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Background Routine therapeutic drug monitoring is a promising approach for the rational use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and anaplastic lymphoma kinase (ALK) inhibitors. The purpose of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of five EGFR-TKIs (afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib) and three ALK inhibitors (alectinib, ceritinib, and crizotinib). Methods A 100-microliter aliquot of serum was diluted with 100 μL of 1% aqueous ammonia containing internal standards and then purified using the supported liquid extraction method. LC-MS/MS was conducted in positive ionization mode, and the method was validated according to published guidelines. Results Calibration curves were linear across concentration ranges examined. The intra- and inter-assay accuracies were 90.7-110.7% and 94.7-107.6%, respectively. All intra- and inter-assay imprecision values were ≤10.1%. The EGFR-TKIs and ALK inhibitors examined in this study, except osimertinib, which could be stored on ice for at least 5 h, were stable at room temperature for 3 h. For the internal standard-normalized matrix factors, the mean recovery and percent coefficient of variation values ranged between 54-112% and 1.7-11.7%, respectively. This method successfully determined serum concentrations of afatinib, alectinib, erlotinib, gefitinib, and osimertinib in clinical samples. Serum levels of kinase inhibitors consistently reflected those reported in previous studies. Conclusions An LC-MS/MS method suitable for the simultaneous determination of five EGFR-TKIs and three ALK inhibitors in serum was developed and validated. The newly developed method enabled the determination of five of eight target drugs examined in clinical samples. However, a large number of clinical samples need to be analyzed to verify the usefulness of the method.

Two types of new lanthanide coordination networks, [Ln3(pdc)4(Hpdc)(H2O)3]·8H2O [H2pdc = pyridine-2,4-dicarboxylic acid; Ln = Ce (1), Pr (2), Sm (3), Eu (4); type A) and [Tb5(pdc)4(Hpdc)]·3H2O (type B), have been synthesized using a hydrothermal synthetic method. The former type A compound has an unfamiliar architecture, even basically comprised of primitive cubic (pcu) topology, and demonstrate porous gas adsorption behavior, giving several hundreds of square meters per gram surface areas after evacuation of the water molecules, while the latter type B compound does not show any porous properties. Most interestingly, the solvothermal synthetic method using N,N-dimethylformamide (DMF) as a solvent gives compounds that crystallize in a structure analogous to that of type A for Ln = La-Ho, probably formulated as [Ln3(pdc)4(Hpdc)·(DMF)m]·nDMF. These compounds also exhibit large surface areas after evacuation of the DMF molecules and also moderate amounts of hydrogen gas uptake at 77 K. The luminescence properties were investigated for Eu and Tb analogues at elevated temperatures, at which an unusual increase in the emission intensity was observed upon the release of solvents, and discussed based on their porous structure.

Olefin polymerization reactions mediated by diamido-supported titanium complexes are a part of post-metallocene studies. In the present work, dichlorido{di(3-methylindol-2-yl)phenylmethane}titanium (1) and dichlorido{di(3-methylindol-2-yl)-2-methoxyphenylmethane}titanium (2) were applied for ethylene polymerization. The results showed that the 2/MMAO catalyst system, where MMAO is a modified methylaluminoxane, exhibits ethylene polymerization activity up to 2494 (kg of polyethylene)/(mol of Ti)·h·atm. This activity is comparable to the highest known activity in catalyst systems based on diamido-supported titanium complexes. The 2/MMAO system was also active for propylene polymerization (344 (kg of polypropylene)/(mol of Ti)·h·atm) to furnish atactic polypropylene. Bis(indolyl)-coordinated titanium dichlorido complexes were applied for ethylene polymerization. The results showed that [{bis(indolyl)}TiCl2]2 activated by modified methyl aluminoxane (MMAO) exhibited ethylene polymerization activity up to 2494 (kg of polyethylene)/(mol of Ti)·h·atm. This activity is comparable to the highest known activity in catalyst systems based on diamido-supported titanium complexes. The [{bis(indolyl)}TiCl2]2/MMAO catalyst system was also active for propylene polymerization (344 (kg of polypropylene)/(mol of Ti)·h·atm) to furnish atactic polypropylene.

Reactive oxygen species (ROS) play essential roles in plant development and environmental stress responses. In this study, ROS dynamics, the glutathione redox status, the expression and subcellular localization of glutathione peroxidases (GPXs), and the effects of inhibitors of ROS-mediated metabolism were investigated along with fertilization and early zygotic embryogenesis in rice (Oryza sativa). Zygotes and early embryos exhibited developmental arrest upon inhibition of ROS production. Egg cells accumulated high ROS levels, and, after fertilization, intracellular ROS levels progressively declined in zygotes in which de novo expression of GPX1 and 3 was observed through upregulation of the genes. In addition to inhibition of GPX activity, depletion of glutathione impeded early embryonic development and led to failure of the zygote to appropriately decrease H2 O2 levels. Moreover, through monitoring of the glutathione redox status, the developing zygotes exhibited a progressive glutathione oxidation, which became extremely delayed under inhibited GPX activity. Our results provide insights into the importance of ROS dynamics, GPX antioxidant activity, and glutathione redox metabolism during zygotic/embryonic development.

Earth-abundant metal-catalyzed oxidative conversion of ammonia into dinitrogen is a promising process to utilize ammonia as a transportation fuel. Herein, we report the manganese-catalyzed ammonia oxidation under chemical or electrochemical conditions using a manganese complex bearing (1S,2S)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine. Under chemical conditions using oxidant, up to 17.1 equivalents of N2 per catalyst are generated. Also, mechanistic studies by stoichiometric reactions reveal that a nucleophilic attack of ammonia on manganese nitrogenous species occurs to form a nitrogen-nitrogen bond leading to dinitrogen. Moreover, we conduct density functional theory (DFT) calculations to confirm the plausible reaction mechanism. In addition, this reaction system is applicable under electrochemical conditions. The catalytic reaction proceeds with 96 % faradaic efficiency (FE) in bulk electrolysis to give up to 6.56 equivalents of N2 per catalyst.

