ABSTRACT
Nanocatalytic therapy, an emerging approach in cancer treatment, utilizes nanomaterials to initiate enzyme-mimetic catalytic reactions within tumors, inducing tumor-suppressive effects. However, the targeted and selective catalysis within tumor cells is challenging yet critical for minimizing the adverse effects. The distinctive reliance of tumor cells on glycolysis generates abundant lactate, influencing the tumor's pH, which can be manipulated to selectively activate nanozymatic catalysis. Herein, small interfering ribonucleic acid (siRNA) targeting lactate transporter-mediated efflux is encapsulated within the iron-based metal-organic framework (FeMOF) and specifically delivered to tumor cells through cell membrane coating. This approach traps lactate within the cell, swiftly acidifying the tumor cytoplasm and creating an environment for boosting the catalysis of the FeMOF nanozyme. The nanozyme generates hydroxyl radical (·OH) in the reversed acidic environment, using endogenous hydrogen peroxide (H2O2) produced by mitochondria as a substrate. The induced cytoplasmic acidification disrupts calcium homeostasis, leading to mitochondrial calcium overload, resulting in mitochondrial dysfunction and subsequent tumor cell death. Additionally, the tumor microenvironment is also remodeled, inhibiting migration and invasion, thus preventing metastasis. This groundbreaking strategy combines metabolic regulation with nanozyme catalysis in a toxic drug-free approach for tumor treatment, holding promise for future clinical applications.
Subject(s)
Neoplasms , Humans , Neoplasms/metabolism , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/therapy , Catalysis , Cell Line, Tumor , Tumor Microenvironment , RNA, Small Interfering/metabolism , Animals , Mitochondria/metabolism , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Hydrogen Peroxide/metabolism , Hydrogen-Ion Concentration , Hydroxyl Radical/metabolism , Nanostructures/chemistryABSTRACT
Nanomaterial-based drug delivery systems are susceptible to premature drug leakage and systemic toxicity due to lack of specific targeting, and live-cell drug delivery is also prone to be restricted by drug carrier-cell interactions. Here, a method is established to adsorb drug-loaded nanomaterials externally to the live cells, which reduces cytotoxicity caused by drug uptake and improves the bioactivity of the carrier cells and drug release at the lesion site. It was found that polyphenols act like "double-sided tape" to bridge metal-organic framework (MOF) nanoparticles with live macrophages (Mφ), attaching MOFs to the Mφ surface and minimizing intracellular uptake, with no negative effect on cell proliferation. On this basis, a "macrophage missile" with peroxymonosulfate (PMS)-loaded MOF nanoparticles on the cell surface was constructed. As a "propellant", the Mφ, in which bioactivity is preserved, can selectively identify and target tumor cells, precisely bringing nanomedicines to the lesion. MOF nanoparticles are used to load and catalyze PMS, which acts as an exogenous source of reactive oxygen species, showing higher efficacy and lower toxicity in an oxygen-independent manner. The primary study results demonstrate that this innovative combination of biology and nanomaterials remarkably enhances tumor targeting and therapeutic efficacy while reducing systemic side effects. This approach is expected to provide a more effective and safer treatment for lung cancer and holds promise for broader applications in other cancer therapies.
ABSTRACT
Background: Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes. Their dysregulation has been closely associated with tumorigenesis. LINC00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer. However, the mechanism underlying its function in cancer progression remains poorly understood. Methods: Here, the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines, clinical samples, and xenografts. Results: We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients, whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in xenografts. Western blot and flow cytometry analyses indicated that silencing of LINC00265 induced autophagy and apoptosis. Moreover, we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a (SIN3A), which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner. Silencing of SIN3A also reduced proliferation of lung cancer cells, which was correlated with the induction of autophagy. These observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma. Conclusions: Our findings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.
