Neutrophil elastase plays pivotal roles in the pathogenesis of pulmonary fibrosis. The neutrophil elastase inhibitor, sivelestat, could alleviate pulmonary fibrosis; however, the antifibrotic ...mechanisms have not yet been clarified. We examined the antifibrotic mechanisms, mainly focusing on a key fibrotic cytokine, transforming growth factor (TGF)-β1, in this study. To elucidate the antifibrotic mechanisms of sivelestat, we examined a murine model of bleomycin-induced early-stage pulmonary fibrosis. After intratracheal instillation of bleomycin, sivelestat was administered intraperitoneally once a day for 7 or 14 days. Bronchoalveolar lavage fluid and lung samples were examined on day 7 or day 14 after bleomycin instillation. In the bleomycin-induced early-stage pulmonary fibrosis model, the neutrophil elastase level was increased in the lungs. Sivelestat significantly inhibited the increase in lung collagen content, fibrotic changes, the numbers of total cells (including macrophages, neutrophils and lymphocytes), the levels of the active form of TGF-β1 and phospho-Smad2 in bleomycin-induced early-stage pulmonary fibrosis. The total TGF-β1 levels and relative changes of TGF-β1 mRNA expression, however, were not decreased significantly by sivelestat. These results suggest that sivelestat alleviated bleomycin-induced pulmonary fibrosis via inhibition of both TGF-β activation and inflammatory cell recruitment in the lung.
In order to realize high performance of organic photovoltaic cells (OPVs), it is indispensable to optimize device structures according to composing materials. In particular, the optical density ...distribution in stacked layers is one of important factors to enhance the optical absorption within the photoactive layer, resulting in the improved photoconversion efficiency. In this study, we optimized the film thickness of the photoactive layer as a fundamental way to control the optical density distribution. The influence of the photoactive layer thickness on photovoltaic performances of OPVs was first investigated using, poly4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)benzo1,2-b;4,5-b′dithiophene-2,6diyl-alt-(4-(2-ethylhexyl)-3-uorothieno3,4-bthiophene-)-2-carboxylate-2-6-diyl) and 6,6-phenyl C71-butyric acid methyl ester blend films in normal and inverted OPV structures, respectively. The short circuit current density (Jsc) showed a peak at the thickness at around 100–120 nm and 80–100 nm in normal and inverted OPVs, respectively. In addition, Jsc of inverted OPVs were higher than those of normal OPVs for all the thicknesses. The FF decreased continuously with increasing the thickness in both device structures. The fill factor of normal OPV decreased with increasing thickness more slowly than that of the inverted OPV at the thickness of over than 200 nm. Furthermore, we simulated the optical density distribution in the stacked layers using the algorithm utilized matrix formulas based on Abeles's formulas. The simulated optical intensity distribution as a function of the position and the wavelength is in a good agreement with the experimental spectra of external quantum efficiency. The result indicates a close correspondence between the optical density distribution and the photovoltaic performance. At the optimum photoactive layer thickness of 116 nm in the normal and 76 nm in the inverted OPVs, we obtained the highest PCEs of 9.25 and 10.4%, respectively.
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•The simulated optical intensity distribution agreed well with the spectral response of EQE.•The PCE didn't increase monotonically with increasing active layer thickness.•The PCE showed a peak at an optimum thickness.•The Jsc of the inverted OPVs is higher than that of the normal OPVs in same thickness.
The residual tumor after surgery is the most significant prognostic factor of patients with epithelial ovarian cancer. Near‐infrared (NIR) fluorescence‐guided surgery is actively utilized for tumor ...localization and complete resection during surgery. However, currently available contrast‐enhancing agents display low on‐target binding, unfavorable pharmacokinetics, and toxicity, thus not ideal for clinical use. Here we report ultrabright and stable squaraine fluorophores with optimal pharmacokinetics by introducing an asymmetric molecular conformation and surface charges for rapid transporter‐mediated cellular uptake. Among the tested, OCTL14 shows low serum binding and rapid distribution into cancer tissue via organic cation transporters (OCTs). Additionally, the charged squaraine fluorophores are retained in lysosomes, providing durable intraoperative imaging in a preclinical murine model of ovarian cancer up to 24 h post‐injection. OCTL14 represents a significant departure from the current bioconjugation approach of using a non‐targeted fluorophore and would provide surgeons with an indispensable tool to achieve optimal resection.
