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1.
Sci Total Environ ; 700: 134509, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31698269

RESUMO

Heavy metal concentrations in Taihu Lake sediment from studies performed between 2000 and 2018 were analyzed and Monte Carlo uncertainty analysis of heavy metal geo-accumulation, potential ecological risk and toxicity data for Taihu Lake sediment was performed to allow heavy metal pollution of Taihu Lake sediment to be described clearly, objectively, and comprehensively. Five main conclusions were drawn. (1) Most attention should be paid to As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn pollution. (2) The geo-accumulation indices showed that Cd is the most important pollutant and that the probabilities of Taihu Lake sediment being moderately polluted, moderately-heavily polluted, and heavily polluted were found to be 53.6%, 34.9%, and 18.7%, respectively. (3) Cd is the main contributor to potential ecological risks and had cumulative low risk, moderate risk, and considerable risk probabilities of 63.0%, 27.0%, and 10.0%, respectively. (4) Toxicity unit evaluation results indicated that Pb is the main contributor of toxicity in Taihu Lake sediment and had cumulative low toxicity, moderate toxicity, and high toxicity probabilities of 53.0%, 36.8%, and 5.6%, respectively. (5) Positive matrix factorization model results indicated that industrial sources are the main suppliers of heavy metals to Taihu Lake sediment, contributing 64.9% of the heavy metals. The summarized results and conclusions will improve local government awareness of heavy metal pollution in Taihu Lake and will aid in the development of appropriate pollution control measures. The results will also provide reference data for future studies of heavy metal pollution in sediment from Taihu Lake and other lakes.

2.
J Cell Physiol ; 235(3): 2195-2208, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31478571

RESUMO

Intervertebral disc degeneration (IDD) is a complex and chronic disease that involves disc cell senescence, death, and extracellular matrix (ECM) degradation. HOTAIR, a long non-coding RNA (lncRNA) is reportedly associated with autophagy, whereas autophagy is shown to promote IDD. However, how it affects nucleus pulposus (NP) cells, the primary component of intervertebral discs is still unclear. We hypothesized that HOTAIR promotes NP cell apoptosis and senescence through upregulating autophagy. Thus, silencing HOTAIR should inhibit autophagy and exert a therapeutic effect on IDD. Our in vitro experiments in human NP cells revealed that HOTAIR expression positively correlated with IDD grade, and overexpression enhanced autophagy. Autophagy inhibition via 3-methyladenine reversed HOTAIR stimulatory effects on apoptosis, senescence, and ECM catabolism, while the AMP-activated protein kinase (AMPK) inhibitor Compound C suppressed HOTAIR-induced autophagy through regulating AMPK/mTOR/ULK1 pathways. Our in vivo experiment then illustrated that silencing HOTAIR ameliorates IDD in rats. Collectively, we demonstrated that HOTAIR stimulates autophagy to promote NP cell apoptosis, senescence, and ECM catabolism. Therefore, silencing HOTAIR has the potential to become a treatment option for IDD.

3.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165575, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31666206

RESUMO

Intervertebral disc degeneration (IVDD) is a well-known cause of lower back pain. Icariin has been shown to exert a protective effect on human nucleus pulposus (NP) cells and accordingly has implications for the prevention and treatment of IVDD; however, the molecular mechanisms underlying its action are not fully established. In this study, the mechanisms underlying its protection against hydrogen peroxide (H2O2)-induced oxidative stress injury were investigated. In vitro, we demonstrated that icariin inhibits H2O2-induced mitochondria-mediated apoptosis. It upregulates oxidative stress mediators, i.e., reactive oxygen species, and downregulates mitochondrial membrane potential. Nuclear factor erythroid 2-related factor 2 (Nrf-2) is a key factor involved in the regulation of the endogenous defense system. It was proved that icariin could activate the Nrf-2 signaling pathway, upregulate the protein expression of nuclear respiratory factor-1 and the mitochondrial transcription factor, promoting mitochondrial biogenesis in human NP cells. An Nrf-2 agonist and inhibitor promoted or partly abolished the protective effects of icariin on mitochondrial homeostasis. Moreover, it was demonstrated that the Nrf-2 signaling pathway could be inhibited by the phosphatidylinositol 3-Kinase/AKT pathway. In vivo, icariin ameliorated IVDD in a rat model by promoting Nrf-2 activity, and preserving extracellular matrix in NP cells. These data suggest that icariin could ameliorate IVDD in rat models in vivo. In summary, the protective effects of icariin on human NP cells may suppress the pathogenesis of IVDD via the Nrf-2 signaling pathway. Our findings suggest that the Nrf-2 signaling pathway is a novel therapeutic target for the treatment of IVDD.