Subject(s)
Apoptosis , Autophagy , Cell Proliferation , Lung Neoplasms , RNA, Long Noncoding , Sin3 Histone Deacetylase and Corepressor Complex , Humans , RNA, Long Noncoding/genetics , Autophagy/genetics , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Apoptosis/genetics , Animals , Mice , Sin3 Histone Deacetylase and Corepressor Complex/genetics , Cell Proliferation/genetics , Cell Line, Tumor , Repressor Proteins/genetics , Repressor Proteins/metabolism , Gene Expression Regulation, Neoplastic , Protein Stability , Gene Silencing , Oncogenes , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism , Xenograft Model Antitumor AssaysABSTRACT
In recent years, magnetic resonance imaging has been widely used in the medical field. During the scan, if the human body moves, then there will be motion artifacts on the scan image, which will interfere with the diagnosis and only be found after the end of the scan sequence, resulting in a waste of manpower and resources. However, there is a lack of technology that halts scanning once motion artifacts arise. Here, we designed a real-time monitoring sensor (RMS) to dynamically perceive the movement of the human body and to pause in time when the movement exceeds a certain amplitude. The sensor has an array structure that can accurately sense the position of the human body in real time. The selection of the RMS ensures that there is no additional interference with the scanning results. Based on this design, the RMS can achieve the monitoring function of motion artifact generation.
Subject(s)
Artifacts , Magnetic Resonance Imaging , Magnetic Resonance Imaging/methods , Humans , Movement , MotionABSTRACT
Long non-coding RNAs play critical roles in the development of lung cancer by functioning as tumor suppressors or oncogenes. Changes in the expression of LINC01279 have been associated with cell differentiation and human diseases. However, the mechanism underlying LINC01279 activity in tumorigenesis is not clear. Here, we analyzed the function of LINC01279 in lung adenocarcinoma using clinical samples, xenografts, and non-small-cell lung cancer cell lines. We found that LINC01279 is highly expressed in lung adenocarcinoma and may be considered as a predictive factor for this cancer. Knockdown of LINC01279 prevents tumor growth in xenografts and in cancer cell lines by activating autophagy and apoptosis. Molecularly, we revealed that LINC01279 regulates the expression of focal adhesion kinase and extracellular-regulated kinase signaling. In addition, it complexes with and stabilizes the transcriptional co-repressor SIN3A protein. Suppression of focal adhesion kinase and SIN3A also induces apoptosis and prevents tumor progression, suggesting that they may at least in part mediate the oncogenic activity of LINC01279. These results identify LINC01279 as a possible oncogene that plays an important role in the development of lung cancer. Our findings provide insights into the mechanism underlying LINC01279-mediated oncogenesis of lung adenocarcinoma. They may help to discover potential therapeutic targets for cancer diagnosis and prognosis.
ABSTRACT
The dielectric barrier discharge (DBD) multi-component system containing plasma, α-Fe2O3/FeVO4, and peroxymonosulfate (PMS) with high catalytic activity was successfully constructed. Thereinto, α-Fe2O3/FeVO4 was loaded on the honeycomb ceramic plate (HCP) surface (α-Fe2O3/FeVO4/HCP) and placed under the water surface below the discharge area. The catalytic activity was evaluated by the removal rate of gatifloxacin (GAT), and the DBD+α-Fe2O3/FeVO4+PMS system exhibited the optimal catalytic activity. The enhanced catalytic activity can be attributed to the fact that the occurrence of synergistic catalysis that simultaneously includes plasma oxidation, photocatalysis, PMS oxidation, O3 catalysis, and Fenton reaction. The effect of various initial degradation parameters including input power, PMS dosage, pH, etc. On GAT removal was investigated. DBD+α-Fe2O3/FeVO4+PMS system has a significant increase in the concentration of H2O2 and O3, and the role played in the multi-component system was analyzed. The identification and analysis of organic matters during GAT degradation were visualized with the help of 3D EEMs. HPLC-MS and theoretical calculations identified the major intermediates and further deduced the possible GAT degradation pathways. Additionally, the acute toxicity of the major intermediates was predicted by the QSAR model. Finally, the possible mechanisms of synergistic catalysis to enhance catalytic activity were discussed based on the characteristics of several advanced oxidation processes (AOPs) and the results of experimental and characterization. This work provides a feasible technical route and theoretical basis for wastewater treatment by plasma combined with other AOPs.
