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1.
Front Genet ; 10: 996, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695722

RESUMO

Background: Congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive diseases characterized by enzyme deficiencies, within steroid hormone anabolism, which lead to disorders in cortisol synthesis. The 17α-hydroxylase/17,20-lyase deficiency (17-OHD) is an uncommon form of CAH caused by variants in the CYP17A1 gene. Aims: We report a novel compound heterozygous CYP17A1 variant and its association with the pathogenesis of 17-OHD. Methods: The patient was assessed for medical history, clinical manifestations, physical examination, laboratory examination, karyotype analysis, and adrenal computed tomography. Mutation screening was conducted using whole-exome sequencing (WES) and Sanger sequencing. The wild-type and mutant CYP17A1 complementary DNAs (cDNAs) were amplified and cloned into a pcDNA3.1(+) vector. These plasmids were transfected transiently into HEK-293T cells. Quantitative PCR and Western blotting analysis were performed to measure the expression level of P450c17. An enzymatic activity assay was conducted to measure the content of 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone (DHEA) in medium using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: The proband was characterized by 17-OHD with rhabdomyolysis, hypokalemia, and adrenal insufficiency. Novel compound heterozygous variants of the CYP17A1 gene (c.1304T > C/p.Phe435Ser and c.1228delG/p.Asp410Ilefs*9) were identified. The enzymatic activity assay revealed that this variant resulted in a complete deficiency of 17α-hydroxylase and 17,20-lyase activity. This was consistent with the hormonal characteristics of the proband's blood. Conclusions: These results suggest that the compound heterozygous variant of c.1304T > C and c.1228delG of the CYP17A1 gene can lead to 17-OHD. Our findings thus provide a novel insight into the clinical evaluations and molecular basis of 17-OHD.

2.
ACS Appl Mater Interfaces ; 11(35): 32135-32143, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31394902

RESUMO

Antiferroelectric (AFE) materials have a tremendous advantage as smart materials and large-strain actuators due to their unique reversible characteristic electric-field-induced strain (electrostrain) responses in comparison to piezoelectric effect and electrostriction. A key limitation to today's AFE actuators, however, is the poor temperature stability of electrostrain. In this work, a large reversible strain of 0.4% and an excellent thermal stability with a variation within ±5.5% from 20 to 190 °C were achieved for (Pb0.97La0.02)(Zr0.85Sn0.08Ti0.07)O3 (PLZST) AFE ceramics. A room-temperature electrostrain of 0.71% was obtained in virgin PLZST ceramics. It is intriguing to observe inconsistent strain curves between the first and further measured cycles, implying an incomplete reversible field-induced AFE-ferroelectric phase transition. A sharp electrostrain response in milliseconds was realized in the as-prepared PLZST ceramics. In addition, a phenomenological explanation was proposed to explain the extraordinary phenomena. Our results may shed light on the origin of the superior strain behaviors in AFE materials from the view of microscopic structure and macroscopic properties, and probably improve the understanding of the AFE phase transition.

3.
J Zhejiang Univ Sci B ; 20(5): 449-456, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31090270

RESUMO

Mitochondrion is a semi-autonomous organelle, important for cell energy metabolism, apoptosis, the production of reactive oxygen species (ROS), and Ca2+ homeostasis. Mitochondrial DNA (mtDNA) mutation is one of the primary factors in mitochondrial disorders. Though much progress has been made, there remain many difficulties in constructing cell models for mitochondrial diseases. This seriously restricts studies related to targeted drug discovery and the mechanism and therapy for such diseases. Here we summarize the characteristics of patient-specific immortalized lymphoblastoid cells, fibroblastoid cells, cytoplasmic hybrid (cybrid) cell lines, and induced pluripotent stem cells (iPSCs)-derived differentiation cells in the study of mitochondrial disorders, as well as offering discussion of roles and advances of these cell models, particularly in the screening of drugs.


Assuntos
DNA Mitocondrial/metabolismo , Descoberta de Drogas , Doenças Mitocondriais/metabolismo , Animais , Apoptose , Cálcio/metabolismo , Diferenciação Celular , Linhagem Celular , Citoplasma/metabolismo , Metabolismo Energético , Fibroblastos/citologia , Homeostase , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Linfócitos/citologia , Mitocôndrias/metabolismo , Mutação , Fenótipo , Espécies Reativas de Oxigênio/metabolismo
4.
Exp Ther Med ; 17(3): 2161-2171, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30867703

