RESUMO
As a kind of human milk oligosaccharide, 6'-sialyllactose (6'-SL) plays an important role in promoting infant brain development and improving infant immunity. The content of 6'-SL in infant formula milk powder is thus one of the important nutritional indexes. Since the lacking of efficient and rapid detection methods for 6'-SL, it is of great significance to develop specific recognition elements and establish fast and sensitive detection methods for 6'-SL. Herein, using 6'-SL specific aptamer as the recognition element, catalytic hairpin assembly as the signal amplification technology and quantum dots as the signal label, a fluorescence biosensor based on fluorescence resonance energy transfer (FRET) was constructed for ultra-sensitive detection of 6'-SL. The detection limit of this FRET-based fluorescent biosensor is 0.3 nM, and it has some outstanding characteristics such as high signal-to-noise ratio, low time-consuming, simplicity and high efficiency in the actual sample detection. Therefore, it has broad application prospect in 6'-SL detection.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Lactose/análogos & derivados , Pontos Quânticos , Humanos , Transferência Ressonante de Energia de Fluorescência/métodos , Leite Humano , Corantes , Técnicas Biossensoriais/métodos , Limite de DetecçãoRESUMO
Although chlorambucil (CHL) is a long-established anticancer drug, the drug failure of CHL, mediated by the intracellular defense system consisting of glutathione (GSH) and GSH S-transferase pi (GST-pi), has significantly limited the application of CHL. To overcome this issue, we first designed a GSH-responsive small-molecule prodrug (EA-SS-CHL) by combining CHL and ethacrynic acid (EA). Subsequently, drug-loaded nanoparticles (ECPP) were formed by the self-assembly between EA-SS-CHL and amphiphilic PEG-PDLLA to improve the water solubility of the prodrug and its ability to target tumor sites. Upon exposure to high intracellular GSH concentration, EA-SS-CHL gradually degrades, leading to the release of EA and CHL. The presence of EA facilitates the depletion of GSH and inhibition of GST-pi, ultimately attenuating the detoxification of the intracellular defense system to CHL. Cytotoxicity studies and apoptosis assays demonstrate that ECPP exhibits higher therapeutic efficiency than CHL. Additionally,in vivotumor suppression effects and biocompatibility provide further evidence for the superiority of ECPP. This work presents a promising strategy to enhance the efficacy of CHL in cancer therapy.
Assuntos
Clorambucila , Ácido Etacrínico , Glutationa , Micelas , Pró-Fármacos , Clorambucila/farmacologia , Clorambucila/química , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Glutationa/metabolismo , Humanos , Animais , Ácido Etacrínico/farmacologia , Ácido Etacrínico/química , Nanopartículas/química , Camundongos , Glutationa S-Transferase pi/metabolismo , Glutationa S-Transferase pi/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Polietilenoglicóis/química , Glutationa Transferase/metabolismo , Portadores de Fármacos/química , Liberação Controlada de FármacosRESUMO
OBJECTIVES: To compare the efficacy and safety of thulium fiber laser (TFL) to holmium: YAG (Ho: YAG) laser in ureteroscopic lithotripsy for urolithiasis. METHODS: PubMed, Web of Science, Embase, CENTRAL, SinoMed, CNKI database, VIP and Wanfang Database were systematically searched for all relevant clinical trials until September 2023. References were explored to identify the relevant articles. Meta-analysis was carried out for the retrieved studies using RevMan5.4.1 software, and the risk ratio, mean difference and 95% confidence interval were expressed. Statistical significance was set at p < 0.05. The main outcomes of this meta-analysis were stone-free rate (SFR), perioperative outcomes and intraoperative or postoperative complications. RESULTS: Thirteen studies, including 1394 patients, were included. According to the results of pooled analysis, TFL was associated with significantly higher stone-free rate (SFR) [0.52, 95% CI (0.32, 0.85), P = 0.009], shorter operation time [-5.47, 95% CI (-8.86, -2.08), P = 0.002], and less stone migration [0.17, 95% CI (0.06, 0.50), P = 0.001]. However, there was no significant difference in terms of the laser time, duration of hospital stay, drop of hemoglobin level, total energy, postoperative ureteral stenting, the incidence of intraoperative complications or postoperative complications between TFL and Ho: YAGs. CONCLUSION: The findings of this study demonstrated several advantages of TFL in terms of higher SFR, shorter operative time and less stone migration. TRIAL REGISTRATION: The protocol of this systematic review was listed in PROSPERO ( www.crd.york.ac.uk/PROSPERO ) (Protocol number: CRD42022362550).
