Search

Spontaneous and isolated dissection of the limb arteries without involvement of the aorta is extremely rare, and has been reported previously in pregnant patients in association with collagen vascular disease, and in cases of high-energy trauma or intensive activity in athletes. There is no consensus yet on indications for medical or surgical therapeutic modality. Due to the rarity of spontaneous dissection of external iliac artery, its natural history has been poorly described. A healthy 50-year-old male with normotension was admitted with an acute onset of left flank pain. Left external iliac artery dissection was diagnosed by abdominal computed tomography.

As mesothelin is overexpressed in various types of cancer, it is an attractive target for therapeutic antibodies. T-cell bispecific antibodies bind to target cells and engage T cells via binding to CD3, resulting in target cell killing by T-cell activation. However, the affinity of the CD3-binding arm may influence CD3-mediated plasma clearance or antibody trapping in T-cell-containing tissues. This may then affect the biodistribution of bispecific antibodies. In this study, we used scFab and knob-into-hole technologies to construct novel IgG-based 1 + 1 MG1122-A and 2 + 1 MG1122-B bispecific antibodies against mesothelin and CD3ε. MG1122-B was designed to be bivalent to mesothelin and monovalent to CD3ε, using a 2 + 1 head-to-tail format. Activities of the two antibodies were evaluated in mesothelin-positive tumor cells in vitro and xenograft models in vivo. Although both antibodies exhibited target cell killing efficacy and produced regression of xenograft tumors with CD8+ T-cell infiltration, the antitumor efficacy of MG1122-B was significantly higher. MG1122-B may improve tumor targeting because of its bivalency for tumor antigen. It may also reduce systemic toxicity by limiting the activation of circulating T cells. Thus, MG1122-B may be useful for treating mesothelin-positive solid tumors.

Rechargeable Ca batteries offer the advantages of high energy density, low cost, and earth-abundant constituents, presenting a viable alternative to lithium-ion batteries. However, using polymer electrolytes in practical Ca batteries is not often reported, despite its potential to prevent leakage and preserve battery flexibility. Herein, a Ca(BH 4 ) 2 -based gel-polymer electrolyte (GPE) is prepared from Ca(BH 4 ) 2 and poly(tetrahydrofuran) (pTHF) and tested its performance in Ca batteries. The electrolyte demonstrates excellent stability against Ca-metal anodes and high ionic conductivity. The results of infrared spectroscopy and 1 H and 11 B NMR indicate that the terminal ─OH groups of pTHF reacted with BH 4 - anions to form B─H─(pTHF) 3 moieties, achieving cross-linking and solidification. Cyclic voltammetry measurements indicate the occurrence of reversible Ca plating/stripping. To improve the performance at high current densities, the GPE is supplemented with LiBH 4 to achieve a lower overpotential in the Ca plating/stripping process. An all-solid-state Ca-metal battery with a dual-cation (Ca 2+ and Li + ) GPE, a Ca-metal anode, and a Li 4 Ti 5 O 12 cathode sustained >200 cycles, confirming their feasibility. The results pave the way for further developing lithium salt-free Ca batteries by developing electrolyte salts with high oxidation stability and optimal electrochemical properties., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The lithium-ion transport mechanism in 0.7Li(CB 9 H 10 )-0.3Li(CB 11 H 12 ) complex hydride solid electrolyte was studied over a wide time-scale (ns-ms) by choosing appropriate techniques for assessing ionic motion on the desired time-scale using nuclear magnetic resonance (NMR) relaxation, AC impedance, and pulsed field gradient-NMR (PFG-NMR) measurements. The 7 Li NMR line width decreased with increasing temperature, and the spin-lattice relaxation time T for the cation and anions showed a minimum near 303 K, indicating that the lithium ions and the anions were highly mobile. The activation energy estimated from the analysis of the NMR relaxation time matched well with the values estimated from the AC impedance and PFG-NMR. This confirms that the lithium-ion motion in 0.7Li(CB 1 for the cation and anions showed a minimum near 303 K, indicating that the lithium ions and the anions were highly mobile. The activation energy estimated from the analysis of the NMR relaxation time matched well with the values estimated from the AC impedance and PFG-NMR. This confirms that the lithium-ion motion in 0.7Li(CB 9 H 10 )-0.3Li(CB 11 H 12 ) is the same over a wide time-scale, suggesting steady Li-ion motion over a wide transport range. This understanding offers insights into strategies for designing complex hydride lithium superionic conductors.

We describe an efficient and stereoselective synthesis of 1'-substituted-β-carbocylic nucleosides 5 via gem -dichlorooxirane intermediate 7 , which directly condensed with weak nucleophiles such as pyrimidines or purines. The formation of gem -dichlorooxirane 7 and direct nucleobase condensation exclusively proceeded in protic polar solvents like MeOH. This method provides a general and modular route for the late-stage diversification of 1'-modified nucleosides.

Hierarchically porous carbon microlattices (HPCMLs) fabricated by using a composite photoresin and stereolithography (SLA) 3D printing is reported. Containing magnesium oxide nanoparticles (MgO NPs) as porogens and multilayer graphene nanosheets as UV-scattering inhibitors, the composite photoresin is formed to simple cubic microlattices with digitally designed porosity of 50%. After carbonization in vacuum at 1000 °C and chemical removal of MgO NPs, it is realized that carbon microlattices possessing hierarchical porosity are composed of the lattice architecture (≈100 µm), macropores (≈5 µm), mesopores (≈50 nm), and micropores (≈1 nm). The linear shrinkage after pyrolysis is as small as 33%. Compressive strength of 7.45 to 10.45 MPa and Young's modulus of 375 to 736 MPa are achieved, proving HPCMLs a robust mechanical component among reported carbon materials with a random pore structure. Having a few millimeters in thickness, the HPCMLs can serve as thick supercapacitor electrodes that demonstrate gravimetric capacitances 105 and 13.8 F g -1 in aqueous and organic electrolyte, reaching footprint areal capacitances beyond 10 and 1 F cm -2 , respectively. The results present that the composite photoresin for SLA can yield carbon microarchitectures that integrate structural and functional properties for structural energy storages ., (© 2023 Wiley-VCH GmbH.)