Background Critical coronavirus disease 2019 (COVID-19) has a high fatality rate, especially in hemodialysis (HD) patients, with this poor prognosis being caused by systemic hyperinflammation; cytokine storms. Steroid pulse therapy or tocilizumab (TCZ) have insufficient inhibitory effects against cytokine storms in critical cases. This study evaluated the clinical effects and safety of combining steroid pulse therapy and TCZ. Methods From September 2020 to May 2021, 201 patients with COVID-19 were admitted to our hospital. Before February 2021, patients with an oxygen demand exceeding 8 L/min were intubated and treated with standard therapy (dexamethasone and antiviral therapy). After February 2021, patients underwent high-flow nasal cannula oxygen therapy and were treated with TCZ (8 mg/kg) and methylprednisolone (mPSL) (500 mg/day [≤ 75 kg], 1000 mg/day [> 75 kg]) for 3 days. We compared background characteristics, laboratory findings, and prognosis between non-HD and HD patients and between patients who received and did not receive TCZ and mPSL pulse therapy. Results Among non-HD patients, the TCZ + mPSL pulse group had significantly higher survival rates and lower secondary infection rates (p Conclusion TCZ combined with mPSL pulse therapy improved the survival rate without significant adverse events in critical HD and non-HD patients with COVID-19 by strongly suppressing systemic hyperinflammation.

This paper reports the first magnetic circularly polarized luminescence (MCPL) characteristics of racemic helicenes, including four unsubstituted [n]helicenes (n=3,4,5,7) and two [4]helicene derivatives bearing methoxy substituents, in tetrahydrofuran (THF) and dimethyl sulfoxide (DMSO) solutions. The value of |gMCPL | was calculated to be of the order of 10-3 T-1 within 350-430 nm under the north-up (N-up) and south-up (S-up) Faraday geometries in an external magnetic field of 1.6 T. The [n]-dependent MCPL signs were altered by the N-up and S-up geometries.

We present the fabrication and evaluation of a microchannel with thin Si windows and a trapping structure for injected liquid samples, including an evaluation using tubing methods of polydimethylsiloxane eyelets, and Kovar. Yeast cells and latex particles were observed using a fluorescence microscope under atmospheric conditions and a scanning electron microscope (SEM) under vacuum. As moving and flowing liquid samples cannot be observed for a long time, a trapping structure in the microchannel is required. In our experiment using pole structures under a thin Si window in microchannels to trap liquid samples, we successfully observed them using the SEM under an accelerating voltage of 15 kV and an emission current of $75~\mu \text{A}$ . This result indicates the possibility of using higher accelerating voltages of electrons for higher observation resolutions at a lower power density of 2.3 kW/cm2. Microfluidic channels with a thin window would be a useful technique for monitoring liquid samples under vacuum. [2020-0367]

In this study, the effect of contact time, temperature, pH, and coexistences on the adsorption of phosphate ions using the complex nickel-aluminum-zirconium hydroxide (NAZ) was evaluated. Moreover, the recovery of adsorbed phosphate ions from NAZ using desorption solution with different concentrations was demonstrated. The results showed that the quantity of phosphate ions adsorbed gradually increased with time, and the adsorption equilibrium was achieved within 24 h after adsorption. This kinetic data could be well described by the pseudo-second-order model with the correlation coefficient in the value of 0.997. Additionally, the quantity of phosphate which was adsorbed increased as temperature increased, and these results corresponded well with both the Langmuir, the correlation coefficient ranged from 0.920-0.949, and Freundlich models, the correlation coefficient ranged from 0.863-0.995. These results showed that the adsorption of phosphate ion was monolayer adsorption onto the NAZ surface. The optimal pH for removal of phosphate ions from aqueous media was during 4-8. In addition, chloride, nitrate, and sulfate ions did not significantly affect to the adsorption capability of phosphate ions in the complex solution system. Finally, the phosphate ions which were adsorbed onto NAZ could be recovered using sodium sulfate solution (recovery percentage: approx. 50% using sodium sulfate solution at 1000 mmol/L). These results highlight the potential of using NAZ as the cost-effectiveness adsorbent for phosphate ions removal from aqueous media.

We evaluated the effects of supplementing cattle feed with difructose anhydride III (DFA III) by measuring urinary sterigmatocystin (STC) concentrations using 20 Japanese Black cattle aged 9–10 months from one herd. DFA III was supplemented for 2 weeks for 10 animals, and non-treated animals served as controls. The natural STC concentration in the dietary feed was 0.06 mg kg−1 (mixture of roughage and concentrate) at the beginning of the study (Day 0). The urine STC concentration was measured using liquid chromatography with tandem mass spectrometry 1 d prior to DFA III administration, 9 and 14 d thereafter, and 9 d following supplementation cessation, concomitant with the measurement of serum amyloid A (SAA). The number of heifers in which STC was detected in the urine was low (10 %) in the DFA III group compared to that (60 %) in the control group on Day 9. After 9 d following supplementation cessation (Day 23), STC concentrations were significantly lower (P=0.032) in the DFA III group than in the control group, although there was no difference in the number of heifers in which urinary STC was detected or in SAA concentrations between the two groups. Our findings demonstrate the effect of DFA III on reducing the urinary concentration of STC in Japanese Black cattle.

The doubly oxonium-embedded picenes have been synthesized for the first time. They have a rigid planar electron-deficient core and are stabilized by the pyrylium aromaticity. The doping positions of oxygen atoms influenced their electrochemical and optoelectronic properties because of the different charge distributions in the skeletons. The donor-acceptor-donor-type molecules baring electron-donating triphenylamine moieties exhibited intramolecular charge-transfer absorption at the visible regions, indicating the large impact of the substituents on their electronic properties.

