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Insufficient intracellular anabolism is a crucial factor involved in many pathological processes in the body1,2. The anabolism of intracellular substances requires the consumption of sufficient intracellular energy and the production of reducing equivalents. ATP acts as an 'energy currency' for biological processes in cells3,4, and the reduced form of NADPH is a key electron donor that provides reducing power for anabolism5. Under pathological conditions, it is difficult to correct impaired anabolism and to increase insufficient levels of ATP and NADPH to optimum concentrations1,4,6-8. Here we develop an independent and controllable nanosized plant-derived photosynthetic system based on nanothylakoid units (NTUs). To enable cross-species applications, we use a specific mature cell membrane (the chondrocyte membrane (CM)) for camouflage encapsulation. As proof of concept, we demonstrate that these CM-NTUs enter chondrocytes through membrane fusion, avoid lysosome degradation and achieve rapid penetration. Moreover, the CM-NTUs increase intracellular ATP and NADPH levels in situ following exposure to light and improve anabolism in degenerated chondrocytes. They can also systemically correct energy imbalance and restore cellular metabolism to improve cartilage homeostasis and protect against pathological progression of osteoarthritis. Our therapeutic strategy for degenerative diseases is based on a natural photosynthetic system that can controllably enhance cell anabolism by independently providing key energy and metabolic carriers. This study also provides an enhanced understanding of the preparation and application of bioorganisms and composite biomaterials for the treatment of disease.
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Condrócitos , Osteoartrite , Fotossíntese , Plantas , Humanos , Trifosfato de Adenosina/metabolismo , Condrócitos/metabolismo , NADP/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoartrite/terapia , Plantas/metabolismo , Cartilagem/citologia , Cartilagem/metabolismo , Homeostase , Metabolismo Energético , Fusão de MembranaRESUMO
BACKGROUND: Pericoronary epicardial adipose tissue (EAT) is a unique visceral fat depot that surrounds the adventitia of the coronary arteries without any anatomic barrier. Clinical studies have demonstrated the association between EAT volume and increased risks for coronary artery disease (CAD). However, the cellular and molecular mechanisms underlying the association remain elusive. METHODS: We performed single-nucleus RNA sequencing on pericoronary EAT samples collected from 3 groups of subjects: patients undergoing coronary bypass surgery for severe CAD (n=8), patients with CAD with concomitant type 2 diabetes (n=8), and patients with valvular diseases but without concomitant CAD and type 2 diabetes as the control group (n=8). Comparative analyses were performed among groups, including cellular compositional analysis, cell type-resolved transcriptomic changes, gene coexpression network analysis, and intercellular communication analysis. Immunofluorescence staining was performed to confirm the presence of CAD-associated subclusters. RESULTS: Unsupervised clustering of 73â 386 nuclei identified 15 clusters, encompassing all known cell types in the adipose tissue. Distinct subpopulations were identified within primary cell types, including adipocytes, adipose stem and progenitor cells, and macrophages. CD83high macrophages and FOSBhigh adipocytes were significantly expanded in CAD. In comparison to normal controls, both disease groups exhibited dysregulated pathways and altered secretome in the primary cell types. Nevertheless, minimal differences were noted between the disease groups in terms of cellular composition and transcriptome. In addition, our data highlight a potential interplay between dysregulated circadian clock and altered physiological functions in adipocytes of pericoronary EAT. ANXA1 (annexin A1) and SEMA3B (semaphorin 3B) were identified as important adipokines potentially involved in functional changes of pericoronary EAT and CAD pathogenesis. CONCLUSIONS: We built a complete single-nucleus transcriptomic atlas of human pericoronary EAT in normal and diseased conditions of CAD. Our study lays the foundation for developing novel therapeutic strategies for treating CAD by targeting and modifying pericoronary EAT functions.
