ABSTRACT
With the recently-booming hydrogen (H2) economy by green H2 as the energy carriers and the newly-emerged exhaled diagnosis by human organ-metabolized H2 as a biomarker, H2 sensing is simultaneously required with fast response, low detection limit, and tolerant stability against humidity, switching, and poisoning. Here, reliable H2 sensing has been developed by utilizing indium oxide nanocubes decorated with palladium and gold nanodots (Pd-Au NDs/In2O3 NCBs), which have been synthesized by combined hydrothermal reaction, annealing, and chemical bath deposition. As-prepared Pd-Au NDs/In2O3 NCBs are observed with surface-enriched NDs and nanopores. Beneficially, Pd-Au NDs/In2O3 NCBs show 300 ppb-low detection limit, 5 s-fast response to 500 ppm H2, 75%RH-high humidity tolerance, and 56 days-long stability at 280 °C. Further, Pd-Au NDs/In2O3 NCBs show excellent stability against switching sensing response, and are tolerant to H2S poisoning even being exposed to 10 ppm H2S at 280 °C. Such excellent H2 sensing may be attributed to the synergistic effect of the boosted Pd-Au NDs' spillover effect and interfacial electron transfer, increased adsorption sites over the porous NCBs' surface, and utilized Pd NDs' affinity with H2 and H2S. Practically, Pd-Au NDs/In2O3 NCBs are integrated into the H2 sensing device, which can reliably communicate with a smartphone.
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Treatment options for patients with biliary tract cancer are limited, and the prognosis is poor. CTX-009, a novel bispecific antibody targeting both DLL4 and VEGF-A, has demonstrated antitumor activity in patients with advanced cancers as both a monotherapy and in combination with chemotherapy. In a phase II study of patients with advanced biliary tract cancer who had received one or two prior therapies, CTX-009 with paclitaxel demonstrated a 37.5% overall response rate (ORR). Described here is the design of and rationale for COMPANION-002, a randomized phase II/III study, which will evaluate the safety and efficacy of CTX-009 in combination with paclitaxel versus paclitaxel alone as second-line treatment for patients with advanced biliary tract cancer. The primary end point is ORR, and crossover is allowed.Clinical Trial Registration: NCT05506943 (ClinicalTrials.gov).
Looking for new options for patients with advanced biliary tract cancer? Explore COMPANION-002, Compass Therapeutics' phase II/III study of CTX-009 + paclitaxel as a second line treatment.#CMPX #biotech #healthcare #rarecancer.
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BACKGROUND Knee stability has an important role in the gait of hemiplegic stroke patients. However, factors affecting knee stability have not been assessed concerning gait. The purpose of this study was to explore whether co-contraction of the lower limb muscles contributes to the knee stability during the stance phase of the gait cycle in hemiplegic stroke patients. MATERIAL AND METHODS A total of 30 hemiplegic stroke patients, ages 36-79 years, were instructed to walk at their natural speed. The root mean square of surface electromyography was used to measure activities of the biceps femoris and rectus femoris muscles, while the co-contraction ratio was computed based on the root mean squares. The peak angle of knee extension was acquired in the stance phase by 3D kinematic analyses. Lower limb function was evaluated using the Fugl-Meyer scale for lower limb motor assessment. RESULTS A statistically significant increase of the muscle co-contraction ratio of the involved extremity was observed compared with that of the uninvolved extremity (t=-4.066, P<0.05). The muscle co-contraction ratio was significantly correlated with the peak angle of knee extension (r=0.387, P=0.035), Fugl-Meyer scale (r=-0.522, P=0.003), and Modified Ashworth Scale (r=0.404, P=0.027) during the stance phase of the gait cycle. CONCLUSIONS Our results showed that co-contraction of the rectus femoris muscle contributes to the stability of the knee and lower limb function in hemiplegic stroke patients, and suggests that co-contraction should be considered in the rehabilitation of knee stability during gait in hemiplegic stroke patients. Appropriate rehabilitation assessment planning with hemiplegic stroke patients, such as muscle co-contraction or knee stability of, might be created based on our results.
