RESUMO
Two-dimensional (2D) nonlayered metal compounds with porous structure show broad application prospects in electrochemistry-related fields due to their abundant active sites, open ions/electrons diffusion channels, and faradaic reactions. However, scalable and universal synthesis of 2D porous compounds still remains challenging. Here, inspired by blowing gum, a metal-organic gel (MOG) rapid redox transformation (MRRT) strategy is proposed for the mass production of a wide variety of 2D porous metal oxides. Adequate crosslinking degree of MOG precursor and its rapid redox with NO3- are critical for generating gas pressure from interior to exterior, thus blowing the MOG into 2D carbon nanosheets, which further act as self-sacrifice template for formation of oxides with porous and ultrathin structure. The versatility of this strategy is demonstrated by the fabrication of 39 metal oxides, including 10 transition metal oxides, one II-main group oxide, two III-main group oxides, 22 perovskite oxides, four high-entropy oxides. As an illustrative verification, the 2D transition metal oxides exhibit excellent capacitive deionization (CDI) performance. Moreover, the assembled CDI cell could act as desalting battery to supply electrical energy during electrode regeneration. This MRRT strategy offers opportunities for achieving universal synthesis of 2D porous oxides with nonlayered structures and studying their electrochemistry-related applications.
Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , China/epidemiologia , Humanos , Cidades , Pandemias , Conceitos MeteorológicosRESUMO
BACKGROUND: Older patients with cancer have a higher risk for malnutrition and impaired quality of life (QoL). The present study aimed to investigate the relationship between malnutrition diagnosed according to the Global Leadership Initiative Malnutrition (GLIM) criteria and QoL across various tumor types, and to evaluate the combined prognostic value of malnutrition and QoL in predicting survival among older patients with cancer. METHODS: This multicenter, observational cohort study included 5310 older patients with cancer and 2184 with malnutrition (moderate stage, n = 1023; severe stage, n = 1161). An empirical cumulative distribution curve was performed to illustrate the correlation between malnutrition and QoL. The primary objective was to investigate the association between malnutrition and QoL using logistic regression analysis. Survival analyses were performed to assess the combined prognostic value of malnutrition and QoL. RESULTS: The median age of the patients (66.9% male, 33.1% female) was 70 years (interquartile range [IQR] 67-74 years) years. The median QoL score was highest in patients without malnutrition (91.88 [IQR 84.44-97.44]), followed by those with moderate (86.15 [IQR 76.18-93.85) and severe (82.31 [IQR 69.87-91.11]) malnutrition. Logistics regression revealed that the risk for developing impaired QoL increased 1.98 (95% confidence interval [CI] 1.64-2.38; P < 0.001) and 2.33 (95% CI 1.93-2.81; P < 0.001) times in patients with moderate and severe malnutrition, respectively. Kaplan-Meier curves showed that QoL in combination with GLIM criteria demonstrated a significant discriminative performance for survival and served as an independent prognostic factor among older patients with cancer, especially for lung and gastric cancers. CONCLUSIONS: Malnutrition diagnosed according to the GLIM criteria was a predictor of impaired QoL. Additionally, the combination of QoL and malnutrition demonstrated utility for predicting survival outcomes in older patients with cancer.