Subject(s)
Hydrogen Peroxide , Peroxides , Gatifloxacin , Peroxides/chemistry , CatalysisABSTRACT
OBJECTIVES: Aberrantly expressed circular RNAs (circRNAs) have been detected in many types of tumors. Hence, they are currently investigated as candidate biomarkers for diagnostic and potential targets for therapy in cancers. The objective of this study was to assess the expression profile of circRNA in lung adenocarcinoma (LUAD). METHODS: This study included 14 pairs of postoperative lung adenocarcinoma specimens, including cancer tissues and matched adjacent tissues. Second-generation sequencing was applied to the specimens to determine the circRNA expression in them among the 5242 distinct circRNAs detected. RESULTS: We identified a total of 18 significantly dysregulated circRNAs in the LUAD tissues: upregulation in four and downregulation in 14. ROC (The receiver operating characteristic curve) further suggested that hsa_circ_0120106, has_circ_0007342, has_circ_0005937, and circRNA_0000826 could potentially be used as biomarkers in the diagnosis of LUAD. Furthermore, study of the circRNA-microRNA (miRNA)-messenger RNA (mRNA) revealed interactions between the 18 dysregulated circRNA and several cancer-related miRNAs. Finally, a further Kyoto Encyclopedia of Genes and Genomes analysis showed that the cell cycle phase transition, p53 signaling pathway, AMP-activated protein kinase (AMPK) relative signaling pathway, and so on were key putative pathways in the process of LUAD. CONCLUSIONS: These findings demonstrated the correlation between abnormality in circRNA expression and LUAD, which lays the foundation of making CircRNAs candidate biomarkers in the diagnosis of LUAD.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , MicroRNAs , Humans , RNA, Circular/genetics , MicroRNAs/genetics , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Biomarkers , High-Throughput Nucleotide Sequencing , Lung Neoplasms/genetics , Lung Neoplasms/pathologyABSTRACT
Degradation of neonicotinoid insecticide dinotefuran (DIN) in dielectric barrier discharge (DBD) non-thermal plasma combined with lanthanum-doped titanium dioxide (La-TiO2) system was investigated. A La-TiO2 catalyst was prepared by the sol-gel method and characterized by SEM, XRD, and DRS. The effects of various factors (initial concentration, initial pH, input power, and addition of metal ions) on the removal rate of DIN were evaluated. The results indicated that when the initial concentration, input power, initial pH, and Fe2+ catalyst ions were 100â mg/L, 150 W, 10.5 and 50â mg/L, respectively, the DIN degradation efficiency was improved to 99.0% by coupling 10â wt% La-TiO2 at 180 min. La-TiO2 showed excellent catalytic performance on DIN degradation in a DBD system. The removal rate decreased with the presence of H2O2 and a scavenger, manifesting that HOâ plays an imperative role in the degradation process. Furthermore, intermediate products were analyzed by MS and the possible degradation pathway of DIN was proposed.
Subject(s)
Hydrogen Peroxide , Lanthanum/chemistry , Titanium , Catalysis , Guanidines , Hydrogen Peroxide/chemistry , Neonicotinoids , Nitro Compounds , Titanium/chemistryABSTRACT
This work investigated the preparation of Ti/Sb-SnO2 electrode co-doped with graphene and europium and the electrochemical degradation of clothianidin in aqueous solution with Ti/Sb-SnO2-Eu&rGO electrode. The physicochemical properties of different electrodes were characterized by using the scanning electron microscopy, X-ray diffraction, oxygen evolution potential and cyclic voltammetry tests. The results indicated that the Ti/Sb-SnO2-Eu&rGO electrodes have a compact structure and fine grain size and have a higher oxygen evolution overpotential than Ti/Sb-SnO2-None, Ti/Sb-SnO2-Eu and Ti/Sb-SnO2-rGO electrodes. Among the four electrodes, the Ti/Sb-SnO2-Eu&rGO electrode showed the highest efficiency and was chosen as the experimental electrode. The main influence factors on the degradation of clothianidin, such as initial pH, electrolyte concentration, current density and initial concentration of clothianidin, were analyzed. The results showed that the removal rate of clothianidin can reach 96.44% under the optimal conditions for 120 min treatment. Moreover, a possible degradation pathway including the fracture of internal bonds of clothianidin such as the N-N bond, the C-N bond that connects nitroguanidine to the thiazole ring and mineralization was elucidated by intermediate products identified by HPLC-MS method and Fourier transform infrared spectroscopy (FTIR). This paper introduces the Ti/Sb-SnO2-Eu&rGO electrode into an electrocatalytic degradation system and could provide basic data and technique support and guidance for the clothianidin wastewater pollution control.
