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2.
Nano Lett ; 19(11): 7918-7926, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31645103

RESUMO

Intracellular protein-protein interactions (PPIs) are a vital and yet underexploited class of therapeutic targets for their crucial roles in cellular processes and involvement in disease initiation and progression. Although some successful chemistry and nanotechnologies have been introduced into peptide PPI modulators to allow cell and tissue permeability, significant challenges remain with regard to the efficient and precise modulation of PPIs within specific cells of diseased tissues, such as solid tumors. Herein, an intratumoral transformable hierarchical framework, termed iPLF, was fabricated via a two-step self-assembly between peptides and lanthanide-doped nanocrystals. In this proof-of-concept study, using NanoEL effect, TME response, and tumor marker targeting, iPLF in vivo delivered the p53-MDM2 modulator DPMI into tumor cells and ß-catenin-Bcl9 modulator Bcl9p into tumor stem cells. This crafted programmed nanomedicine with triple-stage delivery and responsiveness accurately modulated the specific intracellular protein-protein interactions, resulting in the suppression of tumor growth and metastasis in vivo, while maintaining a highly favorable safety profile. iPLF reached the goal of accurate, potent, and hazard-free intracellular PPI modulation, thereby providing a means to improve current knowledge of PPI networks and a novel therapeutic strategy for a great variety of diseases.

3.
J Mater Sci Mater Med ; 30(7): 76, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31218573

RESUMO

Superparamagnetic iron oxide nanoparticles (SPION) were widely employed as targeted drug delivery platform due to their unique magnetic property and effortless surface modification. However, the lack of targeting accuracy has been a big obstacle for SPION used in precise medicine. Herein, the tumor-targeting of SPION was enhanced by the conjugation of an aptamer-hybridized nucleic acid structure. The aptamer modified on the surface of SPION was composed of a double-stranded DNA (dsDNA) and a G-quadruplex DNA (AS1411) structure, which carried a chemical anticancer drug, daunomycin (DNM) and a photosensitizer molecule, namely 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP), respectively. The aptamer-dsDNA conjugated SPION nanocarriers (named Apt-S8@SPION) exhibited good stability in serum and nuclease DNase I. The drug-loaded nanocarriers (TMPyP&DNM&Apt-S8@SPION) have high cellular cytotoxicity to A549 and C26 cells which are represently nucleolin-overexpressing cancer cells. The nucleolin-blocking experiments unambiguously evidenced that the formed nanomedicine could target to the cell surface via the specific AS1411-nucleolin interaction, which increased the efficiency of cell uptake. Meanwhile, the TMPyP&DNM&Apt-S8@SPION nanospheres could produce cytotoxic reactive oxygen species efficiently by irradiation of visible light for establishing a new type of PDT to cancer cells. Therefore, the designed TMPyP&DNM&Apt-S8@SPION nanoparticles have magnetic-aptamer dual targeting and combined chemo-photodynamic therapy, and thus were supposed to be ideal drug delivery vehicles with great potential in the era of precision medicine.

4.
Nat Commun ; 10(1): 2726, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222060

RESUMO

Temporal cloaks have aroused tremendous research interest in both optical physics and optical communications, unfolding a distinct approach to conceal temporal events from an interrogating optical field. The state-of-the-art temporal cloaks exhibit picosecond-scale and static cloaking window, owing to significantly limited periodicity and aperture of time lens. Here we demonstrate a field-programmable silicon temporal cloak for hiding nanosecond-level events, enabled by an integrated silicon microring and a broadband optical frequency comb. With dynamic control of the driving electrical signals on the microring, our cloaking windows could be stretched and switched in real time from 0.449 ns to 3.365 ns. Such a field-programmable temporal cloak may exhibit practically meaningful potentials in secure communication, data compression, and information protection in dynamically varying events.

5.
Molecules ; 24(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060332

RESUMO

Hair-coloring products include permanent, semi-permanent and temporary dyes that vary by chemical formulation and are distinguished mainly by how long they last. Domestic temporary hair dyes, such as fuchsin basic, basic red 2 and Victoria blue B, are especially popular because of their cheapness and facile applications. Despite numerous studies on the relationship between permanent hair dyes and disease, there are few studies addressing whether these domestic temporary hair dyes are associated with an increased cancer risk. Herein, to ascertain the bio-safety of these temporary hair dyes, we comparatively studied their percutaneous absorption, hemolytic effect and cytotoxic effects in this paper. Furthermore, to better understand the risk of these dyes after penetrating the skin, experimental and theoretical studies were carried out examining the interactions between the dyes and serum albumins as well as calf thymus (CT)-DNA. The results showed that these domestic temporary hair dyes are cytotoxic with regard to human red blood cells and NIH/3T3 cell lines, due to intense interactions with bovine serum albumin (BSA)/DNA. We conclude that the temporary hair dyes may have risk to human health, and those who use them should be aware of their potential toxic effects.


