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1.
Nano Lett ; 24(25): 7629-7636, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38874796

RESUMEN

Vaccination for cancers arising from human papillomavirus (HPV) infection holds immense potential, yet clinical success has been elusive. Herein, we describe vaccination studies involving spherical nucleic acids (SNAs) incorporating a CpG adjuvant and a peptide antigen (E711-19) from the HPV-E7 oncoprotein. Administering the vaccine to humanized mice induced immunity-dependent on the oligonucleotide anchor chemistry (cholesterol vs (C12)9). SNAs containing a (C12)9-anchor enhanced IFN-γ production >200-fold, doubled memory CD8+ T-cell formation, and delivered more than twice the amount of oligonucleotide to lymph nodes in vivo compared to a simple admixture. Importantly, the analogous construct with a weaker cholesterol anchor performed similar to admix. Moreover, (C12)9-SNAs activated 50% more dendritic cells and generated T-cells cytotoxic toward an HPV+ cancer cell line, UM-SCC-104, with near 2-fold greater efficiency. These observations highlight the pivotal role of structural design, and specifically oligonucleotide anchoring strength (which correlates with overall construct stability), in developing efficacious therapeutic vaccines.


Asunto(s)
Vacunas contra el Cáncer , Proteínas E7 de Papillomavirus , Animales , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/administración & dosificación , Ratones , Proteínas E7 de Papillomavirus/inmunología , Proteínas E7 de Papillomavirus/química , Humanos , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/inmunología , Ácidos Nucleicos/química , Ácidos Nucleicos/inmunología , ADN/química , ADN/inmunología
2.
Opt Express ; 32(5): 8484-8495, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38439503

RESUMEN

In photonic systems, bilayer or multilayer systems exhibit numerous exciting phenomena induced by twisting. Thus, it is highly desired to explore the twisting effect by engineering the light-matter interactions. Optical torque, an important means in optical micromanipulation, can rotate micro-objects in various ways, enabling a wide range of promising applications. In this study, we present an interesting phenomenon called "pure optical twist" (POT), which emerges when a bilayer structure with specific symmetry is illuminated by counter-propagating lights with opposite spin and/or orbital angular momentum. Remarkably, this leads to zero net optical torque but yet possesses an interesting mechanical effect of bilayer system twisting. The crucial determinant of this phenomenon is the rotational symmetries of each layer, which govern the allowed azimuthal channels of the scattered wave. When the rotational symmetries do not allow these channels to overlap, no resultant torque is observed. Our work will encourage further exploration of the twisting effect through engineered light-matter interactions. This opens up the possibility of creating twisted bilayer systems using optical means, and constructing a stable bilayer optical motor that maintains identical rotation frequencies for both layers.

3.
Inflamm Res ; 73(6): 897-913, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38625657

RESUMEN

OBJECTIVES AND DESIGN: As an interferon-inducible protein, Viperin has broad-spectrum antiviral effects and regulation of host immune responses. We aim to investigate how Viperin regulates interferon-γ (IFN-γ) production in macrophages to control Mycobacterium tuberculosis (Mtb) infection. METHODS: We use Viperin deficient bone-marrow-derived macrophage (BMDM) to investigate the effects and machines of Viperin on Mtb infection. RESULTS: Viperin inhibited IFN-γ production in macrophages and in the lung of mice to promote Mtb survival. Further insight into the mechanisms of Viperin-mediated regulation of IFN-γ production revealed the role of TANK-binding kinase 1 (TBK1), the TAK1-dependent inhibition of NF-kappa B kinase-epsilon (IKKε), and interferon regulatory factor 3 (IRF3). Inhibition of the TBK1-IKKε-IRF3 axis restored IFN-γ production reduced by Viperin knockout in BMDM and suppressed intracellular Mtb survival. Moreover, Viperin deficiency activated the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, which promoted IFN-γ production and inhibited Mtb infection in BMDM. Additionally, a combination of the anti-TB drug INH treatment in the absence of Viperin resulted in further IFN-γ production and anti-TB effect. CONCLUSIONS: This study highlights the involvement of TBK1-IKKε-IRF3 axis and JAK-STAT signaling pathways in Viperin-suppressed IFN-γ production in Mtb infected macrophages, and identifies a novel mechanism of Viperin on negatively regulating host immune response to Mtb infection.


