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1.
Drug Resist Updat ; 66: 100904, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36462375

RESUMO

Lung cancer continues to be a malignant tumor with high mortality. Two obstacles interfere with curative therapy of lung cancer: (i) poor diagnosis at the early stages, as symptoms are not specific or asymptomatic; and (ii) invariably emerging drug resistance after treatment. Some factors contributing to drug resistance include preexisting genetic/genomic drug-resistant alteration(s); activation of adaptive drug resistance pathways; remodeling of the tumor microenvironment; and pharmacological mechanisms or activation of drug efflux pumps. Despite the mechanisms explored to better understand drug resistance, a gap remains between molecular understanding and clinical application. Therefore, facilitating the translation of basic science into the clinical setting is a great challenge. Nanomedicine has emerged as a promising tool for cancer treatment. Because of their excellent physicochemical properties and enhanced permeability and retention effects, nanoparticles have great potential to revolutionize conventional lung cancer diagnosis and combat drug resistance. Nanoplatforms can be designed as carriers to improve treatment efficacy and deliver multiple drugs in one system, facilitating combination treatment to overcome drug resistance. In this review, we describe the difficulties in lung cancer treatment and review recent research progress on nanoplatforms aimed at early diagnosis and lung cancer treatment. Finally, future perspectives and challenges of nanomedicine are also discussed.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Nanopartículas , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Nanotecnologia , Neoplasias/tratamento farmacológico , Nanomedicina , Sistemas de Liberação de Medicamentos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Nanopartículas/química , Microambiente Tumoral
2.
Opt Express ; 31(13): 21225-21238, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37381227

RESUMO

This paper discusses a method for assembling Au-Ag alloy nanoparticles (NPs) using direct current (DC) electric field to fabricate highly active SERS substrates. Different nanostructures could be obtained by regulating the intensity and action time of DC electric field. Under the condition of 5mA*10 min, we obtained Au-Ag alloy nano-reticulation (ANR) substrate with excellent SERS activity (Enhancement factor on order of magnitude of 106). ANR substrate has excellent SERS performance due to the resonance matching between its LSPR mode and excitation wavelength. The uniformity of the Raman signal on ANR is greatly improved than bare ITO glass. ANR substrate also has the ability to detect multiple molecules: ANR substrate can respectively detect Rh6G and CV molecules with a concentration as low as 10-10 M and 10-9 M and the Raman spectral intensity of the probe molecules on the surface of the ANR substrate has good linear correlation with the molecular concentration (R2 > 0.95). In addition, ANR substrate can detect both thiram and aspartame (APM) molecules far below (thiram for 0.0024 ppm and APM for 0.0625 g/L) the safety standard, which demonstrate its practical application potential.

3.
Opt Lett ; 47(24): 6365-6368, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36538439

RESUMO

In this Letter, a method for the rapid and efficient preparation of ultrasensitive detection substrates by assembling gold nanorod suspensions with the application of an alternating current (AC) field is proposed, and it is found that frequency and voltage are the effective means of regulation. A sandwich structure (parallel SiO2 plate) not only effectively slows down the evaporation rate, but also visually reveals the changes in the assembly process. Under the optimal assembly conditions, the sensitivity and uniformity of the substrate to different probe molecules are tested. The Raman detection results experimentally show that the detection limits of Rhodamine 6G (Rh6G), crystal violet (CV), and Aspartame (APM) molecular solutions are 10-14 M, 10-10 M, and 62.5 mg/L, respectively, and the mixed dye molecular solutions can also be effectively distinguished. Furthermore, Rh6G and CV characteristic peaks at 1647 cm-1 and 1619 cm-1 were measured at randomly selected positions, and their relative standard deviations (RSDs) were 5.63% and 8.45%, respectively, indicating that the substrate has good uniformity. The effective regulation of the self-assembly results of nanoparticles will further enhance the practical application effect of surface-enhanced Raman technology and expand the application prospects of this technology.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Nanotubos , Ouro/química , Dióxido de Silício , Nanopartículas Metálicas/química , Nanotubos/química , Violeta Genciana , Análise Espectral Raman/métodos
4.
Phys Chem Chem Phys ; 24(46): 28362-28370, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36385134