Assuntos
Lasers de Estado Sólido , Litotripsia a Laser , Túlio , Ureteroscopia , Humanos , Ureteroscopia/métodos , Lasers de Estado Sólido/uso terapêutico , Litotripsia a Laser/métodos , Resultado do Tratamento , Urolitíase/cirurgia , Urolitíase/terapiaRESUMO
Sialyl-Lewisx (SLex) is a tetrasugar, which plays an important role in initial inflammation and cancer cell metastasis, and can be used as a marker for cancer diagnosis and prognosis or a therapeutic target. Detecting SLex from complex biological media remains a significant challenge. Herein, a single-stranded DNA aptamer of SLex was screened based on the double-stranded DNA library-modified magnetic bead (MB)-SELEX technology. After 14 rounds of screening, 12,639 sequences were obtained and divided into nine families. Three representative sequences were selected based on the number of sequence repeats and Gibbs binding free energy, and the aptamer SLex-Apt2 with 80 nt length (Kd = 23.01 nM) had the best affinity and relatively high specificity for targeting SLex. Then, a novel dual-recognition fluorescent biosensor for SLex-sensitive detection based on aptamer SLex-Apt2 bio-dots and 3-aminobenzoboric acid-modified MB was developed. This method can detect SLex as low as 32 µM and has a good linear response in the range 100 µM to 2 mM. It has the advantages of low preparation cost, good targeting, and avoiding the occurrence of false-positive and false-negative detection results, which makes the biosensor more valuable in biological detection and clinical diagnosis.
Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Técnica de Seleção de Aptâmeros , Antígeno Sialil Lewis X , Técnicas Biossensoriais/métodos , Aptâmeros de Nucleotídeos/química , Humanos , Técnica de Seleção de Aptâmeros/métodos , Corantes Fluorescentes/química , Limite de Detecção , Espectrometria de Fluorescência/métodosRESUMO
Cancer cell metabolism including aerobic glycolysis, amino acid and fatty acid metabolism, has been extensively studied. Metabolic reprogramming is a major hallmark of cancer, which promotes cancer cell proliferation, progression and metastasis, as well as provokes resistance to chemotherapeutic drugs. Several signal transduction pathways, such as BCR, MEK/ERK, Notch, NF-κB and PI3K/AKT/mTOR, regulate tumor metabolism, hence promoting tumor cell growth, proliferation and progression. Therefore, targeting metabolic enzymes, metabolites or their signal transduction pathways may constitute a promising therapeutic strategy to enhance cancer treatment efficacy. Diffuse large B-cell lymphoma (DLBCL) is the most aggressive form of non-Hodgkin lymphoma (NHL), and one-third of DLBCL patients suffer from relapsed/refractory disease after chemotherapy. The mechanisms underlying drug resistance are complex, including target gene mutations, metabolic reprogramming, aberrant signal transduction pathways, enhanced drug efflux via overexpression of multidrug efflux transporters like P-glycoprotein, upregulation of anti-apoptotic proteins, drug sequestration and enhanced DND repair. This review delineates the distinct metabolic reprogramming patterns and the association between metabolism and anticancer drug resistance in DLBCL as well as the emerging strategies to surmount chemoresistance in DLBCL.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Linfoma Difuso de Grandes Células B , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/uso terapêutico , Transdução de Sinais/genéticaRESUMO
The traditional lateral flow immunoassay (LFIA) detection method suffers from issues such as unstable detection results and low quantitative accuracy. In this study, we propose a novel multi-test line lateral flow immunoassay quantitative detection method using smartphone-based SAA immunoassay strips. Following the utilization of image processing techniques to extract and analyze the pigments on the immunoassay strips, quantitative analysis of the detection results was conducted. Experimental setups with controlled lighting conditions in a dark box were designed to capture samples using smartphones with different specifications for analysis. The algorithm's sensitivity and robustness were validated by introducing noise to the samples, and the detection performance on immunoassay strips using different algorithms was determined. The experimental results demonstrate that the proposed lateral flow immunoassay quantitative detection method based on image processing techniques achieves an accuracy rate of 94.23% on 260 samples, which is comparable to the traditional methods but with higher stability and lower algorithm complexity.
