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In contrast to well-established DNA-selective dyes for live cell imaging, RNA-selective dyes have been less developed owing to the challenges of making small molecules have RNA selectivity over DNA. Two kinds of dyes are now commercially available for nucleolar RNA imaging in cells, but these two dyes do not apply to living cells and have limited use in fixed and permeabilized cells. Herein, we report on thiazole orange (TO), a well-known nucleic acid stain, as a promising fluorogenic dye for nucleolar RNA imaging in living cells. TO shows clear response selectivity for RNA over DNA with a significant light-up property upon binding to RNA (λem = 532 nm, I/I0 = 580-fold, and Φbound/Φfree = 380) and is even applicable to wash-free imaging of living cells. More interestingly, 2TO, a regioisomer of TO in which the benzothiazole unit is connected to position 2 in the quinoline ring, performs much better (λem = 532 nm, I/I0 = 430-fold, Φbound/Φfree = 1200), having superior selectivity for RNA in both solution and living cells. The comparison with TO derivatives carrying different substituents at N1 of the quinoline ring reveals that the slight change in the TO framework significantly affects RNA selectivity, photostability and membrane permeability.
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Quinolinas , RNA , RNA/química , Benzotiazóis/química , DNA/química , Quinolinas/química , Corantes , Corantes Fluorescentes/químicaRESUMO
In recent decades, coastal ports have experienced rapid development and become an important economic and ecological hub in China. Atmospheric particle is a research hotspot in atmospheric environmental sciences in inland regions. However, few studies on the atmospheric particle were conducted in coastal port areas in China, which indeed suffers atmospheric particle pollution. Lack of the physicochemical characteristics of fine particles serves as an obstacle toward the accurate control for air pollution in the coastal port area in China. Here, a field observation was conducted in an important coastal port city in Yangtze River Delta from March 6 to March 19, 2019. The average PM2.5 concentration was 63.7 ± 27.8 µg/m3 and NO3-, SO42-, NH4+, and organic matter accounted for ~60% of PM2.5. Fe was the most abundant trace metal element and V as the ship emission indicator was detected. Transmission electron microscopy images showed that SK-rich, soot, Fe, SK-soot and SK-Fe were the major individual particles in the coastal port. V and soluble Fe were detected in sulfate coating of SK-Fe particles. We found that anthropogenic emissions, marine sea salt, and secondary atmosphere process were the major sources of fine particles. Backward trajectory analysis indicated that the dominant air masses were marine air mass, inland air mass from northern Zhejiang and inland-marine mixed air mass from Shandong and Shanghai during the sampling period. The findings can help us better understand the physicochemical properties of atmospheric fine particles in the coastal port of Eastern China.
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Poluentes Atmosféricos , Rios , Poluentes Atmosféricos/análise , China , Cidades , Monitoramento AmbientalRESUMO
A series of 1,1-diaryl tertiary alcohols and some of their dehydration derivatives were designed, synthesized and evaluated for their antifungal activities. Some compounds exhibited moderate inhibitory activities against seven plant pathogens at 50µg/mL in vitro, compounds 5g and 7c displayed nearly the same or higher fungicidal activities against some certain plant pathogens compared with the lead compound pyrimorph. A qualitative structure-activity relationship (SAR) analysis revealed that the Cl substituent and its position at the pyridine ring were crucial for the compounds' activities. Specially, several compounds displayed 100% protection effect against wheat powdery mildew or cucumber anthrax at 400mg/mL in vivo, which suggested that these compounds might be potential fungicidal candidates for certain plant diseases.
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Álcoois/farmacologia , Antraz/tratamento farmacológico , Antifúngicos/farmacologia , Ascomicetos/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Álcoois/síntese química , Álcoois/química , Animais , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Doenças das Plantas , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: To evaluate the effects of Wuziyanzong pill on the levels of serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and the expressions of nuclear-associated antigen Ki67 (Ki67), androgen receptor (AR) in testes of young rats. METHODS: Sixteen 20-day-old Wistar male rats were randomly divided into control and treatment group (n = 8). Rats in treatment group were administered Wuziyanzong pill by gavage; rats in control group administered the same volume of saline. After 10 days of treatment, the rats were killed, and then serum and testes were taken. The levels of FSH, LH and T were measured by radioimmunoassay (RIA). The histology of seminiferous tubule was observed by hematoxylin-eosin (HE) staining. The expression of Ki67 was detected by immunohistochemical assay (IHC). The mRNA level of Ki67, AR and CK-18 was detected with quantitative real-time polymerase chain reaction (Q-RT-PCR), the protein level of AR and CK-18 were tested by Western blot. RESULTS: Compared with control group, T level in treatment group increased significantly (P < 0.05). HE staining showed that both leydig cells and germ cells increased in treatment group. Expressions of Ki67 and AR became higher after treatment. There were no changes in CK-18 expression. CONCLUSION: Wuziyanzong pill can up-regulate AR level to promote germ cell proliferation and differentiation in young male rats.