RESUMO

Induced circular dichroism (ICD) is widely used in miniature polarizers, molecular detection, and negative refractive index media. However, enhancing and the dynamic regulation of ICD signals of achiral nanostructures in the visible and near-infrared range remain the current challenges. Here, monolayer borophene (MB) with anisotropic conductance was incorporated into achiral nanostructures, which consisted of achiral dielectric elliptical hole arrays (DENAs) placed on a silver substrate. Two narrowband ICD signals for DENAs/MB were achieved in the near-infrared range under different circularly polarized lights. The distributions of the magnetic field of DENAs/MB could explain the two narrowband ICD signals originating from the coupling of surface plasmon polariton resonances along the x- and y directions. Not only could the ICD signals be tuned by the structural parameters of DENAs/MB, but they could also be actively tuned by the incident angles of the excitation light and the carrier concentration of MB. In addition, the sensitivity and the figure of merit of DENAs/MB could reach 302/RIU and 61.0. These results provide a concise method for the design of dynamically adjustable chiral devices based on borophene and promote its application in molecular recognition and chiral catalysis.

5.
J Nanobiotechnology ; 20(1): 521, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36496381

RESUMO

BACKGROUND: Antitumor T cell immunotherapy as a novel cancer therapeutic strategy has shown enormous promise. However, the tumor microenvironment (TME) is characterized by the low immunogenicity, hypoxia, and immunosuppressive condition that dramatically limit effective T cell immunotherapy. Thus, an ideal immunotherapy strategy that is capable of reversing the immunosuppressive TME is highly imperative. RESULTS: In this article, we reported that Fe-doped and doxorubicin (DOX) loaded HA@Cu2-XS-PEG (PHCN) nanomaterials were rationally designed as targeted Fe-PHCN@DOX nano-nuclear-reactors, which evoked persistent T cell immune response together with anti-PD-L1 nanobodies. It was confirmed that nano-nuclear-reactors displayed strong nanocatalytic effect for effective antitumor effects. Consequently, they maximized the immunogenic cell death (ICD) effect for antigen presentation and then stimulated T cell activation. In addition, Fe-PHCN@DOX could reprogram M2-phenotype tumor-associated macrophages (TAMs) into M1-phenotype TAMs by relieving tumor hypoxia. Meanwhile, blockade of the anti-PD-L1 nanobody promoted T cell activation through targeting the PD-1/PD-L1 immunosuppressive pathway. Notably, in vivo tumor therapy verified that this nano-nuclear-reactor could be used as an excellent immunotherapy nanoplatform for tumor eradication and metastasis prevention with nanobody. CONCLUSIONS: Our findings demonstrated that nano-nuclear-reactors in combination with nanobody could evoke persistent T cell immune activation, suggesting them potential as a promising immunotherapy option for reversing immunosuppressive immune-cold tumors.


Assuntos
Neoplasias , Anticorpos de Domínio Único , Humanos , Imunoterapia , Ativação Linfocitária , Linfócitos T , Neoplasias/terapia , Neoplasias/metabolismo , Doxorrubicina/farmacologia , Linhagem Celular Tumoral , Microambiente Tumoral
6.
Int Wound J ; 19(3): 679-691, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34414663

RESUMO

The development of biologically active multifunctional hydrogel wound dressings can assist effectively to wound regeneration and also has influenced multiple functions on wound injury. Herein, we designed a carbon-based composited injectable silk fibroin hydrogel as multifunctional wound dressing to provide effective anti-bacterial, cell compatibility and in vivo wound closure actions. Importantly, the fabricated injectable hydrogel exhibit sustained drug delivery properties, anti-oxidant and self-healing abilities, which confirm that composition of hydrogel is highly beneficial to tissue adhesions and burn wound regeneration ability. Frequently, designed injectable hydrogel can be injected into deep and irregular burn wound sites and would provide rapid self-healing and protection from infection environment with thoroughly filled wound area. Meanwhile, incorporated carbon nanofillers improve injectable hydrogel strength and also offer high fluid uptake to hydrogel when applied on the wound sites. In vitro MTT cytotoxicity assay on human fibroblast cell lines establish outstanding cytocompatibility of the injectable hydrogel and also have capability to support cell growth and proliferations. In vivo burn wound animal model results demonstrate that the hydrogel dressings predominantly influenced enhanced wound contraction and also promoted greater collagen deposition, granulation tissue thickness and vascularization. This investigation's outcome could open a new pathway to fabricate multifunctional biopolymeric hydrogel for quicker burn wound therapy and effectively prevents microenvironment bacterial infections.