RESUMO

The current study aimed to evaluate whether luteolin could improve long-term heart preservation; this was achieved by evaluating the heart following long-term storage in University of Wisconsin solution (the control group) and in solutions containing three luteolin concentrations. The effects of different preservation methods were evaluated with respect to cardiac function while hearts were in custom-made ex vivo Langendorff perfusion systems. Different preservation methods were evaluated with respect to the histology, ultrastructure and apoptosis rate of the hearts, and the function of cardiomyocytes. In the presence of luteolin, the rate pressure product of the left ventricle was increased within 60 min of reperfusion following a 12-h preservation, coronary flow was higher within 30 min of reperfusion, cardiac contractile function was higher throughout reperfusion following 12- and 18-h preservations, and the left ventricle peak systolic pressure was significantly higher compared with the control group (all P<0.05). The expression levels of apoptosis regulator Bax and apoptosis regulator Bcl-2 in the luteolin groups were significantly decreased and increased, respectively. Lactate dehydrogenase, creatine kinase and malondialdehyde enzymatic activity was increased following long-term storage, while the activity of superoxide dismutase was significantly decreased. Furthermore, luteolin inhibited L-type calcium currents in ventricular myocytes under hypoxia conditions. Thus, luteolin demonstrated protective effects during long-term heart preservation in what appeared to be a dose-dependent manner, which may be accomplished through inhibiting hypoxia-dependent L-type calcium channels.

5.
Mitochondrion ; 46: 313-320, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30196098

RESUMO

Hypertrophic cardiomyopathy (HCM), affecting approximately 1 in 500 in the general population, is the most prominent cause of sudden heart disease-related mortality in the young. Mitochondrial DNA (mtDNA) mutations are among the primary causes of HCM. We previously identified a novel m.2336T>C homoplasmic mutation in the mitochondrial 16S rRNA gene (MT-RNR2) in a Chinese maternally inherited HCM family. However, the molecular mechanisms by which m.2336T>C mutation contributes to HCM remain elusive. Here we generated transferring mitochondria cell lines (cybrids) with a constant nuclear background by transferring mitochondria from immortalized lymphoblastoid cell lines carrying the HCM-associated m.2336T>C mutation into human mtDNA-less (ρ°) cells. Functional assays showed a decreased stability for 16S rRNA and the steady-state levels of its binding proteins in the mutant cybrids. This mutation impaired the mitochondrial translation capacity and resulted in many mitochondrial dysfunctions, including elevation of ROS generation, reduction of ATP production and impairment of mitochondrial membrane potential. Moreover, the mutant cybrids had poor physiological status and decreased survival ability. These results confirm that the m.2336T>C mutation leads to mitochondrial dysfunction and strongly suggest that this mutation may play a role in the pathogenesis of HCM.


Assuntos
Cardiomiopatia Hipertrófica/genética , DNA Mitocondrial/genética , Mitocôndrias/patologia , Mutação Puntual , RNA Ribossômico 16S/genética , Sobrevivência Celular , Metabolismo Energético , Saúde da Família , Humanos , Mitocôndrias/genética , Biossíntese de Proteínas , Estabilidade de RNA , RNA Ribossômico 16S/metabolismo , Proteínas de Ligação a RNA/metabolismo , Espécies Reativas de Oxigênio/metabolismo
6.
FASEB J ; 33(2): 2646-2658, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30307770

RESUMO

CD133 (AC133/prominin-1) has been identified as a stem cell marker and a putative cancer stem cell marker in many solid tumors. Its biologic function and molecular mechanisms remain largely elusive. Here, we show that a fly mutant for prominin-like, a homolog of mammalian CD133, shows a larger body size and excess weight accompanied with higher fat deposits as compared with the wild type. The expression levels of prominin-like are mediated by ecdysone signaling where its protein levels increase dramatically in the fat body during metamorphosis. Prominin-like mutants exhibit higher Drosophila insulin-like peptide 6 (di lp6) levels during nonfeeding stages and increased Akt/ Drosophila target of rapamycin (dTOR) signaling. On an amino acid-restricted diet, prominin-like mutants exhibit a significantly larger body size than the wild type does, similar to that which occurs upon the activation of the dTOR pathway in the fat body. Our data suggest that prominin-like functions by suppressing TOR and dilp6 signaling to control body size and weight. The identification of the physiologic function of prominin-like in Drosophila may provide valuable insight into the understanding of the metabolic function of CD133 in mammals.-Zheng, H., Zhang, Y., Chen, Y., Guo, P., Wang, X., Yuan, X., Ge, W., Yang, R., Yan, Q., Yang, X., Xi, Y. Prominin-like, a homolog of mammalian CD133, suppresses di lp6 and TOR signaling to maintain body size and weight in Drosophila.


