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Surface coatings are designed to mitigate pervasive biofouling herald, a new era of surface protection in complex biological environments. However, existing strategies are plagued by persistent and recurrent biofilm attachment, despite the use of bactericidal agents. Herein, a chiral metal-organic framework (MOF)-based coating with conformal microstructures to enable a new anti-biofouling mode that involves spontaneous biofilm disassembly followed by bacterial eradication is developed. A facile and universal metal-polyphenol network (MPN) is designed to robustly anchor the MOF nanoarmor of biocidal Cu2+ ions and anti-biofilm d-amino acid ligands to a variety of substrates across different material categories and surface topologies. Incorporating a diverse array of chiral amino acids endows the resultant coatings with widespread signals for biofilm dispersal, facilitating copper-catalyzed chemodynamic reactions and inherent mechano-bactericidal activities. This synergistic mechanism yields unprecedented anti-biofouling efficacy elucidated by RNA-sequencing transcriptomics analysis, enhancing broad-spectrum antibacterial activities, preventing biofilm formation, and destroying mature biofilms. Additionally, the chelation-directed amorphous/crystalline coatings can activate photoluminescent properties to inhibit the settlement of microalgae biofilms. This study provides a distinctive perspective on chirality-enhanced antimicrobial behaviors and pioneers a rational pathway toward developing next-generation anti-biofouling coatings for diverse applications.
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The corrosion behaviors of two bridge steels (Q345q and Q500q) under simulated ultraviolet irradiation and a wet-dry alternating (UVWD) environment were studied. Weight loss measurement, stereomicroscope observation, SEM, XRD, and electrochemical impedance spectroscopy (EIS) were performed to investigate the influence of the coupled environment. The results revealed that the corrosion rates of Q345q and Q500q were significantly accelerated by the synergistic effect of UV light exposure and alternating wet-dry conditions. Numerous voids and cracks could be observed throughout the thickened rust layers, enabling the corrosive substances to easily penetrate through the rust layer. Q500q exhibited better corrosion resistance than Q345q due to the addition of Mo, Cr, and Ni as corrosion-resistant elements, which tended to transform the rust layer into α-FeOOH rather than γ-FeOOH during later stages of corrosion.
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The galvanic corrosion performance of AM60B coupled to DC01 was characterized in simulated environments with varying water salinity. The results showed that the coupled DC01 effectively accelerated the corrosion rate of AM60B, and the increased salt concentration had a significant effect on the deterioration process. The corrosion of AM60B mainly exhibits metal dissolution, and the formed Mg(OH)2 has weak a protective effect on the alloy substrate. Furthermore, the distributions of the corrosion potential and the corrosion current density of the AM60B/DC01 couple were simulated and intensively discussed.
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BACKGROUND: N-acetyltransferase 10 (NAT10), the only RNA cytosine acetyltransferase known in humans, contributes to cancer tumorigenesis and progression. This study aims to investigate the effect of NAT10 on the malignant biological properties of gastric cancer (GC) and its underlying mechanism. METHODS: The expression and prognostic significance of NAT10 in GC were analyzed using The Cancer Genome Atlas (TCGA) and Sun Yat-sen University (SYSU) cohorts. The influence of NAT10 on the malignant biological behaviors of GC was detected by Cell Counting Kit-8 (CCK-8) assay, plate colony formation assay, 5-ethynyl-2'-deoxyuridine (EdU), Transwell migration and invasion assays, scratch wound assay, flow cytometric analysis, and animal studies. The overall level of N4 acetylcytidine (ac4C) in GC was detected by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The downstream signal pathways of NAT10 were analyzed by Gene Set Enrichment Analysis (GSEA) and verified by Western blot (WB) and immunofluorescence (IF). RESULTS: The significant upregulation of NAT10 expression in GC was associated with a poor prognosis. The knockdown of NAT10 markedly suppressed GC cell proliferation, migration, invasion, and cell cycle progression. Downregulating NAT10 reduced ac4C levels and inhibited AKT phosphorylation and epithelial-mesenchymal transition (EMT) in GC. CONCLUSIONS: NAT10 functions as an oncogene and may provide a new therapeutic target in GC.
