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This study aims to examine the prevalence of dental caries and periodontitis among children aged 5-12 years in Jinhua, Zhejiang province, and analyze the influencing factors of dental caries and periodontitis. A total of 280 children meeting the study criteria for a first-time oral examination were retrospectively analyzed and divided into caries (n = 190), no-caries (n = 90), periodontitis (n = 85) and non-periodontitis group (n = 195) groups based on the presence of caries or periodontitis. An analysis of general survey questionnaires and logistic regression of dental caries and periodontitis among children in different groups was conducted. Caries disease was diagnosed in 67.86% with an average decayed missing filled tooth (DMFT) of 2.94, and periodontitis was diagnosed in 30.36% of 280 children. The independent risk factors for dental caries were daily brushing habits, parental supervision (assisted) brushing, place of residence and frequency of eating desserts or beverages (p < 0.05). Periodontitis was not related to parental education and knowledge of oral health care (p > 0.05). Periodontitis is independent of plaque, tartar, mastery of brushing methods, regular oral examination, and gargling after meals (p < 0.05). While daily brushing habits, parental supervision (assisted) brushing, place of residence and frequency of eating desserts or beverages were protective factors for dental caries (p < 0.05). According to the prevalence of dental caries and periodontitis among children aged 5-12 in this area as well as the analysis of influencing factors, further effective measures can be taken to reduce the incidence of adverse influencing factors, thereby reducing the risk of dental caries and periodontitis for children.
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Cárie Dentária , Periodontite , Criança , Humanos , Cárie Dentária/epidemiologia , Cárie Dentária/etiologia , Incidência , Estudos Retrospectivos , Índice CPO , Periodontite/complicações , PrevalênciaRESUMO
OBJECTIVES: To investigate the pathogenic gene of a patient with nonsyndromic oligodontia, and analyze its possible pathogenic mechanism. SUBJECTS AND METHODS: The variant was detected by whole exome sequencing (WES) and Sanger sequencing in a family with oligodontia. Bioinformatic and structural analyses were used to analyze variant. Functional studies including western blotting and immunofluorescent analyses and luciferase reporter assay were conducted to explore the functional effects. RESULTS: We identified a novel frameshift variant of PAX9 (c.491-510delGCCCT-ATCACGGCGGCGGCC, p.P165Qfs*145) outside the DNA-binding domain causing an autosomal-dominant nonsyndromic oligodontia in a Chinese family. Bioinformatic and structural analyses revealed that the variant is pathogenic and conserved evolutionarily, and the changes might affect protein stability or folding. Functional studies demonstrate dramatically reduced ability in activating transcription activity of BMP4 promoter and a marked decrease in protein production, as evaluated by western blotting and immunofluorescent analyses. CONCLUSIONS: We found a novel frameshift variant of PAX9 causing nonsyndromic oligodontia in a Chinese family. Our findings indicate that frameshift variants cause loss of function of PAX9 protein during the patterning of the dentition and the subsequent tooth agenesis, providing new molecular insights into the role of frameshift variant of PAX9 and broaden the pathogenic spectrum of PAX9 variants.
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Anodontia , População do Leste Asiático , Humanos , Anodontia/genética , Mutação da Fase de Leitura , Proteínas/genética , Fator de Transcrição PAX9/genética , Linhagem , MutaçãoRESUMO
In recent years, hydrophobic deep eutectic solvents as new generation of green solvents have attracted wide attention in liquid microextraction technique. In this article, four hydrophobic deep eutectic solvents composed of trioctylmethylammonium chloride and oleic acid were designed and prepared firstly. Combined with high-performance liquid chromatography, these deep eutectic solvents were used as an extraction solvent in vortex-assisted dispersive liquid-liquid microextraction for the selective enrichment and indirect determination of trace nitrite from real water and biological samples. This method is based on the diazotization-coupling reaction of nitrite with p-nitroaniline and diphenylamine in acidic water, and then the nitrite is quantified indirectly by measuring the obtained azo compounds. Some factors influencing the extraction efficiency, including the reaction and extraction conditions, were investigated. Under the optimized conditions, the method has a linear range of 1-300 µg/L with a correlation coefficient of 0.9924, limit of detection of 0.2 µg/L, limit of quantitation of 1 µg/L, intraday and interday relative standard deviations of 4.0 and 6.0%. This method was successfully applied in determination of nitrite from three environmental water and two biological samples with the recovery in the range of 90.5-115.2%. In addition, these results were well agreement with those obtained by the conventional Griess method.