The anionic polymerization of (Z)-1-phenyl[3]dendralene (1Z-P3D) in THF with potassium naphthalenide (K-Naph) as an initiator was investigated. At −78 °C, a polymer of predictable molecular weight ...

Phosphonates represent an important source of bioavailable phosphorus in certain environments. Accordingly, many microorganisms (particularly marine bacteria) possess catabolic pathways to degrade ...

BACKGROUND/AIM Lenvatinib is standard therapy for radioiodine-refractory differentiated thyroid cancer (RR-DTC), although the optimal timing for starting treatment is still controversial. The aim of this study was to evaluate the prognostic impact of baseline tumour size (BTS) in patients with RR-DTC treated with lenvatinib. PATIENTS AND METHODS Fifty-one RR-DTC patients who had at least one measurable lesion and treated with lenvatinib were retrospectively analysed. BTS was defined as the sum of the longest dimensions of all measurable target lesions. RESULTS Median progression-free survival (PFS) and overall survival (OS) in the larger BTS (≥42 mm) group were shorter than those in the smaller (

Women remain underrepresented in clinical trials and those with type 2 diabetes mellitus are at high risk for cardiovascular (CV) events. The sodium–glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin reduces the risk of CV death or heart failure hospitalisations in individuals with type 2 diabetes. Here, we performed a pre-specified analysis to examine whether sex modifies these effects. The DECLARE-TIMI 58 trial randomised 17,160 patients with type 2 diabetes with or at risk for atherosclerotic disease to dapagliflozin or placebo (median follow-up 4.2 years). The dual efficacy outcomes were CV death or heart failure hospitalisations, and major adverse cardiovascular events (MACE; CV death, myocardial infarction or ischaemic stroke). The renal-specific composite outcome was a sustained ≥40% drop in eGFR to

Oxidized high-density lipoprotein (oxHDL), unlike native HDL, is characterized by reduced cholesterol efflux capability and anti-inflammatory properties. The ratio of oxHDL to apolipoprotein A-I (oxHDL/apoAI) is a possible marker of dysfunctional HDL. The aim of this study was to evaluate the association between oxHDL/apoAI and coronary plaque characteristics that increase the likelihood of cardiovascular events as determined by coronary computed tomography (CT) angiography.A total of 297 patients (mean age; 67 years, men; 63%) who underwent coronary CT angiography for suspected stable coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined by three characteristics: positive remodeling; low-density plaques; and spotty calcification. Significant stenosis was defined as a luminal narrowing of70%. Serum concentrations of oxHDL were measured using an enzyme-linked immunosorbent assay.Patients with higher oxHDL/ApoAI showed significantly greater prevalence of HRP (p = 0.03) and significant stenosis (p 0.01) compared with patients with low oxHDL/ ApoAI. The multivariate logistic analysis demonstrated that oxHDL/ApoAI significantly associated with the presence of HRP and significant coronary stenosis (p = 0.01 and 0.01). In the follow-up study including 243 patients for a median period of 1.8 years, univariate cox regression analysis showed that oxHDL/ApoAI, HRP and significant stenosis were significant predictors of cardiovascular events.A high oxHDL/apoAI was associated with the presence of HRP and significant stenosis determined by coronary CT angiography, which can lead to cardiovascular events in patients with suspected stable CAD.

In this paper, we report the molecular weight dependence of the crystal growth of isotactic polystyrene from 10 nm ultrathin films. The growth rate and characteristic length of the branching morphology of a crystal grown in 10 nm ultrathin films change depending on the molecular weight of the sample. Analysis of the molecular weight dependence according to the theory of growth front instability reveals that the diffusion coefficient of molecular chains in ultrathin films around branching crystals scales with the molecular weight as

The base-promoted switchable synthesis of five- and six-membered cyclic carbamates using atmospheric pressure carbon dioxide as the C1 source was developed. The chemoselectivity of products was simply controlled by changing bases and solvents. The reaction proceeds effectively under mild conditions, affording valuable cyclic carbamates. Experimental results and DFT studies revealed the reaction mechanism.

An anthracene-terminated self-assembled monolayer (SAM) material, ANT-PA, was synthesized, which contains an anchor unit corresponding to octadecylphosphonic acid, C18-PA itself. Thanks to the comm...

Background/purpose Indocyanine green (ICG) fluorescence navigation has been adapted for anatomic liver resection (AR) but an objective method for evaluation of its validity is required. This pilot study aimed to propose a new method to evaluate the accuracy of parenchymal division along the plane between hepatic segments and estimate the real-time navigation efficacy for AR by the Medical Imaging Projection System (MIPS), which continuously demonstrates the transection plane using projection mapping with ICG fluorescence. Methods Ten patients who underwent open AR using liver segmentation with ICG fluorescence technique between August 2016 and July 2019 were included: six patients under MIPS guidance (MIPS group), while four using only conventional ICG fluorescence technique before parenchymal resection (non-MIPS group). Densitometry of the captured fluorescence image was performed to evaluate the fluorescence area ratio of each transection plane. The accurate fluorescence area ratio was calculated by subtracting the fluorescence area rate on the resected side from that on the remnant side. Results The accurate fluorescence area ratio of the MIPS group and the non-MIPS group was 23.0 ± 12.6% and 5.6 ± 9.5%, respectively (P = .038). Conclusions Based on the results of our new method, real-time navigation using the MIPS may facilitate performing AR along the plane between hepatic segments.