Assuntos
Queimaduras , Fibroínas , Animais , Antibacterianos , Bandagens , Queimaduras/tratamento farmacológico , Fibroínas/farmacologia , Fibroínas/uso terapêutico , Humanos , Hidrogéis/uso terapêutico , Cicatrização
7.
Small ; 17(43): e2102624, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34378338

RESUMO

Targeting B7-H3 chimeric antigen receptor (CAR) T cells has antitumor potential for therapy of non-small cell lung cancer (NSCLC) in preclinical studies. However, CAR T cell therapy remains a formidable challenge for the treatment of solid tumors due to the heterogeneous and immunosuppressive tumor microenvironment (TME). Nanozymes exhibit merits modulating the immunosuppression of the tumor milieu. Here, a synergetic strategy by combination of nanozymes and CAR T cells in solid tumors is described. This nanozyme with dual photothermal-nanocatalytic properties is endowed to remodel TME by destroying its compact structure. It is found that the B7-H3 CAR T cells infused in mice engrafted with the NSCLC cells have superior antitumor activity after nanozyme ablation of the tumor. Importantly, it is found that the changes altered immune-hostile cancer environment, resulting in enhanced activation and infiltration of B7-H3 CAR T cells. The first evidence that the process of combination nanozyme therapy effectively improves the therapeutic index of CAR T cells is presented. Thus, this study clearly supports that the TME-immunomodulated nanozyme is a promising tool to improve the therapeutic obstacles of CAR T cells against solid tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptores de Antígenos Quiméricos , Animais , Carcinoma Pulmonar de Células não Pequenas/terapia , Linhagem Celular Tumoral , Imunoterapia Adotiva , Camundongos , Linfócitos T , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Mol Pharm ; 17(10): 3720-3729, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32633977

RESUMO

The limited tumor tissue penetration of many nanoparticles remains a formidable challenge to their therapeutic efficacy. Although several photonanomedicines have been applied to improve tumor penetration, the first near-infrared window mediated by the low optical tissue penetration depth severely limits their anticancer effectiveness. To achieve deep optical tissue and drug delivery penetration, a near-infrared second window (NIR-II)-excited and pH-responsive ultrasmall drug delivery nanoplatform was fabricated based on BSA-stabilized CuS nanoparticles (BSA@CuS NPs). The BSA@CuS NPs effectively encapsulated doxorubicin (DOX) via strong electrostatic interactions to form multifunctional nanoparticles (BSA@CuS@DOX NPs). The BSA@CuS@DOX NPs had an ultrasmall size, which allowed them to achieve deeper tumor penetration. They also displayed stronger NIR II absorbance-mediated deep optical tissue penetration than that of the NIR I window. Moreover, the multifunctional nanoplatform preferentially accumulated in tumor sites, induced tumor hyperthermia, and generated remarkably high ROS levels in tumor sites upon NIR-II laser (1064 nm) irradiation. More importantly, our strategy achieved excellent synergistic effects of chemotherapy and phototherapy (chemophototherapy) under the guidance of photothermal imaging. The developed nanoparticles also showed good biocompatibility and bioclearance properties. Therefore, our work demonstrated a facile strategy for fabricating a multifunctional nanoplatform that is a promising candidate for deep tumor penetration as an effective antitumor therapy.