Assuntos
Eritrócitos/citologia , Tinturas para Cabelo/efeitos adversos , Células NIH 3T3/citologia , Corantes de Rosanilina/efeitos adversos , Animais , Bovinos , Sobrevivência Celular/efeitos dos fármacos , DNA/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Tinturas para Cabelo/química , Tinturas para Cabelo/farmacocinética , Hemólise , Humanos , Camundongos , Simulação de Acoplamento Molecular , Células NIH 3T3/efeitos dos fármacos , Fenazinas/efeitos adversos , Fenazinas/química , Fenazinas/farmacocinética , Corantes de Rosanilina/química , Corantes de Rosanilina/farmacocinética , Albumina Sérica Humana/efeitos dos fármacos , Suínos
6.
J Am Chem Soc ; 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31064178

RESUMO

Semiconductive metal-organic frameworks (MOFs) have attracted extraordinary research interest in recent years; however, electronic applications based on these emerging materials are still in their infancy. Herein, we show that a lanthanide-based semiconductive MOF (SCU-12) can effectively convert X-ray photons to electrical current signals under continuous hard X-ray radiation. The semiconductive MOF-based polycrystalline detection device presents a promising X-ray sensitivity with the value of 23.8 µC Gyair-1 cm-2 under 80 kVp X-ray exposure, competitive with the commercially available amorphous selenium ( α-Se) detector. The lowest detectable X-ray dose rate is 0.705 µGy s-1, representing the record value among all X-ray detectors fabricated by polycrystalline materials. This work discloses the first demonstration of hard radiation detection by semiconductive MOFs, providing a horizon that can guide the synthesis of a new generation of radiation detection materials by taking the advantages of structural designability and property tunability in the MOF system.

7.
Biol Trace Elem Res ; 191(2): 276-285, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30661165

RESUMO

The objective of this study is to investigate changes in the expression of enzymes involved in chondroitin sulfate (CS) sulfation in distal articular surface of proximal interphalangeal joint isolated from school-age children patients with Kashin-Beck disease (KBD), using normal children as controls. Articular cartilage samples were collected from four normal and four KBD children (7-12 years old), and these children were assigned to control and KBD groups. Hematoxylin and eosin (H&E), toluidine blue (TB), and immunohistochemical (IHC) stainings were utilized to evaluate changes in joint pathology and expression of enzymes involved in CS sulfation, including carbohydrate sulfotransferase 12 (CHST-12), carbohydrate sulfotransferase 13 (CHST-13), and uronyl 2-O-sulfotransferase (UST). The correspondence results were examined by semi-quantitative analysis. Compared with the control group, the KBD group showed the following: a significant decrease of total chondrocytes in superficial, middle, and deep layers and deposition of sulfated glycosaminoglycans in extracellular matrix of KBD cartilage were observed; positive staining chondrocytes of CHST-12, CHST-13, and UST were significantly less in superficial zone of KBD cartilage; and CHST-13 positive staining chondrocytes was reduced in deep zone of KBD cartilage. In contrast, the positive staining rates of CHST-12, CHST-13, and UST in KBD were significantly higher than those in the control group. The decreased expression of these enzymes and the physiologic compensatory reaction may be the signs of early-stage KBD. The alterations of CS structure modifying sulfotransferases in finger articular cartilage might play an important role in the onset and pathogenesis of school-age KBD children.

8.
Biosci Biotechnol Biochem ; : 1-10, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30387379

RESUMO

Aluminum (Al) toxicity is a primary limiting factor for crop production in acid soils. Callose deposition, an early indicator and likely a contributor to Al toxicity, is induced rapidly in plant roots under Al stress. SbGlu1, encoding a ß-1,3-glucanase for callose degradation, showed important roles in sorghum Al resistance, yet its regulatory mechanisms remain unclear. The STOP1 transcription factors mediate Al signal transduction in various plants. Here, we identified their homolog in sweet sorghum, SbSTOP1, transcriptionally activated the expression of SbGlu1. Moreover, the DNA sequence recognized by SbSTOP1 on the promoter of SbGlu1 lacked the reported cis-acting element. Complementation lines of Atstop1 with SbSTOP1 revealed enhanced transcription levels of SbGlu1 homologous gene and reduced callose accumulation in Arabidopsis. These results indicate, for the first time, that SbSTOP1 is involved in the modulation of callose deposition under Al stress via transcriptional regulation of a ß-1,3-glucanase gene.