A portable chemical analysis system for monitoring ambient carbonyl sulfide (COS) was investigated for the first time. COS is paid attention to from the perspectives of photosynthesis tracer, breath diagnosis marker, and new process-use in the manufacture of semiconductors. Recently, the threshold level value of COS was settled at 5 ppm in volume ratio (ppmv) for workplace safety management. In this work, COS was converted to H2S by a small column packed with alumina catalyzer at 65 °C. Then, the H2S produced was collected in a small channel scrubber to react with fluorescein mercuric acetate (FMA), and the resulting fluorescence quenching was monitored using an LED/photodiode-based miniature detector. The miniature channel scrubber was re-examined to determine its robustness and easy fabrication, and conditions of the catalyzer were optimized. When the FMA concentration used was 1 μM, the limit of detection and dynamic range, which were both proportional to the FMA concentration, were 0.07 and 25 ppbv, respectively. Ambient COS in the background level and even contaminated COS in the nitrogen gas cylinder could be detected. If necessary, H2S was removed selectively by reproducible adsorbent columns. COS concentrations of engine exhaust were measured by the proposed method and by cryo-trap-gas chromatography-flame photometric detection, and the results obtained (0.5–5.9 ppbv) by the two methods agreed well (R2 = 0.945, n = 19). COS in ambient air and exhaust gases was successfully measured without any batchwise pretreatment.

Plasmon-induced carrier transfer at metallic nanoparticle/semiconductor heterojunctions has received great attention because of its tremendous potential in applications, such as photocatalysis and photoelectric and energy conversion. The interfacial structure of the heterojunction is known to play an important role in charge transfer as well as the subsequent chemical reactions. Here, we studied the Au nanoparticle (Au-NP)-loaded (100)-, (110)-, and (111)-oriented single-crystalline strontium titanate (STO) as a model to investigate the effects of interfacial structure on the plasmon-induced charge separation between the metallic nanoparticles and semiconductors. Via photoelectrochemical characterizations, we found that the efficiency of the plasmon-induced water oxidation reaction on STO(100) is more than 1.4 times higher than that on the other two orientation facets. This enhancement was demonstrated to stem from the high oxidation ability of plasmon-induced holes captured in the surface states. Furthermore, the molecular processes of water oxidation were investigated by monitoring the surface oxidation status of Au-NP/STO as intermediates of plasmon-induced water oxidation using in situ electrochemical surface-enhanced Raman spectroscopy. The onset potential of Au-O vibrations on Au-NP/STO(100) was determined to be 0.4 V more negative than that of Au-NP/STO(110), further confirming the higher oxidation ability of the plasmon-induced holes. Our observation provides an opportunity to efficiently modulate plasmon-excited hot-carrier reaction processes for photochemical applications through interfacial engineering.

Obesity and its related diseases have been associated with oxidative stress. Thus, the search for nutritional strategies to ameliorate oxidative stress in obese individuals seems important. We hypothesized that the supplementation with monounsaturated (2-hydroxyoleic acid (2-OHOA)) and with combined n-3 polyunsaturated (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) fatty acids would ameliorate oxidative stress in different organs, including brain, liver, lungs, and kidneys of adult diet-induced obese (DIO) mice. Adult female ICR-CD1 mice were fed a high-fat diet (HFD) for 14 weeks. During the last 6 weeks of HFD feeding, one group of DIO mice received the same HFD, supplemented with 1500 mg of 2-OHOA per kg of HFD and another group with 1500 mg of EPA and 1500 mg of DHA per kg of HFD. At the end of the experiment, several parameters of oxidative stress were assessed. The supplementation with 2-OHOA or with EPA and DHA in DIO mice was able to revert oxidative stress, enhancing the activities of catalase and glutathione reductase, as well as diminishing the activity of xanthine oxidase, the concentration of thiobarbituric acid reactive substances (TBARS) and the ratio between oxidized glutathione and reduced glutathione in several organs. These reached similar values to those of control mice, which were fed a standard diet. These data suggest that supplementation with 2-OHOA and with EPA and DHA could be an effective nutritional intervention to restore an appropriate redox state in DIO mice., C.H. is the recipient of a PhD fellowship from CNP-q-Brazil.

We developed a fast response and high detection efficiency scintillator for high-energy synchrotron X-rays. The scintillator was fabricated using zirconium oxide (ZrO2) nanoparticles loaded into a plastic scintillator (ZrO2-PLS). The ZrO2-PLS was successfully polymerized by mixing it with a styrene- or vinyltoluene-based monomer and a 2-(4-tert-Butylphenyl)-5-(4-phenylphenyl)]1,3,4-oxadiazole (b-PBD) fluorophore. ZrO2-PLSs loaded with ZrO2 20–60 wt% were molded to be 8 mm in diameter and 3 mm in thickness. The optical properties of the ZrO2-PLSs were measured for their transmittance and quantum yield. Even for a scintillator loading 60 wt% of ZrO2 (ZrO2 60-wt%-PLS), the average transmittance in the 380–780 nm range exceeded 70%, and the quantum yield was 45% under UV light (300 nm) excitation. The detection efficiency and light output of the ZrO2-PLS were measured using 67.41-keV X-rays. The detection efficiency of the ZrO2 60-wt%-PLS was 43.7%, which was 6.4 times higher than that of a 5-wt% lead-loaded PLS (EJ-256, Eljen Technology) of the same size. In addition, the ZrO2 30-wt%-PLS achieved a detection efficiency of 19.6%, which was 2.8 times higher than that of EJ-256, while maintaining the same amount of light output as that by EJ-256.

In plants, growth–defense tradeoffs are essential for optimizing plant performance and adaptation under stress conditions, such as pathogen attack. Root-knot nematodes (RKNs) cause severe economic losses in many crops worldwide, although little is known about the mechanisms that control plant growth and defense responses during nematode attack. Upon investigation of Arabidopsis thaliana infected with RKN (Meloidogyne incognita), we observed that the atypical transcription factor DP-E2F-like 1 (DEL1) repressed salicylic acid (SA) accumulation in RKN-induced galls. The DEL1-deficient Arabidopsis mutant (del1-1) exhibited excessive SA accumulation in galls and is more resistant to RKN infection. In addition, excessive lignification was observed in galls of del1-1. On the other hand, the root growth of del1-1 is reduced after RKN infection. Taken together, these findings suggest that DEL1 plays an important role in the balance between plant growth and defense responses to RKN infection by controlling SA accumulation and lignification.

