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Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne illness with a notable morality risk that is becoming increasingly prevalent in East Asia (14–36%). Increasing evidence indicates a more direct role of the SFTS virus in renal impairment. However, few studies have explored the risk factors for and clinical outcomes of AKI in patients with SFTS. Therefore, in this study, we aimed to investigate risk factors and outcomes associated with AKI in patients with SFTS. In this retrospective cohort study, we included the data of 53 patients who were diagnosed with SFTS virus infection at Kangwon National University Hospital between 2016 and 2020. We incorporated laboratory data and medical information including comorbidities, complications, and mortality. Baseline characteristics, clinical features, laboratory parameters, and mortality rates of the non-AKI and AKI groups were compared. Patient survival of non-AKI and AKI groups were compared using the Kaplan–Meier method. To identify the population with poor prognosis, Cox regression analysis was used to identify the independent risk factors for in-hospital mortality in patients with SFTS. Of the 53 individuals, 29 (54.7%) were male, with an average age of 66.5 years. Nine patients (15.1%) died of SFTS. Twenty-seven (50.9%) patients exhibited AKI; the average time interval from fever onset to AKI occurrence was 3.6 days. Notably, 24 (88.9%) patients developed AKI within the first week of fever onset. Patients in the AKI group exhibited a significantly higher prevalence of diabetes and were older than those in the non-AKI group. The mortality rate was notably higher (29.6%) in the AKI group than in the non-AKI group (3.8%). Within the AKI cohort, advanced stages (stages 2 and 3) showed a 50% mortality rate, which was significantly higher than the 17.6% mortality rate in patients with stage 1 AKI. Additionally, Kaplan–Meier curves revealed lower survival rates among patients with AKI than among those without AKI (P = 0.017). Cox regression analysis identified leukopenia and elevated serum creatinine levels as significant risk factors for mortality. AKI is a common complication associated with SFTS. Moreover, the mortality rate was significantly higher in the patients who developed AKI than in those who did not. Our findings underscore the pivotal role of AKI as a prognostic marker of disease severity in patients with SFTS. [ABSTRACT FROM AUTHOR]

The process of texturing silicon surfaces is critical for enhancing the performance of complementary metal–oxide–semiconductor image sensors that utilize silicon-based photodetectors. Traditional wet etching methods using strong acids or alkaline solutions have been commonly used but present challenges in precision, particularly for microscopic devices. As a viable alternative, dry etching processes using patterned metals and plasma are being explored. However, extensive studies across various metals are necessary. This study introduces a silicon nanotexturing process using silver nanowires and Cl2-based plasma. The etching mechanism involves accelerated etching through eddy currents and hole injection coupled with a diffusion phenomenon of silver. In this study, we examined variations in the etching profile with respect to etching time, upper and bottom radio-frequency powers, and process pressure. Additionally, we analyzed the effects of ion bombardment, enhanced by the introduction of Ar gas. The findings are expected to significantly contribute to the improvement of micro-optoelectronic devices. [ABSTRACT FROM AUTHOR]

ATP-binding cassette transporter B6 (ABCB6), a protein essential for heme biosynthesis in mitochondria, also functions as a heavy metal efflux pump. Here, we present cryo-electron microscopy structures of human ABCB6 bound to a cadmium Cd(II) ion in the presence of antioxidant thiol peptides glutathione (GSH) and phytochelatin 2 (PC2) at resolutions of 3.2 and 3.1 Å, respectively. The overall folding of the two structures resembles the inward-facing apo state but with less separation between the two halves of the transporter. Two GSH molecules are symmetrically bound to the Cd(II) ion in a bent conformation, with the central cysteine protruding towards the metal. The N-terminal glutamate and C-terminal glycine of GSH do not directly interact with Cd(II) but contribute to neutralizing positive charges of the binding cavity by forming hydrogen bonds and van der Waals interactions with nearby residues. In the presence of PC2, Cd(II) binding to ABCB6 is similar to that observed with GSH, except that two cysteine residues of each PC2 molecule participate in Cd(II) coordination to form a tetrathiolate. Structural comparison of human ABCB6 and its homologous Atm-type transporters indicate that their distinct substrate specificity might be attributed to variations in the capping residues situated at the top of the substrate-binding cavity. Cryo-EM structure of human ATP-binding cassette transporter 6 (ABCB6) in complex with Cd(II) and glutathione (GSH) provides molecular insight into its dual role, essential for heme biosynthesis and as a heavy metal efflux pump. [ABSTRACT FROM AUTHOR]

Background: Obesity and its associated diseases have become a concerning health issue not only in the middle-aged population but also in young children due to changes in lifestyle and food intake. However, the existing pharmacological therapeutic approaches to address this issue can induce serious problems. Thus, in this study, we aimed to expand the therapeutic approaches based on naturally derived products. The oriental medicine, heated powder of Ostreae Testa, is widely used as a dietary supplement. However, the effect of Ostreae Testa Water extract (OTW) on adipogenesis and adipocyte function remains to be elucidated. Objective: The objective of this study was to evaluate the potential anti-obesity effects of OTW, particularly in adipocytes. Results: OTW extract treatment of fully differentiated mature 3T3-L1 adipocytes demonstrated an inhibitory effect on lipid accumulation and down-regulated lipolysis. Moreover, OTW extract suppressed the cellular oxygen consumption rate and the expression of mitochondrial activity related genes. Conclusion: Taken together, our results suggest that OTW extract plays a role in the inhibition of adipogenesis in the white adipocyte cell line, implying the potential of OTW extract as a novel therapeutic for anti-obesity treatment. [ABSTRACT FROM AUTHOR]