Assuntos
Desnutrição , Neoplasias , Qualidade de Vida , Humanos , Desnutrição/diagnóstico , Feminino , Masculino , Idoso , Neoplasias/complicações , Avaliação Nutricional , Prognóstico , Estado Nutricional , Avaliação Geriátrica/métodos , Estudos de Coortes , Análise de SobrevidaRESUMO
Using silicon/reduced graphene oxide (Si/rGO) composites as lithium-ion battery (LIB) anodes can effectively buffer the volumetric expansion and shrinkage of Si. Herein, we designed and prepared Si/rGO-b with a sandwiched structure, formed by a duple combination of ammonia-modified silicon (m-Si) nanoparticles (NP) with graphene oxide (GO). In the first composite process of m-Si and GO, a core-shell structure of primal Si/rGO-b (p-Si/rGO-b) was formed. The amino groups on the m-Si surface can not only hybridize with the GO surface to fix the Si particles, but also form covalent chemical bonds with the remaining carboxyl groups of rGO to enhance the stability of the composite. During the electrochemical reaction, the oxygen on the m-Si surface reacts with lithium ions (Li+) to form Li2O, which is a component of the solid-electrolyte interphase (SEI) and is beneficial to buffering the volume expansion of Si. Then, the p-Si/rGO-b recombines with GO again to finally form a sandwiched structure of Si/rGO-b. Covalent chemical bonds are formed between the rGO layers to tightly fix the p-Si/rGO-b, and the conductive network formed by the reintroduced rGO improves the conductivity of the Si/rGO-b composite. When used as an electrode, the Si/rGO-b composite exhibits excellent cycling performance (operated stably for more than 800 cycles at a high-capacity retention rate of 82.4%) and a superior rate capability (300 mA h/g at 5 A/g). After cycling, tiny cracks formed in some areas of the electrode surface, with an expansion rate of only 27.4%. The duple combination of rGO and the unique sandwiched structure presented here demonstrate great effectiveness in improving the electrochemical performance of alloy-type anodes.
RESUMO
Lead (Pb) contamination in wheat grain is of great concern, especially in North China. Atmospheric deposition is a major contributor to Pb accumulation in wheat grain. Screening low Pb accumulating wheat varieties has been an effective method for addressing Pb contamination in wheat grain. However, identifying wheat varieties with low Pb accumulation based on foliar uptake of atmospheric Pb has been neglected. Therefore, two field trials with distinct atmospheric Pb deposition were conducted to screen for stable varieties with low Pb accumulation. It was verified that YB700 and CH58, which have high thousand-grain weights and stable low Pb accumulation in field 1 (0.19 and 0.13 mg kg-1) and field 2 (0.17 and 0.20 mg kg-1), respectively, were recommended for cultivation in atmospheric Pb contaminated farmlands in North China. Furthermore, indoor experiments were conducted to investigate Pb uptake by the roots and leaves of different wheat varieties. Our findings indicate that Pb accumulation in different wheat varieties is primarily influenced by foliar Pb uptake rather than root Pb uptake. Interestingly, there was a positive correlation (p < 0.05) between the Pb concentrations in leaves and the stomatal width and trichome length of the adaxial epidermal surface. Additionally, there is a positive correlation (p < 0.01) between the Pb concentration in the wheat grain and trichome length. In conclusion, the screening of wheat varieties with narrower stomatal widths or shorter trichomes based on foliar uptake pathways is an effective strategy for ensuring food safety in areas contaminated by atmospheric Pb.
Assuntos
Chumbo , Folhas de Planta , Poluentes do Solo , Triticum , Triticum/metabolismo , Chumbo/metabolismo , Folhas de Planta/metabolismo , China , Poluentes do Solo/metabolismo , Poluentes do Solo/análise , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análiseRESUMO
Exosomal microRNAs (miRNAs) are valuable biomarkers closely associated with cancer progression. Therefore, sensitive and specific exosomal miRNA biosensing has been employed for cancer diagnosis, prognosis, and prediction. In this study, a miRNA-based DNA nanonet assembly strategy is proposed, enabling the biosensing of exosomal miRNAs through dumbbell dual-hairpin under isothermal enzyme-free conditions. This strategy dexterously designs a specific dumbbell dual-hairpin that can selectively recognize exosomal miRNA, inducing conformational changes to cascade-generated X-shaped DNA structures, facilitating the extension of the X-shaped DNA in three-dimensional space, ultimately forming a DNA nanonet assembly. On the basis of the target miRNA, our design enriches the fluorescence signal through the cascade assembly of DNA nanonet and realizes the secondary signal amplification. Using exosomal miR-141 as the target, the resultant fluorescence sensing demonstrates an impressive detection limit of 57.6 pM and could identify miRNA sequences with single-base variants with high specificity. Through the analysis of plasma and urine samples, this method effectively distinguishes between benign prostatic hyperplasia, prostate cancer, and metastatic prostate cancer. Serving as a novel noninvasive and accurate screening and diagnostic tool for prostate cancer, this dumbbell dual-hairpin triggered DNA nanonet assembly strategy is promising for clinical applications.