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Tecido Adiposo , Doença da Artéria Coronariana , Pericárdio , Transcriptoma , Humanos , Pericárdio/metabolismo , Pericárdio/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/metabolismo , Idoso , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações , Adipócitos/metabolismo , Adipócitos/patologia , Doenças das Valvas Cardíacas/genética , Doenças das Valvas Cardíacas/patologia , Doenças das Valvas Cardíacas/metabolismo , Doenças das Valvas Cardíacas/cirurgia , Perfilação da Expressão Gênica/métodos , Estudos de Casos e Controles , Ponte de Artéria Coronária , Análise de Célula Única , Macrófagos/metabolismo , Macrófagos/patologia , Redes Reguladoras de Genes , Tecido Adiposo EpicárdicoRESUMO
Ocean energy is a kind of clean and renewable energy source, but it cannot be efficiently harvested by traditional electromagnetic generators, due to its low-frequency characteristic. The emergence of triboelectric nanogenerators provides a more promising technology for collecting ocean energy. In this work, a durable roller-based swing-structured triboelectric nanogenerator (RS-TENG) is designed and fabricated for low-frequency water wave energy harvesting. The rolling structure reduces the wear between triboelectric materials and improves the device's durability. After a continuous operation of 1 260 000 cycles, the attenuation of the electrical outputs of the RS-TENG is below 1.6%, exhibiting excellent durability. At the same time, the output current can arrive at 53.2 µA. Under the triggering of water waves, the RS-TENG can generate an output power of 4.27 mW, corresponding to a power density of 1.16 W m-3. After the arraying, the output performance can be doubled, so that the TENG can successfully power an environmental monitoring sensor and ensure long-term stable operation of the sensor. This work provides an effective strategy for improving the device durability, which benefits the practical applications of the TENGs in large-scale blue energy harvesting.
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Triboelectric nanogenerator (TENG) as a means of energy harvesting can effectively harvest ocean wave energy, but the energy conversion efficiency and stability of the device during long-term operations are still problems that must be solved for TENGs. Decreasing the frictional resistance between two triboelectric material surfaces is one of the critical approaches for improving the device efficiency and durability. In this work, a novel stacked disc-type rolling triboelectric nanogenerator (SDR-TENG) is designed and fabricated for low-frequency water wave energy harvesting. After 860 000 working cycles, the electrical output attenuation of the SDR-TENG basic unit is less than 5%, showing excellent device durability. Under the simulated water wave conditions, the SDR-TENG with four rolling TENG units can produce an output current of 84.4 µA and an output power of 7.6 mW, corresponding to an effective power density of 16.8 W m-3. This work not only proposes a strategy to effectively enhance the durability of the devices, but also provides a feasible solution for monitoring the surrounding environment of the charging buoys of unmanned ships.
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BACKGROUND: Emerging evidence suggests that Rho GTPases play a crucial role in tumorigenesis and metastasis, but their involvement in the tumor microenvironment (TME) and prognosis of hepatocellular carcinoma (HCC) is not well understood. METHODS: We aim to develop a tumor prognosis prediction system called the Rho GTPases-related gene score (RGPRG score) using Rho GTPase signaling genes and further bioinformatic analyses. RESULTS: Our work found that HCC patients with a high RGPRG score had significantly worse survival and increased immunosuppressive cell fractions compared to those with a low RGPRG score. Single-cell cohort analysis revealed an immune-active TME in patients with a low RGPRG score, with strengthened communication from T/NK cells to other cells through MIF signaling networks. Targeting these alterations in TME, the patients with high RGPRG score have worse immunotherapeutic outcomes and decreased survival time in the immunotherapy cohort. Moreover, the RGPRG score was found to be correlated with survival in 27 other cancers. In vitro experiments confirmed that knockdown of the key Rho GTPase-signaling biomarker SFN significantly inhibited HCC cell proliferation, invasion, and migration. CONCLUSIONS: This study provides new insight into the TME features and clinical use of Rho GTPase gene pattern at the bulk-seq and single-cell level, which may contribute to guiding personalized treatment and improving clinical outcome in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Carcinogênese , Linhagem Celular , Imunossupressores , Proteínas rho de Ligação ao GTP , Microambiente TumoralRESUMO