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Microextração em Fase Líquida , Nitritos/análise , Poluentes Químicos da Água/química , Cromatografia Líquida de Alta Pressão , Humanos , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Solventes/químicaRESUMO
OBJECTIVE: To investigate the effect of electrical stimulation to sacral spinal nerve 3 (S3 stimulation) on gastrointestinal dysfunction after spinal cord injury (SCI). METHODS: Six rabbits were taken as normal controls to record their gastrointestinal multipoint biological discharge, colon pressure and rectoanal inhibitory reflex. Electrodes were implanted into S3 in another 18 rabbits. Then the model of SCI was conducted following Fehling's method: the rabbit S3 was clamped to induce transverse injury, which was claimed by both somatosensory evoked potential and motion evoked potential. Two hours after SCI, S3 stimulation was conducted. The 18 rabbits were subdivided into 3 groups to respectively record their gastrointestinal electric activities (n=6), colon pressure (n=6), and rectum pressure (n=6). Firstly the wave frequency was fixed at 15 Hz and pulse width at 400 µs and three stimulus intensities (6 V, 8 V, 10 V) were tested. Then the voltage was fixed at 6 V and the pulse width changed from 200 µs, 400 µs to 600 µs. The response was recorded and analyzed. The condition of defecation was also investigated. RESULTS: After SCI, the mainly demonstrated change was dyskinesia of the single haustrum and distal colon. The rectoanal inhibitory reflex almost disappeared. S3 stimulation partly recovered the intestinal movement after denervation, promoting defecation. The proper stimulus parameters were 15 Hz, 400 µs, 6 V, 10 s with 20 s intervals and 10 min with 10 min intervals, total 2 h. CONCLUSION: S3 stimulation is able to restore the intestinal movement after denervation (especially single haustrum and distal colon), which promotes defecation.
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Estimulação Elétrica , Trato Gastrointestinal/fisiopatologia , Sacro/inervação , Traumatismos da Medula Espinal/fisiopatologia , Animais , Modelos Animais de Doenças , Eletrodos Implantados , Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , CoelhosRESUMO
Antibiotics are widely used in clinical medicine due to their excellent antibacterial abilities. As typical emerging pollutants, their misuse can lead to excess antibiotics entering the environment, causing antimicrobial resistance and leading to serious health problems via food chain. Herein, a nano-fluorescent probe based on nitrogen-doped carbon dots (N-CDs) was constructed for the sensitive detection of chlortetracycline (CTC). N-CDs with stable fluorescence were synthesized by hydrothermal method using alizarin red and melamine as raw materials. The N-CDs exhibited significant independence to excitation wavelength. The fluorescence of N-CDs was significantly quenched by CTC ascribing to the fluorescence resonance energy transfer mechanism. The concentration of N-CDs, solution pH and incubation time were optimized to obtain the optimal detection parameters. Under optimal conditions, CTC exhibited excellent linearity over the range of 20-1200 µg/L, and the detection limit was 8.74 µg/L. The method was validated with actual water samples and achieved satisfied spiked recoveries of 97.6-102.6%. Therefore, the proposed method has significant application value in the detection of CTC in waters.