As potential alternatives to Li-ion batteries, rechargeable Ca metal batteries offer advantageous features such as high energy density, cost-effectiveness, and natural elemental abundance. However, challenges, such as Ca metal passivation by electrolytes and a lack of cathode materials with efficient Ca 2+ storage capabilities, impede the development of practical Ca metal batteries. To overcome these limitations, the applicability of a CuS cathode in Ca metal batteries and its electrochemical properties are verified herein. Ex situ spectroscopy and electron microscopy results show that a CuS cathode comprising nanoparticles that are well dispersed in a high-surface-area carbon matrix can serve as an effective cathode for Ca 2+ storage via the conversion reaction. This optimally functioning cathode is coupled with a tailored, weakly coordinating monocarborane-anion electrolyte, namely, Ca(CB 11 H 12 ) 2 in 1,2-dimethoxyethane/tetrahydrofuran, which enables reversible Ca plating/stripping at room temperature. The combination affords a Ca metal battery with a long cycle life of over 500 cycles and capacity retention of 92% based on the capacity of the 10th cycle. This study confirms the feasibility of the long-term operation of Ca metal anodes and can expedite the development of Ca metal batteries., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Despite genetic perturbations resulting in embryo lethality for most mitotic kinases, loss of the histone H3 mitotic kinase HASPIN reveals no adverse effect in mice models, establishing HASPIN as a promising target for anticancer therapy. However, developing a HASPIN inhibitor from conventional pharmacophores poses a technical challenge as this atypical kinase shares slight similarities with eukaryotic protein kinases. Chemically modifying a cytotoxic 4'-thioadenosine analogue through high genotoxicity yielded several novel nongenotoxic kinase inhibitors. In silico apporoaches utilizing transcriptomic and chemical similarities with known compounds and KINOMEscan profiles unveiled the HASPIN inhibitor LJ4827. LJ4827's specificity and potency as a HASPIN inhibitor were verified through in vitro kinase assay and X-ray crystallography. HASPIN inhibition by LJ4827 reduced histone H3 phosphorylation and impeded Aurora B recruitment in cancer cell centromeres but not in noncancer cells. Through transcriptome analysis of lung cancer patients, PLK1 was determined as a druggable synergistic partner to complement HASPIN inhibition. Chemical or genetic PLK1 perturbation with LJ4827 effectuated pronounced lung cancer cytotoxicity in vitro and in vivo. Therefore, LJ4827 is a novel anticancer therapeutic for selectively impeding cancer mitosis through potent HASPIN inhibition, and simultaneous HASPIN and PLK1 interference is a promising therapeutic strategy for lung cancer., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Topological data analysis based on persistent homology has been applied to the molecular dynamics simulation for the fast ion-conducting phase (α-phase) of AgI to show its effectiveness on the ion migration mechanism analysis. Time-averaged persistence diagrams of α-AgI, which quantitatively record the shape and size of the ring structures in the given atomic configurations, clearly showed the emergence of the four-membered rings formed by two Ag and two I ions at high temperatures. They were identified as common structures during the Ag ion migration. The averaged potential energy change due to the deformation of the four-membered ring during Ag migration agrees well with the activation energy calculated from the conductivity Arrhenius plot. The concerted motion of two Ag ions via the four-membered ring was also successfully extracted from molecular dynamics simulations by our approach, providing new insight into the specific mechanism of the concerted motion.

Night foggy road conditions limit visibility distance of drivers and are associated with higher accident and fatality rates than other weather conditions. Therefore, ensuring road visibility in night foggy road is critical. However, it is difficult to reproduce fog on a real road and only a few studies have researched foggy road conditions and visibility in a laboratory as a small scale. Previous studies have suggested that a color temperature of road lighting is related to visibility. However, many have only investigated the effects of relative transmittance in limited indoor experiments, and the impacts of differences in transmittance on visibility have thus far not been studied in real-scale conditions. In this study, a real-scale test involving 91 subjects was conducted to investigate how the visibility distance under night foggy conditions is affected by different lighting color temperatures. Based on the real scale experiments, the correlation between the visibility distance and lighting color temperature was derived. Road lighting with a low color temperature (i.e., yellow) was found to provide longer visibility distances than that with high color temperatures under night foggy conditions having measured visibility of approximately 102m. The impact of the differences in lighting color increased as the visibility distance decreased. In contrast, road lighting with a high color temperature (i.e., white) improved driver visibility in higher-visibility conditions. Therefore, this study confirmed the correlation between lighting color temperature and visibility distance for different visibility conditions and could serve as a foundation for the development of roadway design standards as well as future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The protein p110γ is an isoform of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration and have been implicated in the oncogenesis of various cancers. In this study, p110γ expression in non-small cell lung cancer (NSCLC) and its association with clinicopathological factors and patient survival were evaluated. A total of 230 NSCLC tumors were immunohistochemically stained for p110γ. Of these, 174 (75.7%) and 56 (24.3%) were placed in the low and high expression groups, respectively. The positive rate of p110γ was significantly higher in adenocarcinoma than in squamous cell carcinoma (p⟨0.001). Advanced stage NSCLCs showed higher p110γ expression than those at an early stage (p=0.002). Irrespective of the histological tumor type, the patients with high p110γ expression had significantly worse overall survival than those with low p110γ expression (p=0.004). p110γ expression was an independent poor prognostic factor in the multivariate analysis. Our results suggest that p110γ may be involved in the development and progression of NSCLC, and that p110γ has promising potential as a prognostic factor or novel therapeutic target for NSCLC., (©The Author(s) 2022. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Aim: To determine the normative value of stretched penile length (SPL) for Ethiopian newborns and to set a cut-off point for micropenis., Methods: A total of 221 term newborns were included in the study. Stretched penile length was measured in the first 72 h of postnatal age in neonates with a gestational age of 37-42 completed weeks. SPL < -2 SD was taken as micropenis in this study., Results: The minimum and maximum penile length were 2.5 cm and 5 cm, respectively, with a mean ± SD of 3.28 ± 0.42. SPL at -2 SD and +2 SD were 2.43 and 4.12 cm respectively. A significant correlation was observed between penile length and body length (p = 0.005). Neonates born via instrumental delivery had larger SPL compared to those who were delivered by caesarean section (p = 0.01) or by vaginal delivery (p = 0.006)., Conclusion: The mean stretched penile length in our study mirrors findings from other African studies. SPL < 2.43 cm can be considered as micropenis in our setting. Therefore, routine genital examination and interpretation at birth is crucial to identify micropenis which might herald a serious underlying condition that needs further investigation., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

