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1.
Artigo em Inglês | MEDLINE | ID: mdl-35527378

RESUMO

Due to the large distance or weak electronic conjugation between adjacent Bi-I octahedrons, the charge transport in the low-dimensional bismuth based hybrid perovskites is impeded and thus hinders their future developments. In this work, A-site cation engineering by monoamine BZA (benzylamine) and diamine 3-AMP (3-(aminomethyl)pyridine) has been demonstrated as an efficient strategy to regulate the corresponding activation energy of ionic migration and carrier transport capacity. Given the higher polarity of 3-AMP than BZA, producing a more efficient dielectric screening effect, it gives rise to obtaining the small exciton binding energy (50 meV) and low defect states (3.53 × 109 cm-3). The reduced distance of adjacent Bi-I octahedrons by the bilateral anchoring of the 3-AMP2+ diamine cation enhances both electronic conjugation and charge transport performance. Therefore, the photodetector for (3-AMP)BiI5 SC shows a 243-fold increase in on/off ratio compared with the (BZA)3BiI6 SC.

2.
Nat Commun ; 13(1): 1760, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365663

RESUMO

The evolutionarily conserved serine/threonine kinase mTORC1 is a central regulator of cell growth and proliferation. mTORC1 is activated on the lysosome surface. However, once mTORC1 is activated, it is unclear whether mTORC1 phosphorylates local lysosomal proteins to regulate specific aspects of lysosomal biology. Through cross-reference analyses of the lysosome proteome with the mTORC1-regulated phosphoproteome, we identify STK11IP as a lysosome-specific substrate of mTORC1. mTORC1 phosphorylates STK11IP at Ser404. Knockout of STK11IP leads to a robust increase of autophagy flux. Dephosphorylation of STK11IP at Ser404 represses the role of STK11IP as an autophagy inhibitor. Mechanistically, STK11IP binds to V-ATPase, and regulates the activity of V-ATPase. Knockout of STK11IP protects mice from fasting or Methionine/Choline-Deficient Diet (MCD)-induced fatty liver. Thus, our study demonstrates that STK11IP phosphorylation represents a mechanism for mTORC1 to regulate lysosomal acidification and autophagy, and points to STK11IP as a promising therapeutic target for the amelioration of diseases with aberrant autophagy signaling.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Complexos Multiproteicos , Serina-Treonina Quinases TOR , Animais , Concentração de Íons de Hidrogênio , Lisossomos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Camundongos Knockout , Complexos Multiproteicos/metabolismo , Serina-Treonina Quinases TOR/metabolismo
4.
Adv Sci (Weinh) ; 9(8): e2103478, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35032111

RESUMO

Phase-change material (PCM) devices are one of the most mature nonvolatile memories. However, their high power consumption remains a bottleneck problem limiting the data storage density. One may drastically reduce the programming power by patterning the PCM volume down to nanometer scale, but that route incurs a stiff penalty from the tremendous cost associated with the complex nanofabrication protocols required. Instead, here a materials solution to resolve this dilemma is offered. The authors work with memory cells of conventional dimensions, but design/exploit a PCM alloy that decomposes into a heterogeneous network of nanoscale crystalline domains intermixed with amorphous ones. The idea is to confine the subsequent phase-change switching in the interface region of the crystalline nanodomain with its amorphous surrounding, forming/breaking "nano-bridges" that link up the crystalline domains into a conductive path. This conductive-bridge switching mechanism thus only involves nanometer-scale volume in programming, despite of the large areas in contact with the electrodes. The pore-like devices based on spontaneously phase-separated Ge13 Sb71 O16 alloy enable a record-low programming energy, down to a few tens of femtojoule. The new PCM/fabrication is fully compatible with the current 3D integration technology, adding no expenses or difficulty in processing.