A 75-year-old woman visited a nearby clinic with complaints of right clavicle discomfort, and she underwent diagnostic thoracoscopic lung biopsy, being diagnosed with lung metastasis and a right-upper mediastinal mass. The superior mediastinum mass was extrapulmonary and covered by the pleura, and it was not biopsied. Papillary thyroid carcinoma was diagnosed following biopsy of the lung metastasis. Only a small tumor, with a maximum diameter of 70 mm from the right neck to the superior mediastinum, in the thyroid gland invades the internal jugular vein and subclavian vein, forming a tumor embolus in the right brachiocephalic vein and reaching the vicinity of the superior vena cava. For life-saving purposes, we obtained approval from the Cancer Board of Kanagawa Cancer Center and used lenvatinib according to unresectable undifferentiated cancer IRB approval number 28–41. The tumor had shrunk after 4 months, and surgery was performed. The postoperative course has been good, and the patient is being followed up. The patient is alive three months after surgery, and lung metastases have disappeared on CT images. This case is reported as a successful case of neoadjuvant chemotherapy and interval debulking surgery.

Combining microalgae and nitrifiers in a single photobioreactor has attracted attention as an alternative approach for conventional nitrogen removal from wastewater. However, nitrifiers are known to be sensitive to light exposure. This study demonstrated the effectiveness of using fluidized carriers to mitigate light stress in nitrifiers. An outdoor raceway pond containing microalgae and nitrifiers with fluidized carriers was used to treat two-fold diluted anaerobic digestion effluent (785 mg-N L−1 as a form of dissolved total Kjeldahl nitrogen: TKN) over 50 days. The average daily sunlight intensity reached the inhibition level of nitrifiers (423 μmol photons m−2 s−1); however, stable nitrification with a specific ammonium oxidation rate of 55 mg-N g-total suspended solid−1 day−1 was observed. TKN was mostly removed via nitrifier metabolism (ammonium oxidation and uptake: 40.1%) and partially via microalgae uptake (5.7%). Different microalgae-based processes including that of this study were compared in terms of tolerances to a high dissolved TKN concentration and strong light. Our system showed a relatively higher resistance to not only light exposure but also TKN because the nitrification process decreased the free ammonia level to less than 0.25 mg L−1, which allowed microalgae to grow despite the high ammonium concentration.

Background The initial presentation of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is indistinguishable from that of complex febrile seizures (FS), which poses a great diagnostic challenge for clinicians. Excitotoxicity is speculated to be the pathogenesis of AESD. Vitamin B6 (VB6) is essential for the biosynthesis of gamma-aminobutyric acid, an inhibitory neurotransmitter. The aim of this study is to investigate our hypothesis that VB6 deficiency in the brain may play a role in AESD. Methods We obtained cerebrospinal fluid (CSF) samples from pediatric patients with AESD after early seizures and those with FS. We measured pyridoxal 5′-phosphate (PLP) and pyridoxal (PL) concentrations in the CSF samples using high-performance liquid chromatography with fluorescence detection. Results The subjects were 5 patients with AESD and 17 patients with FS. Age did not differ significantly between AESD and FS. In AESD, CSF PLP concentration was marginally lower (p = 0.0999) and the PLP-to-PL ratio was significantly (p = 0.0417) reduced compared to those in FS. Conclusions Although it is impossible to conclude that low PLP concentration and PLP-to-PL ratio are causative of AESD, this may be a risk factor for developing AESD. When combined with other markers, this finding may be useful in distinguishing AESD from FS upon initial presentation.

The development of efficient technologies to adsorb volatile organic compounds (VOCs) is desirable given their adverse effects on human health and the environment. Herein, we report a crystalline m...

Prostaglandin E2 (PGE2), which is a potent pro-inflammatory lipid mediator, is biosynthesized from arachidonic acid by cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Non-steroidal anti-inflammatory drugs (NSAIDs) are used clinically as COX inhibitors, but they have gastrointestinal and cardiovascular side-effects. Thus, the terminal enzyme mPGES-1 holds promise as the next therapeutic target. In this study, we found that the ellagitannins granatin A and granatin B isolated from pomegranate leaves, and geraniin, which is their structural analog, selectively suppressed mPGES-1 expression without affecting COX-2 in non-small cell lung carcinoma A549 cells. The ellagitannins also down-regulated tumor necrosis factor α, inducible nitric oxide synthase, and anti-apoptotic factor B-cell chronic lymphocytic leukemia/lymphoma 2, and induced A549 cells to undergo apoptosis. These findings indicate that the ellagitannins have anti-inflammatory and anti-carcinogenic effects, due to their specific suppression of mPGES-1. Abbreviations: Bcl-2: B-cell chronic lymphocytic leukemia/lymphoma 2; COX: cyclooxygenase; CRE: cAMP response element; DHHDP: dehydrohexahydroxydiphenoyl; Et2O: diethyl ether; EtOAc: ethyl acetate; GAPDH: glyceraldehyde 3-phosphate dehydrogenase; iNOS: inducible nitric oxide synthase; mPGES-1: microsomal prostaglandin E synthase-1; n-BuOH: water-saturated n-butanol; NSAIDs: non-steroidal anti-inflammatory drugs; NF-κB: nuclear factor-κB; PG: prostaglandin; TNF: tumor necrosis factor; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling Ellagitannins from pomegranate leaves suppressed mPGES-1 expression without affecting COX-2, and showed anti-inflammatory and anti-carcinogenic effects.