High ionic conductivity, suitable mechanical strength, and electrochemical stability are the main requirements for high-performance poly(ethylene oxide)-based electrolytes. However, the low ionic conductivity owing to the crystallinity of the ethylene oxide chain that limits the discharge rate and low-temperature performance has restricted the development and commercialization of these electrolytes. Lithium electrolytes that combine high ionic conductivity with a high lithium transference number are rare and are essential for high-power batteries. Here, we report hexagonal arranged porous scaffolds for holding prototype polyethylene glycol-based composite electrolytes containing solvate ionic liquid. The appealing electrochemical and thermal properties indicate their potential as electrolytes for safer rechargeable lithium-ion batteries. The porous scaffolds in the composite electrolytes ensure better electrochemical performance towing to their shortened pores (sizes of 3-14 μm), interconnected pathways, and improved lithium mobility. We demonstrate that both molecular design and porous microstructures are essential for improving performance in polymer electrolytes., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

The development of anticancer drugs remains challenging owing to the potential for drug resistance. The simultaneous inhibition of multiple targets involved in cancer could overcome resistance, and these agents would exhibit higher potency than single-target inhibitors. Protein kinases represent a promising target for the development of anticancer agents. As most multi-kinase inhibitors are heterocycles occupying only the hinge and hydrophobic region in the ATP binding site, we aimed to design multi-kinase inhibitors that would occupy the ribose pocket, along with the hinge and hydrophobic region, based on ATP-kinase interactions. Herein, we report the discovery of a novel 4'-thionucleoside template as a multi-kinase inhibitor with potent anticancer activity. The in vitro evaluation revealed a lead 1g (7-acetylene-7-deaza-4'-thioadenosine) with potent anticancer activity, and marked inhibition of TRKA, CK1δ, and DYRK1A/1B kinases in the kinome scan assay. We believe that these findings will pave the way for developing anticancer drugs.

High-energy-density and low-cost calcium (Ca) batteries have been proposed as 'beyond-Li-ion' electrochemical energy storage devices. However, they have seen limited progress due to challenges associated with developing electrolytes showing reductive/oxidative stabilities and high ionic conductivities. This paper describes a calcium monocarborane cluster salt in a mixed solvent as a Ca-battery electrolyte with high anodic stability (up to 4 V vs. Ca 2+ /Ca), high ionic conductivity (4 mS cm -1 ), and high Coulombic efficiency for Ca plating/stripping at room temperature. The developed electrolyte is a promising candidate for use in room-temperature rechargeable Ca batteries.

Ectopic calcification is a risk of cardiovascular disease in chronic kidney disease (CKD) patients, and impaired endothelial nitric oxide synthase (eNOS) is involved in the CKD complications. However, whether eNOS dysfunction is a cause of ectopic calcification in CKD remains to be elucidated. To address this issue, we investigated the role of eNOS in ectopic calcification in mice with renal injury caused by an adenine and high-phosphorus (Ade + HP) diet. DBA/2J mice, a calcification-sensitive strain, were fed Ade + HP for 3 weeks. Expression levels of eNOS-related genes were reduced significantly in their calcified aorta. C57BL/6J is a calcification-resistant strain, and wild-type mice showed mild calcified lesions in the aorta and kidney when given an Ade + HP diet for 4 weeks. In contrast, a lack of eNOS led to the development of severe aortic calcification accompanied by an increase in runt-related transcription factor 2, an osteochondrogenic marker. Increased renal calcium deposition and the tubular injury score were remarkable in mice lacking eNOS-fed Ade + HP. Exacerbation of ectopic calcification by a lack of eNOS is associated with increased oxidative stress markers such as nicotinamide adenine dinucleotide phosphate oxidases. In conclusion, eNOS is critically important in preventing ectopic calcification. Therefore, the maintenance of eNOS is useful to reduce cardiovascular disease events and to improve prognosis in CKD patients., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The influence of spark plasma sintering (SPS) conditions on the optical and mechanical properties of MgAl₂O₄ spinel was investigated for application to infrared windows as parts of military systems. The thermal conditions of SPS, including the temperature and heating rate, have a significant impact on optical and mechanical properties. This study shows that the formation and growth of abnormal grains cause mechanical degradation with an increasing SPS temperature. In-line transmittance ( T in ) was affected by the heating rate due to changes in oxygen vacancy and carbon contamination in SPSed samples. The fabricated spinel exhibited excellent flexural strength of 401 MPa and an average mid-infrared transmittance of 84.8% in the range of 3-5 μ m.