5.
Adv Mater ; 34(11): e2109139, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34994023

RESUMO

Ge-Sb-Te ("GST") alloys are leading phase-change materials for digital memories and neuro-inspired computing. Upon fast crystallization, these materials form rocksalt-like phases with large structural and vacancy disorder, leading to an insulating phase at low temperature. Here, a comprehensive description of crystallization, structural disorder, and electronic properties of GeSb2 Te4 based on realistic, quantum-mechanically based ("ab initio") computer simulations with system sizes of more than 1000 atoms is provided. It is shown how an analysis of the crystallization mechanism based on the smooth overlap of atomic positions kernel reveals the evolution of both geometrical and chemical order. The connection between structural and electronic properties of the disordered, as-crystallized models, which are relevant to the transport properties of GST, is then studied. Furthermore, it is shown how antisite defects and extended Sb-rich motifs can lead to Anderson localization in the conduction band. Beyond memory applications, these findings are therefore more generally relevant to disordered rocksalt-like chalcogenides that exhibit self-doping, since they can explain the origin of Anderson insulating behavior in both p- and n-doped chalcogenide materials.

6.
Nat Mater ; 21(3): 290-296, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34824395

RESUMO

Two-phase titanium-based alloys are widely used in aerospace and biomedical applications, and they are obtained through phase transformations between a low-temperature hexagonal closed-packed α-phase and a high-temperature body-centred cubic ß-phase. Understanding how a new phase evolves from its parent phase is critical to controlling the transforming microstructures and thus material properties. Here, we report time-resolved experimental evidence, at sub-ångström resolution, of a non-classically nucleated metastable phase that bridges the α-phase and the ß-phase, in a technologically important titanium-molybdenum alloy. We observed a nanosized and chemically ordered superstructure in the α-phase matrix; its composition, chemical order and crystal structure are all found to be different from both the parent and the product phases, but instigating a vanishingly low energy barrier for the transformation into the ß-phase. This latter phase transition can proceed instantly via vibrational switching when the molybdenum concentration in the superstructure exceeds a critical value. We expect that such a non-classical phase evolution mechanism is much more common than previously believed for solid-state transformations.


Assuntos
Ligas , Titânio , Ligas/química , Temperatura Alta , Molibdênio/química , Transição de Fase , Titânio/química
7.
Biotechnol Prog ; 38(1): e3225, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34775686

RESUMO

In utilizing glycerol to produce 1,3-propanediol by microbial fermentation, the problems of low utilization rate and poor production performance need to be addressed. Based on the analysis of a mathematical model for 1,3-propanediol production from glycerol by Klebsiella pneumoniae, this study theoretically investigated the effects of the dilution rate and the initial glycerol concentration in a two-stage fermentation process and the feasibility of applying the feedback control methods. First, the optimal operation conditions of initial glycerol concentration and dilution rate were obtained. Through the use of feedback control theory, a control strategy for dilution rate was designed and optimized to shorten the settling time (time required for fermentation to reach stability) from 60.92 to 36.68 h for the first reactor, and from 53.66 to 22.68 h for the second reactor. In addition, the yield of 1,3-propanediol in both two reactors reached up to 0.5 g·g-1 . The simulation results indicated that the feedback control strategy for dilution rate increased the product concentration, reduced the residual glycerol in the fermentation broth, and greatly improved the performance of the fermentation. A feeding strategy of automatic control for dilution rate has been established and will be applied as an effective guiding scheme in automatic continuous fermentations for production of 1,3-propanediol.

8.
Shanghai Kou Qiang Yi Xue ; 30(5): 556-560, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34888614

RESUMO

PURPOSE: To investigate the treatment experience and information needs of patients with dentofacial deformities in the process of surgical program design, surgical treatment and postoperative rehabilitation. METHODS: Thirty-six patients with dentofacial deformities at different treatment stages from March to July 2019 were selected for semi-structured interview. Colaizzi content analysis method and QSR NVivo 12.0 software were used to analyze and code the data, as well as extract the theme and genus. RESULTS: Three themes and eight categories were extracted, including① information needs in different treatment stages, mainly specific content of information needs at pre-operative preparation stage, orthognathic perioperative stage and post-operative rehabilitation stage; ② information support methods, i.e., diversified information support methods and patients' recognition of internet information;③ patients' cognition difference,namely the difference between patients' psychological expectation and the results of operation. CONCLUSIONS: Due to the treatment characteristics of orthognathic surgery and individual cognitive differences of patients, there is a large demand for information support at different stages of treatment. However, the current information support mode is limited, so it is necessary to further improve and provide scientific, professional and targeted information support for patients with dentofacial deformities.