Assuntos
Doxorrubicina/administração & dosagem , Portadores de Fármacos/efeitos da radiação , Nanopartículas/efeitos da radiação , Neoplasias/tratamento farmacológico , Fototerapia/métodos , Animais , Linhagem Celular Tumoral/transplante , Sobrevivência Celular , Modelos Animais de Doenças , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Liberação Controlada de Fármacos/efeitos da radiação , Humanos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Lasers , Camundongos , Nanopartículas/química , Neoplasias/patologia , Fototerapia/instrumentação , Distribuição Tecidual
9.
Phys Chem Chem Phys ; 22(37): 21428-21435, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32944724

RESUMO

Tunable optical properties play an important role in the high performance of optoelectronic applications based on two-dimensional (2D) transition metal carbide and nitride (MXene) materials. Herein, the optical properties of functionalized MXene monolayers Sc2CT2 (T = O and OH) are investigated by strain engineering. The strain-dependent linear optical properties of Sc2CT2 possess broadband optical response due to the geometry and orbital overlap effect. The peaks from the second-order nonlinear coefficient elements d (d15, d16, and d31) at around half the band-gap exhibit a redshift for Sc2CO2 (blueshift for Sc2C(OH)2) with the increase of strain. The strain-dependent d reveals that Sc2CO2 with -1268 pm V-1 %-1 has a larger photoelastic coefficient than that of Sc2C(OH)2 with -574 pm V-1 %-1 at 1% strain. Meanwhile, the photoelastic tensors can not only be increased but also reduced with the increase of strain due to the dispersion relation. Moreover, the azimuthal angle-dependent second harmonic generation (SHG) from strained Sc2CT2 monolayers depends highly on the strained states and the pumping photon energy. The results pave the way for the tunable, broadband, and anisotropic applications of nonlinear optoelectronic devices based on MXenes based on strain engineering.

10.
Nanotechnology ; 30(19): 195705, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30699402

RESUMO

Broadband terahertz (THz) impedance matching is important for both spectral resolution improvement and THz anti-radar technology. Herein, graphene-silicon hybrid structure has been proposed for active broadband THz wave impedance matching with optical tunability. The main transmission pulse measured in the time domain indicates a modulation depth as high as 92.7% totally from the graphene-silicon interface. The interface reflection from the graphene-silicon junction implies that an impedance matching condition can be actively achieved by optical doping. To reveal the mechanism, we propose a graphene-silicon heterojunction model, which gives a full consideration of both the THz conductivity of graphene and the loss in doped junction layer. The theory fits well with the experimental results. This work proves active THz wave manipulation by junction effect and paves the way for active anti-reflection coating for THz components.

11.
Biomacromolecules ; 16(4): 1390-400, 2015 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-25756930

RESUMO

Polycations often suffer from the irreconcilable inconsistency between transfection efficiency and toxicity. Polymers with high molecular weight (MW) and cationic charge feature potent gene delivery capabilities, while in the meantime suffer from strong chemotoxicity, restricted intracellular DNA release, and low stability in vivo. To address these critical challenges, we herein developed pH-responsive, reversibly cross-linked, polyetheleneimine (PEI)-based polyplexes coated with hyaluronic acid (HA) for the effective and targeted gene delivery to cancer cells. Low-MW PEI was cross-linked with the ketal-containing linker, and the obtained high-MW analogue afforded potent gene delivery capabilities during transfection, while rapidly degraded into low-MW segments upon acid treatment in the endosomes, which promoted intracellular DNA release and reduced material toxicity. HA coating of the polyplexes shielded the surface positive charges to enhance their stability under physiological condition and simultaneously reduced the toxicity. Additionally, HA coating allowed active targeting to cancer cells to potentiate the transfection efficiencies in cancer cells in vitro and in vivo. This study therefore provides an effective approach to overcome the efficiency-toxicity inconsistence of nonviral vectors, which contributes insights into the design strategy of effective and safe vectors for cancer gene therapy.