Subject(s)
Gait Disorders, Neurologic/physiopathology , Knee/physiology , Walking/physiology , Adult , Aged , Biomechanical Phenomena , China , Female , Gait/physiology , Hemiplegia/physiopathology , Humans , Knee Joint/physiopathology , Lower Extremity/physiopathology , Male , Middle Aged , Muscle Contraction , Muscle, Skeletal/physiopathology , Range of Motion, Articular/physiology , Stroke/physiopathology , Stroke Rehabilitation/methodsABSTRACT
New Cu-doped dual-emission carbon dots (D-CDs) were synthesized rapidly and simply via a one-pot solvothermal method, and its special photoluminescence mechanism was studied. D-CDs have two fluorescence (FL) emission peaks under one-wavelength excitation and can be used as dual-signal sensor which is usually designed with two or more substances. The prepared CDs show excellent water solubility, photostability, salt tolerance, oxidation resistance, and special optical properties. The raw material ratio, solvent, pH, time, and synthesis temperature were optimized. The characterizations of CDs including transmission electron microscopy, X-ray photoelectron spectroscopy, inductively coupled plasma spectroscopic analysis, X-ray diffraction assignation of phases, thermogravimetric analysis and differential scanning calorimetry, Fourier transform infrared (FTIR) spectroscopy, FL spectrum, and ultraviolet-visible spectrum (UV-vis) were conducted. The investigation on mechanism indicates that the unique dual-emissive property is mainly caused by the energy-level gaps generated by the surface defects of CDs. The prepared D-CDs have good potential in dual-signal analysis and visualization sensing. To demonstrate the practical application, ferric ions, vitamin A acetate, and pH have been determined successfully.
ABSTRACT
BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functional pro-survival molecule required for autophagy, has been implicated in brain metastases in experimental models. However, expression of these proteins has not been examined in brain metastases from patients with breast cancer. METHODS: In this retrospective study, specimens from 44 patients with brain metastases of infiltrating ductal carcinoma of the breast (IDC), unpaired samples from 52 patients with primary IDC (primary-BC) and 16 matched-paired samples were analyzed for LC3 puncta, expression of FIP200/Atg17, and p62 staining. RESULTS: LC3-puncta+ tumor cells and FIP200/Atg17 expression were detected in greater than 90% of brain metastases but there were considerable intra- and inter-tumor differences in expression levels. High numbers of LC3-puncta+ tumor cells in brain metastases correlated with a significantly shorter survival time in triple-negative breast cancer. FIP200/Atg17 protein levels were significantly higher in metastases that subsequently recurred following therapy. The percentages of LC3 puncta+ tumor cells and FIP200/Atg17 protein expression levels, but not mRNA levels, were significantly higher in metastases than primary-BC. Meta-analysis of gene expression datasets revealed a significant correlation between higher FIP200(RB1CC1)/Atg17 mRNA levels in primary-BC tumors and shorter disease-free survival. CONCLUSIONS: These results support assessments of precision medicine-guided targeting of autophagy in treatment of brain metastases in breast cancer patients.
Subject(s)
Brain Neoplasms/metabolism , Brain Neoplasms/secondary , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Microtubule-Associated Proteins/metabolism , Protein-Tyrosine Kinases/metabolism , Adult , Aged , Autophagy-Related Proteins , Biomarkers, Tumor/metabolism , Brain/metabolism , Brain/pathology , Brain Neoplasms/mortality , Brain Neoplasms/therapy , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/therapy , Female , Gene Expression Regulation, Neoplastic , Humans , Meta-Analysis as Topic , Middle Aged , RNA, Messenger/metabolism , Retrospective StudiesABSTRACT
As a persistent organic pollutant, perfluorooctane sulfonate has drawn a worldwide attention. In this contribution, a novel molecularly imprinted polymer based on mesoporous silica nanoparticles was prepared for efficient separation and enrichment of perfluorooctane sulfonate in water samples. The polymer was characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and N2 adsorption/desorption experiments. The static adsorption experiments and the adsorption kinetic tests were conducted. The results showed that the adsorbents had high adsorption capacity (21.10 mg/g) and short adsorption equilibration time (25 min). Meanwhile, the effect of mesoporous silica nanoparticles on the adsorption capacity was investigated. The results indicated that the mesoporous structure helped to increase the adsorption capacity of adsorbent to adsorbate. Besides, the adsorbents show good specificity and good reusability with the adsorption capacity of adsorbent toward perfluorooctane sulfonate decreasing <5% after five adsorption-desorption cycles. The mesoporous silica nanoparticles molecularly imprinted polymer has been used successfully for the removal of perfluorooctane sulfonate in environmental water samples with relative standard deviation ≤4.64%.