In nanosized FeWO 4 electrode material, both Fe and W metal cations are suspected to be involved in the fast and reversible Faradaic surface reactions giving rise to its pseudocapacitive signature. In order to fully understand the charge storage mechanism, a deeper insight into the involvement of the electroactive cations still has to be provided. The present paper illustrates how operando X-ray absorption spectroscopy is successfully used to collect data of unprecedented quality allowing to elucidate the complex electrochemical behavior of this multicationic pseudocapacitive material. Moreover, these in-depth experiments are obtained in real time upon cycling the electrode, which allows investigating the reactions occurring in the material within a realistic timescale, which is compatible with electrochemical capacitors practical operation. Both Fe K-edge and W L 3 -edge measurements point out the involvement of the Fe 3+ /Fe 2+ redox couple in the charge storage while W 6+ acts as a spectator cation. The result of this study enables to unambiguously discriminate between the Faradaic and capacitive behavior of FeWO 4 . Beside these valuable insights toward the full description of the charge storage mechanism in FeWO 4 , this paper demonstrates the potential of operando X-ray absorption spectroscopy to enable a better material engineering for new high capacitance pseudocapacitive materials., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

(1) Background: Cervical cancer is one of the most common cancers in Korean women. This study was performed to discover the utility of HPV (Human Papillomavirus) testing in screening of cervical lesions and to provide the prevalence of HPV and the genotype distribution in a single center of Korea. (2) Methods: A total of 15,141 women who underwent both HPV testing and cervical cytology were enrolled in this retrospective medical record review study. (3) Results: HPV testing showed higher sensitivity than cytology for the detection of histological high-grade squamous lesions. Furthermore, the sensitivity and specificity of HPV testing varied depending on the method used. The BD Onclarity™ HPV assay had higher sensitivity (90%) than the MyHPV CHIP™ kit (all types of HPV: 82%; high-risk HPV: 76%) for high-grade squamous lesions. A combination of MyHPV CHIP™ and cytology detected 90.9% (30/33) of histological high-grade squamous lesions. A combination of BD Onclarity™ HPV assay and cytology detected 96.55% (84/87) of histological high-grade squamous lesions. In addition, HPV prevalence and genotype distribution were different depending on the HPV testing method used. (4) Conclusion: HPV testing showed higher sensitivity than cytology, but the sensitivity and specificity of HPV testing had variation depending on the method used.

As mesothelin is overexpressed in various types of cancer, it is an attractive target for therapeutic antibodies. T-cell bispecific antibodies bind to target cells and engage T cells via binding to CD3, resulting in target cell killing by T-cell activation. However, the affinity of the CD3-binding arm may influence CD3-mediated plasma clearance or antibody trapping in T-cell-containing tissues. This may then affect the biodistribution of bispecific antibodies. In this study, we used scFab and knob-into-hole technologies to construct novel IgG-based 1 + 1 MG1122-A and 2 + 1 MG1122-B bispecific antibodies against mesothelin and CD3ε. MG1122-B was designed to be bivalent to mesothelin and monovalent to CD3ε, using a 2 + 1 head-to-tail format. Activities of the two antibodies were evaluated in mesothelin-positive tumor cells in vitro and xenograft models in vivo. Although both antibodies exhibited target cell killing efficacy and produced regression of xenograft tumors with CD8+ T-cell infiltration, the antitumor efficacy of MG1122-B was significantly higher. MG1122-B may improve tumor targeting because of its bivalency for tumor antigen. It may also reduce systemic toxicity by limiting the activation of circulating T cells. Thus, MG1122-B may be useful for treating mesothelin-positive solid tumors., Competing Interests: The authors declare no conflicts of interest.

A fluorine plasma-treated carbon electrode is used in HTM-free perovskite solar cells for high efficiency and moisture resistance. The fluorine-treated device with a champion power conversion efficiency (PCE) of 14.86% is achieved with a highly enhanced FF (FF = 0.69), showing superior long-term stability and excellent moisture penetration suppression.

Pediatric chronic subdural hematoma (CSDH) is a relatively common disorder. Treatment often requires burr hole drainage or subduroperitoneal shunt placement; some patients are managed conservatively. However, the long-term outcome of untreated pediatric CSDH is unknown. The authors report a case of a huge, progressively enlarging subdural granuloma that was surgically treated 26 years after the initial diagnosis of CSDH. This 30-year-old male patient presented with worsening intermittent atonic seizure-like movements, which had been noted since he was 4 years old. At that time, the patient was diagnosed with CSDH at an outside hospital, but an operation was refused by the parents. Magnetic resonance imaging (MRI) performed at 23 years of age showed a huge subdural mass on the right frontoparietal region and a smaller mass on the left side with a significant midline shift. Upon presentation at the age of 30, MRI revealed worsening of the right subdural mass and midline shift. Subsequently, the patient underwent craniotomy and subtotal removal of the mass and capsule. The volume of the content was approximately 430 cc. Untreated pediatric CSDH can grow progressively, even over several decades. Patients with CSDH, especially those managed conservatively, should be closely monitored for worsening symptoms over a long-term follow-up period.