4.
Ultrason Sonochem ; 61: 104834, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31678867

RESUMO

Managing environmental contamination with Benz[a]anthracene (B[a]A) is essential due to its carcinogenic, teratogenic and mutagenic effects on humans and the environment. At present, the mainly B[a]A degradation methods used are photodegradation, bioremediation and traditional advanced oxidation, although they all have disadvantages. In this study, B[a]A was degraded by hydrodynamic cavitation (HC), chlorine dioxide (ClO2), or an innovative combination of the two methods. According to high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analysed the degradation products and degradation pathway of B[a]A, with the kinetics of different degradation methods discussed. Under optimal conditions, HC combined with ClO2 oxidation can further degrade products to achieve ring cleavage. Compared with the two separate degradation process methods, the combined method exerts a synergistic effect on the degradation of B[a]A, with an enhancement factor of 1.48. Experimental results showed that the combination method can realize enhanced complete degradation of B[a]A, reduce ClO2 requirements, improve efficiency, reduce energy consumption and produce less harmful products with ring cleavage achieved.

5.
Support Care Cancer ; 28(1): 373-380, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31049672

RESUMO

BACKGROUND/OBJECTIVES: The assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients' quality of life (QOL). METHODS: We reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients. RESULTS: By using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p < 0.001), female (p = 0.007), residence in a village (p = 0.004), a lower level of education (p < 0.001), and self-paying (p < 0.001) were indicated as risk factors of patients with gastric cancer to be suffering from severe malnutrition. There was a negative correlation between PG-SGA and various nutritional parameters (p < 0.05). The quality of life was significantly different in gastric cancer patients with different nutritional status (p < 0.01). CONCLUSION: Malnutrition of hospitalized patients with gastric cancer in China is common and seriously affects the patients' quality of life. The nutritional status should be evaluated in a timely manner and reasonable nutritional intervention should be provided as soon as possible. The PG-SGA was fit for using as a clinical nutrition assessment method, being worthy of clinical application.

6.
Adv Healthc Mater ; : e1901203, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31814301

RESUMO

Elevated low-density lipoprotein cholesterol (LDL-C) increases the risk of atherosclerotic cardiovascular disease. Peptide-based PCSK9 vaccines have shown a promising prospect of reducing LDL-C. In peptide vaccine (pVax) design, the peptide antigens need to conjugate with carrier protein (CP). However, CP incorporation can induce undesirable anti-CP antibodies, which sterically mask peptide epitopes from being recognized by specific B cells and impair subsequent therapeutically antibody production. This epitopic suppression has posed a barrier in clinical translation of conjugate vaccines all along. A model CP (keyhole limpet hemocyanin, KLH) is herein camouflaged with serum albumin (SA) into hybrid nanocarriers (SA@N), with PCSK9 peptide being anchored onto the surface to form nanovaccine (SA@NVax). Such camouflage of KLH via high "self" SA coverage is able to inhibit KLH from extracellular immune recognition and prevent detectable anti-KLH antibody production. Furthermore, the nanovaccine around 70 nm stabilized by intermolecular disulfide network is ideal for internalization and biodegradation by antigen presenting cells as well as better retention in draining lymph nodes and spleen. As expected, the SA@NVax efficiently primes higher anti-PCSK9 IgG antibody titer than PCSK9 pVax.