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Antibacterianos , Carbono , Clortetraciclina , Corantes Fluorescentes , Limite de Detecção , Nitrogênio , Pontos Quânticos , Poluentes Químicos da Água , Clortetraciclina/análise , Nitrogênio/química , Nitrogênio/análise , Carbono/química , Corantes Fluorescentes/química , Poluentes Químicos da Água/análise , Pontos Quânticos/química , Antibacterianos/análise , Transferência Ressonante de Energia de Fluorescência , FluorescênciaRESUMO
Present work reported a novel nanozyme g-C3N4@Cu, N-CDs with excellent peroxidase-like activity obtained by loading Cu and N co-doped carbon dots on g-C3N4 (graphitic carbon nitride). g-C3N4@Cu, N-CDs can catalyze H2O2 to generate hydroxyl radical â¢OH, which oxidizes o-phenylenediamine to 2,3-diaminophenazine, which emits orange fluorescence under ultraviolet light irradiation. The experimental results confirmed that 1,4-benzenedithiol (BDT) could inhibit the peroxidase-like activity of g-C3N4@Cu, N-CDs. Based the principle above, a colorimetric-fluorescence dual-mode sensor for rapidly sensing of BDT was creatively constructed with assisting of a smartphone. The sensor showed excellent linearity over ranges of 0.75-132 µM and 0.33-60.0 µM with detection limits of 0.32 µM and 0.25 µM for colorimetric and fluorescence detection, respectively. Moreover, a smartphone-assisted colorimetric array sensor was constructed to distinguish six sulfur-containing compounds according to the difference in the degree of inhibition of nanozyme activity by different sulfur-containing compounds. The array sensor could distinguish sulfur-containing compounds at low concentration as low as 0.4 µM. The results validated that the designed sensor was a convenient and fast platform, which could be utilized as a reliably portable tool for the efficient and accurate detection of BDT and the discrimination of multiple sulfur compounds in real water samples.
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Colorimetria , Cobre , Smartphone , Sulfetos , Colorimetria/métodos , Cobre/química , Sulfetos/química , Compostos de Cádmio/química , Poluentes Químicos da Água/análise , Peroxidase/química , Peroxidase/metabolismo , Fluorescência , Compostos de Enxofre/análise , Compostos de Enxofre/química , Limite de Detecção , Espectrometria de Fluorescência/métodos , Compostos de Sulfidrila/química , Compostos de Sulfidrila/análise , Carbono/química , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/análise , Grafite , Compostos de NitrogênioRESUMO
As a typical kind of new pollutants, there are still some challenges in the rapid detection of antibiotics. In this work, a sensitive fluorescent probe based on boron-doped carbon dots (B-CDs) in combination with thermo-responsive magnetic molecularly imprinted polymers (T-MMIPs) was constructed for the detection of oxytetracycline (OTC) in tea drinks. T-MMIPs were designed, fabricated and employed to enrich OTC at trace level from tea drinks, and B-CDs were utilized as the fluorescent probe to detect the concentration of OTC. The proposed method exhibited good linear relationship with OTC concentration from 0.2 to 60 µg L-1 and the limit of detection was 0.1 µg L-1. The established method has been successfully validated with tea beverages. Present work was the first attempt application of T-MMIPs in combination with CDs in detection of OTC, and demonstrated that the proposed method endowed the detection of OTC with high selectivity, sensitivity, reliability and wide application prospect, meanwhile offered a new strategy for the method establishment of rapid and sensitive detection of trace antibiotics in food and other matrices.
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Impressão Molecular , Oxitetraciclina , Oxitetraciclina/análise , Boro , Impressão Molecular/métodos , Carbono , Corantes Fluorescentes , Reprodutibilidade dos Testes , Polímeros , Antibacterianos , Extração em Fase Sólida/métodos , Chá , Fenômenos Magnéticos , Limite de DetecçãoRESUMO
In this study, nitrogen-doped carbon dots (N-CDs) were facilely fabricated by one-pot hydrothermal method with levulinic acid and triethanolamine. A fluorescent sensor array was established for identifying azo compounds including Sudan Orange G (SOG), p-diaminoazobenzene, p-aminoazobenzene, azobenzene and quantitative detection of SOG. Experimental results revealed that azo compounds could quench the fluorescent intensity of N-CDs. Owing to various azo compounds showing different affinities to N-CDs, the sensor array exhibited different fluorescence quenching changes, which were further analyzed with principal component analysis to discriminate azo compounds. The sensor array was able to differentiate and recognize diverse concentrations of azo compounds from 0.25 to 2 mg/L. Simultaneously, a variety of factors affecting the detection of SOG were optimized. Under the optimized conditions, the sensor showed excellent stability and sensitivity. The sensor possessed marvelous linearity in the range of 0.1-1 mg/L and 1-4 mg/L and the detection limit was 27.82 µg/L. Spiked recoveries of 90.8-98.2 % were attained at spiked levels of 0.2 mg/L and 1 mg/L, demonstrating that the constructed fluorescence sensor was dependable and feasible for sensing SOG in environmental water samples.