Human ATP-binding cassette transporter subfamily B6 (ABCB6) is a mitochondrial ATP-driven pump that translocates porphyrins from the cytoplasm into mitochondria for heme biosynthesis. Within the transport pathway, a conserved aromatic residue W546 located in each monomer plays a pivotal role in stabilizing the occluded conformation via π-stacking interactions. Herein, we employed cryo-electron microscopy to investigate the structural consequences of a single W546A mutation in ABCB6, both in detergent micelles and nanodiscs. The results demonstrate that the W546A mutation alters the conformational dynamics of detergent-purified ABCB6, leading to entrapment of the transporter in an outward-facing transient state. However, in the nanodisc system, we observed a direct interaction between the transporter and a phospholipid molecule that compensates for the absence of the W546 residue, thereby facilitating the normal conformational transition of the transporter toward the occluded state following ATP hydrolysis. The findings also reveal that adoption of the outward-facing conformation causes charge repulsion between ABCB6 and the bound substrate, and rearrangement of key interacting residues at the substrate-binding site. Consequently, the affinity for the substrate is significantly reduced, facilitating its release from the transporter. all: W546A mutation in Human ATP-binding cassette transporter subfamily B6 (ABCB6) alters its conformational dynamics, leading to reduced substrate affinity and facilitating release from the transporter. [ABSTRACT FROM AUTHOR]

TAPL is a lysosomal ATP-binding cassette transporter that translocates a broad spectrum of polypeptides from the cytoplasm into the lysosomal lumen. Here we report that, in addition to its well-known role as a peptide translocator, TAPL exhibits an ATP-dependent phosphatidylserine floppase activity that is the possible cause of its high basal ATPase activity and of the lack of coupling between ATP hydrolysis and peptide efflux. We also present the cryo-EM structures of mouse TAPL complexed with (i) phospholipid, (ii) cholesteryl hemisuccinate (CHS) and 9-mer peptide, and (iii) ADP·BeF3. The inward-facing structure reveals that F449 protrudes into the cylindrical transport pathway and divides it into a large hydrophilic central cavity and a sizable hydrophobic upper cavity. In the structure, the peptide binds to TAPL in horizontally-stretched fashion within the central cavity, while lipid molecules plug vertically into the upper cavity. Together, our results suggest that TAPL uses different mechanisms to function as a peptide translocase and a phosphatidylserine floppase. In this work, the authors report an ATP-dependent phosphatidylserine floppase activity for the lysosomal ATP-binding cassette transporter TAPL. In addition, they report the cryo-EM structures of mouse TAPL complexed with (i) phospholipid, (ii) cholesteryl hemisuccinate (CHS) and 9-mer peptide, and (iii) ADP·BeF3. Together, their results suggest that TAPL uses different mechanisms to function as a peptide translocase and a phosphatidylserine floppase. [ABSTRACT FROM AUTHOR]

Vocal cord paralysis caused by recurrent laryngeal nerve (RLN) injury during thyroidectomy results in hoarseness, aspiration, and dyspnea. We evaluated the usefulness of nerve guidance conduits (NGCs) constructed from an asymmetric polycaprolactone (PCL)/Pluronic F127 porous membrane and filled with platelet-rich plasma (PRP) for functional RLN regeneration. We evaluated the proliferation and migration of Schwann cells (SCs) after PRP treatment in vitro. For the in vivo study, rabbits were divided into a non-loaded NGC group and a PRP-loaded NGC group. The left RLNs were resected and interposed with the NGCs. Functional and histological examinations of the vocal cords were performed. SC proliferation and migration increased in a PRP dose-dependent manner, with the PRP increasing the levels of neurotrophic factors, myelin-associated glycoprotein, and ERK. In vivo, the PRP group showed significantly better vocal cord mobility and less vocalis muscle atrophy than the non-loaded NGC group. Histologically, the ingrowth of nerve endings occurred more rapidly in the PRP group, and acetylcholinesterase, neurofilament, and S-100 expression in neural endings were significantly higher in the PRP group. Furthermore, transmission electron microscopy showed that myelinated axons were more tightly packed in the PRP group. This study shows that PRP-loaded NGCs provide a favorable environment for neural regeneration and suggests that this technique has therapeutic potential for promoting RLN recovery. [ABSTRACT FROM AUTHOR]

Based on the excellent performances of nanocrystalline cellulose, sodium alginate, or K-carrageenan in Pb2+ adsorption, nanocrystalline cellulose/sodium alginate/K-carrageenan composite hydrogel beads were prepared to adsorb Pb(II) from aqueous solutions. The objective of this study was to demonstrate the excellent potential of the composite hydrogel beads for heavy metal ion adsorption. We successfully prepared ecofriendly Fe-modified nanocrystalline cellulose/sodium alginate/K-carrageenan composite hydrogel beads and characterized them. The structure and adsorption mechanism were investigated using scanning electron microscopy, Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy, and the optimal adsorption conditions were determined. The tricomponent hydrogel beads were robust and exhibited improved adsorption capacity for Pb2+ and good reusability. The adsorption results could be fitted well with a pseudo-second-order kinetic model and the Langmuir adsorption model. The maximum adsorption capacity obtained by fitting was 351.04 mg g−1. Recycling experiments revealed that the adsorption capacity of the adsorbent remained high after five cycles of reuse. [ABSTRACT FROM AUTHOR]