RESUMO
OBJECTIVE: to investigate the association between cartilage lesion-related features observed in knee osteoarthritis (OA) patients' first MRI examination and incident knee surgery within 5 years. Additionally, to assess the predictive value of these features for the incident knee surgery. METHODS: We identified patients diagnosed with knee OA and treated at our institution between January 2015 and January 2018, and retrieved their baseline clinical data and first MRI examination films from the information system. Next, we proceeded to determine joint space narrowing grade, cartilage lesion size grade, cartilage full-thickness loss grade and cartilage lesion sum score for the medial and lateral compartments, respectively. Generalized linear regression models examined the association of these features with 5-year incident knee surgery. Positive and negative predictive values (PPVs and NPVs) were determined referring to 5-year incident knee surgery. RESULTS: Totally, 878 participants (knees) were found eligible to form the study population. Within the 5 years, surgery was performed on 61 knees. None of the cartilage-related features had been found significantly associated with incident surgery. The results were similar for medial and lateral compartments. The PPVs were low for all the features. CONCLUSIONS: Among symptomatic clinically diagnosed OA knees, cartilage lesions observed in the first MRI examinations were not found to be associated with the occurrence of joint surgery within a 5-year period. All these cartilage-related features appear to have no additional value in predicting 5-year incident joint surgery.
Assuntos
Cartilagem Articular , Articulação do Joelho , Imageamento por Ressonância Magnética , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Cartilagem Articular/cirurgia , Idoso , Articulação do Joelho/cirurgia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Artroplastia do Joelho/estatística & dados numéricosRESUMO
Manipulating the expression of cellular genes through efficient CRISPR/Cas9 delivery is rapidly evolving into a desirable tumor therapeutics. The exposure of CRISPR/Cas9 to a complex external environment poses challenges for conventional delivery carriers in achieving responsive and accurate release. Here, we report a Trojan horse-like nanocapsule for the on-demand delivery of CRISPR/Cas9 in a microRNA-responsive manner, enabling precise tumor therapy. The nanocapsule comprises a nanoassembled, engineered DNAzyme shell encasing a Cas9/sgRNA complex core. The DNAzyme, functioning as a catalytic unit, undergoes a conformational change in the presence of tumor-associated microRNA, followed by activating a positive feedback-driven autonomous catabolic cycle of the nanocapsule shell. This catabolic cycle is accomplished through chain reactions of DNAzyme "cleavage-hybridization-cleavage", which ensures sensitivity in microRNA recognition and effective release of Cas9/sgRNA. Utilizing this Trojan horse-like nanocapsule, as low as 1.7 pM microRNA-21 can trigger the on-demand release of Cas9/sgRNA, enabling the specific editing of the protumorigenic microRNA coding gene. The resulting upregulation of tumor suppressor genes induces apoptosis in tumor cells, leading to significant inhibition of tumor growth by up to 75.94%. The Trojan horse-like nanocapsule, with superior programmability and biocompatibility, is anticipated to serve as a promising carrier for tailoring responsive gene editing systems, achieving enhanced antitumor specificity and efficacy.