Background: Acute kidney injury (AKI) frequently occurs after aortic surgery and has a significant impact on patient outcomes. Early detection or prediction of AKI is crucial for timely interventions. This study aims to develop and validate a novel model for predicting AKI following aortic surgery. Methods: We enrolled 156 patients who underwent on-pump aortic surgery in our hospital from February 2023 to April 2023. Postoperative levels of eight cytokines related to macrophage polarization analyzed using a multiplex cytokine assay. All-subset regression was used to select the optimal cytokines to predict AKI. A logistic regression model incorporating the selected cytokines was used for internal validation in combination with a bootstrapping technique. The model's ability to discriminate between cases of AKI and non-AKI was assessed using receiver operating characteristic (ROC) curve analysis. Results: Of the 156 patients, 109 (69.87%) developed postoperative AKI. Interferon-gamma (IFN- γ ) and interleukin-4 (IL-4) were identified as candidate AKI predictors. The cytokine-based model including IFN- γ and IL-4 demonstrated excellent discrimination (C-statistic: 0.90) and good calibration (Brier score: 0.11). A clinical nomogram was generated, and decision curve analysis revealed that the cytokine-based model outperformed the clinical factor-based model in terms of net benefit. Moreover, both IFN- γ and IL-4 emerged as independent risk factors for AKI. Patients in the second and third tertiles of IFN- γ and IL-4 concentrations had a significantly higher risk of severe AKI, a higher likelihood of requiring renal replacement therapy, or experiencing in-hospital death. These patients also had extended durations of mechanical ventilation and intensive care unit stays, compared with those in the first tertile (all p for group trend < 0.001). Conclusions: We successfully established a novel and powerful predictive model for AKI, and demonstrating the significance of IFN- γ and IL-4 as valuable clinical markers. These cytokines not only predict the risk of AKI following aortic surgery but are also linked to adverse in-hospital outcomes. This model offers a promising avenue for the early identification of high-risk patients, potentially improving clinical decision-making and patient care.
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OBJECTIVES: To determine the safety and efficacy of transcatheter arterial chemoembolization with CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) in the first-line treatment of patients with large (5 cm ≤ maximum diameter < 10 cm) or huge (maximum diameter ≥ 10 cm) hepatocellular carcinoma (HCC). METHODS: Patients were randomly allocated to the CBATO-TACE group and the conventional transcatheter arterial chemoembolization (cTACE) group. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall survival (OS), treatment response, and treatment-related adverse events (TRAEs). The extrahepatic collateral arteries, liver function, and liver fibrosis after the first TACE were also evaluated. RESULTS: From September 2018 to September 2020, a total of 207 patients who underwent TACE were consecutively enrolled in this study. The median PFS was 9.5 months (range: 8.0 - 11.0) in the CBATO group, which was significantly longer than that in the cTACE group (6.0 months, range: 4.0-6.0) (p < 0.0001). Patients in the CBATO group had a median OS of 22 months (range: 20.0 - 27.0) compared with 16 months (range: 15.0 - 20.0) in the cTACE group (p = 0.0084). The most common TRAEs were fever (p = 0.043), and nausea and vomiting (p = 0.002), which were more observed in the cTACE group. In addition, the progressive disease time, pulmonary metastasis rate (p = 0.01), the mean number of extrahepatic collateral arteries (p = 0.01), and