a thickness of 1.84 mm. This study offers a synthesis strategy for designing absorbent composites that possess light weight and excellent absorptive properties, thereby contributing to the advancement of electromagnetic wave absorbing materials.
RESUMO
Nowadays, electromagnetic radiation significantly impacts the normal operation of electronic devices and poses risks to human health. To effectively address this problem, the development of composites that exhibit exceptional electrochemical wave absorption through the combination of different components holds great promise. In this study, we have successfully prepared 1D Ni nanochains@Zn2+ doping polypyrrole/reduced graphene oxide (Ni NCs@Z-P/RGO, denoted as R-x) composites using a combination of hydrothermal, solvothermal, in situ polymerization, and physical blending methods. Notably, the R-2 composite demonstrates a remarkable minimum reflection loss (RLmin) of -63.58 dB at 14.3 GHz, with a thickness of 1.61 mm. Furthermore, the R-2 composite exhibits an impressive effective absorption bandwidth (EAB) of 5.08 GHz (11.92 GHz-17 GHz) at a thickness of 1.67 mm. These outstanding performances can be attributed to the synergistic effect of the different components and a well-thought-out structural design. Moreover, to showcase the practical applicability of the material, we have conducted additional investigations on the reduction of the radar cross-sectional area (RCS). The results strongly demonstrate that the prepared composite material, when used as a coating, effectively reduces the RCS value by up to 26.6 dB m2 for R-2 at θ = 0°. The experimental methods and simulations presented in this study hold significant potential for application in wave absorption research and practical implementations. Additionally, the prepared Ni NCs@Z-P/RGO composites demonstrate feasibility as wave-absorbing materials for future utilization.
RESUMO
With the increased usage of electromagnetic microwaves (EM) in wireless communication technology, the problem of electromagnetic radiation pollution has grown dramatically. This study successfully prepared novel Co/C magnetic nanocomposite fibers for EM absorption using the electrospinning and carbonization methods. The morphology, composition, magnetic properties, and EM absorption performance were extensively characterized. This material shows exceptional EM absorption performance, achieving -72.01 dB (at 2.08 mm) for minimum reflection loss (RLmin) and 5.4 GHz (at 1.68 mm) for effective absorption bandwidth (EAB). The performance surpasses not only any single precursor but also stands as the best in similar investigations. It can be attributed to the microstructure of magnetic Co nanoparticles encapsulated in carbon nanofibers and the macrostructure of cross-linked three-dimensional (3D) conductive networks. The combination of these structures resulted in excellent dielectric loss, magnetic loss, and impedance matching. This research offers new insights into the production of one-dimensional (1D) carbon-based absorbers, while also establishing a theoretical foundation for exploring the application potential of this material. These findings may contribute to the development of more efficient and practical EM absorption materials in the future.
RESUMO
In recent years, electromagnetic pollution has become more and more serious, and there is an urgent need for microwave absorbing materials with superior performance. Prussian blue analogue (PBA) is a metal organic framework material with the advantages of diverse morphology and tunable composition. Therefore, PBA has attracted a lot of attention in the field of microwave absorption. In this work, PBA was coated on the surface of carbon composites by hydrothermal method, and then PPy was compounded on its surface after carbonization treatment to construct hierarchical core-shell CoC@CoFe/C@PPy fibers. The fibers have Co-doped C composites as the core and CoFe/C decorated with PPy as the shell. This unique hierarchical structure and various microwave absorption mechanisms are described in detail. The microwave absorption performance is optimized by adjusting the filling of the sample. The best microwave absorption performances are achieved at 25 wt% filling of CoC@CoFe/C@PPy. At a thickness of just 1.69 mm, CoC@CoFe/C@PPy fiebrs have a minimum reflection loss (RLmin) of -64.32 dB. When the thickness is 1.88 mm, CoC@CoFe/C@PPy achieves a maximum effective absorption bandwidth (EABmax) of 5.38 GHz. The results indicate that the CoC@CoFe/C@PPy composite fibers have a great potential in the field of microwave absorption.