Assuntos
Sistemas CRISPR-Cas , DNA Catalítico , MicroRNAs , Nanocápsulas , Sistemas CRISPR-Cas/genética , DNA Catalítico/química , DNA Catalítico/metabolismo , Humanos , Nanocápsulas/química , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Camundongos , Edição de Genes , Proteína 9 Associada à CRISPR/metabolismo , Proteína 9 Associada à CRISPR/genética , Proteína 9 Associada à CRISPR/químicaRESUMO
Background: Early-onset sarcopenia refers to the progressive loss of muscle mass and function that occurs at an early age. This condition perpetuates the vicious cycle of muscle loss and is associated with adverse outcomes. It is important to identify the contributing factors for early intervention and prevention. While diet is known to impact muscle mass, the association of B vitamins with early-onset sarcopenia remains unexplored. Objectives: To investigate the association of B vitamins intake with early-onset sarcopenia risk in a cross-sectional study. Methods: We conducted data analysis on a total of 8,711 participants aged between 20 and 59 years who took part in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Early-onset sarcopenia was defined as a SMI measured by DXA that was one standard deviation below the sex-specific mean of the reference population. B vitamins intake (B1, B2, B3, B6, B9, and B12) was assessed by 24-h dietary recall. We used weighted multiple logistic regression and RCS models to estimate the OR and 95% CI of sarcopenia by B vitamins intake, adjusting for demographic, physical, lifestyle, comorbidities, and nutritional covariates. Results: Higher intake of vitamin B1 was associated with a 22% lower sarcopenia risk (OR = 0.78, CI = 0.63-0.97, p = 0.022), and higher intake of vitamin B2 with a 16% lower risk (OR = 0.84, CI = 0.74-0.97, p = 0.012) in both genders. Gender-specific analyses showed a 28% reduction in sarcopenia risk among males with each additional mg of vitamin B1 intake (OR = 0.72, CI = 0.52-0.97, p = 0.038), and a 26% decrease among females with each additional mg of vitamin B2 intake (OR = 0.74, CI = 0.57-0.96, p = 0.021). No significant differences were found between vitamin B2 and males, or between vitamin B1 and females. The RCS model suggested a nonlinear relationship between vitamin B2 intake and sarcopenia risk (POverall = 0.001, PNonlinear = 0.033), with a plateau effect above 3 mg/d. Conclusion: Higher intake of vitamin B1 and B2 may lower the risk of early-onset sarcopenia, with gender differences. This suggests the potential of nutritional intervention by increasing these vitamins intake through diet and supplements. Further research is warranted to elucidate the mechanisms and design targeted interventions.
RESUMO
OBJECTIVE: To investigate the potential pharmacological mechanisms of Ganshuang granules (, GSG) in treating non-alcoholic fatty liver (NAFLD). METHODS: All the active components and targets of GSG were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Protein-Protein interaction network, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology function annotation of common targets were analyzed to predict the mechanisms of action of GSG in the treatment of NAFLD. Then, the mouse models of NAFLD were constructed in a diet-induced manner and treated with GSG. The levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins in the liver of mice in each group were measured by enzyme linked immunosorbent assay and Western blot, respectively. RESULTS: Network pharmacology revealed a total of 159 potential targets of GSG for the treatment of NAFLD. Functional enrichment analysis indicated that the PI3K/AKT signaling pathway may be involved during GSG treatment of NAFLD. Further experiments showed that the significantly decreased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels in NAFLD model mice serum after GSG treatment, as well as the expression levels of IL-6 and TNF-α in the liver. Furthermore, drug intervention increased the protein expression levels of phosphorylated-PI3K (P-PI3K) and P-AKT in the liver of the model group mice, and decreased the protein expression level of sterol regulatory element-binding protein 1. CONCLUSION: We found that GSG is effective in treating NAFLD and the potential therapeutic targets may be involved in PI3K/AKT signaling pathway.