average number of TACE sessions (p = 0.025) were significantly decreased in the CBATO group. CONCLUSIONS: CBATO-TACE achieved better therapeutic outcomes and similar safety profile compared to cTACE in large or huge HCC patients. Furthermore, CBATO-TACE was able to reduce extrahepatic collateral arteries production and extrahepatic lung metastasis. CLINICAL RELEVANCE STATEMENT: Our study showed that CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) were effective and safe for the treatment of large and giant HCC. In addition, CBATO-TACE can reduce lateral hepatic branch artery formation and extrahepatic pulmonary metastasis, which provides a new treatment approach for unresectable HCC. KEY POINTS: ⢠We compare long-term efficacy and safety of transcatheter arterial chemoembolization with CalliSpheres® beads loaded with arsenic trioxide (CBATO-TACE) and conventional transcatheter arterial chemoembolization (cTACE) in patients with large (5 cm ≤ maximum diameter < 10 cm) or huge HCC (maximum diameter ≥ 10 cm). ⢠Compared with cTACE, CBATO-TACE significantly improved therapeutic outcomes, overall survival, and progression-free survival in patients with large or huge HCC. The safety assessment suggested that CBATO-TACE is a safe treatment that improves the quality of life and has good treatment adherence.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Trióxido de Arsênio/efeitos adversos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Artéria Hepática/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Carbonaceous aerosols play an important role in radiative forcing in the remote and climate-sensitive Tibetan Plateau (TP). However, the sources of carbonaceous aerosols to the TP remain poorly defined, in part due to the lack of regionally relevant data about the sources of carbonaceous aerosols. To address this knowledge gap, we present the first comprehensive analysis of the δ13C signatures of carbonaceous aerosol endmembers local to the TP, encompassing total carbon, water-insoluble particle carbon, and elemental carbon originating from fossil fuel combustion, biomass combustion, and topsoil. The δ13C signatures of these local carbonaceous endmembers differ from components collected in other regions of the world. For instance, fossil fuel-derived aerosols from the TP were 13C-depleted relative to fossil fuel-derived aerosols reported in other regions, while biomass fuel-derived aerosols from the TP were 13C-enriched relative to biomass fuel-derived aerosols reported in other regions. The δ13C values of fine-particle topsoil in the TP were related to regional variations in vegetation type. These findings enhance our understanding of the unique features of carbonaceous aerosols in the TP and aid in accurate source apportionment and environmental assessments of carbonaceous aerosols in this climate-sensitive region.
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Aerossóis , Isótopos de Carbono , Tibet , Carbono , Monitoramento AmbientalRESUMO
Photothermal immunotherapy is regarded as the ideal cancer therapeutic modality to against malignant solid tumors; however, its therapeutic benefits are often modest and require improvement. In this study, a thermoresponsive nanoparticle (BTN@LND) composed of a photothermal agent (PTA) and pyroptosis inducer (lonidamine) were developed to enhance immunotherapy applications. Specifically, our "two-step" donor engineering strategy produced the strong NIR-II-absorbing organic small-molecule PTA (BTN) that exhibited high NIR-II photothermal performance (ε1064 = 1.51 × 104 M-1 cm-1, η = 75.8%), and this facilitates the diagnosis and treatment of deep tumor tissue. Moreover, the fabricated thermally responsive lipid nanoplatform based on BTN efficiently delivered lonidamine to the tumor site and achieved spatiotemporal release triggered by the NIR-II photothermal effect. In vitro and in vivo experiments demonstrated that the NIR-II photothermal therapy (PTT)-mediated on-demand release of cargo effectively faciliated tumor cell pyroptosis, thereby intensifying the immunogenic cell death (ICD) process to promote antitumor immunotherapy. As a result, this intelligent component bearing photothermal and chemotherapy can maximally suppress the growth of tumors, thus providing a promising approach for pyroptosis/NIR-II PTT synergistic therapy against tumors.