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BACKGROUND: Numerous epidemiological studies were published to investigate the role of microtubule-associated protein tau (MAPT) gene variations (rs7521G/A, rs242557G/A, rs1467967A/G, rs2471738C/T and rs3785883G/A) in SAD, and these genetic polymorphisms may be a risk factor for sporadic Alzheimer's disease (SAD). However, controversial results were revealed. METHODS: The MEDLINE, Embase and HuGEnet databases were searched to identify eligible studies. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the genetic association of MAPT with the risk of SAD. RESULTS: A total of 30 studies were included in this meta-analysis to assess the association between five single-nucleotide polymorphisms and susceptibility to SAD. The pooled results exhibited no significant association between rs1467967A/G, rs3785883G/A, rs2471738C/T and rs7521G/A polymorphisms and the risk of SAD. However, a lower risk of SAD was observed in the GG versus (GA + AA) model of rs242557G/A polymorphism (OR = 0.86, 95% CI = 0.751-0.983, P = 0.027). CONCLUSION: The present meta-analysis showed that rs1467967A/G, rs3785883G/A, rs2471738C/T and rs7521G/A polymorphisms were not associated with the risk of SAD. However, rs242557G/A genetic polymorphism was associated with susceptibility to SAD, and individuals with a GG genotype of rs242557G/A might be at a lower risk of SAD. Further studies with a larger sample size are required to validate these conclusions.
Subject(s)
Alzheimer Disease/genetics , tau Proteins/genetics , HumansABSTRACT
Pancreatic cancer (PDAC) is an aggressive tumor type associated with development of micrometastasis at an early stage. In attempt to eradicate disseminated disease, neoadjuvant therapy has been explored in patients with resectable and borderline resectable PDAC. In large retrospective studies, neoadjuvant therapy was associated with better survival compared with upfront surgery. Previously, trials more commonly used radiotherapy (RT) with small doses of chemotherapy as radiosensitizers. Recent studies, however, have incorporated full systemic doses of chemotherapy with or without RT before surgery with the hope of achieving adequate systemic chemotherapy coverage and improving survival. Several phase II trials have shown encouraging clinical benefits using the neoadjuvant approach. Large cooperative group studies are exploring the role of neoadjuvant treatment with newer combination chemotherapy regimens and modern RT techniques, which will provide more evidence regarding the utility of this approach.
Subject(s)
Neoadjuvant Therapy , Pancreatic Neoplasms/therapy , Chemoradiotherapy , Chemotherapy, Adjuvant , Clinical Trials as Topic , Combined Modality Therapy , Humans , Neoadjuvant Therapy/methods , Neoadjuvant Therapy/trends , Neoplasm Metastasis , Neoplasm Staging , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/mortality , Radiotherapy, Adjuvant , Treatment OutcomeABSTRACT
As a persistent organic pollutant, perfluorooctane sulfonate has drawn a great worldwide attention. In this contribution, a novel material of magnetic molecularly imprinted polymers, based on perfluorooctane sulfonate, as a template, molecule was prepared. The magnetic molecularly imprinted polymers were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and vibrating sample magnetometry. The adsorption isotherm was measured, and adsorption kinetic tests were conducted. The adsorbents possess high recognition ability (2.460 mg/g) and short adsorption equilibration time (60 min). Besides, they show good specificity and good reusability with the adsorption capacities of adsorbent toward perfluorooctane sulfonate decreasing less than 3% after five adsorption-desorption cycles. The magnetic molecularly imprinted polymers were used successfully in the separation and enrichment of perfluorooctane sulfonate in real water sample and exhibited good prospects in environmental treatment and monitoring.