Assuntos
DNA/administração & dosagem , Técnicas de Transferência de Genes , Vetores Genéticos/administração & dosagem , Neoplasias/terapia , Animais , Reagentes de Ligações Cruzadas/química , DNA/genética , DNA/toxicidade , Endossomos/metabolismo , Terapia Genética/métodos , Vetores Genéticos/toxicidade , Células HeLa , Humanos , Ácido Hialurônico/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polietilenoimina/química
12.
Appl Opt ; 54(22): 6732-6, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26368087

RESUMO

Two-dimensional materials such as MoS2 have attracted much attention in recent years due to their fascinating optoelectronic properties. The dielectric response of MoS2 crystal in both the terahertz (THz) and visible regions is studied in this work. Time-domain THz spectroscopy is employed for the THz property investigation. The real and imaginary parts of the complex dielectric constant of MoS2 crystal are found to follow a Drude model, which is due to the intrinsic carrier absorption. In the visible region, ellipsometry is used to investigate the dielectric response. The general trend of the complex dielectric constant is found to be described with a Lorentz model, while two remarkable dielectric response peaks are observed to be located at 1.85 and 2.03 eV, which has been attributed to the splitting arising from the combined effect of interlayer coupling and spin-orbit coupling. This work can be the research foundation for future optoelectronic applications with MoS2.

13.
Poult Sci ; 103(4): 103533, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38359770

RESUMO

Artificial insemination (AI) technology has greatly promoted the development of the chicken industry. Recently, AI technology has also begun to be used in the duck industry, but there are some problems. Numerous researchers have shown that microbes colonizing in semen can degrade semen quality, and AI can increase the harmful microbial load in hen's reproductive tract. Different from the degraded external genitalia of roosters, drakes have well-developed external genitalia, which may cause drake semen to be more susceptible to microbial contamination. However, information on the compositions, sources, and effects of semen microbes on semen quality remains unknown in drakes. In the current study, high-throughput sequencing technology was used to detect microbial communities in drake semen, environmental swabs, cloacal swabs, and the spermaduct after quantifying the semen quality of drakes to investigate the effects of microbes in the environment, cloaca, and spermaduct on semen microbiota and the relationships between semen microbes and semen quality. Taxonomic analysis showed that the microbes in the semen, environment, cloaca, and spermaduct samples were all classified into 4 phyla and 25 genera. Firmicutes and Proteobacteria were the dominant phyla. Phyllobacterium only existed in the environment, while Marinococcus did not exist in the cloaca. Of the 24 genera present in semen: Brachybacterium, Brochothrix, Chryseobacterium, Kocuria, Marinococcus, Micrococcus, Rothia, Salinicoccus, and Staphylococcus originated from the environment; Achromobacter, Aerococcus, Corynebacterium, Desemzia, Enterococcus, Jeotgalicoccus, Pseudomonas, Psychrobacter, and Turicibacter originated from the cloaca; and Agrobacterium, Carnobacterium, Chelativorans, Devosia, Halomonas, and Oceanicaulis originated from the spermaduct. In addition, K-means clustering analysis showed that semen samples could be divided into 2 clusters based on microbial compositions, and compared with cluster 1, the counts of Chelativorans (P < 0.05), Devosia (P < 0.01), Halomonas (P < 0.05), and Oceanicaulis (P < 0.05) were higher in cluster 2, while the sperm viability (P < 0.05), total sperm number (P < 0.01), and semen quality factor (SQF) (P < 0.01) were lower in cluster 2. Furthermore, functional prediction analysis of microbes showed that the activities of starch and sucrose metabolism, phosphotransferase system, ABC transporters, microbial metabolism in diverse environments, and quorum sensing pathways between cluster 1 and cluster 2 were significantly different (P < 0.05). Overall, environmental/cloacal microbes resulted in semen contamination, and microbes from the Chelativorans, Devosia, Halomonas, and Oceanicaulis genera may have negative effects on semen quality in drakes by affecting the activities of starch and sucrose metabolism, phosphotransferase system, ABC transporters, and quorum sensing pathways that are associated with carbohydrate metabolism. These data will provide a basis for developing strategies to prevent microbial contamination of drake semen.