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Indazóis , Nanopartículas , Neoplasias , Humanos , Fototerapia , Piroptose , Neoplasias/tratamento farmacológico , Imunoterapia , Linhagem Celular TumoralRESUMO
Diabetic peripheral neuropathy (DPN) is a significant and frequent complication of diabetes. Bu-Yang-Huan-Wu Decoction (BHD) is a classic traditional Chinese herbal prescription that is commonly used in modern clinical practice for the effective treatment of DPN, but the underlying mechanism is not yet clearly defined. The chemical constituents of BHD were characterized by UPLC-Q-Orbitrap HR MS/MS, and a total of 101 chemical components were identified, including 30 components absorbed into blood. An interaction network of "compound-target-disease" interactions was constructed based on the compounds detected absorbed in blood and their corresponding targets of diabetic neuropathy acquired from disease gene databases, and the possible biological targets and potential signalling pathways of BHD were predicted via network pharmacology analysis. Subsequently, methylglyoxal-induced (MGO-induced) Schwann cells (SCs) were used to identify the active ingredients in blood components of BHD and verify the molecular mechanisms of BHD. Through network topological analysis, 30 shared targets strongly implicated in the anti-DPN effects of BHD were identifed. Combined network pharmacology and in vitro cellular analysis, we found that the active ingredient of BHD may treat DPN by modulating the AGEs/RAGE pathway. This study provides valuable evidence for future mechanistic studies and potential therapeutic applications for patients with DPN.
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A novel "turn-on" aptasensor for kanamycin (Kana) detection based on a new Förster resonance energy transfer (FRET) pair is reported. A new organic small molecule was employed as a high-efficiency quencher for fluorophore. Based on specific interactions between ssDNA and the quencher, an ingenious and amplified strategy was designed. In the absence of the target, the fluorescence of the fluorophore labeled at the end of the aptamer was quenched. After the binding of the aptamer to the target, the fluorescence was recovered and amplified. The proposed aptasensor showed high specificity, selectivity, and stability in complicated systems. With the P3-based strategy, the limit of detection for Kana is estimated to be 10 nM, which is much lower than the maximum allowable concentration in milk. The recoveries of spiked Kana in milk were in the range 99.8 ~ 105.3% (n = 3). Fortunately, this novel method can be easily extended to other antibiotics such as tobramycin by simply replacing the aptamer, showing great potential as a universal platform for selective, sensitive, and rapid detection of hazardous analytes in food samples.
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Antibacterianos , Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , Canamicina , Limite de Detecção , Leite , Aptâmeros de Nucleotídeos/química , Transferência Ressonante de Energia de Fluorescência/métodos , Antibacterianos/análise , Canamicina/análise , Leite/química , Animais , Corantes Fluorescentes/química , Técnicas Biossensoriais/métodos , Contaminação de Alimentos/análise , DNA de Cadeia Simples/químicaRESUMO
Osteoporosis is a global disease caused by abnormal overactivation of osteoclasts. The acidic environment in sealing zone of osteoclasts with H+ pumped from cytoplasm is critical to the maturation of osteoclasts. Therefore, reducing the intracellular H+ concentration can reduce the H+ secretion of osteoclasts from the source. In our study, we developed a novel nanovesicle which encapsulates Na2HPO4 with a liposome hybridizes with preosteoclast membrane (Na2HPO4@Lipo-pOCm). These nanovesicles release Na2HPO4 into the preosteoclast by targeting preosteoclasts and membrane fusion, reducing the intracellular H+ concentration, and achieve biological cascade regulation of osteoclasts through simple pH regulation. In vitro and in vivo experiments confirmed that these nanovesicles reduce mitochondrial membrane potential by decreasing intracellular H+ concentration, thereby reducing the ROS in osteoclasts as well as the expression of the upstream transcription factor FOXM1 of Acp5. In short, this nanovesicle can significantly inhibit the osteoclasts and ameliorate osteoporosis caused by OVX.
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Osteoclastos , Osteoporose , Humanos , Concentração de Íons de Hidrogênio , HomeostaseRESUMO
Organic dyes in natural waters jeopardize human health. Whether semiconductor materials can effectively degrade dyes has become a challenge for scientific research. Based on this, this study rationally prepared different nanocomposites to remove organic dyes effectively. Pure SnO2 quantum dots, ZnO nanosheets, and SnO2/ZnO (ZS) binary nanocomposites are prepared using the hydrothermal method. Subsequently, SnO2/ZnO@GO (ZSG) ternary composites containing different amounts of GO, i.e., ZSG-5, ZSG-15, and ZSG-25, are synthesized by an ultrasonic water bath method, in which ZS was coupled with GO to form Z-type heterojunctions. The ZSG-15 ternary composites exhibited excellent photocatalytic activity for the degradation of rhodamine B by simulating sunlight. The test results show that the degradation rate of ZSG-15 is about 7.6 times higher than ZnO. The increase in photocatalytic activity is attributed to the synergistic effect of SnO2 and GO to improve the separation efficiency of photogenerated carriers in ZnO. Notably, the large specific surface area of GO increases the reactive sites. Compared with binary nanocomposites, ZSG-15 broadens the response range to light while further accelerating the electron transport rate and improving the photoelectric stability.