A new squaraine fluorophore OCTL14 displays ultrabright optical properties and optimal pharmacokinetics, allowing high contrast and durable near‐infrared imaging for fluorescence‐guided surgery of ovarian cancer. The primary mechanisms of the tumor targetability of OCTL14 involve its rapid diffusion across tumor vasculature and cellular uptake via organic cation transporters and retention in the lysosome.
Psoriasis patients have been reported to have a higher prevalence of nonalcoholic fatty liver disease (NAFLD), therefore detection at an early stage is important since it may progress to hepatic ...cirrhosis or hepatocellular carcinoma. We evaluated liver fat accumulation in patients with moderate to severe psoriasis by chest computed tomography (CT). The images were taken for screening purposes prior to the start of any biologics. The prevalence of NAFLD in patients with psoriasis vulgaris, psoriatic arthritis, and control subjects was 19.4%, 33.3% and 9.8%, respectively (P = 0.004). The mean CT score in psoriasis patients was significantly lower (51.684 ± 12.778) than that in control subjects (61.204 ± 9.498, P < 0.001). Multivariate logistic regression analysis showed that only CT scores were associated with the presence of psoriasis (P = 0.001). No significant relationship was observed between the Psoriasis Activity and Severity Index scores and CT scores of psoriasis patients (P = 0.055), suggesting that the presence of psoriasis may contribute to the pathogenesis of NAFLD. By analysis of chest CT imaging, our study successfully assessed liver fat accumulation. Chest CT is a useful diagnostic tool for the quantitative measurement of fat accumulated in the liver, enabling the early noninvasive detection of NAFLD and early therapeutic intervention.
Despite great increases in photovoltaic performance due to the insertion of ligand-exchanged PbS quantum dot layer via 1,2-ethanedithiol (EDT), detailed carrier transport characteristics of solar ...cells with solution-phase ligand-exchanged PbS quantum dot (QD) still remains unknown. In this paper, relaxation time, recombination resistance, chemical capacitance, carrier lifetime, carrier diffusion length, and defect density corresponding to the depletion width were measured through electrochemical impedance spectroscopy using the Schottky diode model to understand limiting factors for photovoltaic performance. The activation energy, which is estimated from the temperature-dependence of resistance, was reduced from 0.06 eV to 0.02 eV by inserting the PbS-EDT layer, leading to the improved photovoltaic performance. We also evaluated QD solar cells with varying thicknesses of PbS QD layers to investigate the impedance analysis and photovoltaic measurements. The depletion width as well as the carrier diffusion length was larger than the physical thickness of the layer, and this indicates that an increased short-circuit current density can be realized at the thick PbS QD layer due to the resulting large absorbance. Furthermore, the reduced trap density of the QD layer improves the open circuit voltage and fill factor. As a result, a high photoconversion efficiency of 9.41% was achieved.
•The effect of ligand-exchanged PbS QD layerwas investigated.•The detailed electrochemical impedance analysis was performed.•The trap density affectsthe open circuit voltageand fill factor.•The photoconversion efficiencyof 9.41% was achieved.
Magnetic resonance (MR) imaging plays an important role in the evaluation of bacterial and tuberculous spondylodiscitis and associated complications. Owing to its high sensitivity and specificity, it ...is a powerful diagnostic tool in the early diagnosis of ongoing infections, and thus provides help in prompt initiation of appropriate, therapy which may be medical or surgical, by defining the extent of involvement and detection of complications such as epidural and paraspinal abscesses. More specifically, MR imaging helps in differentiating bacterial from tuberculous infections and enables follow up of progression or resolution after appropriate treatment. However, other non-infectious pathology can demonstrate similar MR imaging appearances and one should be aware of these potential mimickers when interpreting MR images. Radiologists and other clinicians need to be aware of these potential mimics, which include such pathologies as Modic type I degenerative changes, trauma, metastatic disease and amyloidosis. In this pictorial review, we will describe and illustrate imaging findings of bacterial and tuberculous spondylodiscitis, their complications and non-infectious pathologies that mimic these spinal infections.
