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The rational design of material structures can be an effective approach to enhance the performance of solar-driven clean water production. In this study, a hollow structural nanofibrous membrane was developed by mimicking the hollow structure of polar bear hair using coaxial electrospinning. The shell layer consisted of carbon nanoparticles (C NPs) decorated CuO nanosheets (C@CuO), that exhibited photothermal conversion capacity. Meanwhile, the core layer containing hydrophilic polyvinylpyrrolidone (PVP) was eliminated to generate the hollow structure. The C NPs enhanced the membrane's light absorption to increase thermal energy harvesting, while the CuO nanosheets improved the membrane's wettability enhancing the water supply. Furthermore, the hollow structure limited air convection, prevented heat conduction, and minimized heat radiation, enabling heat localization to be achieved inside the membrane to suppress heat loss during evaporation. For 3.5 wt% saline water and actual dye wastewater, the C@CuO nanofibrous membrane achieved high evaporation rates of 1.36 kg·m -2 ·h -1 and 1.31 kg·m -2 ·h -1 , respectively, under 1 sun illumination. Moreover, even after continuous 6-h evaporation tests, the evaporation rate of the C@CuO membrane remained virtually unchanged, highlighting its long-term stability with regard to salt resistance in real-world applications. Additionally, the remarkable flexibility of the C@CuO membrane offers convenience during operation and guarantees dimensional stability when it is subjected to external stresses. These discoveries should inspire subsequent research on developing delicate architectural materials and exploring their potential applications in various fields, including energy generation, clean water production, and thermal insulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The surge in the use of antibiotics, especially in aquaculture, has led to development of antibiotic resistance genes, which will harm environmental and public health. One of the most commonly used antibiotics in aquaculture is oxytetracycline (OTC). Employing photocatalysis, this study compared OTC degradation efficiency of two different types of common photocatalysts, TiO 2 and graphitic carbon nitride (GCN) in terms of their photochemical properties and underlying photocatalytic mechanism. For reference purpose, self-synthesized GCN from urea precursor (GCN-Urea) and commercial GCN (GCN-Commercial) were both examined. OTC adsorption-photocatalysis removal rates in pure OTC solution by TiO 2 , GCN-Urea and GCN-Commercial were attained at 95%, 60% and 40% respectively. Photochemical properties evaluated included light absorption, band gap, valence and conduction band positions, photoluminescence, cyclic voltammetry, BET surface area and adsorption capability of the photocatalysts. Through the evaluations, this study provides novel insights towards current state-of-the-art heterogeneous photocatalytic processes. The electron-hole recombination examined by photoluminescence is not the key factor influencing the photocatalytic efficacies as commonly discussed. On the contrary, the dominating factors governing the higher OTC degradation efficiency of TiO 2 compared to GCN are the high mobility of electrons that leads to high redox capability and the high pollutant-photocatalyst affinity. These claims are proven by 86% and 40% more intense anodic and cathodic cyclic voltammetry curve peaks of TiO 2 as compared to both GCNs. OTC also demonstrated 1.7 and 2.3 times higher affinity towards TiO 2 than GCN-Urea and GCN-Commercial. OTC removal by TiO 2 in real aquaculture wastewater only achieved 50%, due to significant inhibition effect by dissolved solids, dissolved organic matters and high ionic contents in the wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Recent human decedent model studies 1,2 and compassionate xenograft use 3 have explored the promise of porcine organs for human transplantation. To proceed to human studies, a clinically ready porcine donor must be engineered and its xenograft successfully tested in nonhuman primates. Here we describe the design, creation and long-term life-supporting function of kidney grafts from a genetically engineered porcine donor transplanted into a cynomolgus monkey model. The porcine donor was engineered to carry 69 genomic edits, eliminating glycan antigens, overexpressing human transgenes and inactivating porcine endogenous retroviruses. In vitro functional analyses showed that the edited kidney endothelial cells modulated inflammation to an extent that was indistinguishable from that of human endothelial cells, suggesting that these edited cells acquired a high level of human immune compatibility. When transplanted into cynomolgus monkeys, the kidneys with three glycan antigen knockouts alone experienced poor graft survival, whereas those with glycan antigen knockouts and human transgene expression demonstrated significantly longer survival time, suggesting the benefit of human transgene expression in vivo. These results show that preclinical studies of renal xenotransplantation could be successfully conducted in nonhuman primates and bring us closer to clinical trials of genetically engineered porcine renal grafts., (© 2023. The Author(s).)