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Oceanic facilities and equipment corrosion present considerable economic and safety concerns, predominantly due to microbial corrosion. Early detection of corrosive microbes is pivotal for effective monitoring and prevention. Yet, traditional detection methods often lack specificity, require extensive processing time, and yield inaccurate results. Hence, the need for an efficient real-time corrosive microbe monitoring technology is evident. Pseudomonas aeruginosa, a widely distributed microorganism in aquatic environments, utilizes its production of quinone-like compounds, specifically pyocyanin (PYO), to corrode metals. Here, we report a novel fiber optic surface plasmon resonance (SPR) sensor modified by the C-terminal of BrlR protein (BrlR-C), which is a specific receptor of PYO molecule, to detect P. aeruginosa in aquatic environments. The results showed that the sensor had a good ability to recognize PYO in the concentration range of 0-1 µg/mL, and showed excellent sensing performance in real-time monitoring the growth status of P. aeruginosa. With a strong selectivity of PYO, the sensor could clearly detect P. aeruginosa against other bacteria in seawater environment, and exhibited excellent anti-interference ability against variations in pH, temperature and pressure and other interfering substances. This study provides a useful tool for monitoring corrosive P. aeruginosa biofilm in aquatic environments, which is a first of its kind example that serves as a laboratory model for the application of fiber optic technology in real-world scenarios to monitoring biofilms in microbial corrosion and biofouling.
Sujet(s)
Biofilms , Techniques de biocapteur , Technologie des fibres optiques , Pseudomonas aeruginosa , Pyocyanine , Résonance plasmonique de surface , Pseudomonas aeruginosa/isolement et purification , Résonance plasmonique de surface/méthodes , Pyocyanine/analyse , Pyocyanine/composition chimique , Techniques de biocapteur/méthodes , Corrosion , Fibres optiques , Eau de mer/microbiologie , Eau de mer/composition chimique , Conception d'appareillageRÉSUMÉ
The orpiment (As2S3) is an important secondary mineral in the geochemical process of arsenic (As) in the environment. The dissolution of orpiment has a close relationship with the migration and transformation of As. The dissolved species of As2S3 is closely related to sulfide (S-II) in the anoxic and sulfidic environment. This paper focuses on the various As species formed when As2S3 dissolved in the presence and absence of excess S-II under anoxic conditions with simulation tests via X-ray absorption spectroscopy (XAS), liquid chromatography with (hydride generation) atomic fluorescence spectrophotometry, and Raman spectroscopy. The results showed that the As produced when As2S3 dissolved in the excess S-II contained a mixture of arsenite and thioarsenite (ThioAsIII). Based on the linear combination fitting, ThioAsIII is the dominant As species (88.2 %) with arsenite as the leftover component. However, the percentage of ThioAsIII decreased to 43.7 % if As2S3 dissolved in the absence of excess S-II, indicting ThioAsIII favored under sulfidic conditions. The findings may give further insights about the role and formation mechanism of ThioAsIII in the dissolution process of As2S3. ENVIRONMENTAL IMPLICATION: The dissolution of crystallization orpiment has a close relationship with the transport of As in the environment. Qualitatively and quantitatively identification of the dissolved species of As2S3 in the presence and absence of excess S-II may be helpful for a better understanding and predicting the fate of As. The formed trithioarsenite was the dominant dissolved species compared to arsenite in the sulfidic system. It has higher mobility than AsV and AsIII, and has been found in many As-related adsorption/desorption and redox reactions. Therefore, great cautions should be given when choosing technologies to remediate the As contaminated soils and waters.