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BACKGROUND: Obesity has been demonstrated as a risk factor that seriously affects health. Insoluble dietary fiber (IDF), as a major component of dietary fiber, has positive effects on obesity, inflammation and diabetes. RESULTS: In this study, complex IDF was prepared using 50% enoki mushroom IDF, 40% carrot IDF, and 10% oat IDF. The effects and potential mechanism of complex IDF on obesity were investigated in C57BL/6 mice fed a high-fat diet. The results showed that feeding diets containing 5% complex IDF for 8 weeks significantly reduced mouse body weight, epididymal lipid index, and ectopic fat deposition, and improved mouse liver lipotoxicity (reduced serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), fatty liver, and short-chain fatty acid composition. High-throughput sequencing of 16S rRNA and analysis of fecal metabolomics showed that the intervention with complex IDF reversed the high-fat-diet-induced dysbiosis of gut microbiota, which is associated with obesity and intestinal inflammation, and affected metabolic pathways, such as primary bile acid biosynthesis, related to fat digestion and absorption. CONCLUSION: Composite IDF intervention can effectively inhibit high-fat-diet-induced obesity and related symptoms and affect the gut microbiota and related metabolic pathways in obesity. Complex IDF has potential value in the prevention of obesity and metabolic syndrome. © 2024 Society of Chemical Industry.
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Dieta Hiperlipídica , Fibras na Dieta , Microbioma Gastrointestinal , Fígado , Camundongos Endogâmicos C57BL , Obesidade , Animais , Fibras na Dieta/metabolismo , Dieta Hiperlipídica/efeitos adversos , Obesidade/metabolismo , Obesidade/dietoterapia , Obesidade/microbiologia , Camundongos , Masculino , Fígado/metabolismo , Humanos , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bactérias/genética , Fígado Gorduroso/prevenção & controle , Fígado Gorduroso/metabolismo , Fígado Gorduroso/etiologia , Avena/química , Daucus carota/químicaRESUMO
PURPOSE: Detecting tumor progression of glioma continues to pose a formidable challenge. The role of fibroblast activation protein (FAP) in gliomas has been demonstrated to facilitate tumor progression. Glioma-circulating biomarkers have not yet been used in clinical practice. This study seeks to evaluate the feasibility of glioma detection through the utilization of a serum FAP marker. METHODS: We adopted enzyme-linked immunosorbent assay (ELISA) technique to quantify the relative FAP level of serum autoantibodies in a cohort of 87 gliomas. The correlation between preoperative serum autoantibody relative FAP levels and postoperative pathology, including molecular pathology was investigated. A series of FAP tests were conducted on 33 cases of malignant gliomas in order to ascertain their efficacy in monitoring the progression of the disease in relation to imaging observations. To validate the presence of FAP expression in tumors, immunohistochemistry was conducted on four gliomas employing a FAP-specific antibody. Additionally, the investigation encompassed the correlation between postoperative tumor burden, as assessed through volumetric analysis, and the relative FAP level of serum autoantibodies. RESULTS: A considerable proportion of gliomas exhibited a significantly increased level of serum autoantibody relative FAP level. This elevation was closely associated with both histopathology and molecular pathology, and demonstrated longitudinal fluctuations and variations corresponding to the progression of the disease The correlation between the rise in serum autoantibody relative FAP level and tumor progression and/or exacerbation of symptoms was observed. CONCLUSIONS: The measurement of serum autoantibody relative FAP level can be used to detect the disease as a valuable biomarker. The combined utilization of its detection alongside MR imaging has the potential to facilitate a more accurate and prompt diagnosis.