Assuntos
Algoritmos , Smartphone , Imunoensaio/métodos , Processamento de Imagem Assistida por Computador , Limite de DetecçãoRESUMO
Aeration is an effective approach to sustainable landfilling but may lead to elevated temperatures within landfills, resulting in landfill fires or explosions. Therefore, aeration is usually combined with leachate recirculation to control the elevated temperatures within landfills. To predict landfill temperatures during aeration and recirculation, a local thermal non-equilibrium model is developed considering the heat generation of biodegradation, the heat removal due to evaporation and leachate-gas flow, and the effects of the capillary. The solver is implemented in OpenFOAM based on the finite volume method and validated against a waste-column experiment and an in-situ aeration test. The simulation results demonstrate that the assumption of local thermal equilibrium will distinctly overestimate the temperature, maximally by 15 °C in the studied case. The model is then used to simulate a typical aerobic landfill unit to investigate the formation of explosive gas mixtures and elevated temperatures under different operating conditions. The simulation results of gas composition suggest that aeration will not result in explosive gas within landfills. A reasonable recirculation method for temperature control with corresponding operating parameters under a group of values of aeration pressure (2000-4000 Pa) and recirculation rate (0.0001-0.0008 m/s) are proposed, which can provide some guides for the design of an aeration and recirculation combined system. For a given total volume of added leachate, a higher recirculation rate does not always mean better cooling, and the cooling effect of continuous recirculation is better than that of intermittent recirculation.
Assuntos
Temperatura Baixa , Substâncias Explosivas , Temperatura , Biodegradação Ambiental , Simulação por ComputadorRESUMO
PURPOSE: To explore the efficacy of uterine artery embolization (UAE) in the treatment of uterine fibroid and share the experience of transvaginal fibroid expulsion (FE) after UAE. METHODS: We retrospectively analyzed the changes in uterine and fibroid volume in 152 patients with symptomatic uterine fibroid after UAE at Fujian Provincial Hospital and Fujian Longyan People Hospital from March 2014 to March 2020. After a 12-month follow-up, the improvement in postoperative clinical symptoms and the incidence of complications were evaluated. We also shared the clinical features and imaging findings of four patients with FE after UAE. RESULTS: All 152 patients successfully underwent UAE. After a 12-month follow-up, the postoperative volumes of the uterus and fibroid at 3, 6, and 12 months were significantly reduced or disappeared compared to those before surgery (P < 0.05). Clinical symptoms, such as menorrhagia, dysmenorrhea, prolonged menstrual period, anemia, increased leucorrhea, pelvic discomfort, and urinary tract compression, were significantly improved after UAE. Among the 152 patients, the incidences of postoperative fever, nausea, vomiting, lower abdominal pain, and increased vaginal secretion were 7.89%, 7.24%, 3.95%, 19.08%, and 4.61%, respectively. Additionally, there were six cases of FE, with an incidence of 3.95%. Three cases of fibroid specimens and pathological images of fibroid biopsy, which were expelled through the vagina, were also provided. CONCLUSION: UAE is a satisfactory alternative surgical method for symptomatic uterine fibroid with definitive efficacy and high safety. However, it is necessary to guard against the occurrence of postoperative complications such as FE.