7.
Int J Mol Sci ; 20(23)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795097

RESUMO

Apple sugar and acid are the most important traits of apple fruit. Bud sport cultivars can provide abundant research materials for functional gene studies in apple. In this study, using bud sport materials with a rather different sugar and acid flavor, i.e., "Jonathan" and "Sweet Jonathan", we profiled the whole genome variations and transcriptional regulatory network during fruit developmental stages using whole genome sequencing and RNA-sequencing. Variation analysis identified 4,198,955 SNPs, 319,494 InDels, and 32,434 SVs between the two cultivars. In total, 4313 differentially expressed genes among all of the d 44,399 genes expressed were identified between the two cultivars during fruit development, and functional analysis revealed stress response and signal transduction related genes were enriched. Using 24,047 genes with a more variable expression value, we constructed 28 co-expression modules by weighted correlation network analysis. Deciphering of 14 co-expression modules associated with sugar or acid accumulation during fruit development revealed the hub genes associated with sugar and acid metabolism, e.g., MdDSP4, MdINVE, and MdSTP7. Furthermore, exploration of the intra network of the co-expression module indicated the close relationship between sugar and acid metabolism or sugar and stress. Motif-based sequence analysis of the 17 differentially expressed ATP-binding cassette transporter genes and Yeast one-hybrid assay identified and confirmed a transcription factor, MdBPC6, regulating the ATP-binding cassette (ABC) transporter genes and potentially participating in the apple fruit development or stress response. Collectively, all of the results demonstrated the use of parallel bud mutation sequencing and identified hub genes, and inferred regulatory relationships providing new information about apple fruit sugar and acid accumulation or stress response.

8.
J Food Biochem ; : e13106, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31808175

RESUMO

Barley is an ancient and important functional crop. In this study, the biochemical and antioxidant dynamics of dehusked barley during co-fermentation with Lactobacillus plantarum and Rhizopus oryzae were investigated. Results showed that amino acid nitrogen, soluble protein, <10 kDa peptide, and free phenolic contents increased with fermentation time; whereas the lactic acid bacteria count, reducing sugar, and free flavonoid contents showed a tendency to increase first and then decrease. SDS-PAGE analysis indicated that bands at >25 and <18.4 kDa were shown with improved intensity with time, whereas bands at 18.4-25 kDa were disappeared. Additionally, fermentation time led to an increase in DPPH, hydroxyl, ABTS+ radical scavenging activity, and ferric reducing antioxidant power. Thus, this study demonstrated that co-fermentation with L. plantarum and R. oryzae could improve nutrition and potential bioactivity of barley, and use barley as a good solid-state food carrier for probiotics. PRACTICAL APPLICATIONS: Barley is rich in nutrition and has a huge production. However, due to its high-fiber and special protein composition, there is a certain palatability problem whether it is used to produce flour or other products. Therefore, most of the barley is destined to animal feed and malt, and only a small part is used directly for human consumption. Aiming at this problem, on the basis of the optimization of the fermentation process at early stage, our results further demonstrated co-fermentation with L. plantarum and R. oryzae could enhance the nutritional value and potential bioactivity of barley, thus providing a novel approach to develop functional barley food and improve the direct utilization rate of barley in food processing.