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A physical sensor with a sensing medium comprising multiparallel-connected (MPC) piezoresistive pathways in both the vertical and horizontal directions was developed to achieve improved sensing performance. The MPC sensing medium reduces the total resistance and offsets noise, offering enhanced signal stability and device reliability and providing a high-performance sensing platform. The signal change and gauge factor (GF) of the 3PW-5L strain sensor (comprising three lines and five layers of piezoresistive pathways horizontally and vertically, respectively) were, respectively, 5.9 and 4.7 times higher than those of the 1PW-1L sensor composed of a monosensing pathway; the hysteresis of the detected signal was also significantly reduced. The linearity of the detected signal increased from 0.912 for 1PW-1L to 0.995 for 3PW-5L, indicating a greater sensing reliability. The direction of the applied tensile strain was successfully detected using the MPC sensing medium with an orthogonal configuration. The MPC piezoresistive sensor composing vertically stacked piezoresistive pathways demonstrated excellent performance as a pressure sensor; the 3PW-5L pressure sensor afforded a GF of 0.121 ± 0.002 kPa-1 with a linearity of 0.998 under an applied pressure ≥16.4 kPa. The MPC piezoresistive physical sensor offers a superior sensing performance and should contribute to the future development of wearable sensors and electronic devices.
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In this work, a sensitive fluorescent sensor toward p-nitrophenol (4-NP) integrating magnetic molecularly imprinted materials and carbon dots (CDs) was proposed. Magnetic material and CDs derived from K3 [Fe(CN)6] and glucose were simultaneously obtained through simple one-step hydrothermal process. Introducing of molecularly imprinted materials based magnetic solid phase extraction (MSPE) endowed the constructed fluorescent sensor with higher sensitivity and selectivity. The significant factors affecting the sensitivity of the sensor toward 4-NP were optimized. Good linearity was obtained between fluorescent intensity of CDs and different concentration of 4-NP from 0.08 to 62.5 µg L-1. The sensitivity of constructed sensor was very low with detection limit of 0.02 µg L-1. Reliable applicability was also proved by the well-pleasing recoveries of 94.2-97.8% with different spiked concentrations of 4-NP in real environmental waters.
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2,4-Dinitroaniline is a multifunctional product and has been applicated in various fields. It has absorbed much concerns due to its large consumption and occurrence in many environmental matrices. It is urgent to explore reliable and sensitive measurement technology. Present study described an outstanding fluorescence sensor constructed with carbon dots (CDs) derived from vitamin B1. The CDs were fabricated by dealing with a facile hydrothermal process, and exhibited good water solubility, fluorescence stability and highly fluorescence quenching characteristics in presence of 2,4-dinitroaniline. The excitation and emission wavelengths of the obtained CDs were 305 and 378 nm, respectively. The sensor displayed good selectivity and sensitivity for 2,4-dinitroaniline. Good linearity can be achieved in two-stage of 0.2-3 µmol L-1 and 3-20 µmol L-1. The sensor earned low detection limit for 2,4-dinitroaniline down to 0.05 µmol L-1. The sensor has been commendably employed for analysis of 2,4-dinitroaniline in real aqueous samples with spiked recoveries in the range of 95.0-99.6%. The proposed sensor provided a promising alternative for analysis of environmental pollutants or other meaningful employment.