Herein, five N, S-co-doped carbocatalysts were prepared from different carbonaceous precursors, namely sawdust (SD), biochar (BC), carbon-nanotubes (CNTs), graphite (GP), and graphene oxide (GO) and compared. Generally, as the graphitization degree increased, the extent of N and S doping decreased, graphitic N configuration is preferred, and S configuration is unaltered. As peroxymonosulfate (PMS) activator for ciprofloxacin (CIP) removal, the catalytic performance was in order: NS-CNTs (0.037 min -1 ) > NS-BC (0.032 min -1 ) > NS-rGO (0.024 min -1 ) > NS-SD (0.010 min -1 ) > NS-GP (0.006 min -1 ), with the carbonaceous properties, rather than the heteroatoms content and textural properties, being the major factor affecting the catalytic performance. NS-CNTs was found to have the supreme catalytic activity due to its remarkable conductivity (3.38 S m -1 ) and defective sites (I D /I G  = 1.28) with high anti-interference effect against organic and inorganic matter and varying water matrixes. The PMS activation pathway was dominated by singlet oxygen ( 1 O 2 ) generation and electron transfer regime between CIP and PMS activated complexes. The CIP degradation intermediates were identified, and a degradation pathway is proposed. Overall, this study provides a better understanding of the importance of selecting a suitable carbonaceous platform for heteroatoms doping to produce superior PMS activator for antibiotics decontamination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The severe water pollution from effluent dyes threatens human health. This study created pH-magnetic-photocatalytic polymer microspheres to conveniently separate the photocatalyst nanoparticles from the treated water by applying an external magnetic field. While fabricating magnetic nanoparticles' (MNPs) microspheres, incorporating 0.5 wt.% iron oxide (Fe 3 O 4 ) showed the best magnetophoretic separation ability, as all the MNPs microspheres were attracted toward the external magnet. Subsequently, hybrid organic-inorganic polyoxometalates (HPOM), a self-synthesized photocatalyst, were linked with the functionalized magnetic nanoparticles (f-MNPs) to prepare augmented magnetic-photocatalytic microspheres. The photodegradation dye removal efficiency of the augmented magnetic-photocatalytic microspheres (f-MNPs-HPOM) was then compared with that of the commercial titanium dioxide (TiO 2 ) photocatalyst (f-MNPs-TiO 2 ). Results showed that f-MNPs-HPOM microspheres with 74 ± 0.7% photocatalytic removal efficiency better degraded methylene orange (MO) than f-MNPs-TiO 2 (70 ± 0.8%) at an unadjusted pH under UV-light irradiation for 90 min. The excellent performance was mainly attributed to the lower band-gap energy of HPOM (2.65 eV), which required lower energy to be photoactivated under UV light. The f-MNPs-HPOM microspheres demonstrated excellent reusability and stability in the photo-decolorization of MO, as the microspheres retained nearly the same removal percentage throughout the three continuous cycles. The degradation rate was also found to follow the pseudo-first-order kinetics. Furthermore, f-MNPs-HPOM microspheres were pH-responsive in the photodegradation of MO and methylene blue (MB) at pH 3 (acidic) and pH 9 (alkaline). Overall, it was demonstrated that using HPOM photocatalysts in the preparation of magnetic-photocatalytic microspheres resulted in better dye degradation than TiO 2 photocatalysts.