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PURPOSE: To investigate the roles of a selective MMP-2 and -9 inhibitor (SB-3CT) in corneal inflammatory lymphangiogenesis. METHODS: The expression of MMP-2 and -9 in the cornea after suture inplacement, treated with SB-3CT or negative control, was detected by real-time polymerase chain reaction (PCR). Inflammatory corneal neovascularization (NV) was induced by corneal suture placement. Mice were treated with SB-3CT eye drops (twice daily for 1 week, 5 µL per drop; 50, 100, or 200 µM). The outgrowth of blood and lymphatic vessels, and macrophage recruitment were analyzed by immunofluorescence assay. The expressions of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 were tested by real-time PCR. RESULTS: MMP-2 and -9 expression were suppressed significantly by treatment with SB-3CT. The data demonstrated, for the first time, that SB-3CT strongly reduced corneal lymphangiogenesis and macrophage infiltration during inflammation. Furthermore, expressions of VEGF-C and its receptor VEGFR-3 were significantly inhibited by SB-3CT during corneal lymphangiogenesis. CONCLUSIONS: These novel findings indicated that blockade of MMP-2 and -9 could inhibit lymphangiogenesis. Further investigation of this factor may provide novel therapies for transplant rejection and other lymphatic disorders.
Subject(s)
Corneal Neovascularization/genetics , Gene Expression Regulation/drug effects , Heterocyclic Compounds, 1-Ring/pharmacology , Lymphangiogenesis/drug effects , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , RNA/genetics , Sulfones/pharmacology , Animals , Cornea/pathology , Corneal Neovascularization/drug therapy , Corneal Neovascularization/metabolism , Disease Models, Animal , Lymphatic Vessels/pathology , Male , Matrix Metalloproteinase 2/biosynthesis , Matrix Metalloproteinase 2/drug effects , Matrix Metalloproteinase 9/biosynthesis , Matrix Metalloproteinase 9/drug effects , Mice , Mice, Inbred C57BL , Microscopy, Fluorescence , Real-Time Polymerase Chain ReactionABSTRACT
Neuropilin-2 (NP2), a high-affinity kinase-deficient co-receptor for vascular endothelial growth factor (VEGF)-C, is involved in embryonic vessel development, tumor growth, tumor lymphangiogenesis and metastasis. However, the pathological role of NP2 in other disorders, particularly under inflammatory lymphangiogenic conditions, remains largely unknown. In this study, we investigated the role of NP2 in inflammation-induced lymphangiogenesis in vivo using a lipopolysaccharide (LPS)-induced corneal neovascularization mouse model and in vitro using a macrophage-mouse lymphatic endothelial cell (mLEC) co-culture system. In the mouse model of LPS-induced inflammatory corneal neovascularization, NP2 and VEGFR-3 expression were rapidly up-regulated after LPS stimulation, and microRNA-mediated knockdown of NP2 significantly inhibited the up-regulation of VEGFR-3. Moreover, NP2 knockdown specifically inhibited the increase in the number of corneal lymphatic vessels but did not influence the increase in the number of blood vessels or macrophage recruitment induced by LPS. In a macrophage-LEC co-culture system, LPS up-regulated VEGFR-3 expression and induced mLEC migration and proliferation, and NP2 knockdown inhibited the up-regulation of VEGFR-3 expression and mLEC migration but not proliferation. Taken together, these results suggested that NP2 might be involved in the regulation of lymphangiogenesis via the regulation of VEGFR-3 expression during corneal inflammation. Therefore, NP2-targeted therapy might be a promising strategy for selective inhibition of inflammatory lymphangiogenesis in corneal inflammatory diseases, transplant immunology and oncology.