9.
Front Plant Sci ; 9: 258, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29541086

RESUMO

Aluminum (Al) toxicity in acidic soils affects crop production worldwide. C2H2-type zinc finger transcription factor STOP1/ART1-mediated expression of Al tolerance genes has been shown to be important for Al resistance in Arabidopsis, rice and other crop plants. Here, we identified and characterized four STOP1-like proteins (SbSTOP1a, SbSTOP1b, SbSTOP1c, and SbSTOP1d) in sweet sorghum, a variant of grain sorghum (Sorghum bicolor L.). Al induced the transcription of the four SbSTOP1 genes in both time- and Al concentration-dependent manners. All SbSTOP1 proteins localized to the cell nucleus, and they showed transcriptional activity in a yeast expression system. In the HEK 293 coexpression system, SbSTOP1d showed transcriptional regulation of SbSTAR2 and SbMATE, indicating the possible existence of another SbSTOP1 and SbSTAR2-dependent Al tolerance mechanism in sorghum apart from the reported SbMATE-mediated Al exclusion mechanism. A transgenic complementation assay showed that SbSTOP1d significantly rescued the Al-sensitivity characteristic of the Atstop1 mutant. Additionally, yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays showed that SbSTOP1d interacted with SbSTOP1b and SbSTOP1d itself, suggesting that SbSTOP1 may function as a homodimer and/or heterodimer. These results indicate that STOP1 plays an important role in Al tolerance in sweet sorghum and extend our understanding of the complex regulatory mechanisms of STOP1-like proteins in response to Al toxicity.

10.
J Nanosci Nanotechnol ; 18(7): 4445-4456, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442618

RESUMO

The dose-dependent toxicity and low specificity against cancerous cells have restricted the clinical use of daunomycin (DNM). Titanium dioxide (TiO2) has been wildly used as an inorganic photodynamic therapy (PDT) agent and drug carrier. To facilitate the targeted drug delivery and combined therapy, in the present study, TiO2-coated Fe3O4 nanoparticles (Fe3O4@TiO2 NPs) were employed to load DNM and the drug-loaded Fe3O4@TiO2-DNM Nps exhibited smart pH-controlled releasing and satisfactory cytotoxicity as well as photocytotocity. The combination of prussian blue staining and fluorescence methods evidenced the effortless cell internalization of the fabricated Fe3O4@TiO2-DNM Nps for the cancer cells. The cell cycle status experiments indicated that the as-prepared nanospheres arrested the S and G2/M periods of the cancer cell proliferation in the dark, and further induced the apoptosis under the irradiation of ultraviolet light. The cell apoptotic results revealed that the apoptosis induced by the Fe3O4@TiO2-DNM Nps was in the early stage. The constructed Fe3O4@TiO2-DNM NPs have been endowed with multifunctions that allow them to selectively deliver combinatorial therapeutic payload and exhibit integrated therapeutic effectiveness to tumors.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Daunorrubicina/farmacologia , Nanosferas , Fotoquimioterapia , Titânio , Antibióticos Antineoplásicos/química , Daunorrubicina/química
11.
J Biomater Appl ; 32(8): 1090-1104, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29357775

RESUMO

Magnetic mesoporous silica nanospheres (MMSN) were prepared and the surface was modified with cancer cell-specific ligand folic acid. Calcium carbonate was then employed as acid-activated gatekeepers to cap the mesopores of the MMSN, namely, MMSN-FA-CaCO3. The formation of the MMSN-FA-CaCO3 was proved by several characterization techniques, viz. transmission electron microscopy, zeta potential measurement, Fourier transform infrared spectroscopy, BET surface area measurement, and UV-Vis spectroscopy. Daunomycin was successfully loaded in the MMSN-FA-CaCO3 and the system exhibited sensitive pH stimuli-responsive release characteristics under blood or tumor microenvironment. Cellular uptake by folate receptor (FR)-overexpressing HeLa cells of the MMSN-FA-CaCO3 was higher than that by non-folated-conjugated ones. Intracellular-uptake studies revealed preferential uptake of these nanoparticles into FR-positive [FR(+)] HeLa than FR-negative [FR(-)]A549 cell lines. DAPI stain experiment showed high apoptotic rate of MMSN-FA-DNM-CaCO3 to HeLa cells. The present data suggest that the CaCO3 coating and folic acid modification of MMSN are able to create a targeted, pH-sensitive template for drug delivery system with application in cancer therapy.