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Glioma , Humanos , Glioma/patologia , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Autoanticorpos , Fibroblastos/metabolismo , Endopeptidases , Biomarcadores Tumorais/metabolismoRESUMO
The first carbonatotellurites, AKTeO2(CO3) (A = Li, Na), have been successfully synthesized by using boric acid as the mineralizer. AKTeO2(CO3) (A = Li, Na) crystallize in the monoclinic space group P21/n (no. 14), and their structures exhibit the novel zero-dimensional (0D) [Te2C2O10]4- clusters, in which two [TeO4]4- groups form a [Te2O6]4- dimer via edge-sharing, with each side of the dimer attached by a [CO3]2- group via a Te-O-C bridge. The alkali metal cations occupy the voids between the 0D clusters and maintain the charge balance. The ultraviolet-visible-near-infrared diffuse reflectance spectra show that the short absorption cut-off edges of LiKTeO2(CO3) (LKTC) and NaKTeO2(CO3) (NKTC) are 248 and 240 nm, respectively, and LKTC exhibits the largest experimental band gap (4.58 eV) among all of the tellurites containing the π-conjugated anionic groups reported. Theoretical calculations revealed that they exhibit moderate birefringences of 0.029 and 0.040@1064 nm, respectively.
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The progression of several cancers, including lung cancer, has been linked to long non-coding RNAs (lncRNAs) (LC). The current research concentrated on elucidating the effects of MALAT1 on the course of LC and investigating potential pathways. The qPCR and in situ hybridization (ISH) assays were used to measure MALAT1 expression in LC tissues. Additionally, the overall survival (OS), a percentage of LC patients with various MALAT1 levels was examined. Additionally, it was determined whether MALAT1 was expressed in LC cells through qPCR analysis. LC cells' proliferation, apoptosis, and metastasis were all examined concerning MALAT1 utilizing the following techniques: EdU, CCK-8, western blot and flow cytometry. This study predicted and verified the correlation between MALAT1, microRNA (miR)-338-3p as well as pyrroline-5-carboxylate reductase 2 using bioinformatics and dual-luciferase reporters (PYCR2). On the activity and function of MALAT1/miR-338-3p/PYCR2 in LC cell activities, more study was conducted. The amount of MALAT1 was raised in LC tissues and cells. Low OS was seen in patients with elevated MALAT1 expression. By inhibiting MALAT1, LC cells saw decreased migration, invasion, and proliferation as well as an increase in apoptosis. Additionally, PYCR2 appeared as an objective of miR-338-3p, while MALAT1 was a target of miR-338-3p. Additionally, the over-expression of miR-338-3p had effects that were comparable to those of MALAT1 down-regulation. The function of miR-338-3p inhibitor on the functional activities of LC cells co-transfected with sh-MALAT1 was partially recovered by PYCR2 inhibition. MALAT1/miR-338-3p/PYCR2 maybe the novel target for LC therapy.
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Carcinoma , Neoplasias Pulmonares , MicroRNAs , Pirrolina Carboxilato Redutases , RNA Longo não Codificante , Humanos , Carcinoma/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Pirrolina Carboxilato Redutases/genética , RNA Longo não Codificante/genética , Neoplasias Pulmonares/genéticaRESUMO
The visualization of bone imaging in vivo is of great significance for the understanding of some bone-related diseases or physiological processes. Herein, a bone-targeted NIR-II small molecule (TTQF-SO3), which was modified with multiple sulfonate groups, was successfully fabricated for the second near-infrared (NIR-II) bone imaging. In vitro studies revealed that TTQF-SO3 showed high affinity for hydroxyapatite and excellent macrophage accumulation ability. In in vivo assays, TTQF-SO3 displayed high bone uptake ability and high NIR-II bone imaging quality, demonstrating the specific bone-targeting ability of the sulfonate-containing probe. In addition, the noninvasive NIR-II imaging detection in bone calcium loss was successfully verified in osteoporosis mice models. Moreover, the negative charge characteristic of TTQF-SO3 showed efficient lymphoid enrichment in living mice by intravenous injection. Overall, these warrant that our TTQF-SO3 is an optimal bone-targeted diagnostic agent for high-quality NIR-II imaging, highlighting its potential promise for clinical translation.