Surface modification of cellulose nanocrystals (CNC) is essential for improving their reactivity and adsorption capacity. Oxidation, as a conventional modification method of CNC, has strong reaction conditions, which may partially destroy the structure of CNCs. Herein, we propose a mild cellulose modification method, in which diethylenetriaminepentaacetic acid (DPTA) was grafted onto CNC with an aminosilane coupling agent. To facilitate the enrichment and recovery of adsorbents, we prepared magnetic CNC before grafting DPTA, and finally obtained magnetic carboxylic functionalized CNC (MCNC-DPTA). The effects of the reaction parameters on the adsorption process were systematically studied by transmission electron microscopy, X-ray diffraction, Vibration sample magnetometry, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. Additionally, the effects of the solution pH, the initial concentration of Pb, and the adsorption time on the adsorption properties of the materials were evaluated. Furthermore, the structure, morphology, and thermal properties of the solution were systematically studied. After 6 cycle tests, the adsorption amount of Pb(II) by MCNC-DPTA was only reduced by 7%. These results show that MCNC-DPTA is an environment-friendly adsorption material with an excellent Pb(II) removal effect. [ABSTRACT FROM AUTHOR]

The multi-subunit translation initiation factor eIF2B is a control node for protein synthesis. eIF2B activity is canonically modulated through stress-responsive phosphorylation of its substrate eIF2. The eIF2B regulatory subcomplex is evolutionarily related to sugar-metabolizing enzymes, but the biological relevance of this relationship was unknown. To identify natural ligands that might regulate eIF2B, we conduct unbiased binding- and activity-based screens followed by structural studies. We find that sugar phosphates occupy the ancestral catalytic site in the eIF2Bα subunit, promote eIF2B holoenzyme formation and enhance enzymatic activity towards eIF2. A mutant in the eIF2Bα ligand pocket that causes Vanishing White Matter disease fails to engage and is not stimulated by sugar phosphates. These data underscore the importance of allosteric metabolite modulation for proper eIF2B function. We propose that eIF2B evolved to couple nutrient status via sugar phosphate sensing with the rate of protein synthesis, one of the most energetically costly cellular processes. The activity of translation initiation factor eIF2B is known to be modulated through stress-responsive phosphorylation of its substrate eIF2. Here, the authors uncover the regulation of eIF2B by the binding of sugar phosphates, suggesting a link between nutrient status and the rate of protein synthesis. [ABSTRACT FROM AUTHOR]

Spin thermoelectrics, an emerging thermoelectric technology, offers energy harvesting from waste heat with potential advantages of scalability and energy conversion efficiency, thanks to orthogonal paths for heat and charge flow. However, magnetic insulators previously used for spin thermoelectrics pose challenges for scale-up due to high temperature processing and difficulty in large-area deposition. Here, we introduce a molecule-based magnetic film for spin thermoelectric applications because it entails versatile synthetic routes in addition to weak spin-lattice interaction and low thermal conductivity. Thin films of CrII[CrIII(CN)6], Prussian blue analogue, electrochemically deposited on Cr electrodes at room temperature show effective spin thermoelectricity. Moreover, the ferromagnetic resonance studies exhibit an extremely low Gilbert damping constant ~(2.4 ± 0.67) × 10−4, indicating low loss of heat-generated magnons. The demonstrated STE applications of a new class of magnet will pave the way for versatile recycling of ubiquitous waste heat. Spin-thermoelectrics have great promise for waste heat conversion, however scaling up is challenging for device using standard magnetic insulators. Here, Oh et al demonstrate the molecular-magnet, Prussian blue analogues as a viable candidate for spin-thermoelectrics. [ABSTRACT FROM AUTHOR]

The objective of present work is to evaluate possible interactions among four clinically-used vascular epidermal growth factor receptor (VEGFR)-tyrosine kinase inhibitors (TKIs), including apatinib, cabozantinib, sorafenib, and sunitinib, with epidermal growth factor receptor (EGFR)-TKI gefitinib. This may advance knowledge regarding possible dual-target suppression strategies for advanced NSCLC, including VEGFR-TKI plus EGFR-TKI. The in vitro metabolism study demonstrated that apatinib inhibited the formation of metabolite M537194 with moderate effect, and inhibited another metabolite formation of M523595 with strong effect, in both human and rat liver microsomes. Sorafenib, cabozantinib, and sunitinib had no significant inhibitory effect on gefitinib metabolism. The results of the in vivo pharmacokinetics study were consistent with the in vitro metabolism study: the AUC0-t, AUC0-∞ and Cmax of gefitinib increased significantly when co-administered with apatinib by 26.8, 28.7, and 19.8%, respectively. Cabozantinib, sorafenib, and sunitinib exhibited no effect on gefitinib pharmacokinetics. Molecular docking was applied to investigate the binding mode between TKIs and CYP2D6. The docking results illustrated that binding characteristics of apatinib and gefitinib with CYP2D6 were similar, which accounts for competitive mechanism of apatinib-inhibited gefitinib metabolism. In summary, apatinib inhibited the metabolism of gefitinib in vitro and in vivo that were mediated by CYP2D6 and CYP3A4. In addition, cabozantinib, sorafenib, and sunitinib expressed no interaction with gefitinib. The results of the present study may provide a basis and valuable information for the development of treatment strategies. [ABSTRACT FROM AUTHOR]

The pristine graphene described with massless Dirac fermion could bear topological insulator state and ferromagnetism via the band structure engineering with various adatoms and proximity effects from heterostructures. In particular, topological Anderson insulator state was theoretically predicted in tight-binding honeycomb lattice with Anderson disorder term. Here, we introduced physi-absorbed Fe-clusters/adatoms on graphene to impose exchange interaction and random lattice disorder, and we observed Anderson insulator state accompanying with Kondo effect and field-induced conducting state upon applying the magnetic field at around a charge neutral point. Furthermore, the emergence of the double peak of resistivity at ν = 0 state indicates spin-splitted edge state with high effective exchange field (>70 T). These phenomena suggest the appearance of topological Anderson insulator state triggered by the induced exchange field and disorder. [ABSTRACT FROM AUTHOR]