9.
BMC Ecol ; 19(1): 50, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801501

RESUMO

BACKGROUND: Stellera chamaejasme L. is a poisonous plant widely distributes in degraded grasslands in China. The mechanism underlying its spread remains unknown. In some degraded grasslands, S. chamaejasme has gradually replaced previous dominant species, such as Leymus chinensis, Stipa krylovii, Artemisia eriopoda on typical steppes. Apart from its unpalatability by livestock, we hypothesized that the survival strategy (nutrient uptake and water use efficiency) of S. chamaejasme in degraded grasslands could be distinct from other coexisting species in the community. Recently, ecological stoichiometry has been suggested as a new approach for studying the demand for natural resources of plants in a changing world, and the leaf carbon isotopic composition (δ13C leaf) as a rapid and effective high throughput phenotyping method for water use efficiency (WUE), both of which can reveal the survival and adaptive strategies of plants. Therefore, in this study we aimed to fill the knowledge gap concerning ecological stoichiometry in the leaf, stem, and root of S. chamaejasme and its surrounding soil on grasslands with different degrees of degradation, and comparing the leaf nutrient content and δ13C of S. chamaejasme with the coexisting species (L. chinensis, S. krylovii, A. eriopoda) in the communities. Toward this goal, we conducted a field survey in which plants and soils were sampled from four different degraded grasslands on typical steppes in China. RESULTS: Our results showed that there is no significant difference of carbon content (C%) and nitrogen content (N%) in leaves of S. chamaejasme in different degraded grasslands, and all element contents and element ratios in stems did not differ significantly. Meanwhile, ecological stoichiometry of S. chamaejasme is distinct from the coexisting species, with low C%, high N% and phosphorus content (P%) in the leaf, indicating high nutrient uptake efficiency of S. chamaejasme in nutrient-poor environments like degraded grasslands. Additionally, S. chamaejasme showed significant higher WUE than other species. CONCLUSIONS: Our results indicated that high nutrient uptake efficiency and high WUE of S. chamaejasme might together contribute to the spread of S. chamaejasme in degraded grasslands.

10.
Nat Chem ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792388

RESUMO

Topological transitions between considerably different phases typically require harsh conditions to collectively break chemical bonds and overcome the stress caused to the original structure by altering its correlated bond environment. In this work we present a case system that can achieve rapid rearrangement of the whole lattice of a metal-organic framework through a domino alteration of the bond connectivity under mild conditions. The system transforms from a disordered metal-organic framework with low porosity to a highly porous and crystalline isomer within 40 s following activation (solvent exchange and desolvation), resulting in a substantial increase in surface area from 725 to 2,749 m2 g-1. Spectroscopic measurements show that this counter-intuitive lattice rearrangement involves a metastable intermediate that results from solvent removal on coordinatively unsaturated metal sites. This disordered-crystalline switch between two topological distinct metal-organic frameworks is shown to be reversible over four cycles through activation and reimmersion in polar solvents.

12.
Clin Chim Acta ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31794768

RESUMO

BACKGROUND AND AIMS: The role of monocyte lymphocyte ratio (MLR) in predicting the risk of chronic kidney disease (CKD) is unclear, although inflammation contributes to the development of CKD. This study aimed to investigate whether elevated MLR predicts new-onset CKD. METHODS: This study enrolled 14,033 consecutively Chinese participants. The primary outcome was the new-onset CKD defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the presence of proteinuria after follow-up. After the descriptive analyses of baseline data, Univariate and multivariate Cox proportional models were used to evaluate the independent relationship between MLR and new-onset CKD. RESULTS: 11,280 participants were included in the final analysis, and 58.44% (n = 6592) of them were male. The mean age was 44.67 ± 12.85 years. After a median follow-up of 1.94 years, 2.55% (n = 288) of participants developed new-onset CKD. MLR was associated with the increased risk of CKD (HR = 16.12, 95% CI = 4.52-57.56, p < 0.0001). After adjustment for age, gender, body mass index, history of hypertension, systolic blood pressure, high-density lipoprotein cholesterol, triglyceride, fasting plasma glucose, uric acid and estimated glomerular filtration rate, MLR remained an independent risk factor for CKD (HR = 8.89, 95%CI = 2.18-36.27, p = 0.0023). CONCLUSION: MLR is an independent predictor of the risk of CKD, which might be expected to better guide early prevention and treatment interventions.