Subject(s)
Wastewater , Water Pollutants, Chemical , Electrochemical Techniques , Electrodes , Graphite , Guanidines , Neonicotinoids , Oxidation-Reduction , Thiazoles , Tin Compounds , TitaniumABSTRACT
The series Ag-AgI/BiOI-Bi2O3 visible-light-driven photocataslyts were successfully synthesized by solvothermal method. The as-synthesized samples were systematically characterized by XRD, SEM, TEM, EDS, BET, XPS, FR-IR, UV-vis DRS, photoelectrochemical measurements and EPR. The formation mechanism of the new composite photocataslyts was investigated and the simulate formation process had been illustrated. The photocatalytic properties of the samples were evaluated by degradation of methyl orange under visible-light irradiation. The results shown that the 30% Ag-AgI/BiOI-Bi2O3 photocataslyts possessed the best photocatalytic activity and the kinetics reaction models were followed pseudo-first-order kinetics. The enhanced photocatalytic performance could be attributed to the effective separation and transfer of electron-hole pairs resulting by the deposing of Ag-AgI nanoparticles and Bi2O3. The photocatalytic mechanism was deduced by trapping experiments and EPR, and the results demonstrated that h+, OH, O2- radicals played different roles in the degradation. Furthermore, a new Z-scheme multi-heterojunction mechanism was proposed basing on the results of trapping experiments and EPR.
ABSTRACT
A class of aliphatic short chain nitrocompounds have been reported as being capable of CH4 reduction both in vitro and in vivo. However, the laboratory evidence associated with the metabolic fate of nitrocompounds in the rumen has not been well documented. The present study was conducted to compare in vitro degradation and metabolism of nitroethane (NE), 2-nitroethanol (NEOH), and 2-nitro-1-propanol (NPOH) incubated with mixed rumen microorganisms of dairy cows. After 10 mM supplementation of nitrocompounds, a serious of batch cultures were carried out for 120 h under the presence of two substrates differing in the ratio of maize meal to alfalfa hay (HF, 1:4; LF, 4:1). Compared to the control, methane production was reduced by 59% in NPOH and by >97% in both NE and NEOH, and such antimethanogenic effects were more pronounced in the LF than the HF group. Although NE, NEOH, and NPOH addition did not alter total VFA production, the rumen fermentation pattern shifted toward increasing propionate and butyrate and decreasing acetate production. The kinetic disappearance of each nitrocompound was well fitted to the one-compartment model, and the disappearance rate (k, %/h) of NE was 2.6 to 5.2 times greater than those of NEOH and NPOH. Higher intermediates of nitrite occurred in NEOH in comparison with NPOH and NE while ammonia N production was lowest in NEOH. Consequently, a stepwise accumulation of bacterial crude protein (BCP) in response to the nitrocompound addition was observed in both the HF and LF group. In brief, both NE and NEOH in comparison with NPOH presented greater antimethanogenic activity via the shift of rumen fermentation. In addition, the present study provided the first direct evidence that rumen microbes were able to cleave these nitrocompounds into nitrite, and the subsequent metabolism of nitrite into ammonia N may enhance the growth of rumen microbes or promote microbial activities.