Assuntos
Galinhas , Análise do Sêmen , Masculino , Animais , Feminino , Análise do Sêmen/veterinária , Sementes , Transportadores de Cassetes de Ligação de ATP , Fosfotransferases , Amido , Sacarose
14.
Adv Sci (Weinh) ; : e2404886, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973161

RESUMO

Immune checkpoint blockade (ICB) immunotherapy remains hampered by insufficient immunogenicity and a high-lactate immunosuppressive tumor microenvironment (TME). Herein, a nanobody-engineered NIR-II nanoadjuvant with targeting metabolic reprogramming capability is constructed for potentiating NIR-II photothermal-ferroptosis immunotherapy. Specifically, the nanoadjuvant (2DG@FS-Nb) is prepared by metallic iron ion-mediated coordination self-assembly of D-A-D type NIR-II molecules and loading of glycolysis inhibitor, 2-deoxy-D-glucose (2DG), followed by modification with aPD-L1 nanobody (Nb), which can effectively target the immunosuppressive TME and trigger in situ immune checkpoint blockade. The nanoadjuvants responsively release therapeutic components in the acidic TME, enabling the precise tumor location by NIR-II fluorescence/photoacoustic imaging while initiating NIR-II photothermal-ferroptosis therapy. The remarkable NIR-II photothermal efficiency and elevated glutathione (GSH) depletion further sensitize ferroptosis to induce severe lipid peroxidation, provoking robust immunogenic cell death (ICD) to trigger anti-tumor immune response. Importantly, the released 2DG markedly inhibits lactate generation through glycolysis obstruction. Decreased lactate efflux remodels the immunosuppressive TME by suppressing M2 macrophage proliferation and downregulating regulatory T cell levels. This work provides a new paradigm for the integration of NIR-II phototheranostics and lactate metabolism regulation into a single nanoplatform for amplified anti-tumor immunotherapy combined with ICB therapy.

15.
Int J Biol Sci ; 20(8): 3028-3045, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904022

RESUMO

Following the identification of specific epidermal growth factor receptor (EGFR)-activating mutations, gefitinib, one of the first-generation tyrosine kinase inhibitors (TKIs), has proven efficacious in targeting NSCLC that is driven by specific EGFR-activating mutations. However, most patients who initially respond to gefitinib, develop acquired resistance. In the current study, we devised a novel strategy to enhance the efficacy of gefitinib. We developed a simple and effective, nano-interrupter termed zeolitic imidazolate framework-8@Gefitinib@hyaluraonic nanoparticle (ZIF-8@G@HA NP). This nanoparticle was prepared by loading gefitinib onto a ZIF-8 nanoplatform followed by coating with hyaluronic acid (HA). The burst of Zn2+ release triggered by pH-sensitive degradation of ZIF-8@G@HA NPs was shown to enhance the efficacy of gefitinib in parental lung carcinoma HCC827 cells and overcame acquired gefitinib resistance in gefitinib drug resistant (GDR) HCC827 cells. We found that when treated with ZIF-8@G@HA NPs, Zn2+ acts synergistically with gefitinib via increased apoptosis in both parental and GDR HCC827 cells. Consistently, this in vitro activity was correlated with in vivo tumor growth inhibition. Interestingly, GDR cells were more sensitive to Zn2+ when compared with parental cells. We further found that ZIF-8 NPs overcame gefitinib resistance by triggering reactive oxygen species (ROS) generation and consequent cell cycle arrest at the G2/M phase, resulting in cancer cell apoptosis. Zn2+ was also found to block P-gp activity, facilitating the accumulation of gefitinib in GDR cells, thus enhancing the anti-tumor efficacy of gefitinib resulting in reversal of gefitinib resistance. Thus, this study offers a novel and promising strategy to surmount acquired gefitinib resistance via cell cycle arrest at the G2/M phase by facilitating gefitinib accumulation in GDR cells.