Subject(s)
Disease Models, Animal , Keratitis/metabolism , Lymphangiogenesis/physiology , Neuropilin-2/physiology , Adenoviridae/genetics , Animals , Cell Movement/physiology , Cell Proliferation/physiology , Coculture Techniques , Corneal Neovascularization/chemically induced , Corneal Neovascularization/metabolism , Corneal Neovascularization/pathology , Electrophoresis, Polyacrylamide Gel , Endothelial Cells/metabolism , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique, Indirect , Gene Silencing , Genetic Vectors , Keratitis/chemically induced , Keratitis/pathology , Lipopolysaccharides , Lymphatic Vessels/physiology , Macrophages/metabolism , Male , Mice , Mice, Inbred BALB C , MicroRNAs/genetics , Vascular Endothelial Growth Factor Receptor-3/metabolismABSTRACT
The standard therapy for patients with unrespectable stage III non-small-cell lung cancer (NSCLC) is the combination of chemotherapy and radiotherapy. Although the concurrent use of both treatment modalities has been shown to be superior to sequential therapy, the role for additional chemotherapy, either as induction or as consolidation, remains unclear. Targeted therapy has met limited success in the treatment of unselected patients with stage III NSCLC. New studies using induction therapy with erlotinib or crizotinib for molecularly selected patients and consolidation therapy with checkpoint inhibitors are currently ongoing, and the results are eagerly awaited.
Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Combined Modality Therapy/methods , Lung Neoplasms/therapy , Chemoradiotherapy/methods , Chemoradiotherapy/trends , Combined Modality Therapy/trends , Humans , Immunotherapy/methods , Immunotherapy/trends , Molecular Targeted Therapy/methods , Molecular Targeted Therapy/trendsABSTRACT
Tea (Camellia sinensis) is a beverage beneficial to health and is also a source for extracting bioactive components such as theanine, tea polyphenols (TPP) and tea polysaccharides (TPS). TPS is a group of heteropolysaccharides bound with proteins. There is evidence showing that TPS not only improves immunity but also has various bioactivities, such as antioxidant, antitumor, antihyperglycemia, and anti-inflammation. However, inconsistent results concerning chemical composition and bioactivity of TPS have been published in recent years. The advances in chemical composition and bioactivities of TPS are reviewed in the present paper. The inconsistent and controversial results regarding composition and bioactivities of TPS are also discussed.
Subject(s)
Polysaccharides/chemistry , Polysaccharides/pharmacology , Tea/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacokinetics , Antioxidants/pharmacology , Biological Availability , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/pharmacology , Molecular Structure , Polysaccharides/pharmacokineticsABSTRACT
Ethane is one of major fault characteristic gases dissolved in power transformer, the detection of Ethane with high accuracy and sensitivity is the key of dissolved gas analysis. In this paper, based on optical feedback theory and cavity-enhanced absorption spectroscopy, combined with quantum cascade laser, a detection system for dissolved gas C2 H6 in transformer oil was built up. Based on the symmetry of the individual cavity modes, the phase matching of returning light in resonance with the cavity was achieved through LabVIEW codes. The optical feedback effect that the emitted light return to the laser cavity after a small delay time and lock to the resonance frequency of cavity, even and odd modes effect that the higher modes and lower modes structure will build up alternatively, and threshold current lowering effect of about 1.2 mA were studied and achieved. By cavity ring-down spectroscopy, the effective reflectivity of 99.978% and cavity finesse of 7 138.4 is obtained respectively. The frequency selectivity is 0.005 2 cm(-1). With an acquisition time of 1s, this optical system allows detection for the PQ3 band of C2 H6 with high accuracy of 95.72% ± 0.17% and detection limit of (1.97 ± 0.06) x 10(-3) µL x L(-1) at atmospheric pressure and temperature of 20 degrees C, which lays a foundation for fault diagnose from dissolved gas analysis.