Assuntos
Deformidades Dentofaciais , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Humanos
9.
Biology (Basel) ; 10(12)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34943226

RESUMO

Intermuscular bones (IBs) are small spicule-like bones located in the myosepta of basal teleosts, which negatively affect the edibleness and economic value of fish. Blunt snout bream (Megalobrama amblycephala, with epineural and epipleural IBs) and tilapia (Oreochromis niloticus, without epineural and epipleural IBs) are two major aquaculture species and ideal models for studying the formation mechanisms of fish IBs. Here, we compared myosepta development between M. amblycephala and O. niloticus, based on histological analysis, transcriptome profiling, and expression analysis of bone-related genes. The histological results showed that dye condensation began to appear in the myosepta 20 days post hatching (dph) in M. amblycephala, and IBs could be clearly observed 50 dph in the myosepta, based on different staining methods. However, in O. niloticus, dye condensation was not observed in the myosepta from 10 to 60 dph. Differentially expressed genes (DEGs) at different developmental stages were screened by comparing the transcriptomes of M. amblycephala and O. niloticus, and KEGG analysis demonstrated that these DEGs were enriched in many bone-related pathways, such as focal adhesion, calcium, and Wnt signaling pathways. Quantitative PCR was performed to further compare the expression levels of some bone-related genes (scxa, scxb, runx2a, runx2b, bgp, sp7, col1a2, entpd5a, entpd5b, phex, alpl, and fgf23). All the tested genes (except for alpl) exhibited higher expression levels in M. amblycephala than in O. niloticus. A comparison of the dorsal and abdominal muscle tissues between the two species also revealed significant expression differences for most of the tested genes. The results suggest that scxa, scxb, runx2a, runx2b, entpd5a, col1a2, and bgp may play important roles in IB development. Our findings provide some insights into the molecular mechanisms of IB formation, as well as clues for further functional analysis of the identified genes to better understand the development of IBs.

10.
J Phys Chem Lett ; 12(51): 12210-12217, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34928163

RESUMO

High-resolution measurements of angular scattering distributions provide a sensitive test for theoretical descriptions of collision processes. Crossed beam experiments employing a decelerator and velocity map imaging have proven successful to probe collision cross sections with extraordinary resolution. However, a prerequisite to exploit these possibilities is the availability of a near-threshold state-selective ionization scheme to detect the collision products, which for many species is either absent or inefficient. We present the first implementation of recoil-free vacuum ultraviolet (VUV) based detection in scattering experiments involving a decelerator and velocity map imaging. This allowed for high-resolution measurements of state-resolved angular scattering distributions for inelastic collisions between Zeeman-decelerated carbon C(3P1) atoms and helium atoms. We fully resolved diffraction oscillations in the angular distributions, which showed excellent agreement with the distributions predicted by quantum scattering calculations. Our approach offers exciting prospects to investigate a large range of scattering processes with unprecedented precision.

11.
J Proteome Res ; 20(12): 5379-5391, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34751028

RESUMO

Although targeted MAPK pathway inhibition has achieved remarkable patient responses in many cancers, the development of resistance has remained a critical challenge. Adaptive tumor response underlies the drug resistance. Furthermore, such bypass mechanisms often lead to the activation of many pro-survival kinases, which complicates the rational design of combination therapies. Here, we performed global tyrosine phosphoproteomic (pTyr) analyses and demonstrated that targeted MAPK signaling inhibition in melanoma leads to a profound remodeling of the pTyr proteome. Intriguingly, altered cholesterol metabolism might drive, in a coordinated fashion, the activation of these kinases. Indeed, we found an accumulation of intracellular cholesterol in melanoma cells (with BRAFV600E mutations) and non-small cell lung cancer cells (with KRASG12C mutations) treated with MAPK and KRASG12C inhibitors, respectively. Importantly, depletion of cholesterol not only prevents the feedback activation of pTyr signaling but also enhances the cytotoxic effects of MAPK pathway inhibitors, both in vitro and in vivo. Together, our findings suggest that cholesterol contributes to the tumor adaptive response upon targeted MAPK pathway inhibitors. These results also suggest that MAPK pathway inhibitors could be combined with cholesterol-lowering agents to achieve a more complete and durable response in tumors with hyperactive MAPK signaling.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Melanoma , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Colesterol , Humanos , Neoplasias Pulmonares/metabolismo , Sistema de Sinalização das MAP Quinases , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Mutação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/genética
12.
Eng Life Sci ; 21(10): 643-652, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34690635