The underlying mechanisms of alpha/theta neurofeedback training have not been fully determined. Therefore, this study aimed to test the changes in the brain state feedback during the alpha/theta training. Twenty-seven healthy participants were trained during a single session of the alpha/theta protocol, and the resting quantitative electroencephalography (QEEG) was assessed before and after training. QEEG was recorded at eight scalp locations (F3, F4, C3, C4, T3, T4, O1, and O2), and the absolute power, relative power, ratio of sensory-motor rhythm beta (SMR) to theta (RST), ratio of SMR-mid beta to theta (RSMT), ratio of mid beta to theta (RMT), ratio of alpha to high beta (RAHB), and scaling exponent of detrended fluctuation analysis by each band were measured. The results indicated a significant increase of absolute alpha power, especially the slow alpha band, at all electrodes except T3 and T4. Moreover, the relative alpha power, especially the slow alpha band, showed a significant increase at all electrodes. The relative theta power showed a significant decrease at all electrodes, except T3. A significant decrease in relative beta power, relative lower beta power and relative mid beta power was observed at O1. RST (at C4, O1, and O2), RSMT and RMT (at F4, C4, O1 and O2), and RAHB (at all electrodes) showed significant increase. Scaling exponents at all electrodes except T3 showed a significant decrease. These findings indicate that a one-time session of alpha/theta training might have the possibility to enhance both vigilance and concentration, thus stabilizing the overall brain function. [ABSTRACT FROM AUTHOR]

Oxide interfaces such as LaAlO3/SrTiO3 (LAO/STO) are interesting platforms for the investigation of 'spin-orbitronics' because of their strongly coupled spin and orbital degrees of freedom due to the inversion asymmetry of the structure. In this investigation, we demonstrate a tunable Rashba spin-orbit field at the LAO/STO interface via the application of an external gate electric field. The strength of the Rashba field was indirectly estimated by measuring the planar angle dependence of the anisotropic magnetoresistance (AMR). The asymmetry of the planar AMR between θ = 0 and π indicates the existence of Rashba spin-orbit fields, which are tunable by adjusting the current density and gate electric field. From the AMR measurements, the effective Rashba field exhibits up to 4 T for the application of an external back-gate voltage of 30 V. This controllable and relatively high Rashba field suggests that the LAO/STO is an attractive 2-D interface for potential spin-orbitronic applications, such as spin-charge converters, spin-FETs, and spin-orbit torque devices. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association between self-reported sleep duration and suicidal ideation in Korean employees. We studied 204,629 employees who attended health screenings in 2014. Total sleep duration was assessed with a self-reported question and categorized in one of 7 subcategories: ≤4, 5, 6, 7, 8, 9, and ≥10 h per day. Suicidal ideation was assessed with a self-reported question. Depression and anxiety symptoms were assessed with the Korean version of the Center for Epidemiologic Studies Depression scale and the Beck Anxiety Inventory, respectively. Occupational stress was assessed with the Korean Occupational Stress Scale, Short Form, a self-report questionnaire. We used multiple logistic regressions to calculate odds ratio of suicidal ideation according to self-reported sleep duration category, after adjusting for sex, age, occupational stress and either depression or anxiety. The prevalence rate of suicidal ideation was higher at both extremes of sleep duration and lowest at 7 h per day, showing a U-shaped curve. The odds ratio for suicidal ideation increased in groups of less than or equal to 6 h and greater than or equal to 10 h of sleep. Long and short sleep duration are both associated with suicidal ideation in Korean employees. The results of this study suggest that self-reported sleep duration might be used as a behavioral indicator for screening possible suicidal ideation in employees. [ABSTRACT FROM AUTHOR]

Eleven antioxidative compounds, including five lignin amides, were isolated from the aerial part of Tetragonia tetragonioides (New Zealand spinach) using 1,1-diphenyl-2-picrylhydrazyl radicalscavenging assay-guided purification. The structures were determined by nuclear magnetic resonance and electrospray ionization-mass spectroscopy. These compounds were identified as methyl linoleate ( 1), methyl coumarate ( 2), methyl ferulate ( 3), 1-O-stearoyl-3-O-β-D-galactopyranosyl-sn-glycerol ( 4), 1-O-caffeoyl-β-D-glucopyranoside ( 5), N-trans-caffeoyltyramine ( 6), cannabisin B ( 7), cannabisin A ( 8), Ntrans-feruloyltyramine ( 9), N-cis-feruloyltyramine ( 10), and N-trans-sinapoyltyramine ( 11). Compounds 1, 2, 4, 5, and 8- 11 were isolated for the first time from this plant. [ABSTRACT FROM AUTHOR]

Purpose: Discoloration of protein therapeutics has drawn increased attention recently due to concerns of potential impact on quality and safety. Investigation of discoloration in protein therapeutics for comparability is particularly challenging primarily for two reasons. First, the description of color or discoloration is to certain extent a subjective characteristic rather than a quantitative attribute. Secondly, the species contributing to discoloration may arise from multiple sources and are typically present at trace levels. Our purpose is to development a systematic approach that allows effective identification of the color generating species in protein therapeutics. Methods: A yellow-brown discoloration event observed in a therapeutic protein was investigated by optical spectroscopy, ultra-performance liquid chromatography, and mass spectrometry (MS). Results: Majority of the color generating species were identified as oxidatively modified protein. The location of the oxidized amino acid residues were identified by MS/MS. In addition, the impact of process-related impurities co-purified from media on discoloration was also investigated. Finally a semi-quantitative scale to estimate the contribution of each color source is presented, which revealed oxidized peptides are the major contributors. Conclusions: A systematic approach was developed for identification of the color generating species in protein therapeutics and for estimation of the contribution of each color source. [ABSTRACT FROM AUTHOR]