Ultrasonography and magnetic resonance imaging (MRI) are useful for diagnosing psoriatic arthritis (PsA). However, ultrasonography depends on the skill of the operator and MRI is often disturbed by ...artifacts when distal interphalangeal joints are examined. Although iodine‐enhanced dual‐energy computed tomography (DECT) has the potential to diagnose PsA without these disadvantages, its usefulness over ultrasonography has not yet been examined in detail; therefore, the present study was conducted to address this issue. The acral joint of 13 PsA patients, which was the most severely affected, was scanned with imaging devices. Ultrasonography was performed with a high‐frequency linear 18‐MHz probe. Iodine‐enhanced DECT was conducted in the DE mode with iohexol as a contrast material. Psoriatic Arthritis Screening and Evaluation (PASE) scores were recorded. Synovitis and periarticular inflammation delineated with iodine‐enhanced DECT correlated with the loss of the fibrillar pattern delineated with ultrasonography (p = 0.033 and 0.002, respectively). Peritendinitis delineated with iodine‐enhanced DECT also correlated with tendon thickening delineated with ultrasonography (p = 0.011). Iodine uptake did not correlate with Doppler signal or PASE scores. In conclusion, the present results demonstrated that the qualitative findings of iodine‐enhanced DECT correlated with those of ultrasonography in PsA patients, whereas quantitative findings did not. Iodine‐enhanced DECT may be an alternative imaging modality for the diagnosis of PsA.
MRI biomarkers in osseous tumors Fukuda, Takeshi; Wengler, Kenneth; de Carvalho, Ruben ...
Journal of magnetic resonance imaging,
September 2019, Volume:
50, Issue:
3
Journal Article
Peer reviewed
Although radiography continues to play a critical role in osseous tumor assessment, there have been remarkable advances in cross‐sectional imaging. MRI has taken a lead in this assessment due to high ...tissue contrast and spatial resolution, which are well suited for bone lesion assessment. More recently, although somewhat lagging other organ systems, quantitative parameters have shown promising potential as biomarkers for osseous tumors. Among these sequences are chemical shift imaging (CSI), apparent diffusion coefficient (ADC), and intravoxel incoherent motion (IVIM) from diffusion‐weighted imaging (DWI), quantitative dynamic contrast enhanced (DCE)‐MRI, and magnetic resonance spectroscopy (MRS). In this article, we review the background and recent roles of these quantitative MRI biomarkers for osseous tumors.
Level of Evidence: 3
Technical Efficacy Stage: 3
J. MAGN. RESON. IMAGING 2019. J. Magn. Reson. Imaging 2019;50:702–718.
The aim of this study was to investigate the feasibility of quantitative assessment of the therapeutic response in psoriatic arthritis (PsA) by measuring iodine uptake using a Dual-energy CT (DECT) ...iodine map. The study included 74 symptomatic and 74 matching non-symptomatic joints of 26 consecutive PsA patients who underwent two contrast enhanced DECTs of the hand or foot, pre and post medical interventions. Symptomatic and matched non-symptomatic control joints were scored with the PsA DECT Scoring System (PsADECTS), which was derived by modifying the PsA MRI Scoring System (PsAMRIS), a recently validated scoring system that assesses PsA changes on MRI. Quantified iodine uptake measured using the DECT iodine map was compared to the PsADECTS score. Efficacy of PsA treatment was confirmed by the improved clinical findings. Both PsADECTS and iodine uptake also showed significant improvement after treatment (Wilcoxon signed-rank test: z = 7.38, p < 0.005; z = 6.20, p < 0.005, respectively). The treatment effects of PsADECTS score and iodine uptake showed a good correlation with each other (Spearman's ρ = 0.58 p < 0.005). Inter-reader agreement for PsADECTS score and iodine uptake were either moderate or good. In conclusion, our study showed that the DECT iodine map is a valid tool for quantitative assessment of the therapeutic response of PsA.
This article introduces the new family of living radical polymerizations with germanium (Ge), tin (Sn), phosphorus (P), and nitrogen (N) catalysts which we recently developed. The polymerizations are ...based on a new reversible activation mechanism, Reversible chain Transfer (RT) catalysis. Low-polydispersity polymers are obtained in the homopolymerizations and random and block copolymerizations of styrene, methyl methacrylate, and functional methacrylates. The background, performance, and kinetic features of the polymerizations are described. Attractive features of the catalysts include their high reactivity, low toxicity (Ge, P, and N), low cost (P and N), and ease of handling (robustness).
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