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Peptidoglycan recognition proteins (PGRPs) are a family of pattern recognition receptors that play a critical role in the immune response of invertebrates and vertebrates. Herein, the short ApPGRP-D gene was cloned from the model lepidopteran Antheraea pernyi. Quantitative PCR (qPCR) confirmed that ApPGRP-D is an immune-related protein and that the expression of ApPGRP-D can be induced by microorganisms. ApPGRP-D is a broad-spectrum pattern recognition protein that activates the prophenoloxidase cascade activation system and promotes the agglutination of microbial cells. Likely due to its amidase activity, ApPGRP-D can inhibit the growth of E. coli and S. aureus. In addition, we demonstrated for the first time that zinc ions, as important metal coenzymes, could promote multiple functions of ApPGRP-D but not its amidase activity.
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Protéines de transport , Immunité humorale , Protéines d'insecte , Papillons de nuit , Animaux , Papillons de nuit/immunologie , Papillons de nuit/génétique , Papillons de nuit/métabolisme , Papillons de nuit/microbiologie , Protéines d'insecte/métabolisme , Protéines d'insecte/génétique , Protéines de transport/métabolisme , Protéines de transport/génétique , Escherichia coli , Staphylococcus aureus , Séquence d'acides aminés , Antibactériens/pharmacologie , Catechol oxidase/métabolisme , Clonage moléculaire , Zinc/métabolisme , ProenzymesRÉSUMÉ
In this study, a novel fabrication method was used to synthesize phenolic resin/phosphate hybrid coatings using aluminum dihydrogen phosphate (Al(H2PO4)3, hereafter denoted as Al), SC101 silica sol (Si) as the primary film-forming agent, and phenolic resin (PF) as the organic matrix. This approach culminated in the formation of Al+Si+PF organo-inorganic hybrid coatings. Fourier-transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) results confirmed the successful integration of hybrid structures within these coatings. The crystalline structure of the coatings post-cured at various temperatures was elucidated using X-ray diffraction (XRD). Additionally, the surface and cross-sectional morphologies were meticulously analyzed using scanning electron microscopy (SEM), offering insights into the microstructural properties of the coatings. The coatings' porosities under diverse thermal and temporal regimes were quantitatively evaluated using advanced image processing techniques, revealing a significant reduction in porosity to a minimum of 5.88% following a thermal oxidation process at 600 °C for 10 h. The antioxidant efficacy of the phosphate coatings was rigorously assessed through cyclic oxidation tests, which revealed their outstanding performance. Specifically, at 300 °C across 300 h of cyclic oxidation, the weight losses recorded for phosphate varnish and the phenolic resin-infused phosphate coatings were 0.15 mg·cm-2 and 0.09 mg·cm-2, respectively. Furthermore, at 600 °C and over an identical period, the weight reduction was noted as 0.21 mg·cm-2 for phosphate varnish and 0.085 mg·cm-2 for the hybrid coatings, thereby substantiating the superior antioxidation capabilities of the phenolic resin hybrid coatings in comparison to the pure phosphate varnish.