Asunto(s)
Factor 3 Regulador del Interferón , Interferón gamma , Macrófagos , Ratones Endogámicos C57BL , Mycobacterium tuberculosis , Proteínas Serina-Treonina Quinasas , Proteínas , Transducción de Señal , Animales , Interferón gamma/metabolismo , Interferón gamma/inmunología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Mycobacterium tuberculosis/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Factor 3 Regulador del Interferón/metabolismo , Ratones , Proteínas/genética , Proteínas/metabolismo , Quinasa I-kappa B/metabolismo , Quinasas Janus/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Ratones Noqueados , Tuberculosis/inmunología , Pulmón/inmunología , Pulmón/microbiología , Proteína Viperina
4.
Int J Mol Sci ; 25(4)2024 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-38397085

RESUMEN

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human ß-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , beta-Defensinas , Animales , Humanos , Ratones , Células Epiteliales Alveolares , beta-Defensinas/genética , beta-Defensinas/farmacología , Proteína beta Potenciadora de Unión a CCAAT/genética , Células Epiteliales , Sistema de Señalización de MAP Quinasas , Tuberculosis/metabolismo
5.
J Transl Med ; 21(1): 302, 2023 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-37147666

RESUMEN

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem-like cells (CSLCs) play crucial role in tumor metastasis and drug-resistance. Disheveled3 (DVL3) is involved in malignant behaviors of cancer. However, the role and potential mechanism of DVL3 remain elusive in EMT and CSLCs of colorectal cancer (CRC). METHODS: UALCAN and PrognoScan databases were employed to evaluate DVL3 expression in CRC tissues and its correlation with CRC prognosis, respectively. Transwell, sphere formation and CCK8 assay were used to assess metastasis, stemness and drug sensitivity of CRC cells, respectively. Western blotting and dual luciferase assay were performed to analyze the protein expression and Wnt/ß-catenin activation, respectively. Lentiviral transfection was used to construct the stable cell lines. Animal studies were performed to analyze the effect of silencing DVL3 on tumorigenicity and metastasis of CRC cells in vivo. RESULTS: DVL3 was overexpressed in CRC tissues and several CRC cell lines. DVL3 expression was also higher in CRC tissues with lymph node metastasis than tumor tissues without metastasis, and correlated with poor prognosis of CRC patients. DVL3 positively regulated the abilities of migration, invasion and EMT-like molecular changes in CRC cells. Moreover, DVL3 promoted CSLCs properties and multidrug resistance. We further identified that Wnt/ß-catenin was crucial for DVL3-mediated EMT, stemness and SOX2 expression, while silencing SOX2 inhibited DVL3-mediated EMT and stemness. Furthermore, c-Myc, a direct target gene of Wnt/ß-catenin, was required for SOX2 expression and strengthened EMT and stemness via SOX2 in CRC cells. Finally, knockdown of DVL3 suppressed tumorigenicity and lung metastasis of CRC cells in nude mice. CONCLUSION: DVL3 promoted EMT and CSLCs properties of CRC via Wnt/ß-catenin/c-Myc/SOX2 axis, providing a new strategy for successful CRC treatment.


Asunto(s)
Neoplasias Colorrectales , Proteínas Dishevelled , Transición Epitelial-Mesenquimal , Vía de Señalización Wnt , beta Catenina , Animales , Ratones , beta Catenina/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Humanos , Proteínas Dishevelled/genética , Células Madre Neoplásicas
6.
Opt Express ; 31(6): 9996-10006, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-37157562

RESUMEN

Optical fields and forces can be greatly enhanced for a microparticle when the whispering gallery modes (WGMs) are excited. In this paper, by solving the scattering problem using the generalized Mie theory, the morphology-dependent resonances (MDRs) and resonant optical forces derived from the coherent coupling of WGMs are investigated in multiple-sphere systems. When the spheres approach each other, the bonding and antibonding modes of MDRs emerge and correspond to the attractive and repulsive forces, respectively. More importantly, the antibonding mode is good at propagating light forward, while the optical fields decay rapidly for the bonding mode. Moreover, the bonding and antibonding modes of MDRs in the PT-symmetric system can persist only when the imaginary part of the refractive index is small enough. Interestingly, it is also shown that for a PT-symmetric structure, only a minor imaginary part of the refractive index is required to generate a significant pulling force at MDRs, making the whole structure move against the light propagation direction. Our work deepens the understanding of the collective resonance behavior of multiple spheres and paves the way for potential applications in particle transportation, non-Hermitian systems, integrated optical devices, etc.