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PURPOSE: Accumulating evidence in animals suggests that leukocytes are involved in the pathogenesis of diabetic retinopathy. The present study was designed to investigate whether leukocytes from diabetic patients could kill retinal endothelial cells and whether that cytotoxicity could be inhibited in vivo by administration of berberine. METHODS: Human retinal endothelial cells (HRECs) were cocultured (24 h) with leukocytes freshly isolated from nondiabetic and diabetic patients, and leukocyte-mediated death of HRECs was analyzed with flow cytometry. HRECs or leukocytes were incubated with antibodies against intercellular adhesion molecule-1(ICAM-1) or integrin beta-2, or with various concentrations of berberine. The protein expression levels of inflammatory factors were investigated using western blots, and activities of antioxidant enzymes and malondialdehyde content were examined as markers of oxidative stress. In addition, leukocytes were isolated from 28 diabetic patients with retinopathy and nondiabetic patients before and after 1 month in vivo therapy with berberine. The effects of the berberine on leukocyte-mediated killing of endothelial cells was again assessed. RESULTS: Leukocytes from diabetic patients induced more apoptosis of HRECs in a coculture system than did cells from nondiabetic patients, and this killing occurred primarily via direct cell-cell contact. Berberine inhibited the leukocyte-mediated killing of HRECs in vitro, the decrease in antioxidant enzyme activities, the nuclear translocation of nuclear factor kappa B, and the increase in intercellular adhesion molecule-1 and inducible nitric oxide synthase expression and malondialdehyde content in HRECs cultured in high glucose. Berberine also decreased integrin beta-2 expression of leukocytes in vitro and in vivo. Oral consumption of berberine for 1 month likewise inhibited the diabetes-induced increase in leukocyte-mediated killing of HRECs. CONCLUSIONS: Our findings suggest that leukocytes from diabetic patients kill retinal endothelial cells, and that berberine can inhibit this leukocyte-mediated killing of vascular endothelium. Coculture of leukocytes with HRECs might serve as a biomarker to study the role of leukocytes in the development of diabetic retinopathy, and the data are consistent with berberine being a therapy against diabetic retinopathy.
Subject(s)
Apoptosis/drug effects , Berberine/pharmacology , Diabetes Mellitus, Experimental/pathology , Endothelial Cells/pathology , Leukocytes/pathology , Retina/pathology , Animals , Berberine/administration & dosage , Berberine/chemistry , CD18 Antigens/metabolism , Cell Adhesion/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Female , Glucose/pharmacology , Humans , Intercellular Adhesion Molecule-1/metabolism , Leukocytes/drug effects , Leukocytes/metabolism , Male , Middle Aged , NF-kappa B/metabolism , Oxidative Stress/drug effects , Signal Transduction/drug effectsABSTRACT
AX10479, the phenyl amide of 4-hydroxy-8-methanesulfonylamino-quinoline-2-carboxylic acid, was identified as a Zn(2+)-dependent, 27nM inhibitor of human plasma Lp-PLA(2). Structure-activity relationship studies focused on the AX10479 2-phenylamide group identified equipotent cycloaliphatic amides, an enantioselective preference for chiral amides, and phenyl substitution patterns (e.g., 2-methyl-3-fluoro) that increased potency.
Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/antagonists & inhibitors , Amides/pharmacology , Quinolines/pharmacology , Amides/chemical synthesis , Amides/chemistry , Humans , Quinolines/chemical synthesis , Quinolines/chemistry , Stereoisomerism , Structure-Activity Relationship , Zinc/chemistryABSTRACT
The study about simultaneously enhancing the resistive switching level and ambient-air-stability of perovskite-based memorizers will promote its commercialization. Here, a new 3D perovskite (TAZ-H)PbBr3 (TAZ-H+ = protonated thiazole) has been fabricated as FTO/(TAZ-H)PbBr3/Ag device, which only exhibits binary memory performance with the high tolerant temperature of 170 °C. After encapsulating by polyvinylpyrrolidone (PVP), the (TAZ-H)PbBr3@PVP composite-based device can demonstrate ternary resistive switching behavior with considerable ON2/ON1/OFF ratio (105.9: 103.9:1) and high ternary yield (68 %). Specially, this device presents good ambient-air stability at RH 80 % and thermal tolerance of 100 °C. The binary resistive switching mechanism can be ascribed to the halogen ion migration induced by bromine defects in the (PbBr3)nn- framework. But the ternary resistive switching phenomenon in the (TAZ-H)PbBr3@PVP-based device could be depicted as the carrier transport from filled traps of PVP to (PbBr3)nn- framework (ON1 state) and then carriers flowing in the re-arranged (TAZ-H)nn+ chain in 3D channels (ON2 state). The PVP treatment can not only modify the grain boundary defects, but also facilitate the transport of injected carriers to the perovskite films via Pb-O coordinated bonds and inhibition of order-disorder transformation. This facial strategy for implementing ternary perovskite-based memorizers with good ambient-air-stability is quite meaningful for high-density memory in harsh environments.