RESUMO

Clavulanic acid (CA) is usually used together with other ß-lactam antibiotics as combination drugs to inhibit bacterial ß-lactamases, which is mainly produced from the fermentation of microorganism such as Streptomyces clavuligerus. Recently, it is still a challenge for downstream processing of low concentration and unstable CA from fermentation broth with high solid content, high viscosity, and small cell size. In this study, an integrated process was developed for simultaneous solid-liquid separation and primary purification of CA from real fermentation broth of S. clavuligerus using salting-out extraction system (SOES). First, different SOESs were investigated, and a suitable SOES composed of ethanol/phosphate was chosen and further optimized using the pretreated fermentation broth. Then, the optimal system composed of 20% ethanol/15% K2HPO4 and 10% KH2PO4 w/w was used to direct separation of CA from untreated fermentation broth. The result showed that the partition coefficient (K) and recovery yield (Y) of CA from untreated fermentation broth were 29.13 and 96.8%, respectively. Simultaneously, the removal rates of the cells and proteins were 99.8% and 63.3%, respectively. Compared with the traditional method of membrane filtration or liquid-liquid extraction system, this developed SOES showed the advantages of simple operation, shorter operation time, lower process cost and higher recovery yield of CA. These results demonstrated that the developed SOES could be used as an attractive alternative for the downstream processing of CA from real fermentation broth.

13.
Risk Manag Healthc Policy ; 14: 4253-4256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703337

RESUMO

We present the case of a 60-year-old woman who suddenly suffered a witnessed cardiac arrest and did not achieve return of spontaneous circulation despite being given 150-minute ultra-long cardiopulmonary resuscitation (CPR). During CPR, pulmonary embolism was suspected and was eventually diagnosed based on refractory pulseless electrical activity, elevated serum D-dimmer, and a markedly enlarged right ventricle chamber. After rescue thrombolytic alteplase therapy, the patient was successfully resuscitated and had a good neurological recovery.

14.
World J Clin Cases ; 9(24): 7285-7291, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34540990

RESUMO

BACKGROUND: Intervertebral disc calcification (IDC) combined with ossification of the posterior longitudinal ligament (OPLL) in cervical discs is rarely reported. This case study presents a rare case of IDC combined with OPLL in the C2-C3 segment. CASE SUMMARY: Here, we present a case of a 6-year-old Asian boy with severe neck pain and stiffness. Physical examination showed no neurological or other abnormalities. Digital radiography and computed tomography (CT) revealed a calcified intervertebral disc and OPLL at the C2-C3 vertebrae. The spinal canal compromise at C2-C3 was approximately 50% on magnetic resonance imaging. The final diagnosis was IDC combined with OPLL. We applied a neck brace for the patient to protect the neck. The patient's neck pain and stiffness recovered significantly within approximately 3 wk. At the 3 mo follow-up, the follow-up CT showed resolution of the ossified intervertebral disc herniation, and a small amount of calcification and slight OPLL remained at the involved segment. CONCLUSION: IDC combined with OPLL is a relatively rare condition in children. However, the majority of patients could have a favorable outcome, and the ossified mass in the canal would be spontaneously resolved with conservative therapy.

15.
Org Biomol Chem ; 19(39): 8586-8590, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34559872

RESUMO

Ion transport mediated by an ion pair receptor 1 bearing both cation and anion binding sites is presented. The ion pair binding property was revealed by means of 1H NMR titrations in organic solutions and X-ray analysis in the solid state. Single crystal structures demonstrated that 1 and CaI2 formed a solvent-separated ion-pair complex with two iodides each interacting with a triazine ring through anion-π interactions, whereas the calcium ion is bound by a pentaethylene glycol moiety. The ion transport activity was studied by monitoring the efflux of ions from salt-loaded EYPC large unilamellar vesicles (EYPC-LUVs) using ion selective electrodes. Chloride transport across the membrane mediated by the ion pair receptor through K+/Cl- or Na+/Cl- cotransport with a selectivity towards the K+/Cl- symport was realized.