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Medicamentos de Ervas Chinesas/administração & dosagem , Hormônios Esteroides Gonadais/genética , Antígeno Ki-67/genética , Receptores Androgênicos/genética , Testículo/efeitos dos fármacos , Animais , Hormônios Esteroides Gonadais/metabolismo , Antígeno Ki-67/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Ratos , Ratos Wistar , Receptores Androgênicos/metabolismo , Testículo/metabolismoRESUMO
Medical image segmentation has an important application value in the modern medical field, it can help doctors accurately locate and analyze the tissue structure, lesion areas, and organ boundaries in the image, which provides key information support for clinical diagnosis and treatment, but there are still a large number of problems in the accuracy of the segmentation, so in this paper, we propose a medical image segmentation network combining the Hadamard product and dual-scale attention gate (DAU-Net). First, the Hadamard product is introduced in the structure of the fifth layer of the codec for element-by-element multiplication, which can generate feature representations with more representational capabilities. Second, in the jump connection module, we propose a dual scale attention gating (DSAG), which can highlight more valuable features and achieve more efficient jump connections. Finally, in the decoder feature structure, the final segmentation result is obtained by aggregating the feature information provided by each part, and decoding is achieved by up-sampling operation. Through experiments on two public datasets, Luna and Isic2017, DAU-Net is able to extract feature information more efficiently using different modules and has better segmentation results compared to classical segmentation models such as U-Net and U-Net++, and also verifies the effectiveness of the model.
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This study aims to investigate the differential expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the peritoneal dialysate among patients with different durations of peritoneal dialysis and its association with the angiogenic marker vascular* endothelial growth factor (VEGF), the fibronectin (FN), and various clinical indicators. A cohort of 122 peritoneal dialysis patients was categorized into short-term (≤1 year, n = 33), mid-term (>1 and ≤5 years, n = 55), and long-term (>5 years, n = 34) groups based on dialysis duration. We utilized enzyme-linked immunosorbent assay (ELISA) and western blot assays to quantify the levels of IGF2BP3, VEGF, and FN in the dialysate. Our findings showed a progressive increase in IGF2BP3 levels with the duration of PD, with the long-term group exhibiting significantly higher levels than both the short-term and mid-term groups (p < 0.001). A positive correlation between IGF2BP3 and VEGF (r = 0.386, p = 0.013), as well as between IGF2BP3 and FN (r = 0.340, p = 0.030), was observed. IGF2BP3 levels also correlated positively with serum creatinine, calcium, and phosphorus levels. In vitro analysis further confirmed that IGF2BP3 expression is enhanced in human peritoneal mesothelial cells under high-glucose conditions (p < 0.05). The study highlights the potential of IGF2BP3 in PD effluent as a biomarker for monitoring PF progression, with its expression significantly correlated with the duration of PD (Pearson r = 0.897, p < 0.001). In conclusion, our results underscore a correlation between elevated IGF2BP3 levels and PD duration, suggesting the clinical significance of IGF2BP3 as a biomarker for PF progression.