Rendering a high crystalline perovskite film is integral to achieve superior performance of perovskite solar cells (PSCs). Here, we established a two-dimensional liquid cage annealing system, a unique methodology for remarkable enhancement in perovskite crystallinity. During thermal annealing for crystallization, wet-perovskite films were suffocated by perfluorodecalin with distinctively low polarity, nontoxic, and chemically inert characteristics. This annealing strategy facilitated enlargement of perovskite grain and diminution in the number of trap states. The simulation results, annealing time, and temperature experiments supported that the prolonged diffusion length of precursor ions attributed to the increase of perovskite grains. Consequently, without any complicated handling, the performance of perovskite photovoltaics was remarkably improved, and the monolithic grains which directly connected the lower and upper electrode attenuated hysteresis.

Heat shock protein 90 (HSP90), a molecular chaperone, plays critical roles in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. HSP90 has four human isoforms; HSP90α, HSP90β, glucose related protein 94 (GRP94), and tumor necrosis factor (TNF) receptor-associated protein 1 (TRAP1). We evaluated the differential expression of these HSP90 isoforms in colorectal cancer (CRC) and correlated their expression levels with clinicopathological factors and patient survival rates. We performed immunohistochemical staining for HSP90α, HSP90β, GRP94, and TRAP1 in 129 CRC tumor samples and found that HSP90α expression was significantly associated with advanced pT stage (P = 0.011) and shorter recurrence-free survival (RFS) (P = 0.010), whereas GRP94 expression was correlated with low grade (P = 0.029) and better RFS (P < 0.001). HSP90β and TRAP1 had no prognostic impact, although HSP90β expression was positively correlated with tumor size (P = 0.008). Based on our results, HSP90α and GRP94 are potential prognostic biomarkers of CRC. In addition, the differences in expression and functional activities among four HSP90 isoforms imply that isoform selectivity should be seriously considered when HSP90 inhibitors are studied or adopted for the treatment of CRC., Competing Interests: None., (IJCEP Copyright © 2019.)

Vascular endothelial growth factor (VEGF) inhibitors cause glomerular injury. We have recently shown that activation of protease-activated receptor 2 (PAR2) by factor Xa exacerbated diabetic kidney disease. However, the role of PAR2 in glomerular injury induced by VEGF blockade is not known. Herein, we investigated the effect of the lack of PAR2 on VEGF inhibitor-induced glomerular injury. Although administering an anti-VEGF antibody by itself did not show renal phenotype in wild type mice, its administration to mice lacking endothelial nitric oxide synthase (eNOS) caused glomerular injury. Different from what we expected, administration of an anti-VEGF antibody in mice lacking PAR2 and eNOS exacerbated albuminuria and reduced the expression levels of CD31, pro-angiogenic VEGF, and angiogenesis-related chemokines in their kidneys. Podocyte injury was also evident in this model of mice lacking PAR2. Our results suggest that PAR2 is protective against VEGF inhibitor-induced glomerular endothelial and podocyte injury.

Inverted conducting polymer/metal oxide core/shell structured pPPy/SiO 2 -TiO 2 nanoparticles were prepared as electrorheological (ER) materials using sequential experimental methods. The core was synthesized via the low-temperature self-assembly of PPy and SiO 2 materials, and the outer TiO 2 shell was easily coated onto the core part using a sol-gel method and a titanium isopropoxide precursor. Sonication-mediated etching and redeposition were employed to etch out SiO 2 portions from the core part to blend with TiO 2 shells. Each step in nanoparticle synthesis involved morphological and physical changes to the surface area and porosity, with subsequent changes in the intrinsic properties of the materials. Specifically, the electrical conductivity and dielectric properties were successfully altered. The final pPPy/SiO 2 -TiO 2 nanoparticle configuration was optimized for ER applications, offering low electrical conductivity, high dielectric properties, and increased dispersion stability. pPPy/SiO 2 -TiO 2 nanoparticles exhibited 24.7- and 2.7-fold enhancements in ER performance compared to that of PPy-SiO 2 and PPy-SiO 2 /TiO 2 precursor nanoparticles, respectively. The versatile method proposed in this study for the synthesis of inverted conducting polymer/metal oxide core/shell nanoparticles shows great potential for the development of custom-designed ER materials.

Increased central venous pressure in congestive heart failure causes renal dysfunction; however, the underlying mechanisms are unclear. We created a rat renal congestion model and investigated the effect of renal congestion on hemodynamics and molecular mechanisms. The inferior vena cava (IVC) between the renal veins was ligated by suture in male Sprague-Dawley rats to increase upstream IVC pressure and induce congestion in the left kidney only. Left kidney congestion reduced renal blood flow, glomerular filtration rate, and increased renal interstitial hydrostatic pressure. Tubulointerstitial and glomerular injury and medullary thick ascending limb hypoxia were observed only in the congestive kidneys. Molecules related to extracellular matrix expansion, tubular injury, and focal adhesion were upregulated in microarray analysis. Renal decapsulation ameliorated the tubulointerstitial injury. Electron microscopy captured pericyte detachment in the congestive kidneys. Transgelin and platelet-derived growth factor receptors, as indicators of pericyte-myofibroblast transition, were upregulated in the pericytes and the adjacent interstitium. With the compression of the peritubular capillaries and tubules, hypoxia and physical stress induce pericyte detachment, which could result in extracellular matrix expansion and tubular injury in renal congestion.

A simple one-pot method is reported for the fabrication of uniform wrinkled silica nanoparticles (WSNs). Rapid cooling of reactants at the appropriate moment during synthesis allowed the separation of nucleation and growth stages, resulting in uniform particles. The factors affecting particle size and interwrinkle distance were also investigated. WSNs with particle sizes of 65-400 nm, interwrinkle distances of 10-33 nm, and surface areas up to 617 m 2 g -1 were fabricated. Furthermore, our results demonstrate the advantages of WSNs over comparable nonporous silica nanospheres and fumed silica-based products as an abrasive material in chemical mechanical planarization processes.