Amyloidosis is a rare disorder where abnormal protein aggregates are deposited in tissues forming amyloid fibrils, leading to progressive organ failure. Although any organ can be affected, cardiac involvement is the main cause of morbidity and mortality associated with amyloidosis as diagnosis is often delayed due to the indolent nature of the disease in some forms. An early diagnosis of disease and knowledge of the type/subtype of cardiac amyloidosis (CA) are essential for appropriate management and better outcome. Echocardiography is often the first line of investigation for patients suspected of CA and offers superior hemodynamic assessment. Although cardiovascular magnetic resonance (CMR) imaging is not diagnostic of CA, it provides vital clues to diagnosis and has a role in disease quantification and prognostication. Radiolabeled bone seeking tracers are the mainstay of diagnosis of CA and when combined with screening of monoclonal light chains, bone scintigraphy offers high sensitivity in diagnosing transthyretin type of CA. This review aims to describe the noninvasive imaging assessment and approach to diagnosis of patients with suspected CA. Imaging features of echocardiography, nuclear scintigraphy, and CMR are described with a brief mention on computed tomography., Competing Interests: Conflict of Interest None declared., (World Association of Radiopharmaceutical and Molecular Therapy (WARMTH). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Working memory has been shown to rely on theta oscillations' phase synchronicity for item encoding and recall. At the same time, saccadic eye movements during visual exploration have been observed to trigger theta-phase resets, raising the question of whether the neuronal substrates of mnemonic processing rely on motor-evoked responses. To quantify the relationship between saccades and working memory load, we recorded eye tracking and behavioral data from human participants simultaneously performing an n-back Sternberg auditory task and a hue-based catch detection task. In addition to task-specific interference in performance, we also found that saccade rate was modulated by working memory load in the Sternberg task's preresponse stage. Our results support the possibility of interplay between saccades and hippocampal theta during working memory retrieval of items., (© 2022 Low et al.; Published by Cold Spring Harbor Laboratory Press.)

Since the ancient times, bee products (i.e., honey, propolis, pollen, bee venom, bee bread, and royal jelly) have been considered as natural remedies with therapeutic effects against a number of diseases. The therapeutic pleiotropy of bee products is due to their diverse composition and chemical properties, which is independent on the bee species. This has encouraged researchers to extensively study the therapeutic potentials of these products, especially honey. On the other hand, amid the unprecedented growth in nanotechnology research and applications, nanomaterials with various characteristics have been utilized to improve the therapeutic efficiency of these products. Towards keeping the bee products as natural and non-toxic therapeutics, the green synthesis of nanocarriers loaded with these products or their extracts has received a special attention. Alginate is a naturally produced biopolymer derived from brown algae, the desirable properties of which include biodegradability, biocompatibility, non-toxicity and non-immunogenicity. This review presents an overview of alginates, including their properties, nanoformulations, and pharmaceutical applications, placing a particular emphasis on their applications for the enhancement of the therapeutic effects of bee products. Despite the paucity of studies on fabrication of alginate-based nanomaterials loaded with bee products or their extracts, recent advances in the area of utilizing alginate-based nanomaterials and other types of materials to enhance the therapeutic potentials of bee products are summarized in this work. As the most widespread and well-studied bee products, honey and propolis have garnered a special interest; combining them with alginate-based nanomaterials has led to promising findings, especially for wound healing and skin tissue engineering. Furthermore, future directions are proposed and discussed to encourage researchers to develop alginate-based stingless bee product nanomedicines, and to help in selecting suitable methods for devising nanoformulations based on multi-criteria decision making models. Also, the commercialization prospects of nanocomposites based on alginates and bee products are discussed. In conclusion, preserving original characteristics of the bee products is a critical challenge in developing nano-carrier systems. Alginate-based nanomaterials are well suited for this task because they can be fabricated without the use of harsh conditions, such as shear force and freeze-drying, which are often used for other nano-carriers. Further, conjunction of alginates with natural polymers such as honey does not only combine the medicinal properties of alginates and honey, but it could also enhance the mechanical properties and cell adhesion capacity of alginates., Competing Interests: Author VU is the cofounder of TardigradeNano LLC, a biotech startup with no commercial or financial interest in the topic elaborated here. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Al-Hatamleh, Alshaer, Hatmal, Lambuk, Ahmed, Mustafa, Low, Jaafar, Ferji, Six, Uskoković and Mohamud.)