Background The International Society for Peritoneal Dialysis guidelines recommends the topical application of antibiotics on the exit site for the prevention of peritoneal dialysis (PD)-related infections. However, the recommendation is based on meta-analyses on applying nasal mupirocin ointment or observational or retrospective studies. Here, we evaluated the efficacy of topical application of mupirocin on the exit site for the prevention of PD-related infections. Methods We searched the databases, MEDLINE and CENTRAL, documenting the topical application of antibiotics on the exit site in PD patients in April 2017. We included only randomized controlled trials (RCTs) with adult patients wherein the effects of mupirocin were examined. Exit site infection (ESI), peritonitis, and technical failure were assessed as the main outcomes. Results Overall, six RCTs were included in this study. It was uncertain whether the application of mupirocin ointment prevents ESI (rate ratio (RR), 0.36; 95% CI, 0.13–1.05), peritonitis (RR 0.78, 95% CI 0.50–1.21), and technical failure (RR, 1.35; 95% CI, 0.25–7.21). Moreover, a comparison between mupirocin and gentamicin showed no difference in the incidence of ESI (RR, 1.14; 95% CI, 0.27–4.81), peritonitis (RR, 0.85; 95% CI, 0.32–2.26), and technical failure (RR, 0.58; 95% CI, 0.28–1.20). Conclusions It remains unclear whether topical application of mupirocin on the exit site has any significant effects on PD-related infection or technical failure. Large-scale RCTs with high methodological quality are required to confirm the efficacy of topical application of antibiotics on the exit site. Trial registration UMINR000039267

Objective Although aerobic exercise tests on cycle ergometry have long been used for initial assessments of cases of suspected mitochondrial disease, the test parameters in patients with final diagnoses of other diseases via the widely used 15 W for 15 min exercise protocol have not been fully characterized. Methods and Patients We retrospectively reviewed all patients who underwent the test at our institution. We classified the patients with genetic diagnoses or those who met previously reported clinical criteria as having mitochondrial diseases and those with a final diagnosis of another disease as having other diseases. Results were available from 6 patients with mitochondrial disease and 15 with other diseases. Results During the test, elevated venous peak lactate above the upper normal limit of healthy controls at rest (19.2 mg/dL [2.13 mM]) was observed in 3 patients with mitochondrial diseases (50.0%) and 5 with other diseases (33.3%). In the group of patients with elevated venous peak lactate, a lactate-to-pyruvate ratio of >20 was observed in all 3 patients with mitochondrial disease but in only 1 of the 5 with other diseases. More than a 2-fold increase in venous lactate from baseline was observed in 4 patients with mitochondrial disease (66.7%) and 1 with another disease (6.7%). Conclusion Elevated venous peak lactate levels were observed in patients with final diagnoses of other diseases, even under a low 15-min workload at 15 W. The lactate-to-pyruvate ratio and increase in lactate level from baseline may add diagnostic value to venous peak lactate levels alone.

Background Pneumatosis intestinalis is a rare disease characterized by gas-filled cysts within the submucosa or serosa of the intestinal tract. In recent years, pneumatosis intestinalis was reported in patients undergoing cancer treatment, and some case reports exist that report that pneumatosis intestinalis occurs during administration of vascular endothelial growth factor inhibitors, such as bevacizumab and sunitinib. Here, we report the first case of pneumatosis intestinalis during lenvatinib treatment. Case presentation A 77-year-old Japanese man presented to our hospital with a chief complaint of numbness in the right leg and weakness of the lower limbs 9 years after right thyroid lobectomy. Computed tomography showed a tumor 90 mm in size from the lumbar spine to the sacrum, causing spinal cord compression. Blood tests showed that the patient’s thyroglobulin level was increased to 11,600 ng/ml. We diagnosed him with thyroid cancer with bone metastases. External beam radiotherapy (39 Gy/13 Fr) was performed on the bone metastases, followed by total thyroidectomy and radioactive iodine therapy. Four months after radioactive iodine therapy, lenvatinib was introduced because the symptoms of numbness and weakness recurred. Lenvatinib was introduced at dose of 24 mg, and then it was reduced to 14 mg owing to Common Terminology Criteria for Adverse Event grade 3 paronychia of the right foot. Although no further significant adverse events occurred, a scheduled computed tomography image showed pneumatosis intestinalis of the ascending colon 14 weeks after the introduction of lenvatinib. No abdominal or digestive symptoms were observed; therefore, we selected conservative treatment. We discontinued lenvatinib for a week, but we were required to restart lenvatinib as the numbness in the right leg worsened after withdrawal. Since the introduction of lenvatinib, 3 years and 5 months passed; we continued lenvatinib treatment, and the therapeutic effect remains partial response. There has been no recurrence of pneumatosis intestinalis. Conclusions Although rare, it is important to recognize that pneumatosis intestinalis can occur in association with lenvatinib and should be differentiated from intestinal perforation. Pneumatosis intestinalis association with lenvatinib can be improved by withdrawal.