Assuntos
Leiomioma , Embolização da Artéria Uterina , Neoplasias Uterinas , Feminino , Humanos , Leiomioma/complicações , Leiomioma/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Uterinas/complicações , Neoplasias Uterinas/cirurgiaRESUMO
BACKGROUND: Protein S deficiency (PSD) is an autosomal dominant hereditary disease. In 1984, familial PSD was reported to be prone to recurrent thrombosis. Follow-up studies have shown that heterozygous protein S (PROS1) mutations increase the risk of thrombosis. More than 300 PROS1 mutations have been identified; among them, only a small number of mutations have been reported its possible mechanism to reduce plasma protein S (PS) levels. However, whether PROS1 mutations affect protein structure and why it can induce PSD remains unknown. METHODS: The clinical phenotypes of the members of a family with thrombosis were collected. Their PS activity was measured using the coagulation method, whereas their protein C and antithrombin III activities were measured using methods such as the chromogenic substrate method. The proband and her parents were screened for the responsible mutation using second-generation whole exon sequencing, and the members of the family were verified for suspected mutations using Sanger sequencing. Mutant and wild type plasmids were constructed and transfected into HEK293T cells to detect the mRNA and protein expression of PROS1. RESULTS: In this family, the proband with venous thrombosis of both lower extremities, the proband's mother with pulmonary embolism and venous thrombosis of both lower extremities, and the proband's younger brother had significantly lower PS activity and carried a PROS1 c. 1820 T > C:p.Leu607Ser heterozygous mutation (NM_000313.3). However, no such mutations were found in family members with normal PS activity. The PS expression in the cell lysate and supernatant of the Leu607Ser mutant cells decreased, while mRNA expression increased. Immunofluorescence localization showed that there was no significant difference in protein localization before and after mutation. CONCLUSIONS: The analysis of family phenotype, gene association, and cell function tests suggest that the PROS1 Leu607Ser heterozygous mutation may be a pathogenic mutation. Serine substitution causes structural instability of the entire protein. These data indicate that impaired PS translation and synthesis or possible secretion impairment is the main pathogenesis of this family with hereditary PSD and thrombophilia.
Assuntos
Cistadenoma Mucinoso , Neoplasias Renais , Humanos , Universidades , Pelve Renal , Neoplasias Renais/cirurgia , ChinaRESUMO
Allogeneic haematopoietic stem cell transplantation (HSCT) is the only available curative therapy for patients with thalassaemia major. With the progress in human leucocyte antigen (HLA) antigen typing technology and supportive care, the outcomes of thalassaemia major have greatly improved in recent years, even in high-risk patients. However, the problem of finding a suitable donor is still a major obstacle to curing these patients. In recent decades, the lack of available HSCT donors has led to the increased use of haploidentical donors (HDs) for HSCT in haematological malignancies. Recently, we explored the effect of HD HSCT to eight children with thalassaemia major based on the FBCA conditioning regimen (fludarabine, busulphan, cyclophosphamide, antithymocyte globulin), which is usually used in leukaemia patients receiving haploidentical HSCT in our centre. So far, all of the transplanted patients have a stable engraftment and are transfusion independent in daily life. This encouraging result has revised our previous conception about haploidentical HCST for thalassaemia major and strongly suggests that HD HSCT is a feasible and safe method for thalassaemia major patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Talassemia beta/terapia , Adulto , Aloenxertos , Soro Antilinfocitário/administração & dosagem , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Masculino , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