Assuntos
Medicamentos de Ervas Chinesas , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fator de Necrose Tumoral alfa/genética , Farmacologia em Rede , Interleucina-6 , Fosfatidilinositol 3-Quinases/genética , ColesterolRESUMO
There is an urgent need to accurately quantify tumor-derived exosomes, which have emerged as promising non-invasive tumor diagnostic biomarkers. Herein, a bispecific-aptamer sandwich-type gold nanoparticle-modified electrochemical aptasensor was developed based on a four-way junction (4-WJ)-triggered dual rolling circle amplification (RCA)-assisted methylene blue (MB)/G-quadruplex strategy for extremely specific and sensitive exosome detection. This aptamer/exosome/aptamer sandwich-type design contained a CD63-specific aptamer and a cancerous mucin-1 (MUC1) protein-specific aptamer. The CD63 aptamer modified on a gold electrode captured exosomes, and then the sandwich-type aptasensor was formed with the addition of the MUC1 aptamer. The MUC1 aptamer's 3'-end sequence facilitated the formation of 4-WJ, assisted by a molecular beacon probe and a binary DNA probe. Subsequently, a dual-RCA reaction was triggered by binding to two cytosine-rich circle DNA templates at both ends of 4-WJ. Ultimately, dual-RCA products containing multiple G-quadruplex conformations were generated with the assistance of K+ to trap abundant MB indicators and amplify electrochemical signals. The aptasensor exhibited high specificity, sensitivity, repeatability, and stability toward MCF-7-derived exosomes, with a detection limit of 20 particles/mL and a linear range of 1 × 102 to 1 × 107 particles/mL. Moreover, it showed excellent applicability in clinical settings to recover exosomes in normal human serum. Our aptasensor is anticipated to serve as a versatile platform for detecting various specific aptamer-based targets in biomedical and bioanalytical applications.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exossomos , Nanopartículas Metálicas , Neoplasias , Humanos , Exossomos/metabolismo , Ouro/química , Aptâmeros de Nucleotídeos/química , Limite de Detecção , Técnicas Eletroquímicas , DNA/química , Neoplasias/diagnóstico , Neoplasias/metabolismoRESUMO
Without coordinated strategies to balance the population and activity of tumor cells and polarized macrophages, antitumor immunotherapy generally offers limited clinical benefits. Inspired by the "eat me" signal, a smart tumor cell-derived proximity anchored non-linear hybridization chain reaction (Panel-HCR) strategy is established for on-demand regulation of tumor-associated macrophages (TAMs). The Panel-HCR is composed of a recognition-then-assembly module and a release-then-regulation module. Upon recognizing tumor cells, a DNA nano-tree is assembled on the tumor cell surface and byproduct strands loaded with CpG oligodeoxynucleotides (CpG-ODNs) are released depending on the tumor cell concentration. The on-demand release of CpG-ODNs can achieve efficient regulation of M2 TAMs into the M1 phenotype. Throughout the recognition-then-assembly process, tumor cell-targeted bioimaging is implemented in single cells, fixed tissues, and living mice. Afterward, the on-demand release of CpG-ODNs regulate the transformation of M2 TAMs into the M1 phenotype by stimulating toll-like receptor 9 to activate the NF-κB pathway and increasing inflammatory cytokines. This release-then-regulation process is verified to induce strong antitumor immune responses both in vitro and in vivo. Altogether, this proposed strategy holds tremendous promise for on-demand antitumor immunotherapy.
Assuntos
Macrófagos , Neoplasias , Camundongos , Animais , Macrófagos/metabolismo , Citocinas/metabolismo , Neoplasias/patologia , DNA/metabolismo , ImunoterapiaRESUMO
To investigate the effects of leaves and stems on the accumulation and transport of cadmium(Cd) and arsenic(As) in wheat shoots after flowering, a field experiment was conducted in a typical Cd and As co-contaminated agricultural land to explore the distribution and translocation of Cd and As in the different parts of two wheat cultivars after flowering. The results showed that Cd was mainly distributed in the nodes of two varieties, and the translocation factors of Cd from internode 3 to node 2, from internode 2 to node 1, and from sheath 1 to node 1 were markedly higher than those of other aboveground parts during the grain-filling stage. However, Cd was mainly distributed in the leaves, and the translocation factors of Cd from sheath to leaf and from node 1 to rachis was significantly higher than those of other parts at the mature stage. In addition, the transport capacity of Cd from glume to rachis and from rachis to grain in JM22 was significantly lower than that in SN28, which significantly reduced Cd concentrations in the rachis, glume, and grain of JM22 by 22.3%, 40.8%, and 44.4%, respectively. Meanwhile, As was mainly distributed in the wheat leaves from the grain-filling stage to the mature stage, and As concentrations in the glume and grain of JM22 were 25.8% and 33.3% lower than those of SN28, respectively. Additionally, the translocation factors of As from the sheath to the node were significantly 438% and 190% higher than that from leaf to sheath and from node to internode during the whole grain filling stage and mature stage. Moreover, the translocation factors of As from glumes to grains and from rachis to grains in JM22 were 40.6% and 44.4% lower than that in SN28, respectively. In summary, flag leaf, node 1, and the rachis had regulated Cd transport and accumulation in wheat grains, whereas leaf 3, flag leaf, node 1, the glumes, and the rachis were mainly responsible for As transport and accumulation in wheat grains.