The power conversion efficiency (PCE) of perovskite solar cells (PSCs) has now exceeded 20%; thus, research focus has shifted to establishing the foundations for commercialization. One of the pivotal themes is to curtail the overall fabrication time, to reduce unit cost, and mass-produce PSCs. Additionally, energy dissipation during the thermal annealing (TA) stage must be minimized by realizing a genuine low-temperature (LT) process. Here, tin oxide (SnO 2 ) thin films (TFs) are formulated at extremely high speed, within 5 min, under an almost room-temperature environment (<50 °C), using atmospheric Ar/O 2 plasma energy (P-SnO 2 ) and are applied as an electron transport layer of a "n-i-p"-type planar PSC. Compared with a thermally annealed SnO 2 TF (T-SnO 2 ), the P-SnO 2 TF yields a more even surface but also outstanding electrical conductivity with higher electron mobility and a lower number of charge trap sites, consequently achieving a superior PCE of 19.56% in P-SnO 2 -based PSCs. These findings motivate the use of a plasma strategy to fabricate various metal oxide TFs using the sol-gel route., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Focal segmental glomerulosclerosis (FSGS) is caused by various etiologies, with mitochondrial dysfunction being one of the causes. FSGS is known to be associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), which is a subclass of mitochondrial disease. However, it has rarely been reported in other mitochondrial disease subclasses. Here, we reported a 20-year-old man diagnosed with FSGS associated with chronic progressive external ophthalmoplegia (CPEO) due to mitochondrial DNA (mtDNA) 3243A>G mutation. He presented with left ptosis, short stature, mild sensorineural deafness, and cardiac conduction block. A renal biopsy sample showed segmental sclerosis and adhesions between capillaries and Bowman's capsule, indicating FSGS. Electron microscopy demonstrated abnormal aggregated mitochondria in podocytes, and the basement membrane and epithelial cells of Bowman's capsule. Skeletal muscle biopsy also showed accumulation of abnormal mitochondria. mtDNA analysis identified heteroplasmic mtDNA 3243A>G mutation with no large-scale deletions. From these findings, we diagnosed the case as CPEO with multi-organ involvement including FSGS. Our report demonstrates that CPEO, as well as MELAS, can be associated with FSGS. Because mitochondrial disease presents with a variety of clinical symptoms, atypical cases with non-classical manifestations are observed. Thus, mitochondrial disease should be considered as an underlying cause of FSGS with systemic manifestations even with atypical phenotypes., (© 2017 S. Karger AG, Basel.)

Background: Heparan sulphate proteoglycan (HSPG) is present in the glomerular basement membrane (GBM) and is thought to play a major role in the glomerular charge barrier. Reductions and structural alterations of HSPG are observed in different types of kidney diseases accompanied by proteinuria. However, their causal relations remain unknown., Methods: We generated podocyte-specific exostosin-like 3 gene (Extl3) knockout mice (Extl3KO) using a Cre-loxP recombination approach. A reduction of HSPG was expected in the GBM of these mice, because EXTL3 is involved in its synthesis. Mice were separated into three groups, according to the loads on the glomeruli: a high-protein diet group, a high-protein and high-sodium diet group and a hyperglycaemic group induced by streptozotocin treatment in addition to maintenance on a high-protein and high-sodium diet. The urinary albumin:creatinine ratio was measured at 7, 11, 15 and 19 weeks of age. Renal histology was also investigated., Results: Podocyte-specific expression of Cre recombinase was detected by immunohistochemistry. Moreover, immunofluorescent staining demonstrated a significant reduction of HSPG in the GBM. Electron microscopy showed irregularities in the GBM and effacement of the foot processes in Extl3KO. The values of the urinary albumin:creatinine ratio were within the range of microalbuminuria in all groups and did not significantly differ between the control mice and Extl3KO., Conclusions: The reduction of HSPG in the GBM did not augment urinary albumin excretion. HSPG's anionic charge appears to contribute little to the glomerular charge barrier., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Elevated circulating uremic toxins are associated with a variety of symptoms and organ dysfunction observed in patients with chronic kidney disease (CKD). Indoxyl sulfate (IS) and p -cresyl sulfate (PCS) are representative uremic toxins that exert various harmful effects. We recently showed that IS induces metabolic alteration in skeletal muscle and causes sarcopenia in mice. However, whether organ-specific accumulation of IS and PCS is associated with tissue dysfunction is still unclear. We investigated the accumulation of IS and PCS using liquid chromatography/tandem mass spectrometry in various tissues from mice with adenine-induced CKD. IS and PCS accumulated in all 15 organs analyzed, including kidney, skeletal muscle, and brain. We also visualized the tissue accumulation of IS and PCS with immunohistochemistry and mass spectrometry imaging techniques. The oral adsorbent AST-120 prevented some tissue accumulation of IS and PCS. In skeletal muscle, reduced accumulation following AST-120 treatment resulted in the amelioration of renal failure-associated muscle atrophy. We conclude that uremic toxins can accumulate in various organs and that AST-120 may be useful in treating or preventing organ dysfunction in CKD, possibly by reducing tissue accumulation of uremic toxins., Competing Interests: The authors declare no competing financial interests.

We modified phenyl-C61-butyric acid methyl ester (PCBM) for use as a stable, efficient electron transport layer (ETL) in inverted perovskite solar cells (PSCs). PCBM containing a surfactant Triton X-100 acts as the ETL and NiO X nanocrystals act as a hole transport layer (HTL). Atomic force microscopy and scanning electron microscopy images showed that surfactant-modified PCBM (s-PCBM) forms a high-quality, uniform, and dense ETL on the rough perovskite layer. This layer effectively blocks holes and reduces interfacial recombination. Steady-state photoluminescence and electrochemical impedance spectroscopy analyses confirmed that Triton X-100 improved the electron extraction performance of PCBM. When the s-PCBM ETL was used, the average power conversion efficiency increased from 10.76% to 15.68%. This improvement was primarily caused by the increases in the open-circuit voltage and fill factor. s-PCBM-based PSCs also showed good air-stability, retaining 83.8% of their initial performance after 800 h under ambient conditions.