12.
ACS Nano ; 12(2): 2017-2026, 2018 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-29376322

RESUMO

Developing a sophisticated nanomedicine platform to deliver therapeutics effectively and safely into tumor/cancer cells remains challenging in the field of nanomedicine. In particular, reliable peptide drug delivery systems capable of overcoming biological barriers are still lacking. Here, we developed a simple, rapid, and robust strategy to manufacture nanoclusters of ∼90 nm in diameter that are self-assembled from lanthanide-doped nanoparticles (5 nm), two anticancer peptides with different targets (BIM and PMI), and one cyclic peptide iNGR targeted to cancer cells. The peptide-lanthanide nanoclusters (LDC-PMI-BIM-iNGR) enhanced the resistance of peptide drugs to proteolysis, disassembled in response to reductive conditions that are present in the tumor microenvironment and inhibited cancer cell growth in vitro and in vivo. Notably, LDC-PMI-BIM-iNGR exhibited extremely low systemic toxicity and side effects in vivo. Thus, the peptide-lanthanide nanocluster may serve as an ideal multifunctional platform for safe, targeted, and efficient peptide drug delivery in cancer therapy.

13.
Opt Lett ; 42(17): 3299-3302, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28957088

RESUMO

A novel concept to generate a linear chirped microwave signal is proposed and experimentally demonstrated. The frequency to time mapping method is employed, where the photonic crystal waveguide Mach-Zehnder interferometer structure acts as the spectral shaper thanks to the slow light effect. By optimizing the structural parameters of the photonic crystal waveguide, a linear chirped microwave signal with the time-bandwidth product of about 30 is experimentally obtained. The impact of the slow light photonic crystal waveguide on the generated linear chirped microwave signal is also investigated. The utilization of the slow light effect brings in significant advantages, including the ultra-small footprint of 0.096 mm2 and simple structure to our scheme, which may be of great importance towards its potential applications.

14.
Opt Express ; 25(11): 12455-12462, 2017 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-28786601

RESUMO

We introduce and experimentally demonstrate a flexible temporal illusion at telecommunication data rate in optical fiber communication system. The temporal illusion cannot only transform an event to another event as expected, but also mask the event with high-level signal, providing a novel method to conceal the confidential information. We successfully transform the output temporal waveforms of a return-to-zero (RZ), dark RZ and nonreturn-to-zero (NRZ) event into that of any above modulation format event and high-level signal at different illusion bits and mosaic bits at a data rate of 5 Gb/s, respectively. Our works offer us new perspectives on illusion optics for falsifying event rather than object, which has potential applications in secure communication, data encryption and other military applications.

15.
J Photochem Photobiol B ; 173: 606-617, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28697478

RESUMO

DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations. Biological function analysis demonstrated that these porphyrins show no substantial inhibition to Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad inhibition under visible light. This significantly enhanced photocytotoxicity relative to the dark control is an essential property of photochemotherapeutic agents. The feature of the flexible arms emerges as critical influencing factors in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial dysfunction pathway was suggested for the cell apoptosis induced by these flexible-armed porphyrins. It is found that the porphyrins with positive charges located at the end of the flexible arms represent an exciting opportunity for photochemotherapeutic anti-cancer drug design.


Assuntos
Apoptose/efeitos dos fármacos , Quadruplex G/efeitos dos fármacos , Porfirinas/toxicidade , Telômero/genética , Células A549 , Apoptose/efeitos da radiação , Sítios de Ligação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Dicroísmo Circular , Quadruplex G/efeitos da radiação , Células HeLa , Humanos , Luz , Microscopia de Fluorescência , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Simulação de Acoplamento Molecular , Conformação de Ácido Nucleico , Porfirinas/química , Porfirinas/metabolismo , Oxigênio Singlete/análise
16.
Opt Lett ; 42(8): 1596-1599, 2017 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-28409807

RESUMO

A photonic differentiator (DIFF) plays a crucial role in photonic circuits. Despite the fact that a DIFF having a terahertz bandwidth has been reported, the practical bandwidth is limited to being a bandpass response. In this Letter, we propose the concept of a bandwidth-adaptable DIFF, which exploits the slow light effect in a photonic crystal waveguide (PhCW) to overcome the inherent bandwidth limitation of current photonic DIFFs. We fabricated a PhCW Mach-Zehnder interferometer (PhCW-MZI) on the silicon-on-isolator material platform to validate our concept. Input Gaussian pulses with full width to half-maximums (FWHMs) ranging from 2.7 to 81.4 ps are accurately differentiated using our PhCW-MZI. Our all-passive scheme circumvents the bandwidth bottlenecks of previously reported photonic DIFFs and can greatly broaden the application area of photonic DIFFs.