16.
Cell Rep ; 36(9): 109641, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34469716

RESUMO

The relationship between poor in vivo bioavailability and effective pharmacological activity are not yet fully clarified for many flavonoids. The analysis of flavonoids-induced alterations in the gut microbiota represents a promising approach to provide useful clues to elucidate the mechanism of action. Here, we investigate the effect of myricetin supplementation on high-fat-diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats and explore the associations with the gut microbiota through high-throughput analyses. The 12-week myricetin supplementation and fecal microbiota transplantation outcomes suggest that myricetin significantly slows the development of NAFLD. Meanwhile, the anti-NAFLD effects of myricetin are associated with the modulation of the gut microbiota composition. Myricetin reduces hepatic lipid synthesis and inflammation through modulations in fecal butyric-acid-related gut microbiota and protection of the gut barrier function. This study may facilitate the elucidation of the action mechanism of flavonoids with low bioavailability.


Assuntos
Anti-Inflamatórios/farmacologia , Bactérias/efeitos dos fármacos , Flavonoides/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatite/prevenção & controle , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Biomarcadores/sangue , Butiratos/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Disbiose , Transplante de Microbiota Fecal , Células Hep G2 , Hepatite/metabolismo , Hepatite/microbiologia , Humanos , Mediadores da Inflamação/sangue , Lipídeos/sangue , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia , Ratos Wistar
17.
Ann Palliat Med ; 10(8): 8797-8807, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488368

RESUMO

BACKGROUND: CSF rhinorrhea is a type of CSF leakage caused by an aseptic abnormal passage between the subarachnoid space and the adjacent sinus and nasal cavity due to a cranial dural defect. At present, the value of computed tomography cisternography (CTC) in locating CSF rhinorrhea has been widely recognized, and magnetic resonance hydrography (MRH), as a heavy T2-weighted water imaging, plays a pivotal role in showing the location of the leak. In this paper, we retrospectively summarize the imaging manifestations seen at our hospital of patients with clinically confirmed CSF rhinorrhea at the skull base and evaluate the diagnostic value of different imaging methods in the localization of CSF rhinorrhea by means of preoperative imaging analysis using CTC and MRH. METHODS: Fifty-five patients with CSF rhinorrhea admitted to our department from October 2016 to January 2021 were retrospectively analyzed. The patients' conventional CT, CTC, and MRH imaging data were compared, and the location of the leak determined preoperatively matched the location of the leak found during surgery. Moreover, there was no recurrence during the follow-up period of 4 months to 3 years. RESULTS: There were statistically significant differences between the diagnostic positivity rate of CTC and spiral CT (χ2=16.755, P<0.00), and between the diagnostic positivity rate of cranial MRH and spiral CT (χ2=6.338, 6.338=0.01), and no statistically significant difference between the diagnostic positivity rate of CTC and cranial MRH (χ2=2.625, P=0.1). CONCLUSIONS: The combined use of imaging techniques has important practical significance for the proper treatment and prognostic evaluation of CSF rhinorrhea. CTC has the highest positive rate for the diagnosis of CSF rhinorrhea, followed by MRH, while spiral CT is safer. CTC and MRH can promote the diagnostic rate in determining the location of CSF rhinorrhea, and selective combined application can be an important guide to surgery.