Assuntos
Antígeno AC133/metabolismo , Tamanho Corporal , Peso Corporal , Proteínas de Drosophila/antagonistas & inibidores , Drosophila melanogaster/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Somatomedinas/antagonistas & inibidores , Antígeno AC133/genética , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Mutação , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Somatomedinas/genética , Somatomedinas/metabolismo
8.
Mol Cell ; 72(1): 71-83.e7, 2018 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-30220561

RESUMO

Cancer cells entail metabolic adaptation and microenvironmental remodeling to survive and progress. Both calcium (Ca2+) flux and Ca2+-dependent signaling play a crucial role in this process, although the underlying mechanism has yet to be elucidated. Through RNA screening, we identified one long noncoding RNA (lncRNA) named CamK-A (lncRNA for calcium-dependent kinase activation) in tumorigenesis. CamK-A is highly expressed in multiple human cancers and involved in cancer microenvironment remodeling via activation of Ca2+-triggered signaling. Mechanistically, CamK-A activates Ca2+/calmodulin-dependent kinase PNCK, which in turn phosphorylates IκBα and triggers calcium-dependent nuclear factor κB (NF-κB) activation. This regulation results in the tumor microenvironment remodeling, including macrophage recruitment, angiogenesis, and tumor progression. Notably, our human-patient-derived xenograft (PDX) model studies demonstrate that targeting CamK-A robustly impaired cancer development. Clinically, CamK-A expression coordinates with the activation of CaMK-NF-κB axis, and its high expression indicates poor patient survival rate, suggesting its role as a potential biomarker and therapeutic target.


Assuntos
Carcinogênese/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Microambiente Tumoral/genética , Sinalização do Cálcio/genética , Proteína Quinase Tipo 1 Dependente de Cálcio-Calmodulina/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , NF-kappa B/genética , Neoplasias/patologia , Fosforilação , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
9.
J Phys Chem Lett ; 9(15): 4221-4226, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-29996054

RESUMO

Halide perovskites have recently been a star semiconductor material in photovoltaic field owing to their excellent optoelectronic properties. An in-depth understanding of the photoluminescence and carrier diffusion in these materials may facilitate the implementation of high-performance optolelctronic devices. Here, we report an unusual photoluminescence quenching phenomenon in MAPbI3 single crystals. Interestingly, MAPbI3 single crystal with higher crystalline quality shows a lower photoluminescence emission and a shorter decay time, indicating the surface imperfection plays an important role to the photoluminescence. The quick quenching process is attributed to the synergistic effect of localized effect at the defects and rapid inward diffusion.

10.
Nanoscale ; 10(22): 10538-10544, 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29808184

RESUMO

A stretchable photodetector was fabricated by releasing a prestrained 3 M very high bond (VHB) substrate coated with perovskite CH3NH3PbI3 microwires and graphene. The light harvesting CH3NH3PbI3 microwires were realized through a transformation from CH3NH3PbI3 bulk single crystals. Graphene served as an expressway for photoinduced carriers in the perovskite. Under a very low working voltage bias of 0.01 V and irradiance power of 13.5 mW cm-2 under 785 nm laser illumination, the responsivity could be as high as 2.2 mA W-1. When the device was stretched up to 30%, 50%, and 80% strain, the responsivity was maintained at 0.96, 0.60, and 0.21 mA W-1, respectively. It also showed a fast photoresponse (<0.12 s) after stretching to 10%, 30%, 50%, 80%, and even to 100%. The device performed well after 100 cycles of stretching to 50% strain.

11.
ACS Appl Mater Interfaces ; 10(15): 12847-12853, 2018 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-29617106

RESUMO

A tetragonal (Ba,Ca)(Zr,Ti)O3 (BCZT) single crystal was grown by a flux method, and the piezoelectric coefficient ( d33) was characterized. The piezoelectric response was proved to be associated with polarization extension, which was successfully used to explain the variation in d33*. From the intrinsic aspect, the compositional effect on Landau free-energy profiles was discussed, showing an "extender" nature of the as-grown crystal and the increasing tendency of structural instability toward the morphotropic phase boundary. From the extrinsic aspect, the evolution of domain structure under various external fields (electric and temperature) was studied, revealing that the fine-domain structure of the as-grown BCZT single crystal was stable to E-field and temperature. The results manifest possibilities of further improving the piezoelectric property of the BCZT single crystal, which requires optimization of the crystal growth technique in future work.