BACKGROUND: Radiation-induced kidney damage can severely affect renal function, and have a serious impact on glucose reabsorption. Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is routinely utilized for metabolic imaging of glucose utilization. In this study, we are trying to assess the diagnostic value of 18F-FDG-PET/CT on measuring hyperacute effect of total body irradiation (TBI) on the kidneys. METHODS: Forty-eight Tibet minipigs were treated by TBI of different dosages using an 8-MV X-ray linear accelerator. Whole-body 18F-FDG-PET/CT was performed at 6, 24 and 72 h followed by histologic examination, blood samples' and renal function analysis. RESULTS: The uptake of 18F-FDG was significantly different between 11/14 Gy dose groups and control group, the standard Uptake Values reached a maximal level at 72 h after 14-Gy TBI treatment. At doses over 8 Gy, histological observation showed formation of tube casts, degeneration, necrosis of tubular cells, inflammatory cell infiltration and dilatation of the mitochondria of tubule cells. Renal function analysis confirmed the changes in blood urea nitrogen and creatinine levels at various dosages and time intervals. Immunohistochemistry and western blot results indicate that the expression levels of IL-10 and TNF-α proteins were positively correlated with radiation dose up to 8 Gy. CONCLUSIONS: 18F-FDG PET/CT can reflect pathological changes in kidneys and it may be a useful tool for rapid and non-invasive assessment in cases of suspected radiation-induced kidney damage.
Assuntos
Fluordesoxiglucose F18/química , Rim/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/diagnóstico , Animais , Interleucina-10/metabolismo , Rim/patologia , Rim/fisiopatologia , Rim/ultraestrutura , Testes de Função Renal , Padrões de Referência , Suínos , Porco Miniatura , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo , Irradiação Corporal TotalRESUMO
In recent years, owing to the abuse of antibiotics, the widespread of resistant bacterial strains became a serious threat to public health. This status demands development of new antibacterial agents with novel mechanisms of action. The reason for the limited new antibacterials is the small number of effective therapeutic targets, which cannot meet the current needs for the multiple drug-resistant treatment. Screening for new targets is the key step in the development of novel antibacterial agents. Peptidoglycan is the main component of the cell wall of bacteria, which is essential for survival of pathogenic bacteria. Within the biochemical pathway for peptidoglycan biosynthes is the Murligases, described in this review as highly potential targets for the development of new classes of antibacterial agents. This review provides an in-depth insight into the recent developments in the field of inhibitors of the Mur enzymes (MurA-F). Moreover, the reasons for the lack of candidate inhibitors and the challenges to overcome the hurdles are also discussed.
Assuntos
Antibacterianos/farmacologia , Bactérias/enzimologia , Proteínas de Bactérias/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Peptidoglicano/biossíntese , Parede Celular , Farmacorresistência BacterianaRESUMO
Glutathione (GSH) is an important antioxidant that maintains cellular redox homeostasis and significantly contributes to resistance against various chemotherapeutic agents. To address the challenge of GSH-mediated drug resistance in etoposide (ETS), we developed a facile synthetic method to prepare a biocompatible acid-responsive polycarbonate (PEG-PCA) containing cinnamaldehyde (CA), a potent GSH-depleting agent, as a side chain using nontoxic raw materials. This polymer self-assembled in aqueous solutions to form nanoparticles (ETS@PCA) that encapsulated ETS, enhancing its water solubility and enabling tumor-targeted delivery. In vitro studies demonstrated that ETS@PCA could respond to the acidic tumor microenvironment, releasing CA to rapidly deplete GSH levels. Consequently, ETS@PCA exhibited superior cytotoxicity compared to free ETS. Furthermore, in vivo experiments corroborated the enhanced tumor inhibitory effects of ETS@PCA.