Assuntos
Rinorreia de Líquido Cefalorraquidiano , Rinorreia , Rinorreia de Líquido Cefalorraquidiano/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
18.
Sci Adv ; 7(34)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34417176

RESUMO

Although single-source white emissive perovskite has emerged as a class of encouraging light-emitting material, the synthesis of lead-free halide perovskite materials with high luminous efficiency is still challenging. Here, we report a series of zero-dimensional indium-antimony (In/Sb) alloyed halide single crystals, BAPPIn2-2x Sb2x Cl10 (BAPP = C10H28N4, x = 0 to 1), with tunable emission. In BAPPIn1.996Sb0.004Cl10, bright yellow emission with near 100% photoluminescence quantum yield (PLQY) is yielded when it was excited at 320 nm, which turns into bright white-light emission with a PLQY of 44.0% when excited at 365 nm. Combined spectroscopy and theoretical studies reveal that the BAPP4+-associated blue emission and inorganic polyhedron-afforded orange emission function as a perfect pair of complementary colors affording white light in BAPPIn1.996Sb0.004Cl10 Moreover, the interesting afterglow behavior, together with excitation-dependent emission property, makes BAPPIn2-2x Sb2x Cl10 as high-performance anti-counterfeiting/information storage materials.

19.
Oncol Rep ; 46(2)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34278497

RESUMO

Erythropoietin­producing hepatocellular receptors (Ephs) comprise the largest subfamily of receptor tyrosine kinases and have been reported to be involved in a variety of biological cellular processes, including tumorigenesis and cancer progression. The present study aimed to determine the expression levels and clinicopathological significance of EphA8 in breast cancer (BC) using immunohistochemistry analysis of tissue microarrays. The results of the present study revealed that EphA8 expression levels were upregulated in BC tissue and were associated with tumor size and TNM stage. In addition, upregulated expression levels of EphA8 were identified to be a poor prognostic biomarker for patients with BC. The knockdown of EphA8 expression using short hairpin RNA resulted in increased levels of apoptosis as well as decreased proliferation, migration and invasion of BC cells both in vivo and in vitro. The knockdown of EphA8 also decreased the phosphorylation of AKT, which was accompanied by downregulation of Bcl­2 expression levels and upregulation of p53, Caspase­3 and Bax expression levels. Moreover, knockdown of EphA8 expression increased the chemosensitivity of BC cells to paclitaxel. In conclusion, the results of the present study indicated that EphA8 may be a useful prognostic marker in BC and that knockdown of EphA8 may represent a novel strategy in adjuvant chemotherapy for the treatment of BC.


Assuntos
Neoplasias da Mama/patologia , Paclitaxel/farmacologia , Receptor EphA8/metabolismo , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Células MCF-7 , Camundongos , Pessoa de Meia-Idade , Transplante de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carga Tumoral , Regulação para Cima/efeitos dos fármacos
20.
Anal Chem ; 93(23): 8291-8299, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34082526

RESUMO

Dysfunction of mitochondria is closely related to neurodegenerative diseases, heart diseases, cancers, and so on. Because both proton and oxygen participate in vital biochemical reactions occurring in mitochondria such as adenosine triphosphate (ATP) generation, measuring proton and oxygen concentrations in mitochondria is therefore crucial for monitoring mitochondria activities and understanding cellular behavior. For this purpose, we developed a ratiometric fluorescent nanosensor for simultaneously sensing and imaging O2 and pH in mitochondria. The steps are as follows: (1) Styrene was copolymerized with 2-aminoethyl methacrylate hydrochloride to produce amino-functionalized polymer nanoparticles. (2) The reference dye rhodamine B isothiocyanate (RBITC) and oxygen-sensitive dye platinum(II) octaethylporphyrin (PtOEP) were encapsulated into a polymer sphere during polymerization, while the pH indicator fluorescein isothiocyanate (FITC) and mitochondrial-targeting molecule (3-carboxypropyl)triphenylphosphonium bromide (TPP) were further modified on the surface of the nanoparticles. The developed nanosensor shows a narrow distribution of particle size, high sensitivity toward O2 and pH, excellent stability, and low cytotoxicity. These remarkable features of the dual nanosensor render them capable of real-time sensing and imaging of O2 and pH in mitochondria with high spatial resolution. Applying the mitochondrial-targeted dual nanosensor in HeLa cells, we quantitatively measured and imaged mitochondrial proton and oxygen concentration variations after carbonyl cyanide m-chlorophenylhydrazone (CCCP) treatment.


Assuntos
Técnicas Biossensoriais , Prótons , Corantes Fluorescentes , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Mitocôndrias , Oxigênio , Polímeros
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