Assuntos
Arsênio , Poluentes do Solo , Cádmio/análise , Triticum , Grão Comestível/química , Agricultura , Poluentes do Solo/análise , SoloRESUMO
As energy and environmental issues become more prominent, people must find sustainable, green development paths. Bio-based polymeric phase change energy storage materials provide solutions to cope with these problems. Therefore, in this paper, a fully degradable polyethylene glycol (PEG20000)/polylactic acid (PLA)/g-C3N4 composite phase change energy storage material (CPCM) was obtained by confinement. The CPCM was characterized by FTIR and SEM for compatibility, XRD and nanoindentation for mechanical properties and DSC, LFA, and TG for thermal properties. The results showed that the CPCM was physical co-mingling; when PLA: PEG: g-C3N4 was 6:3:1, the consistency was good. PEG destroys the crystallization of PLA and causes the hardness to decrease. When PLA: PEG: g-C3N4 was 6: 3: 1, it had a maximum hardness of 0.137 GPa. The CPCM had a high latent enthalpy, and endothermic and exothermic enthalpies of 106.1 kJ/kg and 80.05 kJ/kg for the PLA: PEG: g-C3N4 of 3: 6: 1. The CPCM showed an increased thermal conductivity compared to PLA, reaching 0.30 W/(m·K),0.32 W/(m·K) when PLA: PEG: g-C3N4 was 6: 3: 1 and when PLA: PEG: g-C3N4 was 3: 6: 1, respectively. Additionally, the CPCM was stable within 250 °C, indicating a wide appliable temperature range. The CPCM can be applied to solar thermal power generation, transportation, and building construction.
RESUMO
Changes in atomic bonding configuration in carbon from sp3 to sp2 are known to exist in certain structural defects in diamond, such as twin boundaries, grain boundaries, and dislocations, which have a significant impact on many properties of diamond. In this work, the atomic structure of fivefold twinning in detonation synthesized ultra-dispersed diamonds is investigated using a combination of techniques, including spherical aberration-corrected high-resolution electron microscopy (HREM), HREM image simulations, and molecular mechanics (MM) calculations. The experimental HREM images reveal clearly that the fivefold twinning in diamond has two distinct structures. In addition to the concentric fivefold twins, where the core structure is the intersection of five {111} twinning boundaries, a new extended core structure with co-hybridization of bonding is identified and analyzed in fivefold twinning. The atomic structure forming these fivefold twinning boundaries and their respective core structures is proposed to involve both the tetrahedral sp3 and planar graphitic sp2 bonding configurations, in which a co-hybridized planar hexagon of carbon serves as a fundamental structural unit. The presence of this sp2 -bonded planar unit of hexagonal carbon rings in general grain boundaries is also discussed.