RESUMO
BACKGROUND: Lipid metabolism factors may play a role in the development of arthritis and hepatic steatosis and fibrosis. The aim of this study was to explore the potential association between arthritis and hepatic steatosis and liver fibrosis. MATERIALS AND METHODS: The nationally representative sample from the National Health and Nutrition Examination Survey was analyzed, with data on arthritis diagnosis, subtype, and liver status obtained. Liver status was assessed using transient elastography. Hepatic steatosis was defined as a Controlled Attenuation Parameter (CAP) score ≥263 dB/m, and liver fibrosis status was defined as F0âF4. Logistic regression models and subgroup analyses stratified by sex were used to evaluate the associations. Smooth curve fitting was used to describe the associations. RESULTS: The present study of 6,840 adults aged 20 years or older found a significant positive correlation between arthritis and CAP in multivariate logistic regression analysis (ß = 0.003, 95 % CI 0.001 to 0.0041, p < 0.001). Participants with arthritis had a higher risk of hepatic steatosis (OR = 1.248, 95 % CI 1.036 to 1.504, p = 0.020), particularly those with osteoarthritis or degenerative arthritis, but not rheumatoid arthritis (p = 0.847). The positive correlation was maintained in females (ß = 0.004, 95 % CI 0.002 to 0.006, p < 0.001), but not in males. There was no significant relationship between arthritis and liver fibrosis (p = 0.508). CONCLUSION: This study indicates that there is a positive correlation between arthritis and hepatic steatosis, particularly in females. Nonetheless, there is no significant relationship between arthritis and the risk of liver fibrosis.
Assuntos
Artrite , Técnicas de Imagem por Elasticidade , Cirrose Hepática , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Fatores de Risco , Artrite/epidemiologia , Artrite/complicações , Estados Unidos/epidemiologia , Fígado Gorduroso/complicações , Fígado Gorduroso/epidemiologia , Adulto Jovem , Idoso , Fatores Sexuais , Estudos Transversais , Modelos Logísticos , Distribuição por SexoRESUMO
This study aims to identify optimal parameters for using Thulium fiber lasers (TFL) in ureteral stone lithotripsy to ensure laser safety and maximize efficacy. Our goal is to improve the outcomes of single-use semi-rigid ureteroscopy for treating stones located in the proximal ureter. A clinically relevant thermal testing device was designed to investigate heating effects during TFL stone fragmentation. The device was utilized to identify safe power thresholds for TFL at various irrigation rates. Three other devices were used to assess varying pulse energy effects on stone fragmentation efficiency, dusting, retropulsion, and depth of tissue vaporization. Comparative experiments in fresh porcine renal units were performed to validate the efficacy and safety of optimal TFL parameters for semi-rigid ureteroscopy in proximal ureteral stone procedures. Our study found that the improved device generated a higher thermal effect. Furthermore, the safe power threshold for laser lithotripsy increased as the irrigation rate was raised. At an irrigation rate of 40 ml/min, it is safe to use an average power of less than 30 watts. Although increasing pulse energy has a progressively lower effect on fragmentation and dust removal efficiency, it did lead to a linear increase in stone displacement and tissue vaporization depth. Thermal testing showed 20 W (53.87 ± 2.67 °C) indicating potential urothelial damage. In our study of laser lithotripsy for proximal ureteral stones, the group treated with 0.3 J pulses had several advantages compared to the 0.8 J group: Fewer large fragments (> 4 mm): 0 vs. 1.67 fragments (1-2.25), p = 0.002, a lower number of collateral tissue injuries: 0.50 (0-1.25) vs. 2.67 (2-4), p = 0.011, and lower stone retropulsion grading: 0.83 (0.75-1) vs. 1.67 (1-2), p = 0.046. There was no significant difference in operating time between the groups (443.33 ± 78.30 s vs. 463.17 ± 75.15 s, p = 0.664). These findings suggest that TFL irradiation generates a greater thermal effect compared to non-irradiated stones. Furthermore, the thermal effect during laser lithotripsy is influenced by both power and irrigation flow rate. Our study suggests that using a power below 15 W with an irrigation flow rate of 20 ml/min is safe. Moreover, a pulse energy of 0.3 J appears to be optimal for achieving the best overall stone fragmentation effect.