The easiness-to-handle of the magnetic dispersive solid phase extraction (Mag-dSPE) procedure was developed for preconcentration of 24 steroid hormones in river water. Ethylenediamine-functionalized magnetic carbon nanotubes (EDA@Mag-CNTs) were synthesised by a simple one-pot reaction and were used as sorbent in Mag-dSPE procedure. The properties of the EDA@Mag-CNTs were characterized by transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). An ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) method for determination of 24 steroid hormones in river water at nanograms per liter had been developed with pretreatment of the samples by Mag-dSPE. The obtained results demonstrated the higher extraction capacity of EDA@Mag-CNT Mag-dSPE with recoveries between 82.1 and 113 %. The limits of quantification (LOQs) for the steroid hormone were between 0.020 and 1.00 ng/L. The developed method had been successfully applied to 60 river water samples, and it was confirmed that EDA@Mag-CNT Mag-dSPE was a highly effective extraction method for the steroid hormone analyses. [ABSTRACT FROM AUTHOR]

P-glycoprotein (P-gp) is an ATP-binding cassette transporter that confers multidrug resistance in cancer cells. It also affects the absorption, distribution and clearance of cancer-unrelated drugs and xenobiotics. For these reasons, the structure and function of P-gp have been studied extensively for decades. Here we present biochemical characterization of P-gp from Caenorhabditis elegans and its crystal structure at a resolution of 3.4?ångströms. We find that the apparent affinities of P-gp for anticancer drugs actinomycin?D and paclitaxel are approximately 4,000 and 100 times higher, respectively, in the membrane bilayer than in detergent. This affinity enhancement highlights the importance of membrane partitioning when a drug accesses the transporter in the membrane. Furthermore, the transporter in the crystal structure opens its drug pathway at the level of the membrane's inner leaflet. In the helices flanking the opening to the membrane, we observe extended loops that may mediate drug binding, function as hinges to gate the pathway or both. We also find that the interface between the transmembrane and nucleotide-binding domains, which couples ATP hydrolysis to transport, contains a ball-and-socket joint and salt bridges similar to the ATP-binding cassette importers, suggesting that ATP-binding cassette exporters and importers may use similar mechanisms to achieve alternating access for transport. Finally, a model of human P-gp derived from the structure of C. elegans P-gp not only is compatible with decades of biochemical analysis, but also helps to explain perplexing functional data regarding the Phe335Ala mutant. These results increase our understanding of the structure and function of this important molecule. [ABSTRACT FROM AUTHOR]

The aggregation of proteins is central to many aspects of daily life, including food processing, blood coagulation, eye cataract formation disease and prion-related neurodegenerative infections. However, the physical mechanisms responsible for amyloidosis—the irreversible fibril formation of various proteins that is linked to disorders such as Alzheimer's, Creutzfeldt–Jakob and Huntington's diseases—have not yet been fully elucidated. Here, we show that different stages of amyloid aggregation can be examined by performing a statistical polymer physics analysis of single-molecule atomic force microscopy images of heat-denatured β-lactoglobulin fibrils. The atomic force microscopy analysis, supported by theoretical arguments, reveals that the fibrils have a multistranded helical shape with twisted ribbon-like structures. Our results also indicate a possible general model for amyloid fibril assembly and illustrate the potential of this approach for investigating fibrillar systems. [ABSTRACT FROM AUTHOR]

Fat fractions composed by different proportions of low (LMT) or high (HMT) melting temperature triacylglycerols were used, alone or in mixture with α-tocopherol for the preparation of oil-in-water protein stabilised nano-emulsions. Addition of α-tocopherol to the LMT or HMT fat fractions was accompanied by different changes in the emulsion characteristics such as fat droplet size distributions, under-cooling and polymorphic transitions, in parallel with different extent of α-tocopherol degradation reactions. Our results showed higher immobilisation pattern of α-tocopherol molecules and higher protection against degradation when incorporated in higher size fat droplets, which presented 2Lα → 2Lβ′ polymorphic transitions under cooling and re-heating cycles. [ABSTRACT FROM AUTHOR]

Pindone is a highly effective anticoagulant rodenticide. In this paper, an improved assay for the analysis and confirmation of pindone in human plasma has been proposed. After the samples protein precipitation with 10% ( v/v) methanol in acetonitrile and cleaning with solid-phase extraction, the separation was carried out on an IonPac AS11-HC analytical column (250 mm × 2 mm) using 20 mmol L−1 KOH containing 10% ( v/v) methanol as organic modifier by eluent generator reagent free ion chromatography. Quantification was performed by a negative electrospray ionization ion trap mass spectrometry using diphacinone as an internal standard. The transition for quantitative analysis was m/ z 229 → 172, and for qualitative analysis were m/ z 229 → 145 and m/ z 229 → 214 for pindone. The transition for quantitative analysis was m/ z 339 → 167 for IS. The limit of detection, the limit of quantification, recovery, linearity, precision, and stability were well validated. The cracking approach of characteristic fragments for pindone and IS were proposed. It was confirmed that this method could be used in clinical diagnosis and forensic toxicology analysis. [ABSTRACT FROM AUTHOR]