13.
FEBS Open Bio ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31788976

RESUMO

Long-term or heavy use of glucocorticoids (GC) can cause severe necrosis of the femoral head, but the underlying mechanisms are still unclear. Recent studies have found that mitochondrial dynamics play an important role in femoral head necrosis. Here, we investigated the effect of dexamethasone on the mitochondrial function of mesenchymal stem cells (MSCs). We observed that high concentrations of dexamethasone (10-6 mol/L) decreased cell activity, promoted apoptosis, elevated levels of reactive oxygen species (ROS), and disrupted mitochondrial dynamics. Furthermore, dexamethasone (10-6 mol/L) inhibited osteogenesis of stem cells and promoted adipogenesis. These findings may facilitate greater understanding of the adverse effects of dexamethasone on the femoral head.

14.
Eur J Pharmacol ; 865: 172787, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31712061

RESUMO

Zinc finger E-box binding homeobox 1 (ZEB1) (previously known as TCF8), a transcriptional repressor, is a member of the zinc-finger family of proteins. Numerous studies have demonstrated that abnormal expression of ZEB1 in many types of liver disease including hepatocellular carcinoma (HCC). Liver fibrosis is the basis and central link in the progression of liver disease. Thereby, the function of ZEB1 in liver fibrosis has been investigated. The aim of the present study was to investigate the role of ZEB1 in liver fibrosis and to elucidate the mechanism. In this study, we explored the effect of ZEB1 in hepatic stellate cells (HSCs) activation and the regulatory mechanism of the Wnt/ß-catenin signaling pathway. Additionally, ZEB1 positively regulated the expression levels of α-SMA and Col.I in vivo and in vitro, which were correlated with the activated HSCs. Furthermore, overexpression of ZEB1 could inhibit HSCs apoptosis and promote IL-6 and TNF-α secretion in LX-2 cells. Conversely, ZEB1 silencing led to the promotion of cell proliferation and the reduction of IL-6 and TNF-α secretion in LX-2 cells. Mechanically, canonical Wnt/ß-catenin signaling pathway could be regulated by ZEB1. Collectively, the data suggested that ZEB1 might play a significant role in the activation of LX-2 cells, and Wnt/ß-catenin signaling pathway might participate in this progression.

15.
Int J Biol Macromol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31730962

RESUMO

The objective of this study was to synthesize and characterize cystamine dihydrochloride (CYS) crosslinked carboxymethyl cellulose/quaternized chitosan (CMC/HACC) composite hydrogel film. Firstly, the glycidyl-based quaternary ammonium chitosan derivative (HACC) was synthesized using nucleophilic substitution reaction. Then HACC was analyzed by FTIR, 1HNMR spectra and the composite films at different blending ratio of CMC and HACC were studied by rheology measurement, mechanical and swelling tests. When the composite films were prepared under optimized conditions (CMC: HACC = 7:1), they showed excellent mechanical properties (with improved 93.3% tensile strength and 2.3% elongation at break) and swellability (equilibrium swelling ratio increased 270%) compared to pure CMC film. 5-Fluorouracil (5-FU) was used as drug model which has broad-spectrum anticancer properties. The 5-FU/CMC/HACC composite films showed redox and pH responsive of drug release properties along with well biocompatibility. The in vitro cytotoxicity and cell apoptosis studies showed the drug loaded composite films with obvious toxicity against HepG2 cells especially in the presence of GSH. In addition, CMC/HACC composite films showed good antibacterial against S. aureus and E. coli, while pure CMC film had no antimicrobial activities. It can be concluded that CMC/HACC composite films can be potentially used as targeted drug delivery system.