RESUMO
The design of heterostructures with reasonable chemical composition and spatial structure is one of the effective strategies to achieve high performances electromagnetic wave (EMW) absorption. Herein, reduced graphene oxide (rGO) nanosheets decorated with hollow core-shell Fe3O4@PPy (FP) microspheres have been prepared by the combination of hydrothermal method, in situ polymerization method, directional freeze-drying and hydrazine vapor reduction. FP acting as traps can consume EMW trapped into their interior through the magnetic and dielectric losses. RGO nanosheets forming the conductive network are served as multi-reflected layers. Moreover, the impedance matching is optimized by the synergistic effect between FP and rGO. As expected, the synthetic Fe3O4@PPy/rGO (FPG) composite shows excellent EMW absorption performances with the minimum reflect loss (RLmin) of -61.20 dB at 1.89 mm and the effective absorption bandwidth (EAB) of 5.26 GHz at 1.71 mm. The excellent performances for the heterostructure are attributed to the synergistic effect of conductive loss, dielectric loss, magnetic loss, multiple reflection loss, and optimized impedance matching. This work provides a simple and effective strategy for the fabrication of lightweight, thin and high-performances EMW absorbing materials.
RESUMO
Promoting ecological conservation and high-quality development in the Yellow River basin is an important objective in China's 14th Five-Year Plan. Understanding the spatio-temporal evolution of and factors affecting the resources and environmental carrying capacity (RECC) of the urban agglomerations is critical for boosting high-quality green-oriented development. We first combined the Driver-Pressure-State-Impact-Response (DPSIR) framework and the improved Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) model to evaluate the RECC of Shandong Peninsula urban agglomeration in 2000, 2010 and 2020; we then used trend analysis and spatial autocorrelation analysis to understand the spatio-temporal evolution and distribution pattern of RECC. Furthermore, we employed Geodetector to detect the influencing factors and classified the urban agglomeration into six zones based on the weighted Voronoi diagram of RECC as well as specific conditions of the study area. The results show that the RECC of Shandong Peninsula urban agglomeration increased consistently over time, from 0.3887 in 2000 to 0.4952 in 2010 and 0.6097 in 2020, respectively. Geographically, RECC decreased gradually from the northeast coast to the southwest inland. Globally, only in 2010 the RECC presented a significant spatial positive correlation, and that in the other years were not significant. The high-high cluster was mainly located in Weifang, while the low-low cluster in Jining. Furthermore, our study reveals three key factors-advancement of industrial structure, resident consumption level, and water consumption per ten thousand yuan of industrial added value-that affected the distribution of RECC. Other factors, including the interactions between residents' consumption level and environmental regulation, residents' consumption level and advancement of industrial structure, as well as between the proportion of R&D expenditure in GDP and resident consumption level also played important roles resulting in the variation of RECC among different cities within the urban agglomeration. Accordingly, we proposed suggestions for achieving high-quality development for different zones.
Assuntos
Conservação dos Recursos Naturais , Desenvolvimento Econômico , Cidades , Análise Espacial , Indústrias , China , Rios , UrbanizaçãoRESUMO
Introduction: Diffuse alveolar hemorrhage (DAH) is a serious complication caused by systemic lupus erythematosus (SLE). Tissue damage and changes in immune response are all associated with excessive free radical production. Therefore, removing excess reactive oxygen species are considered a feasible scheme for diffuse alveolar hemorrhage treatment. Cyclophosphamide is often used as the main therapeutic drug in clinics. However, CTX carries a high risk of dose-increasing toxicity, treatment intolerance, and high recurrence rate. The combination of therapeutic drugs and functional nanocarriers may provide an effective solution. PDA is rich in phenolic groups, which can remove the reactive oxygen species generated in inflammatory reactions, and can serve as excellent free radical scavengers. Methods: We developed a hollow polydopamine (HPDA) nanocarrier loaded with CTX by ionization to prepare the novel nanoplatform, CTX@HPDA, for DAH treatment. The monodisperse silica nanoparticles were acquired by reference to the typical Stober method. PDA was coated on the surface of SiO2 by oxidation self-polymerization method to obtain SiO2@PDA NPs. Then, HPDA NPs were obtained by HF etching. Then HPDA was loaded with CTX by ionization to prepare CTX@HPDA. Then we tested the photothermal effect, animal model therapeutics effect, and biosafety of CTX@HPDA. Results: Material tests showed that the CTX@ HPDA nanoplatform had a uniform diameter and could release CTX in acidic environments. The vitro experiments demonstrated that CTX@HPDA has good photothermal conversion ability and photothermal stability. Animal experiments demonstrated that the CTX@HPDA nanoplatform had good biocompatibility. The nanoplatform can dissociate in acidic SLE environment and trigger CTX release through photothermal conversion. Combining HPDA, which scavenges oxygen free radicals, and CTX, which has immunosuppressive effect, can treat pulmonary hemorrhage in SLE. Micro-CT can be used to continuously analyze DAH severity and lung changes in mice after treatment. The pulmonary exudation in the various treatment groups improved to varying degrees. Discussion: In this study, we report a photothermal/PH-triggered nanocarrier (CTX@HPDA) for the precise treatment of SLE-DAH. CTX@HPDA is a simple and efficient nanocarrier system for DAH therapy. This work provides valuable insights into SLE treatment.