ABSTRACT
To study the pollution characteristics of atmospheric heavy metal elements in a living area of Zhengzhou City, assess the potential ecological risks, and determine risks to resident health in this city, the Wuhan Tianhong TH-16A Airborne Particles Intelligent Sampler was used to collect atmospheric PM2.5 in Zhengzhou City. The mass concentrations of 17 metal elements were analyzed by ambient air determination of inorganic elements by ambient particle matter wavelength dispersive X-ray fluorescence spectrometry. The source of heavy metals was analyzed by the enrichment factor method and principal component analysis. The ecological risk index method and the US Environmental Protection Agency's health risk assessment method were used to evaluate the potential ecological risks and residents' health risks from Cr, Cd, Cu, Zn, Ni, Pb, As, and other elements. The results showed that metals with higher enrichment factor values were Cd, Sb, Pb, and As, and Cd had the highest enrichment factor value. The sources of metal elements in a living area of Zhengzhou City were mainly crust/burning coal, fuel, garbage burning, metallurgical dust, and vehicle emission. The single factor potential ecological hazard index values of Cd, Pb, Zn, As, Cu, Ni, and Cr were 70420.2, 255.3, 204.6, 71.5, 36.9, 24.0, and 5.1, respectively. Cd, As, and Cr in a living area of Zhengzhou City posed a cancer risk, and Cd was the most harmful. Mn had a non-carcinogenic risk.
Subject(s)
Environmental Health , Environmental Monitoring , Environmental Pollution , Metals, Heavy , China , Cities , Humans , Risk AssessmentABSTRACT
The three typical carbon enterprises in Zhengzhou were selected as research targets, and the emission characteristics of volatile organic compounds (VOCs) and their ozone formation potential (OFP) in different functional areas were studied. The US Environmental Protection Agency (EPA) health risk assessment model was used to evaluate the health risks of VOCs emitted by the carbon industry. The results showed that the concentration of VOCs in the production areas of the three research enterprises was between 89.77-964.60 µg·m-3, and the management area was between 51.46-121.59 µg·m-3. Naphthalene and carbon disulfide were at the highest concentrations in the carbon plants. The ozone formation potential of VOCs in the production area was between 75.42-1416.73 µg·m-3, and in the management area was between 65.32-202.42 µg·m-3, mainly from the contribution of aromatic hydrocarbons and olefins. The carcinogenic health risk (Risk) of VOCs in the production area was 3.5×10-5-2.8×10-3, and in the management area was 2.0×10-5-9.4×10-5, which was higher than the maximum acceptable level recommended by the EPA (10-6). The non-carcinogenic health risk index (HI) of the VOCs in the production area was 3.2-1.4×102, and in the management area was 4.3×10-1-3.8, except for the management area of the first enterprise, which was greater than 1, which may expose the workers. These health factors cause cancer and non-carcinogenic hazards.
Subject(s)
Air Pollutants , Environmental Health , Risk Assessment , Volatile Organic Compounds , Carbon , Environmental Monitoring , HumansABSTRACT
This study reports a simple and effective technique for the high-throughput fabrication of flexible all-carbon nanotube (CNT) electronics using a photosensitive dry film instead of traditional liquid photoresists. A 10 in. sized photosensitive dry film is laminated onto a flexible substrate by a roll-to-roll technology, and a 5 µm pattern resolution of the resulting CNT films is achieved for the construction of flexible and transparent all-CNT thin-film transistors (TFTs) and integrated circuits. The fabricated TFTs exhibit a desirable electrical performance including an on-off current ratio of more than 105, a carrier mobility of 33 cm2 V-1 s-1, and a small hysteresis. The standard deviations of on-current and mobility are, respectively, 5% and 2% of the average value, demonstrating the excellent reproducibility and uniformity of the devices, which allows constructing a large noise margin inverter circuit with a voltage gain of 30. This study indicates that a photosensitive dry film is very promising for the low-cost, fast, reliable, and scalable fabrication of flexible and transparent CNT-based integrated circuits, and opens up opportunities for future high-throughput CNT-based printed electronics.