16.
Br J Anaesth ; 123(6): 777-794, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31668347

RESUMO

BACKGROUND: Dexmedetomidine (DEX) is a highly selective alpha2 adrenoceptor agonist with broad pharmacological effects, including sedation, analgesia, anxiolysis, and sympathetic tone inhibition. Here we report a systematic review and meta-analysis of its effects on stress, inflammation, and immunity in surgical patients during the perioperative period. METHODS: We searched MEDLINE, METSTR, Embase, and Web of Science for clinical studies or trials to analyse the effects of DEX on perioperative stress, inflammation, and immune function. RESULTS: Sixty-seven studies (including randomised controlled trials and eight cohort studies) with 4842 patients were assessed, of which 2454 patients were in DEX groups and 2388 patients were in control (without DEX) groups. DEX infusion during the perioperative period inhibited release of epinephrine, norepinephrine, and cortisol; decreased blood glucose, interleukin (IL)-6, tumour necrosis factor-α, and C-reactive protein; and increased interleukin-10 in surgical patients. In addition, the numbers of natural killer cells, B cells, and CD4+ T cells, and the ratios of CD4+:CD8+ and Th1:Th2 were significantly increased; CD8+ T-cells were decreased in the DEX group when compared with the control group. CONCLUSIONS: DEX, an anaesthesia adjuvant, can attenuate perioperative stress and inflammation, and protect the immune function of surgical patients, all of which may contribute to decreased postoperative complications and improved clinical outcomes.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Inflamação/tratamento farmacológico , Complicações Intraoperatórias/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Estresse Fisiológico/efeitos dos fármacos , Humanos , Imunidade , Período Pré-Operatório
17.
Chemosphere ; 241: 125044, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31683426

RESUMO

A novel ball milled Fe0-biochar composite was synthesized by ball milling the mixture of biochar (pyrolyzed at 300 °C, 500 °C, and 700 °C) and micron grade iron powder. FTIR, SEM, TEM-EDS, XRD, and XPS were applied to characterize this composite. XRD results showed that iron carbide phase was formed during the ball milling process. The ability of this synthesized composited to remove aqueous Cr(VI) was tested. Removal rates of Cr(VI) (49.6%, 65.8%, and 97.8%, respectively) by ball milled Fe0-biochar composite consisting of biochar pyrolyzed at 300 °C (300BMFe0-BC), 500 °C (500BMFe0-BC), and 700 °C (700BMFe0-BC) were much higher than those (19%, 11%, and 4%, respectively) by pristine biochar pyrolyzed at 300 °C (300BC), 500 °C (500BC), and 700 °C (700BC). Cr(VI) removal rate by 700BMFe0-BC increased from 15.4% to 97.8% when prolonging ball milling time from 6 h to 48 h. Ball milling promoted the combination of Fe0 and biochar as well as reduced the hydrodynamic diameter of the composite. Acidic conditions favored Cr(VI) removal. Ball milling exposed the functional groups of biochar and improved its Cr(VI) removal rate. Raman spectra showed that the degree of graphitization in 700 °C ball milled biochar (700BMBC) was the highest. Electrochemical analysis demonstrated that 700BMBC had the highest electron transfer capacity. In the presence of Fe0, graphitized structure in 700BMBC acted as an electron conductor, facilitating electron transfer from Fe0 to Cr(VI). Ball milling also destroyed the surface iron oxide layer to regenerate the composite.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31705175