Analysis of diphacinone is often performed on C18 column by reserved phase liquid chromatographic methods coupled with ultraviolet detection or by ion-pair chromatography coupled with mass spectrometry. In this work, a sensitive and selective method using eluent generator reagent free ion chromatography coupled with electrospray ionization ion trap mass spectrometric detection for the quantification of diphacinone in animal livers has been developed. Samples were extracted with 10% ( v/v) methanol in acetonitrile after spiking with warfarin (internal standard, IS) and cleaned by solid-phase extraction. The analytes were separated on an IonPac AS11 analytical column (250 mm × 4.0 mm) using 30.0 mmol L−1 KOH (achieved by a KOH eluent generator) containing 10% ( v/v) methanol as organic modifier at a flow rate of 1.0 mL min−1. Detection was performed by negative electrospray ionization and ion trap tandem mass spectrometry in multiple reaction monitoring mode with a transition of m/z 339 → 167 for diphacinone, and 307 → 161 for IS, respectively. The calibration curve was linear ( r 2 = 0.993) in the concentration range of 1.0–200.0 ng mL−1 with a lower limit of quantification of 0.3 ng g−1 in animal livers. Intra- and inter-day relative standard deviations (RSDs) were less than 8.7 and 12.5%, respectively. Recoveries of diphacinone ranged from 81.2 to 89.5%. It was confirmed that this method could be used in clinical diagnosis or forensic toxicology. [ABSTRACT FROM AUTHOR]

This study presents a method for designing the layout of container yards where transfer cranes and yard trucks are used for stacking containers in the yard and delivering them between the yard and the quay. A method to determine the layout type, the outline of the yard, and the numbers of vertical and horizontal aisles is suggested. For estimating the effects of the design variables on operational cost terms, formulas for estimating the number of relocations by yard cranes and the expected travel distance of trucks are derived. Numerical examples are provided to illustrate the design procedure. It was also shown that the layout in which blocks are laid out parallel to the side with the gate or the quay outperforms that in which blocks are laid out perpendicular to the side with the gate or the quay. [ABSTRACT FROM AUTHOR]

The transient receptor potential V1 channel (vanilloid receptor, TRPV1) represents a promising therapeutic target for inflammatory pain and other conditions involving C-fiber sensory afferent neurons. Sensitivity of TRPV1 is known to be subject to modulation by numerous signaling pathways, in particular by phosphorylation, and we wished to determine whether TRPV1 structure activity relations could be differentially affected. We demonstrate here that the structure activity relations of TRPV1, as determined by 45Ca2 uptake, were substantially altered by treatment of the cells with cyclosporin A, an inhibitor of protein phosphatase 2B. Whereas the potency of resiniferatoxin for stimulation of 45Ca2 was not altered by cyclosporin A treatment, the potencies of some other agonists were increased up to 8-fold. Among the antagonists examined, potencies were reduced to a lesser extent, ranging from 1- to 2.5-fold. Finally, the efficacy of partial agonists was increased. In contrast to cyclosporin A, okadaic acid, an inhibitor of protein phosphatases 1 and 2A, had little effect on agonist potencies, and calyculin A, an inhibitor of protein phosphatases 1 and 2A but with somewhat different selectivity from that of okadaic acid, caused changes in structure activity relations distinct from those induced by cyclosporin A. Because phosphatase activity differentially modulates the structure activity relations of TRPV1 agonists and antagonists, our findings predict that it may be possible to design agonists and antagonists selective for TRPV1 in a specific regulatory environment. A further implication is that it may be desirable to tailor screening approaches for drug discovery to reflect the desired regulatory state of the targeted TRPV1. [ABSTRACT FROM AUTHOR]

In this study, the development and validation of an analytical method for triptolide in whole blood using high-performance liquid chromatography coupled with atmospheric-pressure chemical ionization ion trap tandem mass spectrometry (LC–APCI-IT-MS-MS) is reported. This is the first report of the systematic development and validation of an LC–MS-MS method for the quantitation of triptolide in human whole blood using prednisolone as an internal standard (IS). Prior to LC–MS-MS analysis, liquid–liquid extraction with ethyl acetate was used to isolate them from the biological matrix. Validation parameters such as specificity/selectivity, limit of quantitation (LOQ), linearity, precision, accuracy and stability are evaluated for this method. The calibration curve was linear ( r 2 = 0.9973) in the concentration range of 0.5–100.0 ng mL−1 in human whole blood with a lower limit of quantitation of 0.5 ng mL−1. Intra- and inter-day relative standard deviations (RSDs) were less than 8.6 and 11.7%, respectively. Extraction recoveries of triptolide ranged from 81.5 to 88.1%. This assay can be used to determine trace triptolide in human whole blood. [ABSTRACT FROM AUTHOR]

A rapid and sensitive method has been developed and validated to determine 6-benzyladenine (6-BA) residues in bean sprout using high-performance liquid chromatography coupled with electrospray ionization ion trap tandem mass spectrometry. Liquid–liquid extraction, using acidified methanol, was used to isolate 6-BA from the sample matrix. The separation was carried out on a Zorbax SB C18 column (150 mm × 4.6 mm i.d., 5 μm) with 0.1% acetic acid/methanol (25:75 v/ v) as mobile phase in isocratic mode. The quantitation of 6-BA was based on fragmentation of the molecular ion at m/ z 226.1 to a product ion at m/ z 91.1. In addition, the recoveries of three extraction solvents by ultrasound extraction and conventional extraction method were compared, and it was found that acidified methanol as the extraction solvent was the best. The calibration curve was linear ( r 2 > 0.997) in the concentration range of 0.04–10.0 ng mL−1 with a lower limit of quantification of 0.5 ng g−1 for 6-BA in bean sprout. Intra-day and inter-day relative standard deviations (RSDs) were less than 7.1 and 9.8%. Recoveries of 6-BA were between 85.0 and 88.5%. This assay has been successfully applied to the determination of trace 6-BA residues in bean sprout and monitoring the market in Ningbo, China. [ABSTRACT FROM AUTHOR]