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Diálise Peritoneal , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/metabolismo , Peritônio/química , Peritônio/metabolismo , Relevância Clínica , Soluções para Diálise/metabolismo , Biomarcadores/metabolismoRESUMO
Acquired resistance represents a critical clinical challenge to molecular targeted therapies such as tyrosine kinase inhibitors (TKIs) treatment in hepatocellular carcinoma (HCC). Therefore, it is urgent to explore new mechanisms and therapeutics that can overcome or delay resistance. Here, a US Food and Drug Administration (FDA)-approved pleuromutilin antibiotic is identified that overcomes sorafenib resistance in HCC cell lines, cell line-derived xenograft (CDX) and hydrodynamic injection mouse models. It is demonstrated that lefamulin targets interleukin enhancer-binding factor 3 (ILF3) to increase the sorafenib susceptibility of HCC via impairing mitochondrial function. Mechanistically, lefamulin directly binds to the Alanine-99 site of ILF3 protein and interferes with acetyltransferase general control non-depressible 5 (GCN5) and CREB binding protein (CBP) mediated acetylation of Lysine-100 site, which disrupts the ILF3-mediated transcription of mitochondrial ribosomal protein L12 (MRPL12) and subsequent mitochondrial biogenesis. Clinical data further confirm that high ILF3 or MRPL12 expression is associated with poor survival and targeted therapy efficacy in HCC. Conclusively, this findings suggest that ILF3 is a potential therapeutic target for overcoming resistance to TKIs, and lefamulin may be a novel combination therapy strategy for HCC treatment with sorafenib and regorafenib.
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Carcinoma Hepatocelular , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas , Mitocôndrias , Proteínas do Fator Nuclear 90 , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Humanos , Animais , Camundongos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Proteínas do Fator Nuclear 90/metabolismo , Proteínas do Fator Nuclear 90/genética , Linhagem Celular Tumoral , Diterpenos/farmacologia , Compostos Policíclicos/farmacologia , Compostos Policíclicos/uso terapêutico , Homeostase/efeitos dos fármacos , Sorafenibe/farmacologia , Modelos Animais de Doenças , Limoninas/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Benzofuranos , NaftoquinonasRESUMO
Noble metal nanoparticles show good application prospects in biosensors and anti-tumor drug research. Herein, the near-spherical silverpalladium bimetallic nanoparticles supported by elm pod polysaccharide (EPP-AgPd1.5 NPs) were prepared by using the elm pod polysaccharide (EPP). EPP acts as a stabilizer and reducing agent due to its water solubility and weak reducing ability. The particle size of EPP-AgPd1.5 NPs was 33.6 ± 5.5 nm. In addition, EPP-AgPd1.5 NPs had peroxidase-like activity to catalyze 3,3',5,5'-tetramethylbenzidine (TMB) to oxidized TMB by catalyzing H2O2 to OH. Based on the peroxidase-like activity of EPP-AgPd1.5 NPs, a method for detecting glutathione was established, and the detection limit and linear range of glutathione concentration were 0.279 µM and 0-400 µM, respectively. More importantly, the photothermal conversion efficiency of EPP-AgPd1.5 NPs reached 39.7 %, and their inhibition rate in HeLa cells reached 69.9 %. Silverpalladium bimetallic nanoparticles stabilized by EPP had good performance in glutathione detection and anti-tumor drugs.
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Nanopartículas Metálicas , Peroxidase , Humanos , Prata , Paládio , Peróxido de Hidrogênio , Células HeLa , Polissacarídeos/farmacologia , Glutationa , Colorimetria/métodosRESUMO
Intratumoral delivery of mRNA encoding immunostimulatory molecules can initiate a robust, global antitumor response with little side effects by enhancing local antigen presentation in the tumor and the tumor draining lymph node. Neoantigen-based mRNA nanovaccine can inhibit melanoma growth in mice by intratumoral injection. Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune responses by secreting immunosuppressive agents, such as reactive oxygen species (ROS). Suppression of STAT3 activity by stattic may reduce MDSC-mediated immunosuppression in the TME and promote the antitumor immune responses. In this study, in vitro transcribed mRNA encoding tumor antigen survivin was prepared and injected intratumorally in BALB/c mice bearing subcutaneous colon cancer tumors. In vivo studies demonstrated that intratumoral survivin mRNA therapy could induce antitumor T cell response and inhibit tumor growth of colon cancer. Depletion of CD8+ T cells could significantly inhibit survivin mRNA-induced antitumor effects. RT-qPCR and ELISA analysis indicated that survivin mRNA treatment led to increased expression of receptor activator nuclear factor-κB ligand (RANKL). In vitro experiment showed that MDSCs could be induced from mouse bone marrow cells by RANKL and RANKL-induced MDSCs could produce high level of ROS. STAT3 inhibitor stattic suppressed activation of STAT3 and NF-κB signals, thereby inhibiting expansion of RANKL-induced MDSCs. Combination therapy of survivin mRNA and stattic could significantly enhance antitumor T cell response, improve long-term survival and reduce immunosuppressive tumor microenvironment compared to each monotherapy. In addition, combined therapy resulted in a significantly reduced level of tumor cell proliferation and an obviously increased level of tumor cell apoptosis in CT26 colon cancer-bearing mice, which could be conducive to inhibit the tumor growth and lead to immune responses to released tumor-associated antigens. These studies explored intratumoral mRNA therapy and mRNA-based combined therapy to treat colon cancer and provide a new idea for cancer therapy.