12.
Inorg Chem ; 57(7): 4098-4103, 2018 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-29561597

RESUMO

Doping has been a reliable way to improve the properties of black phosphorus (BP). However, a uniform and large amount of doping in BP remains a challenge. Herein, the synthesis of tellurium-doped black phosphorus (Te-doped BP) single crystals with high crystalline quality is achieved by the chemical vapor transport reaction method. The synthetic route enables a uniform and relatively large amount (up to 0.5% atomic ratio) of Te-doping in BP single crystals. The electrocatalytic oxygen evolution reaction (OER) properties of few-layer Te-doped BP nanosheets prepared by liquid exfoliation were also investigated for the first time. Electrochemical tests demonstrated that the OER onset-potential of undoped and Te-doped BP nanosheets was 1.63 and 1.49 V, respectively. The result implies that doping provides an effective route to enhance the electrochemical OER performance of BP.

13.
ACS Appl Mater Interfaces ; 10(14): 11747-11755, 2018 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-29565114

RESUMO

(Pb0.97La0.02)(Zr xSn0.94- xTi0.06)O3 (PLZST) antiferroelectric ceramics with x = 0.75-0.90 have been fabricated and found to be a novel electrocaloric material system with a giant negative electrocaloric effect (Δ T = -11.5 K) and a large electrocaloric strength (|Δ T/Δ E| = 0.105 K cm kV-1) near room temperature. Additionally, the PLZST antiferroelectric ceramic also exhibits a large positive electrocaloric effect around the Curie temperature. The giant negative effect and the coexistence of both positive and negative electrocaloric effects in one material indicate a promising possibility to develop mid- to large-scale solid-state cooling devices with high efficiency.

14.
Stem Cell Reports ; 10(3): 808-821, 2018 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-29456182

RESUMO

Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young individuals. A potential role of mtDNA mutations in HCM is known. However, the underlying molecular mechanisms linking mtDNA mutations to HCM remain poorly understood due to lack of cell and animal models. Here, we generated induced pluripotent stem cell-derived cardiomyocytes (HCM-iPSC-CMs) from human patients in a maternally inherited HCM family who carry the m.2336T>C mutation in the mitochondrial 16S rRNA gene (MT-RNR2). The results showed that the m.2336T>C mutation resulted in mitochondrial dysfunctions and ultrastructure defects by decreasing the stability of 16S rRNA, which led to reduced levels of mitochondrial proteins. The ATP/ADP ratio and mitochondrial membrane potential were also reduced, thereby elevating the intracellular Ca2+ concentration, which was associated with numerous HCM-specific electrophysiological abnormalities. Our findings therefore provide an innovative insight into the pathogenesis of maternally inherited HCM.


Assuntos
Cardiomiopatia Hipertrófica/patologia , Células-Tronco Pluripotentes Induzidas/patologia , Mitocôndrias/patologia , Proteínas Mitocondriais/genética , Miócitos Cardíacos/patologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/metabolismo , Fenômenos Eletrofisiológicos/fisiologia , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Potencial da Membrana Mitocondrial/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação/genética , Miócitos Cardíacos/metabolismo , RNA Ribossômico 16S/genética
15.
Exp Ther Med ; 15(2): 1433-1441, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29399124

RESUMO

Heart transplantation has been applied in the clinic as an optimal solution for patients with end stage cardiac failure for a number of years. However, hypothermic preservation of the heart remains limited to 4-6 h and calcium accumulation over time is an important factor resulting in cell death. To provide longer and safer storage for donor hearts, it was demonstrated in our previous study that luteolin, a traditional Chinese medicine used to treat cardiovascular diseases, inhibits cell death and L-type calcium currents during hypothermic preservation. In the current study, the protective role of luteolin in modulating cardiomyocyte calcium cycling was further investigated. Intracellular calcium overload has already been implicated in hypothermia-induced dysfunction of cardiomyocytes. University of Wisconsin (UW) solution supplemented with 7.5, 15 or 30 µmol/l luteolin was used to preserve fresh isolated cardiomyocytes at 4°C. The results demonstrated that all three doses of luteolin supplementation attenuated calcium overload over a 6 h preservation period. Luteolin also suppressed the accumulation of important regulatory proteins and enzymes for cardiomyocyte calcium circulation, mitochondria Ca2+ uniporter and calmodulin, which are normally induced by cold storage in UW solution. Protein Kinase A activity was also suppressed in cardiomyocytes preserved in luteolin supplemented UW solution, while Ca2+-Mg2+-ATPase activity was increased. The results demonstrated that luteolin confers a cardioprotective effect through inhibiting the changes of calcium regulators during cold storage and therefore ameliorates Ca2+ overload in rat cardiomyocytes.