Collaborative product commerce (CPC) is a newly emerging technology to support inter-enterprise collaboration through the product life-cycle. From the point of view of information technology, CPC is a software technology to integrate products, processes and resources of different enterprises using web technologies. In this paper, we propose a framework for integrating product information across enterprises, which is being developed by the Electronics and Telecommunications Research Institute (ETRI) as a part of a CPC project. The product metadata represented by an XML schema, which is compatible with the ISO STEP PDM (product Data Management) schema standard, is presented to semantically and schematically integrate distributed product information. Web services technologies are discussed to support the interoperability of application systems related to the product development, such as computer-aided design (CAD) and PDM, where most of these applications run in a distributed environment. Finally, we implement the framework to integrate distributed product information and application systems. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cells (EPCs) participate in neovascularization and are consistent with postnatal vasculogenesis. In vitro, they differentiate into endothelial cells (ECs). Prior reports have suggested that circulating human AC133+ cells have the capacity to differentiate into ECs as progenitor cells. However, recent studies have demonstrated that circulating CD34−CD14+ cells also have EPC-like properties in vitro and in vivo. We tested whether AC133−CD14+ cells from human umbilical cord blood (HUCB) have the potential to differentiate into ECs. The AC133−CD14+ cells were isolated from HUCB by magnetic bead selection and cultured on fibronectin-coated six-well trays in M199 medium supplemented with fetal bovine serum (FBS), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and insulin growth factor (IGF-1). The AC133−CD14+ cells adhered slightly within 1 day of culture and subsequently underwent a distinct process of morphological transformation to spindle-shaped cells that sprouted from the edge of the cell clusters. After 14 days, the cells formed cord- and tubular-like structures. The AC133−CD14+ cells showed a strong increase in the endothelial marker P1H12 over time, whereas CD14 decreased, and CD45 did not change, respectively. In addition, the cells expressed endothelial markers von Willebrand’s factor (vWF), platelet/endothelial cell adhesion molecule-1 (PECAM-1), vascular endothelial growth factor receptor-1 (VEGFR-1)/Flt-1, VEGFR-2/Flk-1, eNOS, and VE-cadherin, but did not express Tie-2 after 7 days of culture. The present data indicate that AC133−CD14+ cells from HUCB are able to develop endothelial phenotype with expression of endothelial-specific surface markers and even form cord- and tubular-like structures in vitro as progenitor cells. [ABSTRACT FROM AUTHOR]

p-(2,2,3-Tricyano-3-carbomethoxycyclopropyl)phenoxyethyl acrylate ( 5a) and p-(2,2,3-tricyano-3-carbomethoxycyclopropyl)phynoxyethyl methacrylate ( 5b) were prepared by the reactions of bromomalononitrile with methyl p-(2-acryloyloxyethoxy)benzylidene-cyanoacetate ( 4a) and methyl p-(2-methacryloyloxyethoxy)benzylidenecyanoacetate ( 4b), respectively. Monomers 5a and 5b were polymerized with free-radical initiators to obtain the polymers with multicyanocyclopropane functionalities in the pendant group. The resulting polymers 6a and 6b were soluble in acetone and the inherent viscosities were in the range of 0.20–0.25 dL/g. Solution-cast films showed T g values in the range of 130–150°C and piezoelectric coeffcients (d31) of the poled films were 1.5–1.6 pC/N, which are acceptable for piezoelectric device applications. [ABSTRACT FROM AUTHOR]

o-(2-Vinyloxyethoxy)benzylidenemalononitrile ( 3a), methyl o-(2-vinyloxyethoxy)benzylidenecyanoacetate ( 3b), 1,3-di-(2'-dicyanovinyl)-5-methyl-2-(2'-vinyloxyethoxy)benzene ( 4a), methyl 1,3-di-(2'-carbomethoxy-2'-cyanovinyl)-5-methyl-2-(2'-vinyloxyethoxy)benzene ( 4b), 2,3,4-tri-(2'-vinyloxyethoxy)benzylidenemalononitrile ( 5a), methyl 2,3,4-tri-(2'-vinyloxyethoxy)benzylidenecyanoacetate ( 5b), 2,4,6-tri-(2'-vinyloxyethoxy)benzylidenemalononitrile ( 6a), and methyl 2,4,6-tri-(2'-vinyloxyethoxy)benzylidenecyanoacetate ( 6b) were prepared by the condensation of o-(2-vinyloxyethoxy) benzaldehyde ( 1a), 2-(2'-vinyloxyethoxy)-5-methylisophthaldehyde ( 1b), 2,3,4-tri-(2'-vinyloxyethoxy)benzaldehyde ( 2a), 2,4,6-tri-(2'-vinyloxyethoxy)benzaldehyde ( 2b) with malononitrile or methyl cyanoacetate, respectively. Vinyl ether compounds 3a–b and 5a–b were polymerized readily by free radical initiators to give optically transparent swelling poly(vinyl ethers) 7a–b and 9a–b. Compounds 4a–b and 6a–b did not polymerize by radical initiators due to the steric hindrance. Polymers 7a–b and 9a–b were not soluble in common organic solvents such as acetone and DMSO due to crosslinking. Polymers 7a–b and 9a–b showed a thermal stability up to 300°C in TGA thermograms. [ABSTRACT FROM AUTHOR]