RESUMO
Bioactive small molecules serve as invaluable biomarkers for recognizing modulated organismal metabolism in correlation with numerous diseases. Therefore, sensitive and specific molecular biosensing and imaging in vitro and in vivo are particularly critical for the diagnosis and treatment of a large group of diseases. Herein, a modular DNA tetrahedron-based nanomachine was engineered for the ultrasensitive detection of intracellular small molecules. The nanomachine was composed of three self-assembled modules: an aptamer for target recognition, an entropy-driven unit for signal reporting, and a tetrahedral oligonucleotide for the transportation of the cargo (e.g., the nanomachine and fluorescent markers). Adenosine triphosphate (ATP) was used as the molecular model. Once the target ATP bonded with the aptamer module, an initiator was released from the aptamer module to activate the entropy-driven module, ultimately activating the ATP-responsive signal output and subsequent signal amplification. The performance of the nanomachine was validated by delivering it to living cells with the aid of the tetrahedral module to demonstrate the possibility of executing intracellular ATP imaging. This innovative nanomachine displays a linear response to ATP in the 1 pM to 10 nM concentration range and demonstrates high sensitivity with a low detection limit of 0.40 pM. Remarkably, our nanomachine successfully executes endogenous ATP imaging and is able to distinguish tumor cells from normal ones based on the ATP level. Overall, the proposed strategy opens up a promising avenue for bioactive small molecule-based detection/diagnostic assays.
Assuntos
Técnicas Biossensoriais , DNA , Oligonucleotídeos , Trifosfato de Adenosina , Técnicas Biossensoriais/métodos , Limite de DetecçãoRESUMO
MicroRNAs (miRNAs) can act as oncogenes or tumor suppressors, capable of up or down-regulating gene expression during tumorigenesis; they are diagnostic biomarkers or therapeutic targets for tumors. To detect low abundance of intracellular oncogenic miRNAs (onco-miRNAs) and realize synergistic gene therapy of onco-miRNAs and tumor suppressors, a smart nano-theranostic platform based on dual-miRNAs guided self-feedback tetrahedral entropy-driven DNA circuit is created. The platform as a delivery vehicle is a DNA tetrahedral framework, in which the entropy-driven DNA circuit achieves a dual-miRNAs guided self-feedback, between an in situ amplification of the onco-miRNAs and activation of suppressor miRNAs release. To test this platform, dual-miRNAs are selected, miRNA-155, an up-regulated miRNA, as cancer indicators, and miRNA-122, a down-regulated miRNA as therapy targets in hepatocellular carcinoma, respectively. Through the circuit, the platform to detect onco-miRNAs at femtomolar level as well as visualized miRNAs inside cells, fixed tissues, and mice is programmed. Furthermore, triggered by miRNA-155, preloaded miRNA-122 is amplified via the self-feedback and released into target cells; the sudden increase of miRNA-122 and simultaneous decrease of miRNA-155 synergistically served as therapeutic drugs for gene regulation with enhanced antitumor efficacy and superior biosafety. It is envisioned that this nano-theranostic platform will initiate an essential step toward tumor theranostics in personalized/precise medicine.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Medicina de Precisão , Retroalimentação , Entropia , DNARESUMO
OBJECTIVE: To investigate the antitumour efficacy of luteolin on gastric cancer (GC) and study the mechanism underpinning the action. METHODS: Effects of luteolin on cell growth inhibition, apoptosis, and cell cycle arrest in MKN45 cells were investigated using the cell counting kit-8 assay. Changes in the mitochondrial membrane potential after luteolin treatment were assessed using 5,5',6,6'-tetra-chloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanineiodi-de (JC-1) staining. To investigate whether apoptotic effect by luteolin is related to the phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene (PI3K/Akt) pathway, cells were additionally treated with LY294002, a PI3K/Akt pathway inhibitor. Moreover, the expressions of apoptosis-related proteins, namely B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein (Bax), Akt, p-Akt, caspase-3, and cytochrome C, were detected after luteolin treatment. RESULTS: The study revealed that in MKN45 cells, luteolin could inhibit the cell proliferation in a time- and dose-dependent manner; block the cell cycle in the S-phase; induce apoptosis; reduce the mitochondrial membrane potential; increase the expression of Bax, caspase-3, and cytochrome C; and decrease the expression of Bcl-2 and p-Akt. Luteolin might be involved in the PI3K/Akt signalling pathway, indicating that this pathway could be a therapeutic target for GC treatment. CONCLUSION: Luteolin could inhibit the proliferation of GC cells and block the cell cycle in the S-phase. The mechanism of inducing apoptosis in these cells was related to the PI3K/Akt signalling pathway.