We investigate the quench and real-time formation of the Mott state and photoexcited carrier relaxation dynamics in the Mott insulator $\ensuremath{\kappa}\text{\ensuremath{-}}{(\mathrm{B}\mathrm{E}\mathrm{D}\mathrm{T}\text{\ensuremath{-}}\mathrm{T}\mathrm{T}\mathrm{F})}_{2}\mathrm{Cu}[\mathrm{N}{(\mathrm{C}\mathrm{N})}_{2}]\mathrm{Cl}(\ensuremath{\kappa}\text{\ensuremath{-}}\mathrm{Cl})$ and the superconductor $\ensuremath{\kappa}\text{\ensuremath{-}}{(\mathrm{B}\mathrm{E}\mathrm{D}\mathrm{T}\text{\ensuremath{-}}\mathrm{T}\mathrm{T}\mathrm{F})}_{2}\mathrm{Cu}[\mathrm{N}{(\mathrm{C}\mathrm{N})}_{2}]\mathrm{Br}(\ensuremath{\kappa}\text{\ensuremath{-}}\mathrm{Br})$ using three-pulse femtosecond optical spectroscopy, where BEDT-TTF is bis(ethylenedithio)tetrathiafulvalene. In both salts, we find that transient reflectivity amplitude gradually recovers with time after strong near-infrared pulse quench, but its relaxation time is nearly constant throughout. This indicates that in $\ensuremath{\kappa}$-Cl, the energy gap for charge excitations is filled rather than closed by photoinduced carriers of only $\ensuremath{\sim}0.5$% per dimer. The Mott state is re-formed on a few-picosecond timescale with the disappearance of the in-gap photodoping-induced states near the Fermi energy. In $\ensuremath{\kappa}$-Br, a behavior similar to that in $\ensuremath{\kappa}$-Cl is observed and attributed to the disorder-induced phase-separated Mott insulating regions.

A fast response potentiometric flow-through pH sensor was applied for organic acid determination. The analyte response with the pH sensor was obtained by eluent pH modification following ion exclusion chromatography with HClO4 as an eluent. The response characteristics depend on the adjusted baseline pH. The baseline pH adjustment was successfully done with an ammonia permeation device without solution mixing, which may cause analyte dilution, dispersion, and mixing noise. After pH adjustment, the pH response was universal to the equivalent of introduced analyte acids because the pH response was obtained by the titration of the permeant ammonia by the analytes. The average of limit of detections (S/N = 3) was 0.06 mM for seven target organic acids. Furthermore, the pH response follows the theoretical pH calculation with the concentrations of the eluent, pH modifier, and analyte. Thus, the analyte concentration in the sample can be theoretically calculated from the pH response without calibration by the analyte standard. Predicted concentrations of injected standards were within 5% of the actual standard concentration. Additionally, analysis of real samples was performed and compared with the conventional post-column reaction with a bromothymol blue (BTB) method. The results obtained with the present system (absolute quantification with theoretical calculation) and conventional BTB method agreed within 10% of errors.

In partial hepatectomy, the risks of positive surgical margin (SM) and iatrogenic spread should be avoided. SM is usually secured using intraoperative ultrasound (IOUS), but SM positive cases are often experienced. Indocyanine green (ICG) fluorescent imaging for hepatobiliary surgery was recently developed.1 Ishizawa et al.2 first reported that colorectal liver metastases (CRLMs) were delineated as rim fluorescing lesions.

This work reports synthesize of polypyrrole nano powder by chemical in-situ polymerization of pyrrole in aqueous solution and ammonium persulfate solution which acts as oxidant. It is characterized by X-ray diffraction (XRD), Fourier infra-red spectroscopy (FTIR) and scanning electron microscopy (SEM). The XRD spectrum reveals that the materials are amorphous in nature. FTIR analysis confirms that all peaks are the main characteristic of PPy. SEM analysis showed that the powder has a uniform granular morphology and the size varies from ∼500 nm to 1 μm. The micrograph of polypyrrole reveals the presence of globular particles. The formed particles are irregular in nature. The results show that the fibers are chemically formed as spherical nanostructures.

In an online survey, we found that nearly one fifth of physicians in the United States who responded had seen or heard about a case of invasive pulmonary aspergillosis after severe influenza at their institution. However

An olivine-type Eu2+-activated NaMgPO4 (NMP:Eu2+) material was previously discovered as a new red-emitting oxide phosphor with a high quantum efficiency under blue light excitation; however, the use of a special and nonuniversal optical system of an arc-imaging furnace was necessary for its synthesis. To realize the synthesis of NMP:Eu2+ using a conventional tubular furnace, in this work, we employed a new synthetic strategy of rapid quenching from a high temperature, which imitates the synthesis process using the arc-imaging furnace. As a result, we succeeded in stabilizing the olivine structure in the NMP:Eu2+ phosphor. Thermogravimetric-differential thermal analysis (TG-DTA) revealed the presence of the polymorphism of glaserite (low-temperature phase) and olivine (high-temperature phase) phases in the NaMgPO4:0.025Eu2+ composition, and the stabilized region of the olivine phase was found to be around 1000 °C, which indicated that the rapid quenching process effectively acted as an olivine phase stabilizer. According to X-ray diffraction (XRD) measurements, the NMP:Eu2+ phosphor samples have the olivine structure as the main phase. Additionally, the photoluminescence (PL) intensity of the phosphor was 1.3 times that of the previous NMP:Eu2+ phosphor prepared using the arc-imaging furnace. The internal quantum efficiency of the NMP:Eu2+ phosphor was found to be 72.3%, which is the highest among the known Eu2+-activated red-emitting oxide phosphors. Moreover, other properties relevant to light-emitting diode (LED) phosphors, such as the chemical composition, chemical state of Eu, particle morphology, PL lifetime, thermal quenching properties, humidity resistance and electroluminescence (EL) properties of a fabricated phosphor-converted (pc)-LED, were investigated in detail.