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Carbono , Pontos Quânticos , Espectrometria de Fluorescência , Corantes Fluorescentes , Tiamina , Limite de Detecção , VitaminasRESUMO
Bisphenols (BPs) are typical endocrine disruptors, which can cause great effects on environmental, organisms and human health. In this study, ß-Cyclodextrin (ß-CD) functionalized polyamidoamine dendrimers-modified Fe3O4 nanomaterials (MNPs@PAMAM (G3.0)@ß-CD) were facilely synthesized. It exhibited good adsorption capacities for BPs, which was utilized to construct a sensitive tool in combination with high performance liquid chromatography for monitoring BPs such as bisphenol A (BPA), tetrabromobisphenol A (TBBPA), bisphenol S (BPS), bisphenol AF (BPAF) and bisphenol AP (BPAP) in beverage samples. The factors affecting the enrichment were examined such as generation of adsorbent, dosage of adsorbent, type and volume of eluting solvent, elution time and pH value of sample solution. The optimal parameters for enrichment was as follows: dosage of adsorbent, 60 mg; adsorption time, 50min; sample pH, pH7; elutent, 9 mL mixture of methanol and acetone(1:1); elution time, 6min; sample volume, 60 mL. The experimental results demonstrated that the adsorption conformed to pseudo-second-order kinetic model and Langmuir adsorption isotherm model. The results showed the maximum adsorption capacities of BPS, TBBPA, BPA, BPAF and BPAP were 131.80 µgg-1, 139.84 µgg-1, 157.08 µgg-1, 142.11 µgg-1 and 134.23 µgg-1, respectively. Under optimal conditions, BPS had good linear relationship over range from of 0.5-300 µgL-1, and the linear ranges of BPA, TBBPA, BPAF and BPAP ranged from 0.1 to 300 µgL-1. The limits of detection (S/N = 3) for BPs were good in range of 0.016-0.039 µgL-1. The spiked recoveries of target bisphenols (BPs) in beverages were approving over range from 92.3% to 99.2%. The established method possessed merits of easy to operate, good sensitivity, rapidness as well as environmental friendliness, and which earned great application potential for the enrichment and detection of trace BPs in practical samples.
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Dendrímeros , Poluentes Ambientais , beta-Ciclodextrinas , Humanos , Poluentes Ambientais/análise , Bebidas/análise , Poliaminas , Compostos Benzidrílicos/análise , Fenômenos MagnéticosRESUMO
Due to the strong metal-sulfur interaction between mercapto groups and metal ions, which can be used to functionalize polyamidoamine dendrimer decorated Fe3O4 nanoparticles for high enrichment of trace heavy metal ions from waters. Based on this concept, polyamidoamine dendrimer modified Fe3O4 nanomaterials were functionalized with l-Cysteine and a new magnetic solid phase extraction for rapid adsorption and separation of Hg2+, Pb2+, Co2+ and Cd2+ from waters was established. The factors affecting extraction efficiency have been optimized. Upon the optimal parameters, the established method provided good linear ranges of 0.1-200 µg L-1 for Hg2+ and 0.05-200 µg L-1 for Pb2+, Co2+ and Cd2+, and high sensitivity with limits of detection (LOD) of 0.018 µg L-1, 0.014 µg L-1, 0.013 µg L-1 and 0.025 µg L-1 for Cd2+, Pb2+, Co2+ and Hg2+, respectively. Real water samples were utilized to validate the proposed method, and achieved results revealed that the proposed method was sensitive, effective, stable and suitable for monitoring Pb2+, Cd2+, Co2+and Hg2+ in environmental waters. This work provided a novel strategy for the simultaneous analysis of target cations in waters, and a new direction for developing decoration method of nanomaterials according to specific purpose.