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Neoplasias do Colo , Óxidos S-Cíclicos , Camundongos Endogâmicos BALB C , RNA Mensageiro , Fator de Transcrição STAT3 , Survivina , Animais , Survivina/genética , Survivina/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , RNA Mensageiro/genética , Neoplasias do Colo/terapia , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Neoplasias do Colo/genética , Óxidos S-Cíclicos/farmacologia , Linhagem Celular Tumoral , Injeções Intralesionais , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Camundongos , Feminino , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Humanos , Carga Tumoral/efeitos dos fármacos , Transdução de SinaisRESUMO
BACKGROUND: Long term peritoneal dialysis leads to peritoneal epithelial-mesenchymal transformation (EMT), angiogenesis, and ultrafiltration failure. Although recent evidence suggests that inhibiting STAT3 (signal transducer and activator of transcription 3) can prevent kidney fibrosis, and that STAT3 can enhance glucose metabolism, the effect of STAT3 in peritoneal fibrosis (PF) has not been clarified. METHODS: Our study determined the effects of STAT3 on EMT and key glycolysis enzymes in mesothelial HMrSV5 cells by knockdown and overexpression of STAT3. In addition, we established a rat PF model to examine the role of pharmacologic inhibition of STAT3 or 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) in this process. RESULTS: High glucose (HG) caused the upregulation of α-smooth muscle actin and transforming growth factor beta 1 and the downregulation of E-cadherin, and induced STAT3 activation in HMrSV5 cells. In addition, HMrSV5 cells cultured in high glucose showed high expression of key glycolysis enzymes, which could be inhibited by STAT3 siRNA. Furthermore, treating mesothelial cells with 3PO, the PFKFB3 inhibitor, could attenuate high glucose-induced EMT. Moreover, daily administration of dialysis fluid could induce peritoneal fibrosis. The peritoneal fibrosis was accompanied by enhanced phosphorylation of STAT3 and the upregulation of PFKFB3. The administration of BP-1-102 or 3PO prevented fibrosis and inhibited angiogenesis in PF rats. CONCLUSIONS: si-STAT3 attenuated the HG-induced EMT and hyperglycolysis, and the overexpression of STAT3 could induce EMT in HMrSV5 cells. 3PO could markedly attenuate HG-induced EMT by decreasing PFKEB3 in HMrSV5 cells. In addition, we demonstrated that inhibiting STAT3 signaling or peritoneal hyperglycolysis could attenuate peritoneal fibrosis and angiogenesis in vivo. Our findings linked the STAT3/PFKFB3 signaling to the development of PF. HG/STAT3/PFKFB3 might promote the progression of PF through regulating profibrosis and angiogenesis.
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The green synthesis of silver nanoparticles (Ag NPs) for catalysis and biological applications has gained great interest. Natural elm pods are a type of food that possesses anti-inflammatory and pain-relieving effects. In this study, elm pod polysaccharide (EPP) was extracted from elm pods using hot water extraction for the first time. Biocompatible EPP-stabilized silver nanoparticles (EPP-Agn NPs) were prepared by using a green synthesis method. The EPP-Ag25 NPs had a hydrodynamic size of 40.9 nm and a highly negative surface charge of -27.4 mV. Furthermore, EPP-Ag25 NPs exhibited high catalytic activity for the reduction of 4-nitrophenol, and the catalytic reaction followed a pseudo-first order kinetic equation. More importantly, the inhibition rate of EPP-Ag25 NPs on Escherichia coli was 71 % when samples were treated with an 808 nm laser. Besides, EPP-Agn NPs effectively inhibited the proliferation of tumor cells irradiated by an 808 nm laser. The improved performance of EPP-Agn NPs was due to the good stability of EPP. Taken together, EPP-Agn NPs had good stability, catalytic activity, antibacterial and antitumor ability under laser irradiation. EPP is a good stabilizer for many nanoparticles which have broad applications in the field of catalysis and biomedicine in the future.