Assuntos
Litotripsia a Laser , Túlio , Cálculos Ureterais , Cálculos Ureterais/terapia , Cálculos Ureterais/cirurgia , Litotripsia a Laser/métodos , Litotripsia a Laser/instrumentação , Litotripsia a Laser/efeitos adversos , Animais , Suínos , Lasers de Estado Sólido/uso terapêutico , Ureteroscopia/métodos , Ureteroscopia/instrumentação , Ureteroscopia/efeitos adversosRESUMO
Simultaneously achieving a high photoluminescence quantum yield (PLQY), ultrashort exciton lifetime, and suppressed concentration quenching in thermally activated delayed fluorescence (TADF) materials is desirable yet challenging. Here, a novel acceptor-donor-acceptor type TADF emitter, namely, 2BO-sQA, wherein two oxygen-bridged triarylboron (BO) acceptors are arranged with cofacial alignment and positioned nearly orthogonal to the rigid dispirofluorene-quinolinoacridine (sQA) donor is reported. This molecular design enables the compound to achieve highly efficient (PLQYs up to 99%) and short-lived (nanosecond-scale) blue TADF with effectively suppressed concentration quenching in films. Consequently, the doped organic light-emitting diodes (OLEDs) base on 2BO-sQA achieve exceptional electroluminescence performance across a broad range of doping concentrations, maintaining maximum external quantum efficiencies (EQEs) at over 30% for doping concentrations ranging from 10 to 70 wt%. Remarkably, the nondoped blue OLED achieves a record-high maximum EQE of 26.6% with a small efficiency roll-off of 14.0% at 1000 candelas per square meter. By using 2BO-sQA as the sensitizer for the multiresonance TADF emitter ν-DABNA, TADF-sensitized fluorescence OLEDs achieve high-efficiency deep-blue emission. These results demonstrate the feasibility of this molecular design in developing TADF emitters with high efficiency, ultrashort exciton lifetime, and minimal concentration quenching.
RESUMO
OBJECTIVE: N6-methyladenosine (M6A) is the most prevalent epigenetic alteration. Methyltransferase-like 3 (METTL3) is a key player in the control of M6A modification. Methyltransferase promote the processing of mature miRNA in an M6A-dependent manner, thereby participating in disease occurrence and development. However, the regulatory mechanism of M6A in NK/T cell lymphoma (NKTCL) remains unclear. PATIENTS AND METHODS: We determined the expression of METTL3 and its correlation with clinicopathological features using qRT-PCR and immunohistochemistry. We evaluated the effects of METTL3 on NKTCL cells using dot blot assay, CCK8 assay and subcutaneous xenograft experiment. We then applied M6A sequencing combined with gene expression omnibus data to screen candidate targets of METTL3. Finally, we investigated the regulatory mechanism of METTL3 in NKTCL by methylated RNA immunoprecipitation and RNA immunoprecipitation (RIP) assays. RESULTS: We demonstrated that METTL3 was highly expressed in NKTCL cells and tissues and indicated poor prognosis. The METTL3 expression was associated with NKTCL survival. Functionally, METTL3 promoted the proliferation capability of NKTCL cells in vitro and in vivo. Furthermore, EBV-miR-BART3-3p was identified as the downstream effector of METTL3, and silencing EBV-miR-BART3-3p inhibited the proliferation of NKTCL. Finally, we confirmed that PLCG2 as a target gene of EBVmiR-BART3-3p by relative assays. CONCLUSIONS: We identified that METTL3 is significantly up-regulated in NKTCL and promotes NKTCL development. M6A modification contributes to the progression of NKTCL via the METTL3/EBV-miR-BART3-3p/PLCG2 axis. Our study is the first to report that M6A methylation has a critical role in NKTCL oncogenesis, and could be a potential target for NKTCL treatment.