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Dendrímeros , Mercúrio , Metais Pesados , Oligoelementos , Dendrímeros/química , Cisteína , Cádmio/análise , Cromatografia Líquida de Alta Pressão/métodos , Chumbo , Metais Pesados/análise , Mercúrio/análise , Oligoelementos/análise , Cátions , Adsorção , Água/química , Extração em Fase Sólida/métodos , Fenômenos MagnéticosRESUMO
OBJECTIVE: To evaluate the effectiveness and safety of nab-paclitaxel plus platinum as first-line chemotherapy for ovarian cancer (OC). METHODS: Patients administered platinum combined with nab-paclitaxel as first-line chemotherapy for epithelial OC, fallopian tube cancer, or primary peritoneal cancer from July 2018 to December 2021 were retrospectively evaluated. The primary outcome was progression-free survival (PFS). Adverse events (AEs) were examined. Subgroup analysis was performed. RESULTS: Seventy-two patients (median age, 54.5 years; range, 20.0-79.0 years) were evaluated, including 12 and 60 administered neoadjuvant therapy and primary surgery with subsequent chemotherapy, respectively. The median follow-up duration was 25.6 months, and the median PFS was 26.7 (95% confidence interval [CI]=24.0-29.3) months in the whole patient population. In the neoadjuvant subgroup, the median PFS was 26.7 (95% CI=22.9-30.5) months vs. 30.1 (95% CI=23.1-37.1) months in the primary surgery subgroup. Twenty-seven patients were administered nab-paclitaxel plus carboplatin and had a median PFS of 30.3 (95% CI=not available [NA]-NA) months. The commonest grade 3-4 AEs included anemia (15.3%), white blood cell decreased (11.1%), and neutrophil count decreased (20.8%). No drug-related hypersensitivity reactions occurred. CONCLUSION: Nab-paclitaxel plus platinum as first-line treatment in OC was associated with a favorable prognosis and was tolerable in patients with OC.
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Neoplasias Ovarianas , Platina , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Platina/uso terapêutico , Paclitaxel , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/etiologia , Carboplatina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Pesticides are useful products for agriculture and human life, but they are often released into surface waters and are hazardous to aquatic ecosystems. Pesticides monitoring in surface waters is challenging due to the great variety, ultratrace levels and nonpoint source pollution of pesticides; however, continuous passive sampling may be conducive to solving these problems. This work evaluated the performance of a newly developed passive sampler (hydrophilic-lipophilic balance sorbent-embedded cellulose acetate membrane, HECAM) for six types of currently used/present pesticides. The uptake kinetics and equilibrium partitioning of nineteen pesticides in different dissolved concentrations were studied by dynamic accumulation and equilibrium partitioning experiments, respectively. In the dynamic accumulation experiments, pesticides gradually accumulated in the HECAM and followed a first-order kinetic model. The same type of pesticides had roughly comparable accumulation concentrations. The estimated uptake rate constants ranged from 1.04 to 13.5 L g-1 d-1, and sampling rates ranged from 0.02 to 0.31 L d-1 for the pesticides in the HECAM (size of 2 cm × 3 cm). Pesticide accumulation concentrations in the HECAM increased linearly with increasing dissolved concentrations, which means that varying concentrations can also be monitored by the HECAM. In the equilibrium partitioning experiments, the pesticide partitioning behavior at varying dissolved concentrations can be described by the Freundlich model. The calculated equilibrium partition coefficients (log KD) for pesticides ranged from 3.32 to 4.54, and different pesticide types showed different changes with log Kow. Comparable results were found when estimating chemical equilibrium partition coefficients by the dynamic accumulation and equilibrium partitioning methods. Field deployment of the HECAM in river waters resulted in the detection of four pesticides, and the measured results were comparable to those of active sampling coupled with liquid-liquid extraction. These results suggest that the HECAM would be a promising strategy for simultaneously monitoring diverse pesticides in waters.