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This study investigates the corrosion behavior of Ni-Cr binary alloys, including Ni-10Cr, Ni-15Cr, Ni-20Cr, Ni-25Cr, and Ni-30Cr, in a NaCl-KCl-MgCl2 molten salt mixture through gravimetric analysis. Corrosion tests were conducted at 700 °C, with the maximum immersion time reaching up to 100 h. The corrosion rate was determined by measuring the mass loss of the specimens at various time intervals. Verifying corrosion rates by combining mass loss results with the determination of element dissolution in molten salts using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Detailed examinations of the corrosion products and morphology were conducted using X-ray diffraction (XRD) and scanning electron microscopy (SEM). Micro-area elemental analysis on the corroded surfaces was performed using an energy dispersive spectrometer (EDS), and the elemental distribution across the corrosion cross-sections was mapped. The results indicate that alloys with lower Cr content exhibit superior corrosion resistance in the NaCl-KCl-MgCl2 molten salt under an argon atmosphere compared to those with higher Cr content; no corrosion products were retained on the surfaces of the lower Cr alloys (Ni-10Cr, Ni-15Cr). For the higher Cr alloys (Ni-20Cr, Ni-25Cr, Ni-30Cr), after 20 h of corrosion, a protective layer was observed in certain areas. The formation of a stable Cr2O3 layer in the initial stages of corrosion for high-Cr content alloys, which reacts with MgO in the molten salt to form a stable MgCr2O4 spinel structure, provides additional protection for the alloys. However, over time, even under argon protection, the MgCr2O4 protective layer gradually degrades due to chloride ion infiltration and chemical reactions at high temperatures. Further analysis revealed that chloride ions play a pivotal role in the corrosion process, not only facilitating the destruction of the Cr2O3 layer on the alloy surfaces but also possibly accelerating the corrosion of the metallic matrix through electrochemical reactions. In conclusion, the corrosion behavior of Ni-Cr alloys in the NaCl-KCl-MgCl2 molten salt environment is influenced by a combination of factors, including Cr content, chloride ion activity, and the formation and degradation of protective layers. This study not only provides new insights into the corrosion resistance of Ni-Cr alloys in high-temperature molten salt environments but also offers significant theoretical support for the design and optimization of corrosion-resistant alloy materials.
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Microbiologically influenced corrosion (MIC) caused by corrosive microorganisms poses significant economic losses and safety hazards. Conventional corrosion prevention methods have limitations, so it is necessary to develop the eco-friendly and long-term effective strategies to mitigate MIC. This study investigated the inhibition of Vibrio sp. EF187016 biofilm on Geobacter sulfurreducens on carbon steel. Vibrio sp. EF187016 biofilm reduced the corrosion current density and impeded pitting corrosion. A thick and uniform Vibrio sp. EF187016 biofilm formed on the coupon surfaces, acting as a protective layer against corrosive ions and electron acquisition by G. sulfurreducens. The pre-grown mature Vibrio sp. EF187016 biofilms, provided enhanced protection against G. sulfurreducens corrosion. Additionally, the extracellular polymeric substances from Vibrio sp. EF187016 was confirmed to act as a green corrosion inhibitor to mitigate microbial corrosion. This study highlights the potential of active biofilms for eco-friendly corrosion protection, offering a novel perspective on material preservation against microbial corrosion.
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Caustiques , Geobacter , Acier , Carbone , Corrosion , Caustiques/pharmacologie , BiofilmsRÉSUMÉ
Low back pain (LBP) is a leading cause of long-term disability globally. Intervertebral disk degeneration (IVDD) is mainly responsible for discogenic pain in LBP-affected young patients. There is no effective therapy to reverse disease severity and IVDD progression. This study investigates the effect of human peripheral blood-derived mononuclear cells (PBMCs) on pain relief and life quality improvement in IVDD patients. The enriched monocytes of the PBMCs could differentiate into CD14 and CD206 double-positive M2 macrophages in vitro. Preclinical evidence in rats showed that the transplanted PBMCs exhibited anti-inflammatory and moderate tissue-repair effects on controlling IVDD progress in the rat model. The PBMCs significantly steered the aggrecan and type II collagen expressions and attenuated the pro-inflammatory cytokines in the affected disk. Based on the animal results, 36 patients with chronic low back pain (CLBP) were included in clinical trials. The control group was conservative care only, and the experimental group was platelet-rich plasma (PRP) and PBMCs intradiscal injections. We first confirmed the single lumbar disk causing the discogenic pain by provocative discography or magnetic resonance imaging (MRI). Discogenic LBP participants received one intradiscal injection of autologous PBMCs and followed for 6 months. Our clinical trial showed that patients' LBP and disability were significantly ameliorated after the PBMCs transplantation rather than PRP. These preclinical and pilot clinical studies indicate that intradiscal injection of the enriched PBMCs might be a feasible and potential cell therapy to control pain and disability in IVDD patients.