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Nanopartículas Metálicas , Prata , Antibacterianos/farmacologia , Catálise , Escherichia coli , Testes de Sensibilidade Microbiana , Polissacarídeos/farmacologia , Prata/farmacologiaRESUMO
Water-soluble ions and some trace gases during the Spring Festival in Ningbo were observed using an ion online gas composition and aerosol monitoring system. Combined with meteorological elements data, the source analysis and composition characteristics of water-soluble ions and trace gases were analyzed. The average concentration of ρ(PM2.5) during the observation period was 33.1 µg·m-3, and there was light pollution. The order of concentration of water-soluble ions was NO3->SO42->NH4+>K+>Cl->Na+>Ca2+>Mg2+. The secondary inorganic ions ρ(NO3-), ρ(SO42-), and ρ(NH4+) were the most water-soluble ions, which were 12.5, 10.5, and 7.2 µg·m-3, respectively. According to the PMF source analysis, firecracker combustion, secondary generation (background, industrial source), and dust sources were the major sources of fine particles during the observation period, and their contribution rates of PM2.5 were 21.9%, 64.5%, and 13.6%, respectively. When the secondary generation was the main pollution, NH4+ accounted for 92.2% of the cations. When firecracker combustion was the main pollution from New Year's Eve to the second day, the proportion of K+ions significantly increased. Dust sources were affected by regional transport from the northwest direction. When the dust source was the main pollution, the proportion of K++Ca2+and Na++Mg2+ increased.
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Poluentes Atmosféricos , Material Particulado , Aerossóis/análise , Poluentes Atmosféricos/análise , Poeira/análise , Monitoramento Ambiental , Gases/análise , Férias e Feriados , Íons/análise , Material Particulado/análise , Estações do Ano , Água/análiseRESUMO
Development of a simple method to enhance targeting and anti-tumor effect of the chemotherapeutic agents in vivo is a major problem. Amphipathic and natural daptomycin is biocompatible antibacterial polypeptide used in clinical practice. Herein, doxorubicin (DOX) was stabilized by zwitterionic daptomycin (Dap) micelles in aqueous solution to form a zwitterionic nanodrug (Dap-DOX micelles). The hydrodynamic size and zeta potential of Dap-DOX micelles were 85 nm and -10 mV, respectively. The study on the controlled release showed that more DOX molecules were released from Dap-DOX micelles at acidic condition of tumor tissue than that at neutral condition of normal tissue which was due to pH responsiveness of Dap-DOX micelles. Dap-DOX micelles exhibited good stability in fibrinogen solution. Moreover, MTT studies showed that Dap-DOX micelles had higher cytotoxicity than free DOX. Notably, the results of flow cytometry indicated that the average fluorescence intensity of Dap-DOX micelle-treated cells was higher than that of free DOX-treated cells, and acidic conditions were more favorable for Dap-DOX micelles than normal pH in cell uptake assay. More importantly, Dap-DOX micelles were biocompatible in vivo based on the changes of weight and blood indexes of mice. Dap-DOX micelles were selectively accumulated at tumor sites in vivo through EPR effect, which reduced the toxicity of free DOX and achieved excellent tumor inhibition effect. The tumor inhibition rate of Dap-DOX micelles reached 96%. Dap-DOX micelles also effectively inhibited the growth of bacterial. Taken together, Dap-based drug delivery systems are promising and effective in cancer therapy.
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Antibacterianos/farmacologia , Antibióticos Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Daptomicina/farmacologia , Doxorrubicina/farmacologia , Animais , Antibacterianos/química , Antibióticos Antineoplásicos/química , Produtos Biológicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Daptomicina/química , Relação Dose-Resposta a Droga , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Humanos , Camundongos , Micelas , Estrutura Molecular , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Ascorbic acid is an organic compound with antioxidant properties that can protect the human body from the threat of free radicals. Therefore, it is important to detect the existence and measure the concentration of ascorbic acid to regulate its content in the human body. In this work, we prepared bitter gourd polysaccharide (BGP)-stabilized platinum nanoclusters (Pt-BGP NCs) by reacting BGP with K2PtCl4. Pt-BGP NCs and catalyzed the decomposition of H2O2 to generate â¢OH radicals, which could oxidize TMB to form oxidized TMB (oxTMB), indicating their peroxidase-like properties. The kinetics followed the Michaelis-Menten equation. Furthermore, the colorimetric detection of ascorbic acid using Pt-BGP NCs showed high selectivity and a low detection limit of 0.191 µM. The accuracy of real sample detection using Pt-BGP NCs was as high as 98.9%. More importantly, Pt-BGP NCs had high cell biocompatibility and extremely low hemolysis rate due to the component of BGP. In summary, the prepared Pt-BGP NCs with reductive activity and good biocompatibility have good application prospects in colorimetric detection of ascorbic acid.