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Doxycycline (DOX), a typical tetracycline antibiotic, is widely used because of its excellent antibacterial activity. To develop effective method for DOX has attracted much more attention. Herein, a new detection technology integrating magnetic solid phase extraction (MSPE) based on thermosensitive magnetic molecularly imprinted polymers (T-MMIPs) and fluorescence spectrometry based on carbon dots (CDs) was established. Thermosensitive magnetic molecularly imprinted polymers (T-MMIPs) was designed for selective enrichment of trace DOX. The synthesized T-MMIPs showed excellent selectivity for DOX. The adsorption performance of T-MMIPs varied with temperature in different solvents, which could achieve the enrichment and rapid desorption of DOX. In addition, the synthesized CDs had stable fluorescent property and better water-solubility, and the fluorescence of CDs was significantly quenched by DOX due to the internal filtration effect (IFE). Under the optimized conditions, the method resulted in good linearity over the range from 0.5 to 30 µg L-1, and the limit of detection was 0.2 µg L-1. The constructed detection technology was validated with real water samples, and excellent spiked recoveries from 92.5 % to 105.2 % were achieved. These data clearly indicated that the proposed technology was rapid, highly selective, environmentally friendly, and possessed significant potential application and development prospects.
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Impressão Molecular , Nanoestruturas , Impressão Molecular/métodos , Doxiciclina , Polímeros Molecularmente Impressos , Corantes Fluorescentes , Polímeros/química , Antibacterianos , Adsorção , Água/química , CarbonoRESUMO
Silver-containing wound dressings have shown attractive advantages in the treatment of wound infection due to their excellent antibacterial activity. However, the introduction of silver ions or AgNPs directly into the wound can cause deposition in the body as particles. Here, with the aim of designing low-silver wound dressings, a bimetallic-MOF antibacterial material called AgCu@MOF was developed using 3, 5-pyridine dicarboxylic acid as the ligand and Ag+ and Cu2+ as metal ion sites. PCbM (PVA/chitosan/AgCu@MOF) hydrogel was successfully constructed in PVA/chitosan wound dressing loaded with AgCu@MOF. The active sites on the surface of AgCu@MOF increased the lipophilicity to bacteria and caused the bacterial membrane to undergo lipid peroxidation, which resulted in the strong bactericidal properties of AgCu@MOF, and the antimicrobial activity of the dressing PCbM was as high as 99.9%. The chelation of silver ions in AgCu@MOF with chitosan occupied the surface functional groups of chitosan and reduced the crosslinking density of chitosan. PCbM changes the hydrogel crosslinking network, thus improving the water retention and water permeability of PCbM hydrogel so that the hydrogel has the function of binding wet tissue. As a wound adhesive, PCbM hydrogel reduces the amount of wound bleeding and has good biocompatibility. PCbM hydrogel-treated mice achieved 96% wound recovery on day 14. The strong antibacterial, tissue adhesion, and hemostatic ability of PCbM make it a potential wound dressing.
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Lp was a generally recognized as safe microorganism. Lactobacillus plantarum 590 was obtained by inserting nisI gene into Lp genome to help it tolerate higher concentration nisin. As the unintended effects of the genetically modified microorganism (GMM) are the most important barriers to the progress of GMM, we have performed a useful exploration to establish a new in vivo evaluation model for GMM from the point of view of intestinal health. In this study, Sprague-Dawley rats were orally administered with Lp 590 and Lp for 4 weeks. Fecal samples were collected to determine the number of beneficial bacteria Bifidobacterium and harmful bacteria Clostridium perfringens. Denaturing gradient gel electrophoresis was used to detect the bacterial profiles of every group. Fecal enzyme activities and short-chain fatty acids as main metabolites were also examined. Real time PCR (RT-PCR) and immunohistochemistry were used to analyze two proteins (ZO-1 and occludin) and secretory immunoglobulin A to detect intestinal permeability and mucosal immunity, gut permeability and gut mucosal immunity were analyzed to see whether GM Lp 590 can induce changes of the gut health when compared with non-GM Lp group, andeventually we concluded that there is no significant difference between GM Lp 590-fed group and non-GM Lp-fed group. The conclusion of gut health test was comparable withthat from traditional subchronic test. Evaluation of intestinal health will be a new approach of assessing the safety of GMM.