17.
Sci Rep ; 7: 41876, 2017 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-28139775

RESUMO

To simply and multitudinously synthesize hollow microspheres in a pure system is important for relevant research and application. Here, a simple and novel one-pot synthetic strategy to prepare polystyrene (PS) hollow microspheres via irradiation-assisted free-radical polymerizing and self-assembly (IFPS) approach under γ-ray irradiation with no additives introduced into the system is presented. And PS/2,5-Diphenyloxazole (PPO) fluorescent microspheres have been prepared successfully by IFPS reaction, which can be used as scintillators for the detection of ionizing radiation. A linear relationship between emitted luminescence and dose-activity in water is obtained, which suggests that composite microspheres could be used as liquid scintillation in specific environment.

18.
Nat Commun ; 8: 14411, 2017 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-28181531

RESUMO

Slow light has been widely utilized to obtain enhanced nonlinearities, enhanced spontaneous emissions and increased phase shifts owing to its ability to promote light-matter interactions. By incorporating a graphene on a slow-light silicon photonic crystal waveguide, here we experimentally demonstrate an energy-efficient graphene microheater with a tuning efficiency of 1.07 nmmW-1 and power consumption per free spectral range of 3.99 mW. The rise and decay times (10-90%) are only 750 and 525 ns, which, to the best of our knowledge, are the fastest reported response times for microheaters in silicon photonics. The corresponding figure of merit of the device is 2.543 nW s, one order of magnitude better than results reported in previous studies. The influence of the length and shape of the graphene heater to the tuning efficiency is further investigated, providing valuable guidelines for enhancing the tuning efficiency of the graphene microheater.

19.
Exp Ther Med ; 12(5): 3130-3136, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27882128

RESUMO

Poor elucidation of the mechanisms involved in regulating the radiosensitivity of cancers prevents the extensive application of low-dose radiotherapy in clinical settings. The present study was conducted to investigate the role of microRNA-145 (miR-145) in the modulation of cervical cancer cell radiosensitivity, as well as to identify the underlying target of miR-145 during this process. Cervical cancer tera cells were initially exposed to doses of radiation between 1 and 6 Gy before the assessments of the cell viability and apoptosis rate. Irradiation at dose of 1 Gy was screened as optimum dose and used in subsequent experiments. A dual luciferase reporter assay was performed to demonstrate that octamer-binding transcription factor 4 (OCT4) is a target of miR-145 in cervical cancer. Consequently, OCT4 was suggested to be a target of miR-145, as a dual luciferase vector that was ligated to a fragment corresponding to the predicted target site of miR-145 in OCT4 3'-UTR showed an 83% reduction in fluorescence. Following exposure to 1 Gy irradiation, tera cells transfected with miR-145 mimics, which showed downregulation of OCT4 and cyclin D1, had lower cell viability and cell migration rate and higher apoptosis rate compared to non-transfected cells. However, the co-transfection of miR-145 mimics and OCT4 expression vector restored OCT4 and cyclin D1 expression levels and made no significant difference in terms of cell viability, cell migration rate and apoptosis rate. The present results indicate that miR-145 increases the radiosensitivity of cervical cancer cells by silencing OCT4, that cyclin D1 is putatively under the positive regulation of OCT4 and mediates miR-145 function.

20.
Opt Express ; 24(21): 24390-24400, 2016 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-27828168

RESUMO

Arbitrary waveform generation has been widely used in optical communication, radar system and many other applications. We propose and experimentally demonstrate a silicon-on-insulator (SOI) on chip optical arbitrary waveform generator, which is based on Taylor synthesis method. In our scheme, a Gaussian pulse is launched to some cascaded microrings to obtain first-, second- and third-order differentiations. By controlling amplitude and phase of the initial pulse and successive differentiations, we can realize an arbitrary waveform generator according to Taylor expansion. We obtain several typical waveforms such as square waveform, triangular waveform, flat-top waveform, sawtooth waveform, Gaussian waveform and so on. Unlike other schemes based on Fourier synthesis or frequency-to-time mapping, our scheme is based on Taylor synthesis method. Our scheme does not require any spectral disperser or large dispersion, which are difficult to fabricate on chip. Our scheme is compact and capable for integration with electronics.

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