Assuntos
Apoptose , Resistencia a Medicamentos Antineoplásicos , Gefitinibe , Neoplasias Pulmonares , Zinco , Gefitinibe/farmacologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Camundongos , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Nanopartículas/química , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Zeolitas/química , Camundongos Endogâmicos BALB C
16.
Biomaterials ; 305: 122455, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160626

RESUMO

The therapeutic efficacy of cuproptosis combined with phototheranostics is still hindered by easy copper efflux, nonspecific accumulation and limited light penetration depth. Here, a high-performance NIR-II semiconductor polymer was first synthesized through dual-donor engineering. Then a biomimetic cuproptosis amplifier (PCD@CM) was prepared by Cu(II)-mediated coordinative self-assembly of NIR-II ultrasmall polymer dots and the chemotherapeutic drug DOX, followed by camouflaging of tumor cell membranes. After homologous targeting delivery to tumor cells, overexpressed GSH in the tumor microenvironment (TME) triggers the disassembly of the amplifier and the release of therapeutic components through the reduction of Cu(II) to Cu(I), which enable NIR-II fluorescence/photoacoustic imaging-guided NIR-II photothermal therapy (PTT) and chemotherapy. The released Cu(I) induces the aggregation of lipoylated mitochondrial proteins accompanied by the loss of iron-sulfur proteins, leading to severe proteotoxic stress and eventually cuproptosis. NIR-II PTT and GSH depletion render tumor cells more sensitive to cuproptosis. The amplified cuproptosis sensitization provokes significant immune surveillance, triggering the immunogenic cell death (ICD) to promote cytotoxic T lymphocyte infiltration together with aPD-L1-mediated immune checkpoint blockade. This work proposes a new strategy to develop cuproptosis sensitization systems enhanced by NIR-II phototheranostics with homologous targeting and anti-tumor immune response capabilities.


Assuntos
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Fototerapia , Cobre/uso terapêutico , Biomimética , Polímeros/uso terapêutico , Neoplasias/terapia , Imunoterapia , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Microambiente Tumoral
17.
Artigo em Inglês | MEDLINE | ID: mdl-37883251

RESUMO

With the help of neural network-based representation learning, significant progress has been recently made in data-driven online dynamic stability assessment (DSA) of complex electric power systems. However, without sufficient attention to diverse data loss conditions in practice, the existing data-driven DSA solutions' performance could be largely degraded due to practical defective input data. To address this problem, this work develops a robust representation learning approach to enhance DSA performance against multiple input data loss conditions in practice. Specifically, focusing on the short-term voltage stability (SVS) issue, an ensemble representation learning scheme (ERLS) is carefully designed to achieve data loss-tolerant online SVS assessment: 1) based on an efficient data masking technique, various missing data conditions are handled and augmented in a unified manner for lossy learning dataset preparation; 2) the emerging spatial-temporal graph convolutional network (STGCN) is leveraged to derive multiple diversified base learners with strong capability in SVS feature learning and representation; and 3) with massive SVS scenarios deeply grouped into a number of clusters, these STGCN-enabled base learners are distinctly assembled for each cluster via multilinear regression (MLR) to realize ensemble SVS assessment. Such a divide-and-conquer ensemble strategy results in highly robust SVS assessment performance when faced with various severe data loss conditions. Numerical tests on the benchmark Nordic test system illustrate the efficacy of the proposed approach.

18.
Nanoscale ; 15(47): 19219-19228, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-37987530

RESUMO

Narrow-band circular dichroism (CD) has attracted considerable attention in the high-sensitivity detection of chiral molecules and chiral catalysis. However, achieving dynamic adjustment of narrow-band CD signals is challenging. In this study, we introduce a disruption layer (DL) and molybdenum disulfide (MoS2) into an L-shaped chiral nanohole array based on a distributed Bragg reflector (DBR), forming L-shaped chiral nanoholes (LCNAs/DL-DBR/MoS2), and investigate the mechanism of CD signal generation. Simulation results show that LCNAs/DL-DBR/MoS2 generate three narrow-band CD signals in the visible region. Analysis of the near-field electric field maps reveals that the three CD peaks of LCNAs/DL-DBR/MoS2 are caused by three Tamm resonances in the DBR layer. The producing and adjusting mechanisms of the CD signals are achieved by changing the structural parameters and the number of MoS2 layers. Dynamic adjustment of the CD signals of LCNAs/DL-DBR/MoS2 can be achieved by changing the environmental temperature. Furthermore, by altering the refractive index of the environment and the DBR layer, it is demonstrated that LCNAs/DL-DBR/MoS2 has a high-quality factor. Our theoretical simulations aid in the design of UNB chiral devices, opening up new avenues for environmental monitoring and the detection of chiral molecules with exceptional sensitivity.