7.
Inflamm Res ; 72(1): 27-41, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36315280

RESUMEN

OBJECTIVES AND DESIGN: Dendritic cells (DCs) are one of the key immune cells in bridging innate and adaptive immune response against Mycobacterium tuberculosis (Mtb) infection. Interferons (IFNs) play important roles in regulating DC activation and function. Virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (Viperin) is one of the important IFN-stimulated genes (ISGs), and elicits host defense against infection. METHODS: We investigated the effects and mechanisms of Viperin on DC activation and function using Viperin deficient bone marrow-derived dendritic cells (BMDCs) during Mtb infection. RESULTS: Viperin deficiency enhanced phagocytic activity and increased clearance of Mtb in DCs, produced higher abundance of NO, cytokine including interleukin-12 (IL-12), Tumor necrosis factor-α (TNF-α), IL-1ß, IL-6 and chemokine including CXCL1, CXCL2 and CXCL10, elevated MHC I, MHC II and co-stimulatory molecules expression, and enhanced CD4+ and CD8+ T cell responses. Mechanistically, Viperin deficiency promoted DC activation and function through NF-κB p65 activation. NF-κB p65 inhibitor prevented cytokine and chemokine production, and co-stimulatory molecules expression promoted by Viperin deficiency. CONCLUSIONS: These results suggest that Mtb induced Viperin expression could impair the activation of host defense function of DCs and DC-T cell cross talk during Mtb infection. This research may provide a potential target for future HDT in TB therapy.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Proteína Viperina , Quimiocinas/metabolismo , Citocinas , Células Dendríticas , Mycobacterium tuberculosis/metabolismo , FN-kappa B/metabolismo , Proteína Viperina/metabolismo , Animales
8.
J Immunol ; 206(11): 2623-2637, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34001657

RESUMEN

Mycobacterium tuberculosis, the pathogen that causes tuberculosis, exhibits complex host-pathogen interactions. Pattern recognition receptors and their downstream signaling pathways play crucial roles in determining the outcome of infection. In particular, the scaffold protein ß-arrestin 2 mediates downstream signaling of G protein-coupled receptors. However, the role of ß-arrestin 2 in conferring immunity against M. tuberculosis has not yet been explored. We found that ß-arrestin 2 was upregulated in the lesioned regions of lung tissues in patients with tuberculosis. M. tuberculosis infection upregulated ß-arrestin 2 expression in human macrophages, and silencing of ß-arrestin 2 significantly enhanced bactericidal activity by enhancing the expression of proinflammatory cytokines such as TNF-α. ß-Arrestin 2 was shown to inhibit the activation of the TLR2/ERK1/2 pathway and its transcriptional regulation activity upon M. tuberculosis infection. Furthermore, ß-arrestin 2 transcriptionally regulates TNF-α by binding to CREB1. These observations revealed that the upregulation of ß-arrestin 2 is critical for M. tuberculosis to escape immune surveillance through an unknown mechanism. Our research offers a novel interference modality to enhance the immune response against tuberculosis by targeting ß-arrestin 2 to modulate the TLR2-ß-arrestin 2-ERK1/2-CREB1-TNF-α regulatory axis.


Asunto(s)
Inflamación/inmunología , Tuberculosis/inmunología , Arrestina beta 2/inmunología , Adolescente , Células Cultivadas , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/inmunología , Masculino , Persona de Mediana Edad
9.
J Am Chem Soc ; 144(41): 18756-18760, 2022 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-36201634