In this study, nickel-aluminium complex hydroxides at different molar ratios (nickel-aluminium = 1 : 2, 1 : 1, 2 : 1, 3 : 1, and 4 : 1, referred to as NA12, NA11, NA21, NA31, and NA41) were prepared, and their adsorption capability for chromium(VI) ion was investigated. Firstly, physicochemical characteristics (SEM images, X-ray diffraction (XRD) patterns, specific surface area, amount of hydroxyl groups, and surface pH) of nickel-aluminum complex hydroxide were evaluated. The amount of chromium(VI) ion adsorbed onto NA11 (15.3 mg/g) was greater than that adsorbed onto the other adsorbents. This research elucidated that the amount of chromium(VI) ion adsorbed using nickel-aluminium complex hydroxide was related to the adsorbent surface properties (r = 0.818-0.875). Subsequently, the adsorbent (NA11) surface before and after adsorption of chromium(VI) ion was evaluated, and chromium energy (577 and 586 eV) detected after adsorption onto the NA11 surface. These results revealed that the NA11 surface properties were very important for the removal of chromium(VI) ion from aqueous solution. In addition, the effects of pH, contact time, and temperature on the adsorption of chromium(VI) ion were evaluated. We confirmed a high recovery percentage of chromium(VI) ion when using sodium hydroxide solution at 10-1000 mmol/L (approximately greater than 80%) in this experimental condition. Thus, NA11 is a promising adsorbent for the removal of chromium(VI) ion from aqueous solution.

Heavy metals in particulate matter (PM) are of great concern, and their effects on the environment and human health depend on their solubilities and species present. In this study, the solubility of As, Se, Sb, V and Cr and their species eluted in water was investigated. As, Se, Sb, and V were present mostly in fine particles, and they were predominantly water-soluble in fine particles ( 2.5 μm). Solubility of Cr was poor even in fine particles. It was found that for fine particles, solubilities of the heavy metals were related to the nitrate and sulfate contents. This suggests that the higher the acidity of the particles, the higher the solubility of the heavy metals. Oxoanions of the five kinds of heavy metals in water extracts of fine particles were determined by inductively coupled plasma mass spectrometry preceded by ion chromatography. The results suggested the presence of atmospheric oxidation during the aerosol transportation. Also, the As(iii)/As(v) (arsenite/arsenate) ratios for the fine particle extracts were related to the transition metal concentrations, which indicated that Fe, Cu, etc. in fine particles affected the As redox equilibrium. It was suggested that the heavy metals exist as complexes with iron hydroxide and dissolved organic matter in addition to the free oxoanions. These investigations were performed for PM samples collected in winter and summer in Kumamoto, west Japan, where the site is strongly exposed to westerly winds from continental East Asia. The obtained results improve our understanding of the behavior of the heavy metals in airborne PM after depositing on a wet environment and biota.

Introduction: Pulmonary metastasis originating from differentiated thyroid cancer is rare. Pulmonary metastasis generally progresses slowly and results in a relatively long prognosis when treated with radioactive iodine therapy and thyroid-stimulating hormone suppression therapy. However, some cases still result in death. Since 2015, lenvatinib administration for pulmonary metastases with disease progression has yielded satisfactory results. Materials and methods: Among the 798 patients with differentiated thyroid cancer treated at Kanagawa Cancer Center, Japan, between April 2015 and March 2020, 194 had distant metastasis. Of these 194 patients, 118 diagnosed with pulmonary metastasis had lesions that influence the prognosis. We retrospectively investigated the transition of the maximum diameter of pulmonary metastases, serum thyroglobulin, follow-up, and survival time. Results: We included 83 follow-up cases and 35 patients treated with lenvatinib. Considering that the disease progressed, 35 patients were treated with lenvatinib, and 4 died from cancer-specific disease. Treatment results were evaluated as progressive disease, stable disease, and partial response in 2, 11, and 22 patients, respectively. Conclusions: Among pulmonary metastases, no death occurred because of relatively slow disease progression up to a maximum diameter of 10 mm. However, when the size exceeded 15 mm, radioactive iodine treatment and thyroid-stimulating hormone suppression therapy did not work, and disease progression accelerated. As long as the lenvatinib treatment could be continued, the disease could be controlled satisfactorily. The patients who discontinued lenvatinib died from disease progression.

Summary Bundle Sheath Defective 2, BSD2, is a stroma‐targeted protein initially identified as a factor required for the biogenesis of ribulose 1,5‐bisphosphate carboxylase/oxygenase (RuBisCO) in maize. Plants and algae universally have a homologous gene for BSD2 and its deficiency causes a RuBisCO‐less phenotype. As RuBisCO can be the rate‐limiting step in CO2 assimilation, the overexpression of BSD2 might improve photosynthesis and productivity through the accumulation of RuBisCO. To examine this hypothesis, we produced BSD2 overexpression lines in Arabidopsis. Compared with wild type, the BSD2 overexpression lines BSD2ox‐2 and BSD2ox‐3 expressed 4.8‐fold and 8.8‐fold higher BSD2 mRNA, respectively, whereas the empty‐vector (EV) harbouring plants had a comparable expression level. The overexpression lines showed a significantly higher CO2 assimilation rate per available CO2 and productivity than EV plants. The maximum carboxylation rate per total catalytic site was accelerated in the overexpression lines, while the number of total catalytic sites and RuBisCO content were unaffected. We then isolated recombinant BSD2 (rBSD2) from E. coli and found that rBSD2 reduces disulfide bonds using reductants present in vivo, for example glutathione, and that rBSD2 has the ability to reactivate RuBisCO that has been inactivated by oxidants. Furthermore, 15% of RuBisCO freshly isolated from leaves of EV was oxidatively inactivated, as compared with 0% in BSD2‐overexpression lines, suggesting that the overexpression of BSD2 maintains RuBisCO to be in the reduced active form in vivo. Our results demonstrated that the overexpression of BSD2 improves photosynthetic efficiency in Arabidopsis and we conclude that it is involved in mediating RuBisCO activation., Significance Statement Catalytic properties of RuBisCO are susceptible to oxidation of its thiols, but the underlying process resulting in a change in RuBisCO activation has been largely elusive. Here we identify BSD2, known as a chaperone for RuBisCO assembly, as a protein that takes an essential role in the redox homeostasis of mature RuBisCO. We show that overexpression of BSD2 improves RuBisCO carboxylation efficiency through manipulating the redox potential.