19.
Poult Sci ; 102(4): 102560, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36881978

RESUMO

Libido can affect the semen quality of male, and the sperm motility in semen quality parameters is a reliable index to evaluate the fertility of male. In drakes, the sperm motility is gradually acquired in testis, epididymis, and spermaduct. However, the relationship between libido and sperm motility in drakes has not been reported and the mechanisms of testis, epididymis, and spermaduct regulating the sperm motility of drakes are unclear. Therefore, the purpose of the present study was to compare the semen quality of drakes with libido level 4 (LL4) and libido level 5 (LL5), and tried to identify the mechanisms regulating the sperm motility in drakes by performing RNA-seq in testis, epididymis, and spermaduct. Phenotypically, the sperm motility of drakes (P < 0.01), weight of testis (P < 0.05), and organ index of epididymis (P < 0.05) in the LL5 group were significantly better than those in LL4 group. Moreover, compared with the LL4 group, the ductal square of seminiferous tubule (ST) in testis was significantly bigger in the LL5 group (P < 0.05), and the seminiferous epithelial thickness (P < 0.01) of ST in testis and lumenal diameter (P < 0.05) of ductuli conjugentes/dutus epididymidis in epididymis were significantly longer in the LL5 group. In transcriptional regulation, in addition to KEGG pathways related to metabolism and oxidative phosphorylation, lots of KEGG pathways associated with immunity, proliferation, and signaling were also significantly enriched in testis, epididymis, and spermaduct, respectively. Furthermore, through the integrated analysis of coexpression network and protein-protein interaction network, 3 genes (including COL11A1, COL14A1, and C3AR1) involved in protein digestion and absorption pathway and Staphylococcus aureus infection pathway were identified in testis, 2 genes (including BUB1B and ESPL1) involved in cell cycle pathway were identified in epididymis, and 13 genes (including DNAH1, DNAH3, DNAH7, DNAH10, DNAH12, DNAI1, DNAI2, DNALI1, NTF3, ITGA1, TLR2, RELN, and PAK1) involved in Huntington disease pathway and PI3K-Akt signaling pathway were identified in spermaduct. These genes could play crucial roles in the sperm motility of drakes with different libido, and all data the present study obtained will provide new insights into the molecular mechanisms regulating sperm motility of drakes.


Assuntos
Análise do Sêmen , Motilidade dos Espermatozoides , Masculino , Animais , Análise do Sêmen/veterinária , Libido , Fosfatidilinositol 3-Quinases , Galinhas , Testículo/fisiologia , Perfilação da Expressão Gênica/veterinária , Espermatozoides
20.
ACS Appl Mater Interfaces ; 15(38): 45378-45387, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37708439

RESUMO

Narrowband circular dichroism (CD) has attracted wide attention for its high sensitivity in detecting chiral molecules and catalysis. However, designing a chiral metasurface with excellent sensing performance that can be dynamically tuned still poses challenges. This paper introduces lithium niobate, an electrically tunable material, and a distributed Bragg reflector into chiral nanorod structures to form multilayer chiral nanorod arrays (MCNAs). Simulation results show that MCNAs can generate four strong ultra-narrowband (UNB) CD signals in the visible light spectrum. The UNB CD signal intensity was up to 0.86, and the minimum full width at half-maximum (FWHM) was up to 0.21 nm. The surface electric field and current distribution of MCNAs indicate that the four UNB CD signals mainly originate from the x and y direction Tamm resonances in the chiral nanorod layer. The refractive index of lithium niobate can be tuned by changing the electric field, allowing the active tuning of UNB CD signals. In addition, the sensing performance of MCNAs in the SARS-CoV-2 solution was analyzed, and the figure of merit (FOM) can reach an astonishing 2092. These findings not only assist with the design of UNB chiral devices but also offer new possibilities for the environmental monitoring and ultrasensitive detection of chiral molecules.

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