RESUMO

PURPOSE: Accurate evaluation of hypoxia is particularly important in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. The aim of this study was to propose a novel imaging strategy for quantitative three-dimensional (3D) evaluation of hypoxia in a small animal model of NPC. METHODS: A carbonic anhydrase IX (CAIX)-specific molecular probe (CAIX-800) was developed for imaging of hypoxia. Mouse models of subcutaneous, orthotopic, and spontaneous lymph node metastasis from NPC (5 mice per group) were established to assess the imaging strategy. A multi-modality imaging method that consisted of a hybrid combination of fluorescence molecular tomography-computed tomography (FMT-CT) and multispectral optoacoustic tomography (MSOT) was used for 3D quantitative evaluation of tumour hypoxia. Magnetic resonance imaging, histological examination, and immunohistochemical analysis were used as references for comparison and validation. RESULTS: In the early stage of NPC (2 weeks after implantation), FMT-CT enabled precise 3D localisation of the hypoxia biomarker with high sensitivity. At the advanced stage (6 weeks after implantation), MSOT allowed multispectral analysis of the biomarker and haemoglobin molecules with high resolution. The combination of high sensitivity and high resolution from FMT-CT and MSOT could not only detect hypoxia in small-sized NPCs but also visualise the heterogeneity of hypoxia in 3D. CONCLUSIONS: Integration of FMT-CT and MSOT could allow comprehensive and quantifiable evaluation of hypoxia in NPC. These findings may potentially benefit patients with NPC undergoing radiotherapy in the future. Graphical abstract A novel multimodality imaging strategy for three-dimensional evaluation of tumour hypoxia in an orthotopic model of nasopharyngeal carcinoma.

19.
Biosens Bioelectron ; : 111883, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31767349

RESUMO

Nanozymes with peroxidase-like activity have been widely used as signal labels in electrochemical immunosensors. However, these sensors always suffer from some shortcomings during the processes underlying nanozyme labeling, including complex reactions, nanozyme inactivation after being decorated on the antibodies. To solve these problems, a novel electrochemical immunosensor was designed for ultrasensitive detection of sulfonamides (SAs), in which the synthesized 2D Cu-TCPP(Fe) with peroxidase-like property was used as a nanozyme that was directly modified on the electrode surface. Meanwhile, the structure of 2D Cu-TCPP(Fe) could be destroyed by the polyethyleneimine (PEI) from PEI-GO@Ab2 due to the stronger affinity between PEI and Cu2+, leading to an activity change of the prepared nanozyme. When H2O2 was introduced to the system, the electrochemical current was significantly declined owing to the peroxidase activity of 2D Cu-TCPP(Fe) decreased, which led to signal amplifications. Under the optimized conditions, this strategy had a wide detection range (1.186-28.051 ng/mL), satisfactory accuracy and precision (recoveries, 64-118%; CV, 2.16-7.27%) with a low detection limit of 0.395 ng/mL. The findings of this study indicate that the electrochemical immunosensor we developed has great potential and can be used for enzyme-free detection of SAs in environmental samples.

20.
Eur J Radiol ; 121: 108711, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677544

RESUMO

PURPOSE: We developed and validated a radiomic model based on mammography and assessed its value for predicting the pathological diagnosis of Breast Imaging Reporting and Data System (BI-RADS) category 4 calcifications. MATERIALS AND METHODS: Patients with a total of 212 eligible calcifications were recruited (159 cases in the primary cohort and 53 cases in the validation cohort). In total, 8286 radiomic features were extracted from the craniocaudal (CC) and mediolateral oblique (MLO) images. Machine learning was used to select features and build a radiomic signature. The clinical risk factors were selected from the independent clinical factors through logistic regression analyses. The radiomic nomogram incorporated the radiomic signature and an independent clinical risk factor. The diagnostic performance of the radiomic model and the radiologists' empirical prediction model was evaluated by the area under the receiver operating characteristic curve (AUC). The differences between the various AUCs were compared with DeLong's test. RESULTS: Six radiomic features and the menopausal state were included in the radiomic nomogram, which discriminated benign calcifications from malignant calcifications with an AUC of 0.80 in the validation cohort. The difference between the classification results of the radiomic nomogram and that of radiologists was significant (p < 0.05). Particularly for patients with calcifications that are negative on ultrasounds but can be detected by mammography (MG+/US- calcifications), the identification ability of the radiomic nomogram was very strong. CONCLUSIONS: The mammography-based radiomic nomogram is a potential tool to distinguish benign calcifications from malignant calcifications.

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