The mixed geometrical effect on the electrorheological (ER) activity of bimodal ER fluids was investigated by mixing SiO 2 spheres and rods of different dimensions. To gain an in-depth understanding of the mixed geometrical effect, 12 bimodal ER fluids were prepared from 4 sizes of SiO 2 spheres (50, 100, 150, and 350 nm) and 3 types of SiO 2 rods with different aspect ratios (L/D = 2, 3, and 5). Five concentrations of SiO 2 spheres and rods were created for each bimodal ER fluid, resulting in a total of 60 sets of comprehensive ER measurements. Some bimodal ER fluids exhibited enhanced ER performance, as high as 23.0%, compared to single SiO 2 rod-based ER fluids to reveal the mixed geometrical effect of bimodal ER fluids. This interesting experimental result is based on the structural reinforcement provided by spheres to fibrillated rod materials, demonstrating the mixed geometrical effect on ER activity.

Paintable carbon electrode-based perovskite solar cells (PSCs) are of particular interest due to their material and fabrication process costs, as well as their moisture stability. However, printing the carbon paste on the perovskite layer limits the quality of the interface between the perovskite layer and carbon electrode. Herein, an attempt to enhance the performance of the paintable carbon-based PSCs is made using a modified solvent dripping method that involves dripping of the carbon nanotubes (CNTs), which is dispersed in chlorobenzene solution. This method allows CNTs to penetrate into both the perovskite film and carbon electrode, facilitating fast hole transport between the two layers. Furthermore, this method is results in increased open circuit voltage (V oc ) and fill factor (FF), providing better contact at the perovskite/carbon interfaces. The best devices made with CNT dripping show 13.57% power conversion efficiency and hysteresis-free performance., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

There remains tremendous interest in perovskite solar cells (PSCs) in the solar energy field; the certified power conversion efficiency (PCE) now exceeds 20%. Along with research focused on enhancing PCE, studies are also underway concerning PSC commercialization. It is crucial to simplify the fabrication process and reduce the production cost to facilitate commercialization. Herein, we successfully fabricated highly efficient hole-blocking layer (HBL)-free PSCs through vigorously interrupting penetration of hole-transport material (HTM) into fluorine-doped tin oxide by a large grain based-CH 3 NH 3 PbI 3 (MAPbI 3 ) film, thereby obtaining a PCE of 18.20%. Our results advance the commercialization of PSCs via a simple fabrication system and a low-cost approach in respect of mass production and recyclability.

Sarcopenia is associated with increased morbidity and mortality in chronic kidney disease (CKD). Pathogenic mechanism of skeletal muscle loss in CKD, which is defined as uremic sarcopenia, remains unclear. We found that causative pathological mechanism of uremic sarcopenia is metabolic alterations by uremic toxin indoxyl sulfate. Imaging mass spectrometry revealed indoxyl sulfate accumulated in muscle tissue of a mouse model of CKD. Comprehensive metabolomics revealed that indoxyl sulfate induces metabolic alterations such as upregulation of glycolysis, including pentose phosphate pathway acceleration as antioxidative stress response, via nuclear factor (erythroid-2-related factor)-2. The altered metabolic flow to excess antioxidative response resulted in downregulation of TCA cycle and its effected mitochondrial dysfunction and ATP shortage in muscle cells. In clinical research, a significant inverse association between plasma indoxyl sulfate and skeletal muscle mass in CKD patients was observed. Our results indicate that indoxyl sulfate is a pathogenic factor for sarcopenia in CKD.

Inflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 ( HSVtk ) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibily other cell-surface receptors in human tumors., Competing Interests: Conflict of interest statement: W.A. and R.P. are founders of AAVP BioSystems, which has licensed intellectual property related to the AAVP technology. A.H., W.A., and R.P. are named as inventors on patent applications and are entitled to standard royalties if commercialization occurs. The M. D. Anderson Cancer Center and the University of New Mexico Comprehensive Cancer Center manage these arrangements according to their established institutional conflict-of-interest policies.

Objective: The role of hypercoagulability in the pathogenesis of diabetic nephropathy (DN) remains elusive. We recently reported the increased infiltration of macrophages expressing tissue factor in diabetic kidney glomeruli; tissue factor activates coagulation factor X (FX) to FXa, which in turn stimulates protease-activated receptor 2 (PAR2) and causes inflammation., Approach and Results: Here, we demonstrated that diabetes mellitus increased renal FX mRNA, urinary FXa activity, and FX expression in glomerular macrophages. Administration of an oral FXa inhibitor, edoxaban, ameliorated DN with concomitant reductions in the expression of PARs (Par1 and Par2) and of proinflammatory and profibrotic genes. Diabetes mellitus induced PAR2, and lack of Par2 ameliorated DN. FXa or PAR2 agonist increased inflammatory cytokines in endothelial cells and podocytes in vitro., Conclusions: We conclude that enhanced FXa and PAR2 exacerbate DN and that both are promising targets for preventing DN. Alleviating inflammation is probably more important than inhibiting coagulation per se when treating kidney diseases using anticoagulants., (© 2016 American Heart Association, Inc.)