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Dégénérescence de disque intervertébral , Disque intervertébral , Lombalgie , Humains , Animaux , Rats , Dégénérescence de disque intervertébral/thérapie , Disque intervertébral/anatomopathologie , Lombalgie/traitement médicamenteux , Lombalgie/étiologie , Injections/effets indésirables , Anti-inflammatoires/pharmacologie , Résultat thérapeutiqueRÉSUMÉ
Harmful algal blooms, particularly those of Microcystis aeruginosa, present significant ecological and health risks. To address this issue, this study utilized a custom static algal growth assessment apparatus to investigate the anti-algal performance of a copper-alloyed 316L stainless steel (SS), named 316L-Cu SS. This material was compared with traditional 316L SS, which is widely utilized in freshwater systems for its corrosion resistance. Algal growth dynamics were monitored through optical density (OD) and chlorophyll A concentration measurements. Notably, 316L-Cu SS exhibited superior inhibitory effects on Microcystis aeruginosa growth compared to 316L SS and control groups. Inductively coupled plasma mass spectrometry (ICP-MS) confirmed that the copper ion release from 316L-Cu SS played a critical role in this algal suppression, which interfered with photosynthesis, induced oxidative stress, and damaged algal cell membranes. In contrast, other metal ions (Ni, Cr, Fe) had a negligible impact on algal growth. The study highlights 316L-Cu SS as a promising material for mitigating harmful algal blooms, thereby offering potential benefits for both aquatic ecosystem conservation and public health protection.
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Cyanobactéries , Microcystis , Cuivre/composition chimique , Acier inoxydable/composition chimique , Chlorophylle A , ÉcosystèmeRÉSUMÉ
Understanding the nature of arsenic (As) adsorbed on FeIII oxyhydroxides, and the subsequent behavior of As during the crystallization process, is critical to predicting its fate in a range of natural and engineered settings. In this work, As adsorbed on FeIII oxyhydroxides formed in the different reaction media at different pH values were characterized with X-ray diffraction (XRD), Raman spectra, transmission electron microscopy (TEM), and extended X-ray absorption fine structure spectroscopy (EXAFS) to determine how As is redistributed during the crystallization process. Results showed that at pH 12, a quarter of the added As was still left in the liquid phase with the formation of goethite and hematite as the major and minor product. The concentration of As was found to be the lowest at pH 4 which is independent of the reaction media, indicating the importance of pH value in the crystallization process of the As adsorbed FeIII oxyhydroxides. Under acidic conditions, sulfate and chloride media favored the formation of goethite and hematite, respectively. Arsenic can indeed be incorporated into the structure of the formed goethite at pH 4. The morphology of the formed products changed to rhombus-like particles if both goethite and hematite appeared as the later as the dominant product.
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The purpose of this study is to improve the number and distribution of active particles on the MAO layer by changing the activation method, thus improving the corrosion resistance of the coating. The structure of the coatings was characterized by SEM, XRD, XPS, and AFM, as well as the corrosion resistance of the coatings by polarization curves, EIS tests, immersion tests, and salt spray tests. The conductive resistance and adhesion of different composite coatings were compared. The results demonstrate that the properties of the composite coating are significantly affected by different activation methods, and the Ni-P coating prepared with more active particles offers superior corrosion protection to the inner layer. The quantity and distribution of active particles affect the compactness of the coating by influencing the initial deposition process. The size of nickel particles is larger and the inter-grain porosity increases in the case of fewer active sites, and as the number of active sites increases, the size of nickel particles decreases, and the coating compactness increases. The mechanism of the effect of the number of active particles on the deposition process of electroless Ni-P coating was proposed.