16.
J Colloid Interface Sci ; 509: 318-326, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28918374

RESUMO

In this paper, we present a general fabrication strategy to achieve the structure control and the flexible photonic stop band regulation of (2+1) D photonic crystal heterostructures (PCHs) by layer-by-layer depositing the annealed colloidal crystal monolayers of different sphere size. The optical properties of the resulting (2+1) DPCHs with different lattice constants were systematically studied and a universal photonic stopband variation rule was proposed, which makes it possible to program any kind of stopband structure as required, such as dual- or multi-stopbands PCH and ultra-wide stopband PCH. Furthermore, PCH with dual-stopbands overlapping the excitation wavelength (E) and emission wavelength(F) of Ru complex was fabricated by finely manipulating the spheres' diameter of colloidal monolayers. And an additional 2-fold fluorescence enhancement in comparison to that on the single stopband sample was achieved. This strategy affords new opportunities for delicate engineering the photonic behaviour of PCH, and also is of great significance for the practical application based on their bandgap property.

17.
Chem Commun (Camb) ; 54(9): 1049-1052, 2018 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-29242858

RESUMO

With the aid of formic acid, CH3NH3PbI3 single crystal of 9 mm in length was directly harvested within 3 days via a nonseeded solution temperature-lowering (STL) method. It showed a record-narrow full width at half maximum of 13 arcsec for the high-resolution X-ray rocking curve, a low trap-state density of 3.1 × 109 cm-3, a high carrier mobility of 162 cm2 V-1 s-1 and high moisture stability. The addition of formic acid could suppress the oxidation of iodide ions in a conventional STL process, resulting in rapid growth of high-quality CH3NH3PbI3 single crystals.

18.
Nanotechnology ; 28(50): 500201, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29148429
19.
Nanotechnology ; 28(42): 424001, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28825413

RESUMO

Few-layer black phosphorus, also known as phosphorene, is a new two-dimensional material which is of enormous interest for applications, mainly in electronics and optoelectronics. Herein, we for the first time employ phosphorene for directing the self-assembly of asymmetric polystyrene-block-polymethylmethacrylate (PS-b-PMMA) block copolymer (BCP) thin film to form the perpendicular orientation of sub-10 nm PS nanopore arrays in a hexagonal fashion normal to the interface. We experimentally demonstrate that none of the PS and PMMA blocks exhibit preferential affinity to the phosphorene-modified surface. Furthermore, the perpendicularly-oriented PS nanostructures almost stay unchanged with the variation of number of layers of few-layer phosphorene nanoflakes between 15-30 layers. Differing from the neutral polymer brushes which are widely used for chemical modification of the silicon substrate, phosphorene provides a novel physical way to control the interfacial interactions between the asymmetric PS-b-PMMA BCP thin film and the silicon substrate. Based on our results, it is possible to build a new scheme for producing sub-10 nm PS nanopore arrays oriented perpendicularly to the few-layer phosphorene nanoflakes. Furthermore, the nanostructural microdomains could serve as a promising nanolithography template for surface patterning of phosphorene nanoflakes.

20.
Small ; 13(32)2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28696584

RESUMO

A systematic cytotoxicity study of layered black phosphorus (BP) is urgently needed before moving forward to its potential biomedical applications. Herein, bulk BP crystals are synthesized and exfoliated into layered BP with different lateral size and thickness. The cytotoxicity of as-exfoliated layered BP is evaluated by a label-free real-time cell analysis technique, displaying a concentration-, size-, and cell type-dependent response. The IC50 values can vary by 40 and 30 times among the BP sizes and cell types, respectively. BP-1 with the largest lateral size and thickness has the highest cytotoxicity; whereas the smallest BP-3 only shows moderate toxicity. The sensitivity of three tested cell lines follows the sequence of 293T > NIH 3T3 > HCoEpiC. Two possible mechanisms for BP to induce cytotoxicity are proposed and verified: (1) the generation of intracellular reactive oxygen species (ROS) is detected by a ROS sensitive probe using the inverted fluorescence microscopy and flow cytometry; (2) the interaction of layered BP and model cell membrane is examined by quartz crystal microbalance with dissipation, illustrating the disruption of cell membrane integrity especially by the largest BP-1. This systematic study of BP's cytotoxicity will shed light on its future biomedical and environmental applications.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Fósforo/farmacologia , Animais , Citometria de Fluxo , Células HEK293 , Humanos , Camundongos , Microscopia de Fluorescência , Células NIH 3T3 , Fósforo/química
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