Nanocrystalline Li3VO4 dispersed within multiwalled carbon nanotubes (MWCNTs) was prepared using an ultracentrifugation (uc) process and electrochemically characterized in Li-containing electrolyte. When charged and discharged down to 0.1 V vs Li, the material reached 330 mAh g(-1) (per composite) at an average voltage of about 1.0 V vs Li, with more than 50% capacity retention at a high current density of 20 A g(-1). This current corresponds to a nearly 500C rate (7.2 s) for a porous carbon electrode normally used in electric double-layer capacitor devices (1C = 40 mA g(-1) per activated carbon). The irreversible structure transformation during the first lithiation, assimilated as an activation process, was elucidated by careful investigation of in operando X-ray diffraction and X-ray absorption fine structure measurements. The activation process switches the reaction mechanism from a slow "two-phase" to a fast "solid-solution" in a limited voltage range (2.5-0.76 V vs Li), still keeping the capacity as high as 115 mAh g(-1) (per composite). The uc-Li3VO4 composite operated in this potential range after the activation process allows fast Li(+) intercalation/deintercalation with a small voltage hysteresis, leading to higher energy efficiency. It offers a promising alternative to replace high-rate Li4Ti5O12 electrodes in hybrid supercapacitor applications.

Preeclampsia (PE) is a pregnancy-induced hypertension with proteinuria that typically develops after 20 weeks of gestation. A reduction in uterine blood flow causes placental ischemia and placental release of anti-angiogenic factors such as sFlt-1 followed by PE. Although the reduced uterine perfusion pressure (RUPP) model is widely used in rats, investigating the role of genes on PE using genetically engineered animals has been problematic because it has been difficult to make a useful RUPP model in mice. To establish a RUPP model of PE in mice, we bilaterally ligated ovarian vessels distal to ovarian branches, uterine vessels, or both in ICR-strain mice at 14.5 days post coitum (dpc). Consequently, these mice had elevated BP, increased urinary albumin excretion, severe endotheliosis, and mesangial expansion. They also had an increased incidence of miscarriage and premature delivery. Embryonic weight at 18.5 dpc was significantly lower than that in sham mice. The closer to the ligation site the embryos were, the higher the resorption rate and the lower the embryonic weight. The phenotype was more severe in the order of ligation at the ovarian vessels < uterine vessels < both. Unlike the RUPP models described in the literature, this model did not constrict the abdominal aorta, which allowed BP to be measured with a tail cuff. This novel RUPP model in mice should be useful for investigating the pathogenesis of PE in genetically engineered mice and for evaluating new therapies for PE.

In meso-superstructured perovskite solar cells, the scaffolding layer, composed of insulating metal oxide nanoparticles, plays an important role in the loading efficiency of the perovskite layer. This communication describes 1D mesoporous silica nanoparticles that were successfully used as scaffolds to enhance the electron extraction from the perovskite absorber layer to the working electrode.

[Purpose] The purpose of this study was to investigate the effects of different height of high heels on muscle activation of the paraspinalis cervicis and erector spinae in healthy young women. [Subjects and Methods] Thirteen healthy women were recruited in this study. To examine the effects of different heights of heels on muscle activation, the paraspinalis cervicis (cervical spine) and erector spinae (lumbar spine) were measured at the time of heel strike and toe off during gait on three different conditions (barefoot, 4 cm high heels, and 10 cm high heels). There are no previous trials or reports that have evaluated this approach in patients with chronic neck pain. [Results] A significant increase in muscle activation of the paraspinalis cervicis and erector spinae at heel strike and toe off (except that of the paraspinalis cervicis at toe off in healthy subjects) was observed in the under 10 cm high heel condition as, compared to that with barefoot condition, in all the subjects. [Conclusion] The height of the high heels affects to the activation demand of the paraspinalis cervicis and erector spinae in patients with neck pain.

A novel approach to enhance the light scattering effect was explored by applying hierarchical silica nanoparticles in DSSCs as scattering layers. The WSN-incorporated cells showed a PCE value of 9.53% and a PCE enhancement of 30.19% compared with those of the reference cells.

BL2D-SMC at the Pohang Light Source II is a supramolecular crystallography beamline based on a bending magnet. The beamline delivers high-flux tunable X-rays with energies from 8.3 to 20.7 keV and a 100 µm (horizontal) × 85 µm (vertical) full width at half-maximum focal spot. Experiments involving variable temperature, photo-excitation and gas sorption are supported by ancillary equipment and software in the beamline. The design of the beamline, its role and the main components are described.

Juxtaglomerular apparatus (JGA) hyperplasia rarely happened in renal biopsy and has been controversial clinically, because synthesis and secretion of renin were susceptible to the effect of clinical condition and medication. Here we present the case of a 39-year-old who got JGA hyperplasia of IgA nephropathy (IgAN) after long-term inhibition of the renin-angiotensin system (RAS) with an angiotensin receptor blocker (ARB), and a direct renin inhibitor (DRI) in combination with a diuretic. He was diagnosed with IgAN in his first renal biopsy, and was treated with supra-maximal dosages of ARB, DRI and a diuretic. In the second biopsy, because of the massive proteinuria and occurrence of steroid-induced diabetes, it was revealed that the area and the number of JGA cells were strikingly increased in observed glomeruli. Immunohistopathologically, the both specimens were stained by human renin antibody. The hyperplastic JG cells contained a large amount of renin granules. Putative renin granules were observed in some interstitial cells adjacent to an afferent arteriole by electron microscopy. The increasing response of renin granules co-localized in prominent JGA hyperplasia should be worried while physicians treat hypertensive patients with potent RAS inhibitors and diuretics even though they have diabetes. This is the first report showing a clinical course of forming prominent JGA hyperplasia directly after a full combination of RAS inhibitors and diuretics in adult IgA nephropathy.