RESUMEN

The use of CRISPR/Cas9 systems in genome editing has been limited by the inability to efficiently deliver the key editing components to and across tissues and cell membranes, respectively. Spherical nucleic acids (SNAs) are nanostructures that provide privileged access to both but have yet to be explored as a means of facilitating gene editing. Herein, a new class of CRISPR SNAs are designed and evaluated in the context of genome editing. Specifically, Cas9 ProSNAs comprised of Cas9 cores densely modified with DNA on their exteriors and preloaded with single-guide RNA were synthesized and evaluated for their genome editing capabilities in the context of multiple cell lines. The radial orientation of the DNA on the Cas9 protein surface enhances cellular uptake, without the need for electroporation or transfection agents. In addition, the Cas9 proteins defining the cores of the ProSNAs were fused with GALA peptides on their N-termini and nuclear localization signals on their C-termini to facilitate endosomal escape and maximize nuclear localization and editing efficiency, respectively. These constructs were stable against protease digestion under conditions that fully degrade the Cas9 protein, when not transformed into an SNA, and used to achieve genome editing efficiency between 32 and 47%. Taken together, these novel constructs and advances point toward a way of significantly broadening the scope of use and impact of CRISPR-Cas9 genome editing systems.


Asunto(s)
Ácidos Nucleicos , ARN Guía de Kinetoplastida , ARN Guía de Kinetoplastida/genética , ARN Guía de Kinetoplastida/metabolismo , Proteína 9 Asociada a CRISPR/genética , Proteína 9 Asociada a CRISPR/metabolismo , Sistemas CRISPR-Cas/genética , Señales de Localización Nuclear/genética , Señales de Localización Nuclear/metabolismo , Péptido Hidrolasas/metabolismo
10.
Mikrochim Acta ; 189(4): 153, 2022 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-35322310

RESUMEN

A method is described to achieve accurate quantitative detection of atrazine (ATZ) in maize by using lateral flow strips based on gold nanoparticles (GNPs) and a handheld scanning reader. GNPs of 15 nm in diameter were applied as label, and a lateral flow immune assay strip was prepared. The linear range was 5.01-95.86 ng mL-1 with a detection limit of 4.92 ng mL-1 in phosphate buffer, 4 times better than the readout by the naked eye. ATZ-spiked corn samples were also analysed. The accuracy of results of spiked samples was confirmed by ELISA and liquid chromatography-tandem mass spectrometry (HPLC), which proved the reliability of the proposed method. A handhold device with an optical scanning system was designed for on-site quantitative detection. Combined with the pretreatment, the assay could be completed in less than 20 min.


Asunto(s)
Atrazina , Nanopartículas del Metal , Atrazina/análisis , Oro/química , Inmunoensayo/métodos , Nanopartículas del Metal/química , Sistemas de Atención de Punto , Reproducibilidad de los Resultados
11.
J Am Chem Soc ; 143(23): 8925-8934, 2021 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-34096291

RESUMEN

Proteins are exquisite nanoscale building blocks: molecularly pure, chemically addressable, and inherently selective for their evolved function. The organization of proteins into single crystals with high positional, orientational, and translational order results in materials where the location of every atom can be known. However, controlling the organization of proteins is challenging due to the myriad interactions that define protein interfaces within native single crystals. Recently, we discovered that introducing a single DNA-DNA interaction between protein surfaces leads to changes in the packing of proteins within single crystals and the protein-protein interactions (PPIs) that arise. However, modifying specific PPIs to effect deliberate changes to protein packing is an unmet challenge. In this work, we hypothesized that disrupting and replacing a highly conserved PPI with a DNA-DNA interaction would enable protein packing to be modulated by exploiting the programmability of the introduced oligonucleotides. Using concanavalin A (ConA) as a model protein, we circumvent potentially deleterious mutagenesis and exploit the selective binding of ConA toward mannose to noncovalently attach DNA to the protein surface. We show that DNA association eliminates the major PPI responsible for crystallization of native ConA, thereby allowing subtle changes to DNA design (length, complementarity, and attachment position) to program distinct changes to ConA packing, including the realization of three novel crystal structures and the deliberate expansion of ConA packing along a single crystallographic axis. These findings significantly enhance our understanding of how DNA can supersede native PPIs to program protein packing within ordered materials.