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Ácido Ascórbico/análise , Momordica charantia/química , Nanoestruturas/química , Ácido Ascórbico/química , Catálise , Colorimetria/métodos , Corantes/química , Radicais Livres/química , Peróxido de Hidrogênio , Indicadores e Reagentes/química , Cinética , Limite de Detecção , Nanopartículas Metálicas/química , Momordica charantia/metabolismo , Oxirredução , Oxirredutases , Tamanho da Partícula , Peroxidases , Platina/química , Polissacarídeos/químicaRESUMO
Objectives: Gait and balance disturbances are common symptoms of idiopathic normal pressure hydrocephalus (iNPH). This study aimed to quantitatively evaluate gait and balance parameters after external lumbar drainage (ELD) using APDM inertial sensors. Methods: Two-minute walkway tests were performed in 36 patients with suspected iNPH and 20 healthy controls. A total of 36 patients underwent ELD. According to clinical outcomes, 20 patients were defined as responders, and the other 16 as non-responders. The gait parameters were documented, and the corresponding differences between responders and non-responders were calculated. Results: When compared with healthy controls, patients with suspected iNPH exhibited decreased cadence, reduced gait speed, a higher percentage of double support, decreased elevation at mid-swing, reduced foot strike angle, shorter stride length, difficulty in turning, and impaired balance functions. After the ELD, all these manifestations, except elevation at mid-swing and balance functions, were significantly improved in responders. The change of Z-score absolute value in the six parameters, except for foot strike angle, was >1. No significant improvement was observed in non-responders. Conclusion: APDM inertial sensors are useful for the quantitative assessment of gait impairment in patients with iNPH, which may be a valuable tool for identifying candidates that are suitable for shunting operations.
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A practical computation of fast Fourier transformation (FFT) based generalized two-dimensional (2D) correlation spectroscopy is described. Using simple sinusoids, we tested and confirmed that the method served effectively and properly, invariant to the changes of the number of data points of the time profiles. This computation is applicable to any type of waveforms in a versatile manner.
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For reversing the treatment failure in P-glycoprotein (P-gp)-associated MDR (multidrug resistance) of breast cancer, a high dose of Lapatinib (Lap), a substrate of breast cancer-resistant protein, was encapsulated into safe and effective acid-cleavable polysaccharide-doxorubicin (Dox) conjugates to form targeted HPP-Dox/Lap nanoparticles with an optimal drug ratio and appropriate nanosize decorated with oligomeric hyaluronic acid (HA) for specially targeting overexpressed CD44 receptors of MCF-7/ADR. The markedly increased cellular uptake and the strongest synergetic cytotoxicity revealed the enhanced reversal efficiency of HPP-Dox/Lap nanoparticles with reversal multiples at 29.83. This was also verified by the enhanced penetrating capacity in multicellular tumor spheroids. The reinforced Dox retention and substantial down-regulation of P-gp expression implied the possible mechanism of MDR reversal. Furthermore, the efficient ex vivo accumulation and distribution of nanoparticles in the tumor site and the high tumor growth inhibition (93%) even at a lower dosage (1 mg/kg) as well as lung metastasis inhibition in vivo with negligible side effects revealed the overwhelming advantages of targeted polysaccharide nanoparticles and Lap-sensitizing effect against drug-resistant tumor. The development of an efficient and nontoxic-targeted polysaccharide delivery system for reversing MDR by synergistic therapy might provide a potential clinical application value.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lapatinib/farmacologia , Nanopartículas/química , Polissacarídeos/química , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Receptores de Hialuronatos/antagonistas & inibidores , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/química , Lapatinib/química , Lapatinib/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Células MCF-7 , Camundongos , Camundongos Nus , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Distribuição Tecidual , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We report herein a facile synthetic method for converting unactivated (hetero)aryl electrophiles into ß-fluoroethylated (hetero)arenes via nickel-catalyzed reductive cross-couplings. This coupling reaction features the involvement of FCH2 CH2 radical intermediate rather than ß-fluoroethyl manganese species which provides effective solutions to the problematic ß-fluoride side eliminations. The practical value of this protocol is further demonstrated by the late-stage modification of several complex ArCl or ArOH-derived bioactive molecules.