Assuntos
Adenosina , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Herpesvirus Humano 4 , Linfoma Extranodal de Células T-NK , Metiltransferases , MicroRNAs , Humanos , Metiltransferases/genética , Metiltransferases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Linfoma Extranodal de Células T-NK/genética , Linfoma Extranodal de Células T-NK/virologia , Linfoma Extranodal de Células T-NK/patologia , Linfoma Extranodal de Células T-NK/metabolismo , Animais , Adenosina/análogos & derivados , Adenosina/metabolismo , Camundongos , Feminino , Masculino , Herpesvirus Humano 4/genética , Linhagem Celular Tumoral , Metilação , Prognóstico , Pessoa de Meia-Idade , Camundongos Nus , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Photocatalysis has been widely used for the removal of hexavalent chromium from wastewater as an efficient and environmental friendly method. However, conventional photocatalysts generally exhibit poor adsorption properties toward Cr(VI), resulting in unsatisfactory performance in high concentrated wastewaters. In this study, we synthesized a novel composite material with high Cr(VI) adsorption ability by blending prepared CuS nanocrystals into triethylenetetramine modified sodium alginate for the enhanced photocatalytic removal of Cr(VI). Effect of CuS dosage, pH value, light source and intensity were discussed for the optimum Cr(VI) removal conditions. The synthesized composite has shown good adsorption performance toward Cr(VI) and the overall removal rate reached 98.99 % within 50 min under UV light irradiation with citric acid as hole scavenger. Adsorption isotherm, thermodynamics, and kinetics with corresponding model fitting were discussed, which suggested that the monolayer and chemical adsorption dominated the adsorption process. Characterization results indicated that amino and hydroxyl groups contributed electrons in the photocatalysis reaction for the reduction of Cr(VI) to Cr(III). CuS nanocrystals can enhance the surface charge and light absorbance ability of the composite, and the Cr(VI) removal was governed by electrostatic interaction and photo-induced redox reaction.
Assuntos
Nanopartículas , Poluentes Químicos da Água , Trientina , Alginatos , Cromo/química , Águas Residuárias , Adsorção , Poluentes Químicos da Água/química , Cinética , Concentração de Íons de HidrogênioRESUMO
PURPOSE: This retrospective study aimed to evaluate the clinical safety and efficacy of super-selective transcatheter vesical arterial chemoembolization with epirubicin-loaded CalliSpheres® beads (DEB-TACE) for treating muscle-invasive bladder cancer with hematuria. METHODS: We reviewed the retrospective records of 20 muscle-invasive bladder cancer patients with hematuria who were treated with super-selective transcatheter vesical arterial by oxaliplatin and 100-300-µm CalliSpheres loaded with epirubicin. The primary outcomes were the technical and clinical success rates. The secondary outcomes were complications, treatment responses, quality of life (QOL), median overall survival, and 1- and 2-year survival rates. QOL was routinely assessed by nurses at admission and during telephone follow-up 4 weeks after discharge. RESULTS: The technical success rate was 80.0% (16/20). Bleeding was controlled after the first embolization in 18/20 patients and after re-embolization within 7 days of the first embolization in the remaining two patients. The clinical success rate was 90% (18/20). After 4 weeks of follow-up, the mean hematocrit and hemoglobin levels improved significantly (P < 0.05). Four patients (20.0%) showed hematuria recurrence during a 4-8-month follow-up period. There were no severe complications, such as necrosis of the bladder, genitals, perineal skin, or procedure-related deaths. The complete response, partial response, stable disease, and progressive disease frequencies were 5.0%, 55.0%, 25.0%, and 15.0%, respectively, resulting in an objective response rate of 60.0% and a disease control rate of 85.0% after 1 month. 4 weeks after embolization, QOL was significantly higher than that pre-operation, except for social/family status (P < 0.05). The median overall survival was 18.5 months, and the 1- and 2-year survival rates were 75.0% and 46.7%, respectively. CONCLUSION: DEB-TACE is safe and effective for treating muscle-invasive bladder cancer with hematuria, preserving bladder function and improving the QOL.