Asunto(s)
Concanavalina A/química , ADN/química , Cristalografía por Rayos X , Modelos Moleculares
12.
Biosci Biotechnol Biochem ; 85(7): 1720-1728, 2021 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-33960377

RESUMEN

A simple and effective direct competitive chemiluminescence immunoassay for the detection of 4 kinds of quinolone antibiotics in milk was established using Nor-Biotin (biotin-modified norfloxacin [NOR]) bifunctional ligand and alkaline phosphatase-conjugated streptavidin signal amplification technology. The polyclonal antibody was obtained after the immunization of New Zealand White rabbits using norfloxacin-derived antigen. "Click chemistry" was used for the rapid and facile synthesis of the Nor-Biotin bifunctional ligand. After the optimization of the incubation time and reaction buffer, the direct competitive chemiluminescence assay method was developed and used for sensitive detection of 4 kinds of quinolone drugs (NOR, pefloxacin, ciprofloxacin, and danofloxacin). The IC50 of the 4 kinds of quinolone drugs ranged from 7.35 to 24.27 ng/mL, and the lowest detection limits ranged from 0.05 to 0.16 ng/mL, which were below their maximum residue levels, approved by the EU for treatment of food-producing animals. To demonstrate the applicability of the assay, artificially contaminated milk samples with the 4 quinolone drugs were analyzed. The mean recovery rates of the drugs ranged from 86.31% to 112.11%.


Asunto(s)
4-Quinolonas/análisis , Fosfatasa Alcalina/química , Antibacterianos/análisis , Química Clic , Ligandos , Límite de Detección , Luminiscencia
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(2): 304-8, 2015 Feb.
Artículo en Zh | MEDLINE | ID: mdl-25970882

RESUMEN

The present paper presents an auto-focus laser-induced breakdown spectroscopy (LIBS) remote measuring system. This system contains a Schwarzschild telescope, which consists of a convex mirror and a concave mirror. The two spherical mirrors are coaxially placed. The convex mirror is mounted on a motorized linear translation stage. With this motorized linear translation stage, the convex mirror can move along the optical axis to change the spacing between the convex mirror and the concave mirror. Therefore the focal length can be adjusted to focus the laser on samples at different distances and collect the plasma spectra. The advantages of the telescope system include, firstly, the light path of laser focusing and spectra signal collection is the same, which make it easier for mounting and collimation; secondly, the light path of the telescope uses total reflection type, which is fit for the detection in ultra-violate region; finally, the telescope consists of only two spherical mirrors which are relatively easier to manufacture. Within the translation range of the motorized linear translation stage, the focal length of the telescope in this paper can be adjusted from 1.5 to 3.6 m. The diameter of the focusing spot varies from 0.5 to 1.0 mm. Utilizing this telescope system, LIBS experiments were conducted using copper sample. And the characteristic lines of Cu element (Cu I 223.01 nm, Cu I 224.43 nm) obtained are used for the auto focusing. By investigating the relation of the area of spectral lines covered and the spacing between the mirrors, the optimal laser focusing location was obtained. The LIBS experiment results show that the system functions well, fulfilling the demand of remote ablation of sample and LIBS spectral measuring, and the telescope is able to auto-focus the laser on samples at different position to perform remote LIBS experiment.

14.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(4): 865-8, 2014 Apr.
Artículo en Zh | MEDLINE | ID: mdl-25007588

RESUMEN

Laser-Induced Breakdown Spectroscopy (LIBS) is strongly time related. Time-resolved LIBS measurement is an important technique for the research on laser induced plasma evolution and self-absorption of the emission lines. Concerning the temporal characteristics of LIBS spectrum, a method is proposed in the present paper which can achieve micros-scale time-resolved LIBS measurement by using general ms-scale detector. By setting different integration delay time of the ms-scale spectrum detector, a series of spectrum are recorded. And the integration delay time interval should be longer than the worst temporal precision. After baseline correction and spectrum fitting, the intensity of the character line was obtained. Calculating this intensity with differential method at a certain time interval and then the difference value is the time-resolved line intensity. Setting the plasma duration time as X-axis and the time-resolved line intensity as Y-axis, the evolution curve of the character line intensity can be plotted. Character line with overlap-free and smooth background should be a priority to be chosen for analysis. Using spectrometer with ms-scale integration time and a control system with temporal accuracy is 0.021 micros, experiments carried out. The results validate that this method can be used to characterize the evolution of LIBS characteristic lines and can reduce the cost of the time-resolved LIBS measurement system. This method makes high time-resolved LIBS spectrum measurement possible with cheaper system.