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Mutation-induced malfunction of ten-eleven translocation methylcytosine dioxygenase 2 (TET2) is widely reported in haematological malignancies. However, the role of TET2 in solid cancers, including colorectal cancer (CRC), is unclear. Here, we found that TET2 malfunction in CRC is mostly due to decreased nuclear localization and that nuclear localization of TET2 is correlated with better survival of patients. To explore the underlying mechanisms, 14 immortalized solid tumour cell lines and 12 primary CRC cell lines were used. TET2 was mostly detected in the nucleus, and it induced significant DNA demethylation and suppressed cell growth by demethylating RORA and SPARC in cell lines like SW480. While in cell lines like SW620, TET2 was observed in the cytosol and did not affect DNA methylation or cell growth. Further examination with immunoprecipitation-mass spectrometry illustrated that ß-catenin activation was indispensable for the nuclear localization and tumour suppression effects of TET2. In addition, the ß-catenin pathway activator IM12 and the TET2 activator vitamin C were used simultaneously to enhance the effects of TET2 under low-expression conditions, and synergistic inhibitory effects on the growth of cancer were observed both in vitro and in vivo. Collectively, these data suggest that ß-catenin-mediated nuclear localization of TET2 is an important therapeutic target for solid tumours.
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Tumeurs colorectales , Protéines de liaison à l'ADN , Dioxygenases , bêta-Caténine , Humains , Lignée cellulaire tumorale , Noyau de la cellule , Tumeurs colorectales/génétique , Cytosol , Dioxygenases/génétique , Protéines de liaison à l'ADN/génétiqueRÉSUMÉ
Electrobiocorrosion, the process in which microbes extract electrons from metallic iron (Fe0 ) through direct Fe0 -microbe electrical connections, is thought to contribute to the costly corrosion of iron-containing metals that impacts many industries. However, electrobiocorrosion mechanisms are poorly understood. We report here that electrically conductive pili (e-pili) and the conductive mineral magnetite play an important role in the electron transfer between Fe0 and Geobacter sulfurreducens, the first microbe in which electrobiocorrosion has been rigorously documented. Genetic modification to express poorly conductive pili substantially diminished corrosive pitting and rates of Fe0 -to-microbe electron flux. Magnetite reduced resistance to electron transfer, increasing corrosion currents and intensifying pitting. Studies with mutants suggested that the magnetite promoted electron transfer in a manner similar to the outer-surface c-type cytochrome OmcS. These findings, and the fact that magnetite is a common product of iron corrosion, suggest a potential positive feedback loop of magnetite produced during corrosion further accelerating electrobiocorrosion. The interactions of e-pili, cytochromes, and magnetite demonstrate mechanistic complexities of electrobiocorrosion, but also provide insights into detecting and possibly mitigating this economically damaging process.
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Oxyde ferrosoferrique , Geobacter , Oxydoréduction , Électrons , Corrosion , Transport d'électrons , Cytochromes/métabolisme , Fer , Geobacter/génétique , Geobacter/métabolismeRÉSUMÉ
To solve the problems of high nitriding temperature and long nitriding time with conventional plasma nitriding technologies, a kind of low-temperature plasma oxy-nitriding technology containing two-stage processes with different ratios of N to O was developed on a TC4 alloy in this paper. A thicker permeation coating can be obtained with this new technology compared to conventional plasma nitriding technology. The reason for this is that the oxygen introduction in the first two-hour oxy-nitriding step can break the continuous TiN layer, which facilitates the quick and deep diffusion of the solution-strengthening elements of O and N into the titanium alloy. Moreover, an inter-connected porous structure was formed under a compact compound layer, which acts as a buffer layer to absorb the external wear force. Therefore, the resultant coating showed the lowest COF values during the initial wear state, and almost no debris and cracks were detected after the wear test. For the treated samples with low hardness and no porous structure, fatigue cracks can easily form on the surface, and bulk peeling-offcan occur during the wear course.