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Osso e Ossos , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Camundongos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Osso e Ossos/diagnóstico por imagem , Imagem Óptica/métodos , Corantes FluorescentesRESUMO
Drug-resistant bacterial biofilm infections (BBIs) are refractory to elimination. Near-infrared-II photothermal therapy (NIR-II PTT) and chemodynamic therapy (CDT) are emerging antibiofilm approaches because of the heavy damage they inflict upon bacterial membrane structures and minimal drug-resistance. Hence, synergistic NIR-II PTT and CDT hold great promise for enhancing the therapeutic efficacy of BBIs. Herein, we propose a biofilm microenvironment (BME)-responsive nanoplatform, BTFB@Fe@Van, for use in the synergistic NIR-II PTT/CDT/antibiotic treatment of BBIs. BTFB@Fe@Van was prepared through the self-assembly of phenylboronic acid (PBA)-modified small-molecule BTFB, vancomycin, and the CDT catalyst Fe2+ ions in DSPE-PEG2000. Vancomycin was conjugated with BTFB through a pH-sensitive PBA-diol interaction, while the Fe2+ ions were bonded to the sulfur and nitrogen atoms of BTFB. The PBA-diol bonds decomposed in the acidic BME, simultaneously freeing the vancomycin and Fe2+ irons. Subsequently, the catalytic product hydroxyl radical was generated by the Fe2+ ions in the oxidative BME overexpressed with H2O2. Moreover, under 1064 nm laser, BTFB@Fe@Van exhibited outstanding hyperthermia and accelerated the release rate of vancomycin and the efficacy of CDT. Furthermore, the BTFB@Fe@Van nanoplatform enabled the precise NIR-II imaging of the infected sites. Both in-vitro and in-vivo experiments demonstrated that BTFB@Fe@Van possesses a synergistic NIR-II PTT/CDT/antibiotic mechanism against BBIs.
Assuntos
Infecções Bacterianas , Nanopartículas , Neoplasias , Humanos , Antibacterianos/farmacologia , Vancomicina/farmacologia , Terapia Fototérmica , Peróxido de Hidrogênio , Biofilmes , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
BACKGROUND: Statins are routinely prescribed to lower cholesterol and have been demonstrated to have significant benefits in atherosclerotic cardiovascular disease. However, whether statin therapy has effects on cancer risk remains controversial. In this study, we investigated the influence of statin therapy on cancer incidence and mortality by conducting a comprehensive meta-analysis of randomized controlled trials. METHODS: Systematic searches by Cochrane, Embase, Medline, and PubMed were performed to locate data from eligible randomized controlled trials related to statin therapy and oncology. Our main endpoints were cancer incidence and mortality. Fixed-effects models were used in this study. RESULTS: This meta-analysis comprised thirty-five randomized controlled studies. Twenty-eight included studies reported cancer incidence, and eighteen reported cancer mortality. The pooled results indicated no reduction in cancer incidence with statins compared to placebo [OR = 0.99, 95% CI (0.95, 1.03)]. In addition, statins did not decrease cancer mortality [OR = 0.99, 95% CI (0.91, 1.07)]. This study also performed a number of subgroup analyses, which showed no effect of statins on cancer subtypes such as genitourinary and breast cancer. Neither the type of statin nor long-term treatment with statins had an effect on cancer incidence and mortality. CONCLUSION: Through comprehensive analysis, we found that statin therapy does not reduce cancer incidence or mortality while protecting the cardiovascular system. TRIAL REGISTRATION: Prospero CRD42022377871.