A novel method using liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry in the negative selected ion monitoring mode has been developed and validated for rapid simultaneous determination of triptolide and tripdiolide in the extract of Tripterygium wilfordii Hook. f. The molecular ions m/z [M–H]− 359 and 375 were selected for the quantification in selected ion monitoring mode for triptolide and tripdiolide. Standard calibration curve was linear over the concentration range of 0.12–24 and 0.15–30 μg mL−1 for triptolide and tripdiolide. The relative standard deviations of intra- and inter-day were in the range of 4.7–9.9 and 8.9–12.6%. The average recoveries were between 96.4 and 104.6%. The limits of quantitation were 2.0 × 10−3 and 2.5 × 10−3 μg mL−1 for triptolide and tripdiolide. [ABSTRACT FROM AUTHOR]

A polar conductor, where inversion symmetry is broken, may exhibit directional propagation of itinerant electrons, i.e., the rightward and leftward currents differ from each other, when time-reversal symmetry is also broken. This potential rectification effect was shown to be very weak due to the fact that the kinetic energy is much higher than the energies associated with symmetry breaking, producing weak perturbations. Here we demonstrate the appearance of giant nonreciprocal charge transport in the conductive oxide interface, LaAlO3/SrTiO3, where the electrons are confined to two-dimensions with low Fermi energy. In addition, the Rashba spin–orbit interaction correlated with the sub-band hierarchy of this system enables a strongly tunable nonreciprocal response by applying a gate voltage. The observed behavior of directional response in LaAlO3/SrTiO3 is associated with comparable energy scales among kinetic energy, spin–orbit interaction, and magnetic field, which inspires a promising route to enhance nonreciprocal response and its functionalities in spin orbitronics. Complex oxide heterostructures can host two-dimensional electron systems with better properties than bulk materials. Choe et al. show that the combination of the Rashba spin-orbit interaction and Fermi energy at LAO/STO interfaces gives a larger nonreciprocal response than in bulk polar conductors. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection can cause cirrhosis and hepatocellular carcinoma and is therefore a serious public health problem. Infected patients are currently treated with nucleoside/nucleotide analogs and interferon α, but this approach is not curative. Here, we screen 978 FDA-approved compounds for their ability to inhibit HBV replication in HBV-expressing HepG2.2.15 cells. We find that ciclopirox, a synthetic antifungal agent, strongly inhibits HBV replication in cells and in mice by blocking HBV capsid assembly. The crystal structure of the HBV core protein and ciclopirox complex reveals a unique binding mode at dimer-dimer interfaces. Ciclopirox synergizes with nucleoside/nucleotide analogs to prevent HBV replication in cells and in a humanized liver mouse model. Therefore, orally-administered ciclopirox may provide a novel opportunity to combat chronic HBV infection by blocking HBV capsid assembly. Current treatments for chronic hepatitis B virus (HBV) infection are not curative. Here, the authors show that an antifungal drug, ciclopirox, inhibits HBV capsid assembly and synergizes with nucleoside/nucleotide analogs to prevent HBV replication in cells and in a humanized liver mouse model. [ABSTRACT FROM AUTHOR]

Allergic asthma is a chronic inflammatory disease induced by the inhalation of allergens, which trigger the activation of T helper type 2 (Th2) cells that release Th2 cytokines. Recently, herbal medicines are being considered a major source of novel agents to treat various diseases. In the present study, we evaluated the anti-asthmatic effects of a Codonopsis lanceolata extract (CLE) and the mechanisms involved in its anti-inflammatory effects. Treatment with CLE reduced infiltration of inflammatory cells, especially eosinophils, and the production of mucus in lung tissues. Levels of Th2 cytokines, such as IL-4, IL-5, and IL-13, and chemokines were also decreased following treatment with CLE. Moreover, Th2 cell proportion in vivo and differentiation in vitro were reduced as evidenced by the decreased expression of GATA3+. Furthermore, the expression of superoxide dismutase (SOD)2, a mitochondrial ROS (mROS) scavenger, was increased, which was related to Th2 cell regulation. Interestingly, treatment with CLE increased the number of macrophages in the lungs and enhanced the immune-suppressive property of macrophages. Our findings indicate that CLE has potential as a novel therapeutic agent to inhibit Th2 cell differentiation by regulating mROS scavenging. [ABSTRACT FROM AUTHOR]

Metal ions at the active site of an enzyme act as cofactors, and their dynamic fluctuations can potentially influence enzyme activity. Here, we use λ-exonuclease as a model enzyme with two Mg2+ binding sites and probe activity at various concentrations of magnesium by single-molecule-FRET. We find that while MgA2+ and MgB2+ have similar binding constants, the dissociation rate of MgA2+ is two order of magnitude lower than that of MgB2+ due to a kinetic-barrier-difference. At physiological Mg2+ concentration, the MgB2+ ion near the 5’-terminal side of the scissile phosphate dissociates each-round of degradation, facilitating a series of DNA cleavages via fast product-release concomitant with enzyme-translocation. At a low magnesium concentration, occasional dissociation and slow re-coordination of MgA2+ result in pauses during processive degradation. Our study highlights the importance of metal-ion-coordination dynamics in correlation with the enzymatic reaction-steps, and offers insights into the origin of dynamic heterogeneity in enzymatic catalysis. Metal ions at the active site of an enzyme act as cofactors and their dynamic fluctuations might influence enzyme activity. Here authors use single-molecule FRET to study λ-exonuclease and find that metal-ion-coordination is correlated with enzymatic reaction-steps. [ABSTRACT FROM AUTHOR]