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Elevating the charging cut-off voltage is one of the efficient approaches to boost the energy density of Li-ion batteries (LIBs). However, this method is limited by the occurrence of severe parasitic reactions at the electrolyte/electrode interfaces. Herein, to address this issue, we design a non-flammable fluorinated sulfonate electrolyte by multifunctional solvent molecule design, which enables the formation of an inorganic-rich cathode electrolyte interphase (CEI) on high-voltage cathodes and a hybrid organic/inorganic solid electrolyte interphase (SEI) on the graphite anode. The electrolyte, consisting of 1.9 M LiFSI in a 1:2 v/v mixture of 2,2,2-trifluoroethyl trifluoromethanesulfonate and 2,2,2-trifluoroethyl methanesulfonate, endows 4.55 V-charged graphite||LiCoO2 and 4.6 V-charged graphite||NCM811 batteries with capacity retentions of 89% over 5329 cycles and 85% over 2002 cycles, respectively, thus resulting in energy density increases of 33% and 16% compared to those charged to 4.3 V. This work demonstrates a practical strategy for upgrading the commercial LIBs.
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Osteoarthritis (OA) is a common chronic skeletal disease in the elderly. There is no effective therapy to reverse disease severity and knee OA (KOA) progression, particularly at the late stage. This study aims to examine the effect of peripheral blood-derived mononuclear cells (PBMNCs) on pain and motor function rescue in patients with Kellgren-Lawrence (KL) grade II to IV KOA. Participants received one intra-articular (IA) injection of autologous PBMNCs. The mononuclear cells were isolated from peripheral blood, enriched by a specialized medium (MoFi medium), and separated by Ficoll-Paque solution. The isolated and enriched PBMNCs could differentiate into M1 and M2 macrophages in vitro. The in vivo anti-inflammatory effect of the PBMNCs was similar to that of bone marrow mesenchymal stem cells, evaluated by complete Freund's adjuvant-induced arthritis in rodents. A single-arm and open-label pilot study showed that patients' knee pain and motor dysfunction were significantly attenuated after the cell transplantation, assessed by visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 12 months post-treatment. Notably, the therapeutic effect of the PBMNCs treatment can be stably maintained for 24 months, as revealed by the KOOS scores. These preclinical and pilot clinical data suggest that IA injection of MoFi-PBMNCs might serve as a novel medical technology to control the pain and the progress of KOA.
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Gonarthrose , Humains , Gonarthrose/thérapie , Projets pilotes , Résultat thérapeutique , Articulation du genou , Injections articulaires , Douleur/traitement médicamenteuxRÉSUMÉ
PURPOSE: Nicotinamide adenine dinucleotide (NAD+) is closely related to the pathogenesis of tumors. However, the effect of NAD+ metabolism of gastric cancer (GC) cells on immune cells remains unexplained. We targeted nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD+ synthesis salvage pathway, to observe its effect in the immune microenvironment. METHODS: NAMPT of GC cell lines was inhibited by using the small molecule inhibitor (FK866) and short hairpin RNA (shRNA). CCK-8 test and flow cytometry were performed to detect cell viability and apoptosis. Immunofluorescence was used to observe changes in mitochondrial membrane potential (MMP).The transfected GC cells (AGS) and patient-derived organoids (PDOs) were cocultured with activated PBMCs, followed by flow cytometric analysis (FCA) for cytokines and inhibitory marker. The level of NAD and ATP of GC cells (AGS & MKN45) was tested combined with NMN and CD39 inhibitor. RESULTS: Targeting NAD+ by FK866 obviously reduced MMP, which ultimately inhibited proliferation and increased the apoptosis of GC cells. NAMPT silencing reduced intracellular NAD and ATPï¼further decreased extracellular adenosine. Meawhile, the cytokines of CD8+T cells were significantly increased after cocultured with transfected AGS, and the expression of PD-1 was distinctly decreased. NMN reversed the effect of shNAMPT and enhanced the immunosuppression. Consistent results were obtained by coculturing PBMCs with PDOs. CONCLUSION: Restraining the function of NAMPT resulted in the functional improvement of effector CD8+ T cells by decreasing extracellular adenosine levels and inducing apoptosis of GC cells simultaneously. Therefore, this study demonstrates that NAMPT can be an effective target for gastric cancer immunotherapy.