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To enhance denitrification in a process of solute infiltration through a soil, a two-section mixed-medium soil infiltration system (TMSIS) for urban non-point pollution was developed. The artificial aerobic respiration and nitrification took place in the upper aerobic section (AES), while grass powders and sawdust were mixed in the bottom anaerobic section (ANS) to supply organic carbon source for denitrification bacteria, and the reduction was increased by iron addition in the ANS. Measured resident concentrations from the bottom of each ANS column were assumed to represent mean values averaged over the column cross-sectional area. The TMSIS with hydraulic loading rates (HLR) of 0.32, 0.24, and 0.16 m3 m-2 day-1 and with wetting-drying ratio (RWD) of 1.0 showed remarkable removal efficiencies for chemical oxygen demand (COD), NH4+-N, and TP, respectively. The hydraulic loading rate of 0.32 m3 m-2 day-1 was selected as the optimal HLR due to the high contaminated runoff treatment efficiency. When RWD was 1.0, 0.5, or 0.2 with hydraulic loading rate of 0.32 m3 m-2 day-1, the TMSIS could treat synthetic urban runoff contaminants very well. The corresponding effluent water met the China's national quality standard for class V surface water. The wetting-drying ratio of 0.5 with hydraulic loading of 0.32 m3 m-2 day-1 was selected as the optimal operation conditions for the TMSIS. Aerobic respiration and nitrification mainly took place in the upper AES, in which most of the COD and the NH4+-N were removed. Mixed sawdust and grass powders used as a carbon source and heterotrophic denitrification were put at the bottom of the ANS. The developed TMSIS has the potential to be applied for urban non-point pollution removal.
Assuntos
Carbono/química , Solo , Análise da Demanda Biológica de Oxigênio , China , Desnitrificação , PoaceaeRESUMO
Size-fractioned aerosol samples were collected by an eight-stage Anderson sampler for four seasons from November 2014 to August 2015 at a coastal and suburban site in Ningbo, China, with a total of 270 samples were obtained. The seasonal variations and size distributions of water-soluble inorganic ions (WSIIs), carbonaceous aerosols (OC and EC), which consist of four organic carbon (OC1-OC4), pyrolyzed carbon (OP) and three elemental carbon fraction (EC1-EC3), were investigated. For the sampling periods, the average total concentration of WSIIs, OC and EC in PM1.1, PM1.1-2.1 and PM2.1-9.0 were 21.3⯱â¯7⯵g/m3, 6.7⯱â¯2.7⯵g/m3 and 12.8⯱â¯1.9⯵g/m3, constituting 75.5%, 62.7% and 43.2% of the different size particle mass, respectively. The predominant chemical species were SO42-, NO3-, and OC. WSIIs, OC and EC all exhibited significant difference between PM2.1 and PM2.1-9.0, reflecting their different sources. Ion balance calculations showed that the acidity of aerosols increased with a decrease in size, with the maximum of 1.07 in 1.1-2.1⯵m and the minimum of 0.47 in 2.1-9⯵m. It showed that size distributions of high-temperature carbon fraction such as OC4, OP and EC1 were almost unimodal during all seasons as well as SO42- and NH4+, in contrast, that of lower temperature carbon fraction (OC1-OC3), Mg2+, and Ca2+ appear like bimodal. Furthermore, the high consistency between the size distribution of OC4, OP and SO42-, NH4+ in all seasons suggests that the similar or related generation process for the secondary organic and inorganic/ionic species, which contribute the most significant component of the particulate matter. Besides the secondary aerosols, primary carbonaceous aerosols (PC), which may originate in emissions from mixed combustion or natural source, also contributed a significant fraction of haze pollution, especially in autumn, spring and summer.