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Intestinos/microbiologia , Lactobacillus plantarum/genética , Lactobacillus plantarum/metabolismo , Animais , DNA/metabolismo , Eletroforese em Gel de Gradiente Desnaturante/métodos , Fezes , Feminino , Imuno-Histoquímica/métodos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Proteínas de Membrana/biossíntese , Ocludina , Organismos Geneticamente Modificados , Permeabilidade , Fosfoproteínas/biossíntese , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Proteína da Zônula de Oclusão-1RESUMO
OBJECTIVE: Elevated myeloid-derived suppressor cells (MDSCs) in many malignancies are associated with the increased risk for metastases and poor prognosis. Therefore, a mouse model of intraocular melanoma was established to explore how MDSCs influence liver metastases. METHODS: In this study, murine B16LS melanoma cells were transplanted into the posterior compartment (PC) of the eye of C57BL/6 mice. Leucocytes from the liver of naive mice and mice bearing melanoma liver metastasis were isolated using isotonic Percoll centrifugation, examined by flow cytometry for their expression of Gr1, CD11b, F4/80, RAE-1, and Mult-1, and further isolated for MDSCs and natural killer (NK) cells. The effects of MDSCs on NK cells were tested by coculturing and assessing the ability of NK cells to produce interferon-gamma (IFN-γ) by ELISA and NK cell cytotoxicity by 3H-thymidine incorporation assay. The impact of IFN-γ on liver metastases was examined via selectively depleting IFN-γ in vivo. RESULTS: The results showed that mice with liver metastases had increased levels of CD11b+Gr1+F4/80+ as well as CD11b+Gr1+F4/80- MDSCs. MDSCs significantly enhanced the generation of IFN-γ together with the cytotoxicity of the NK cells. Furthermore, these effects were cell-cell contact-dependent. Although IFN-γ was not of a toxic nature to the melanoma cells, it profoundly inhibited B16LS cell proliferation. Depleting IFN-γ in vivo led to increased liver metastases. CONCLUSION: All these findings first revealed that MDSCs accumulated in liver metastasis of intraocular melanoma could activate the NK cells to produce an effective anti-tumor immune response. Thus, the MDSCs' performance in different tumor models would need more investigation to boost current immunotherapy modalities.
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Neoplasias Hepáticas , Melanoma , Células Supressoras Mieloides , Camundongos , Animais , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , Interferon gama/genética , Interferon gama/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Melanoma/metabolismo , Melanoma/patologia , Células Matadoras Naturais , Neoplasias Hepáticas/patologia , Timidina/metabolismoRESUMO
Continuous cell division is a hallmark of cancer, and the underlying mechanism is tumor genomics instability. Cell cycle checkpoints are critical for enabling an orderly cell cycle and maintaining genome stability during cell division. Based on their distinct functions in cell cycle control, cell cycle checkpoints are classified into two groups: DNA damage checkpoints and DNA replication stress checkpoints. The DNA damage checkpoints (ATM-CHK2-p53) primarily monitor genetic errors and arrest cell cycle progression to facilitate DNA repair. Unfortunately, genes involved in DNA damage checkpoints are frequently mutated in human malignancies. In contrast, genes associated with DNA replication stress checkpoints (ATR-CHK1-WEE1) are rarely mutated in tumors, and cancer cells are highly dependent on these genes to prevent replication catastrophe and secure genome integrity. At present, poly (ADP-ribose) polymerase inhibitors (PARPi) operate through "synthetic lethality" mechanism with mutant DNA repair pathways genes in cancer cells. However, an increasing number of patients are acquiring PARP inhibitor resistance after prolonged treatment. Recent work suggests that a combination therapy of targeting cell cycle checkpoints and PARPs act synergistically to increase the number of DNA errors, compromise the DNA repair machinery, and disrupt the cell cycle, thereby increasing the death rate of cancer cells with DNA repair deficiency or PARP inhibitor resistance. We highlight a combinational strategy involving PARP inhibitors and inhibition of two major cell cycle checkpoint pathways, ATM-CHK2-TP53 and ATR-CHK1-WEE1. The biological functions, resistance mechanisms against PARP inhibitors, advances in preclinical research, and clinical trials are also reviewed.