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Significant progress has been made in deep learning-based retinal vessel segmentation in recent years. However, the current methods suffer from low performance and the robust of the models is not that good. Our work introduces an novel framework for retinal vessel segmentation based on deep ensemble learning. The results of benchmarking comparisons indicate that our model outperforms the existing ones on multiple datasets, demonstrating that our models are more effective, superior, and robust for the retinal vessel segmentation. It evinces the capability of our model to capture the discriminative feature representations through introducing the ensemble strategy to integrate different base deep learning models like pyramid vision Transformer and FCN-Transformer. We expect our proposed method can benefit and accelerate the development of accurate retinal vessel segmentation in this field.
Subject(s)
Benchmarking , Retinal Vessels , Retinal Vessels/diagnostic imaging , Machine Learning , Image Processing, Computer-Assisted/methods , AlgorithmsABSTRACT
AX10185, the phenyl amide of xanthurenic acid, was found to be a sub-100nM inhibitor of Lp-PLA(2). However, in the presence of EDTA the inhibitory activity of AX10185 was extinguished while the enzymatic activity of Lp-PLA(2) did not change. Subsequent metal screening experiments determined the inhibition to be Zn(2+) dependent. Structure-activity relationship studies indicated the presence of the 4-hydroxy group to be critical and selected substituted phenyl, polycyclic, and cycloaliphatic amides of xanthurenic acid to be well tolerated.
Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/antagonists & inhibitors , Amides/chemistry , Enzyme Inhibitors/pharmacology , Organometallic Compounds/pharmacology , Xanthurenates/chemistry , Zinc/chemistry , 1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Molecular Structure , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Structure-Activity RelationshipABSTRACT
RATIONALE: Airway mucous cell metaplasia and chronic inflammation are pathophysiological features that influence morbidity and mortality associated with asthma and other chronic pulmonary disorders. Elucidation of the molecular mechanisms regulating mucous metaplasia and hypersecretion provides the scientific basis for diagnostic and therapeutic opportunities to improve the care of chronic pulmonary diseases. OBJECTIVES: To determine the role of the airway epithelialspecific transcription factor NK2 homeobox 1 (NKX2-1, also known as thyroid transcription factor-1 [TTF-1]) in mucous cell metaplasia and lung inflammation. METHODS: Expression of NKX2-1 in airway epithelial cells from patients with asthma was analyzed. NKX2-1 +/-gene targeted or transgenic mice expressing NKX2-1 in conducting airway epithelial cells were sensitized to the aeroallergen ovalbumin. In vitro studies were used to identify mechanisms by which NKX2-1 regulates mucous cell metaplasia and inflammation. MEASUREMENTS AND MAIN RESULTS: NKX2-1 was suppressed in airway epithelial cells from patients with asthma. Reduced expression of NKX2-1 in heterozygous NKX2-1 +/- gene targeted mice increased mucous metaplasia in the small airways after pulmonary sensitization to ovalbumin. Conversely, mucous cell metaplasia induced by aeroallergen was inhibited by expression of NKX2-1 in the respiratory epithelium in vivo. Genome-wide mRNA analysis of lung tissue from ovalbumin-treated mice demonstrated that NKX2-1 inhibited mRNAs associated with mucous metaplasia and Th2-regulated inflammation,including Spdef, Ccl17, and Il13. In vitro, NKX2-1 inhibited SPDEF, a critical regulator of airway mucous cell metaplasia,and the Th2 chemokine CCL26. CONCLUSIONS: The present data demonstrate a novel function for NKX2-1 in a gene network regulating mucous cell metaplasia and allergic inflammation in the respiratory epithelium.