15.
Sci Adv ; 10(17): eado8020, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38657068

RESUMEN

Molecular strain can be introduced to influence the outcome of chemical reactions. Once a thermodynamic product is formed, however, reversing the course of a strain-promoted reaction is challenging. Here, a reversible, strain-promoted polymerization in cyclic DNA is reported. The use of nonhybridizing, single-stranded spacers as short as a single nucleotide in length can promote DNA cyclization. Molecular strain is generated by duplexing the spacers, leading to ring opening and subsequent polymerization. Then, removal of the strain-generating duplexers triggers depolymerization and cyclic dimer recovery via enthalpy-driven cyclization and entropy-mediated ring contraction. This reversibility is retained even when a protein is conjugated to the DNA strands, and the architecture of the protein assemblies can be modulated between bivalent and polyvalent states. This work underscores the utility of using DNA not only as a programmable ligand for assembly but also as a route to access restorable bonds, thus providing a molecular basis for DNA-based materials with shape-memory, self-healing, and stimuli-responsive properties.


Asunto(s)
ADN , Polimerizacion , ADN/química , Ciclización , Termodinámica , Conformación de Ácido Nucleico
16.
Adv Healthc Mater ; 13(9): e2303394, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38288911

RESUMEN

Due to the inherent radiation tolerance, patients who suffered from glioma frequently encounter tumor recurrence and malignant progression within the radiation target area, ultimately succumbing to treatment ineffectiveness. The precise mechanism underlying radiation tolerance remains elusive due to the dearth of in vitro models and the limitations associated with animal models. Therefore, a bioprinted glioma model is engineered, characterized the phenotypic traits in vitro, and the radiation tolerance compared to 2D ones when subjected to X-ray radiation is assessed. By comparing the differential gene expression profiles between the 2D and 3D glioma model, identify functional genes, and analyze distinctions in gene expression patterns. Results showed that 3D glioma models exhibited substantial alterations in the expression of genes associated with the stromal microenvironment, notably a significant increase in the radiation tolerance gene ITGA2 (integrin subunit A2). In 3D glioma models, the knockdown of ITGA2 via shRNA resulted in reduced radiation tolerance in glioma cells and concomitant inhibition of the p-AKT pathway. Overall, 3D bioprinted glioma model faithfully recapitulates the in vivo tumor microenvironment (TME) and exhibits enhanced resistance to radiation, mediated through the ITGA2/p-AKT pathway. This model represents a superior in vitro platform for investigating glioma radiotherapy tolerance.


Asunto(s)
Glioma , Proteínas Proto-Oncogénicas c-akt , Animales , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Proliferación Celular , Glioma/genética , Glioma/radioterapia , Glioma/metabolismo , Transducción de Señal , Microambiente Tumoral
17.
ACS Nano ; 18(20): 12994-13005, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38721844

RESUMEN

In this paper, N-doped TiO2 mixed crystals are prepared via direct calcination of TiN for highly selective oxidation of CH4 to HCHO at room temperature. The structures of the prepared TiO2 samples are characterized to be N-doped TiO2 of anatase and rutile mixed crystals. The crystal structures of TiO2 samples are determined by XRD spectra and Raman spectra, while N doping is demonstrated by TEM mapping, ONH inorganic element analysis, and high-resolution XPS results. Significantly, the production rate of HCHO is as high as 23.5 mmol·g-1·h-1 with a selectivity over 90%. Mechanism studies reveal that H2O is the main oxygen source and acts through the formation of ·OH. DFT calculations indicate that the construction of a mixed crystal structure and N-doping modification mainly act by increasing the adsorption capacity of H2O. An efficient photocatalyst was prepared by us to convert CH4 to HCHO with high yield and selectivity, greatly promoting the development of the photocatalytic CH4 conversion study.

