RESUMO
Telomerase has long been considered as a biomarker for cancer diagnosis and a therapeutic target for drug discovery. Detecting telomerase activity in vivo could provide more direct information of tumor progression and response to drug treatment, which, however, is hampered by the lack of an effective probe that can generate an output signal without a tissue penetration depth limit. In this study, using the principle of distance-dependent magnetic resonance tuning, we constructed a telomerase-activated magnetic resonance imaging probe (TAMP) by connecting superparamagnetic ferroferric oxide nanoparticles (SPFONs) and paramagnetic Gd-DOTA (Gd(III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) complexes via telomerase-responsive DNA motifs. Upon telomerase-catalyzed extension of the primer in TAMP, Gd-DOTA-conjugated oligonucleotides can be liberated from the surface of SPFONs through a DNA strand displacement reaction, restoring the T1 signal of the Gd-DOTA for a direct readout of the telomerase activity. Here we show that, by tracking telomerase activity, this probe provides consistent monitoring of tumor growth kinetics during progression and in response to drug treatment and enables in situ screening of telomerase inhibitors in whole-animal models. This study provides an alternative toolkit for cancer diagnosis, treatment response assessment, and anticancer drug screening.
Assuntos
Telomerase , Animais , Linhagem Celular Tumoral , Telomerase/metabolismo , Cinética , Imageamento por Ressonância MagnéticaRESUMO
Ecological environmental issues are global focus problems. Achieving carbon neutrality is a fundamental measure to protect the ecological environment. Government environmental governance plays a key role in the process of moving towards a carbon neutral vision since the externality of the environment. Therefore, it is of great signiï¬cance for achieving the goal of carbon neutrality to evaluate the governmental ecological environment performance and propose improved suggestions based on the evaluation results. However, most existing evaluation methods have the disadvantages that it is difficult to avoid information distortion and loss during the evaluation process. To overcome these problems, an evaluation model based on a DPSIR-improved matter-element extension cloud model is proposed in this study, which combines the Drivers-Pressures-State-Impact-Response (DPSIR) model, the entropy weight method, the cloud model, matter element extension theory, and the cloud entropy optimization algorithm. The ecological environmental performance of China in 2019 was evaluated based on the proposed model, exampling as Jiangsu province. The results showed that the cloud digital eigenvalues of ecological environmental performance was (2.1852, 0.2956, 0.1), indicating that the ecological environmental performance was good level. However, the ambient air quality needed to be improved. To achieve carbon neutrality, suggestions including strengthening propagating, increasing investment, optimizing the industrial structure, and building a modern environmental governance system are proposed.
Assuntos
Carbono , Conservação dos Recursos Naturais , China , Política Ambiental , IndústriasRESUMO
In metal metallurgy, precipitation strengthening is widely used to increase material strength by utilizing the impediment effect of the second-phase particles on dislocation movements. Inspired by this mechanism, in this paper, novel multiphase heterogeneous lattice materials are developed with enhanced mechanical properties utilizing a similar hindering effect of second-phase lattice cells on the shear band propagation. For this purpose, biphase and triphase lattice samples are fabricated using high-speed multi jet fusion (MJF) and digital light processing (DLP) additive manufacturing techniques, and a parametric study is carried out to investigate their mechanical properties. Different from the conventional random distribution, the second-phase and third-phase cells in this work are continuously distributed along the regular pattern of a larger-scale lattice to form internal hierarchical lattice structures. The results show that the triphase lattices possess balanced mechanical properties. Interestingly, this indicates that introducing a relatively weak phase also has the potential to improve the stiffness and plateau stress, which is distinct from the common mixed rule. This work is aimed at providing new references for the heterogeneous lattice design with outstanding mechanical properties through material microstructure inspiration.
RESUMO
Bioorthogonal catalysis mediated by transition metals has inspired a new subfield of artificial chemistry complementary to enzymatic reactions, enabling the selective labelling of biomolecules or in situ synthesis of bioactive agents via non-natural processes. However, the effective deployment of bioorthogonal catalysis in vivo remains challenging, mired by the safety concerns of metal toxicity or complicated procedures to administer catalysts. Here, we describe a bioorthogonal catalytic device comprising a microneedle array patch integrated with Pd nanoparticles deposited on TiO2 nanosheets. This device is robust and removable, and can mediate the local conversion of caged substrates into their active states in high-level living systems. In particular, we show that such a patch can promote the activation of a prodrug at subcutaneous tumour sites, restoring its parent drug's therapeutic anticancer properties. This in situ applied device potentiates local treatment efficacy and eliminates off-target prodrug activation and dose-dependent side effects in healthy organs or distant tissues.
Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos , Nanopartículas Metálicas , Paládio , Pró-Fármacos , Titânio , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Catálise , Células Hep G2 , Humanos , Melanoma Experimental , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Paládio/química , Paládio/farmacocinética , Paládio/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Titânio/química , Titânio/farmacocinética , Titânio/farmacologiaRESUMO
Aiming at improved crystallization performance and simultaneously enhanced solid-state properties of poly(l-lactide) such as mechanical properties and enzymatic hydrolysis. A novel functionalized eggshell powder decorated with calcium phenylphosphonic acid (NES) was synthesized via the chemical reaction between phenylphosphonic acid and calcium ion on the surface of eggshell powder to form effective nucleating surface for poly(l-lactide). The resultant NES was incorporated into PLLA matrix to form fully biodegradable composites by melt blending, which exhibited superior crystallization, mechanical properties, and enzymatic hydrolysis. Upon the addition of 20 wt% NES, the crystallization half-time of a PLLA/NES composite decreased from 27.09 to 0.69 min at 130°C, compared to that of neat PLLA. The storage and tensile moduli of the composites increased with increasing NES loadings. Even with 20 wt% NES, the composite still exhibited good mechanical properties with tensile strength of 53.4 MPa, tensile modulus of 2460MPa and elongation at break of 2.5%, respectively. Moreover, it was interesting to find that the enzymatic hydrolytic degradation rates had been enhanced pronouncedly in the PLLA/NES composites than in neat PLLA. Such high performance biocomposites have great potential in expanding the utilization of eggshell powder from sustainable resources and practical application as PLLA-based bioplastic.