RESUMO
Gas sensors are essential for detecting toxic gases that can harm social life or industrial production. Traditional metal oxide semiconductor (MOS)-based sensors suffer from shortcomings such as high operating temperature and slow response time, which limits their detection capabilities. Thus, there is a need to improve their performance. One useful technique is noble metal functionalization, which can effectively enhance the response/recovery time, sensitivity and selectivity, sensing response, and optimum operating temperature of MOS gas sensors. Among the noble metals, Au NPs are considered a promising material for forming composite sensing materials to achieve better sensing performance. This paper aims to review and discuss the recent research on Au-decorated MOS-based sensors, including Au/n-type MOS-based sensors, Au/p-type MOS-based sensors, Au/MOS/carbon composite materials, and Au/MOS/perovskite composite materials. The sensing mechanism of Au-functionalized MOS-based materials will also be examined.
RESUMO
With the improvement of economic level and the development of science and technology, the problem of water pollution needs to be solved now. Various water pollutants have a negative impact on nature and restrict its development. In recent years, photocatalysis is considered to be a promising wastewater treatment method. Two-dimensional carbon materials have become the hotspot of photocatalytic degradation of pollutants because of their excellent conductivity, large specific surface area, and good hydrophilicity. Nevertheless, it is very hard for these photocatalysts based on carbon materials to separate and recover from the system. For solving such a problem, the composition with magnetic components is an effective way which can facilitate separation and keep the catalytic activity of the samples. In this review, the main roles of magnetic carbon-based composites in the field of pollutant degradation are introduced, and their synthesis technology, classification, and application are summarized. In the end, the current challenges and prospects in this field are involved, aiming to provide useful insights and enlightments into the fields of pollutant treatment and photocatalytic degradation.
Assuntos
Poluentes Ambientais , Catálise , Carbono , Águas Residuárias , Fenômenos MagnéticosRESUMO
Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.
Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Proteínas , Ligação ProteicaRESUMO
The PI3K-Akt-mTOR signaling pathway is a highly frequently activated signal transduction pathway in human malignancies, which has been a hot target for anti-tumoral drug discovery. Based on our previous research, a function-oriented synthesis (FOS) of imidazo[1,2-a]pyrazines and imidazo[1,2-b]pyridazines was conducted, and their anticancer activities in vitro and in vivo were evaluated. Among them, compound 42 exhibited excellent dual PI3K/mTOR inhibitory activity, with IC50 values on PI3Kα and mTOR of 0.06 nM and 3.12 nM, respectively, much better than our previous reported compound 15a. Furthermore, compound 42 exhibited significant in vitro and in vivo anti-tumoral activities, great kinase selectivity, low hepatotoxicity, modest plasma clearance and acceptable oral bioavailability, which is a promising PI3K/mTOR targeted anti-cancer drug candidate.
Assuntos
Antineoplásicos , Piridazinas , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Inibidores de MTOR , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Pirazinas/farmacologia , Piridazinas/farmacologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
Recently, electromagnetic radiation is a serious threat to equipment accuracy, military safety and human health. The combination with different materials to fabricate absorber composites with well-designed morphology is expected to ameliorate this issue. In here, CuS/Fe3O4@polypyrrole (CuS/Fe3O4@PPy) flower-like composites are constructed by the combination of hydrothermal method, solvothermal method and in-situ polymerization. CuS with flower-like structure consisting of nanosheets can provide a conductive backbone and large specific surface area. Hollow Fe3O4 microspheres play a key role in deciding magnetic loss, and electromagnetic waves can penetrate their hollow structure, result in multiple reflection and refraction. PPy coating can enhance the combined strength of composite, and effectively consume microwaves by scattering and multiple refraction in the intercalated structure. As expected, the minimum reflection loss (RLmin) of CuS/Fe3O4@PPy composites is -74.12 dB at 8.16 GHz with a thickness of 2.96 mm, and the effective absorption bandwidth (EAB) is 4.6 GHz (13.4-18.0 GHz) at 1.68 mm. The excellent electromagnetic wave absorption performances are attributed to the synergy effect of different components. This work provides a unique strategy for the structural design of flower-like microspheres in the field of electromagnetic wave absorption.