18.
Nat Commun ; 15(1): 2930, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575640

RESUMEN

Gradient matters with hierarchical structures endow the natural world with excellent integrity and diversity. Currently, direct ink writing 3D printing is attracting tremendous interest, and has been used to explore the fabrication of 1D and 2D hierarchical structures by adjusting the diameter, spacing, and angle between filaments. However, it is difficult to generate complex 3D gradient matters owing to the inherent limitations of existing methods in terms of available gradient dimension, gradient resolution, and shape fidelity. Here, we report a filament diameter-adjustable 3D printing strategy that enables conventional extrusion 3D printers to produce 1D, 2D, and 3D gradient matters with tunable heterogeneous structures by continuously varying the volume of deposited ink on the printing trajectory. In detail, we develop diameter-programmable filaments by customizing the printing velocity and height. To achieve high shape fidelity, we specially add supporting layers at needed locations. Finally, we showcase multi-disciplinary applications of our strategy in creating horizontal, radial, and axial gradient structures, letter-embedded structures, metastructures, tissue-mimicking scaffolds, flexible electronics, and time-driven devices. By showing the potential of this strategy, we anticipate that it could be easily extended to a variety of filament-based additive manufacturing technologies and facilitate the development of functionally graded structures.

19.
JCI Insight ; 9(1)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38016036

RESUMEN

Tuberculosis has the highest mortality rate worldwide for a chronic infectious disease caused by a single pathogen. RNA-binding proteins (RBPs) are involved in autophagy - a key defense mechanism against Mycobacterium tuberculosis (M. tuberculosis) infection - by modulating RNA stability and forming intricate regulatory networks. However, the functions of host RBPs during M. tuberculosis infection remain relatively unexplored. Zinc finger NFX1-type containing 1 (ZNFX1), a conserved RBP critically involved in immune deficiency diseases and mycobacterial infections, is significantly upregulated in M. tuberculosis-infected macrophages. Here, we aimed to explore the immunoregulatory functions of ZNFX1 during M. tuberculosis infection. We observed that Znfx1 knockout markedly compromised the multifaceted immune responses mediated by macrophages. This compromise resulted in reduced phagocytosis, suppressed macrophage activation, increased M. tuberculosis burden, progressive lung tissue injury, and chronic inflammation in M. tuberculosis-infected mice. Mechanistic investigations revealed that the absence of ZNFX1 inhibited autophagy, consequently mediating immune suppression. ZNFX1 critically maintained AMPK-regulated autophagic flux by stabilizing protein kinase AMP-activated catalytic subunit alpha 2 mRNA, which encodes a key catalytic α subunit of AMPK, through its zinc finger region. This process contributed to M. tuberculosis growth suppression. These findings reveal a function of ZNFX1 in establishing anti-M. tuberculosis immune responses, enhancing our understanding of the roles of RBPs in tuberculosis immunity and providing a promising approach to bolster antituberculosis immunotherapy.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Animales , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia/genética , Macrófagos/metabolismo
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 33(12): 3388-91, 2013 Dec.
Artículo en Zh | MEDLINE | ID: mdl-24611408

RESUMEN

Laser-induced breakdown spectroscopy (LIBS) is one of the most promising technologies to be applied to metallurgical composition online monitoring in these days. In order to study the spectral characters of LIBS spectrum and to investigate the quantitative analysis method of material composition under vacuum and high temperature environment, a LIBS measurement system was designed and set up which can be used for conducting experiments with high-temperature or molten samples in different vacuum environment. The system consists of a Q-switched Nd : YAG laser used as the light source, lens with different focus lengths used for laser focusing and spectrum signal collecting, a spectrometer used for detecting the signal of LIBS spectrums, and a vacuum system for holding and heating the samples while supplying a vacuum environment. The vacuum was achieved and maintained by a vacuum pump and an electric induction furnace was used for heating the system. The induction coil was integrated to the vacuum system by attaching to a ceramic sealing flange. The system was installed and testified, and the results indicate that the vacuum of the system can reach 1X 10(-4) Pa without heating, while the heating temperature could be about 1 600 degreeC, the system can be used for melting metal samples such as steel and aluminum and get the LIBS spectrum of the samples at the same time. Utilizing this system, LIBS experiments were conducted using standard steel samples under different vacuum or high-temperature conditions. Results of comparison between LIBS spectrums of solid steel samples under different vacuum were achieved, and so are the spectrums of molten and solid steel samples under vacuum environment. Through data processing and theoretical analyzing of these spectrums, the initial results of those experiments are in good agreement with the results that are presently reported, which indicates that the whole system functions well and is available for molten metal LIBS experiment under vacuum environment.

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