Over the past decade, there has been a surge of interest in using char (hydrochar or biochar) derived from biomass as persulfate (PS, either peroxymonosulfate or peroxydisulfate) activator for anthropogenic pollutants removal. While extensive investigation showed that char could be used as a PS activator, its sustainability over prolonged application is equivocal. This review provides an assessment of the knowledge gap related to the sustainability of char as a PS activator. The desirable char properties for PS activation are identified, include the high specific surface area and favorable surface chemistry. Various synthesis strategies to obtain the desirable properties during biomass pre-treatment, hydrochar and biochar synthesis, and char post-treatment are discussed. Thereafter, factors related to the sustainability of employing char as a PS activator for anthropogenic pollutants removal are critically evaluated. Among the critical factors include performance uncertainty, competing adsorption process, char stability during PS activation, biomass precursor variation, scalability, and toxic components in char. Finally, some potential research directions are provided. Fulfilling the sustainability factors will provide opportunity to employ char as an economical and efficient catalyst for sustainable environmental remediation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A spiral wound membrane (SWM) is employed to separate acid gases (mainly CO 2 ) from natural gas due to its robustness, lower manufacturing cost, and moderate packing density compared to hollow fiber membranes. Various mathematical models are available to describe the separation performance of SWMs under different operating conditions. Nevertheless, most of the mathematical models deal with only binary gas mixtures (CO 2 and CH 4 ) that may lead to an inaccurate assessment of separation performance of multicomponent natural gas mixtures. This work is aimed to develop an SWM separation model for multicomponent natural gas mixtures. The succession stage method is employed to discretize the separation process within the multicomponent SWM module for evaluating the product purity, hydrocarbon loss, stage cut, and permeate acid gas composition. Our results suggest that multicomponent systems tend to generate higher product purity, lower hydrocarbon loss, and augmented permeate acid gas composition compared to the binary system. Furthermore, different multicomponent systems yield varied separation performances depending on the component of the acid gas. The developed multicomponent SWM separation model has the potential to design and optimize the spiral wound membrane system for industrial application.

Widespread atrazine use is associated with an increasing incidence of contamination of drinking water. Thus, a biosensor using molecularly imprinted polymers (MIPs) was developed to detect the amount of atrazine in water to ensure prevention of exposure levels that could lead to reproductive effects in living organisms. In this study, the influence of the porogen on the selectivity of MIPs was investigated. The porogen plays a pivotal role in molecular imprinting as it affects the physical properties and governs the prepolymerization complex of the resulting polymer, which in turn firmly defines the recognition properties of the resulting molecularly imprinted polymer (MIP). Therefore, bulk MIPs against atrazine (Atr) were synthesized based on methacrylic acid (MAA) as a functional monomer and ethyleneglycol dimethacrylate (EGDMA) as a crosslinker; they were prepared in toluene and dimethyl sulfoxide (DMSO). The imprinting factor, binding capacity, and structural stability were evaluated using the respective porogenic solvents. Along with the characterization of the morphology of the obtained polymers via SEM and BET analysis, the kinetic and adsorption analyses were demonstrated and verified. The highest imprinting factor, binding capacity, and the highest structural stability were found to be on polymer synthesized in a medium of MAA and EGDMA, which contained 90% toluene and 10% DMSO as porogen. Moreover, the response for Atr concentrations by the PVC-based electrochemical sensor was found to be at a detection limit of 0.0049 μM (S/N = 3). The sensor proved to be an effective sensor with high sensitivity and low Limit of Detection (LOD) for Atr detection. The construction of the sensor will act as a baseline for a fully functionalized membrane sensor.

In recent years, mixed matrix membranes (MMMs) have received worldwide attention for their potential to offer superior gas permeation and separation performance involving CO 2 and CH 4 . However, fabricating defect-free MMMs still remains as a challenge where the incorporation of fillers into MMMs has usually led to some issues including formation of undesirable interfacial voids, which may jeopardize the gas separation performance of the MMMs. This current work investigated the incorporation of zeolite RHO and silane-modified zeolite RHO (NH 2 -RHO) into polysulfone (PSf) based MMMs with the primary aim of enhancing the membrane's gas permeation and separation performance. The synthesized zeolite RHO, NH 2 -RHO, and fabricated membranes were characterized by X-ray diffraction (XRD) analysis, Fourier transform infrared-attenuated total reflection (FTIR-ATR), thermogravimetric analysis (TGA) and field emission scanning election microscopy (FESEM). The effects of zeolite loading in the MMMs on the CO 2 /CH 4 separation performance were investigated. By incorporating 1 wt% of zeolite RHO into the MMMs, the CO 2 permeability and ideal CO 2 /CH 4 selectivity slightly increased by 4.2% and 2.7%, respectively, compared to that of a pristine PSf membrane. On the other hand, a significant enhancement of 45% in ideal CO 2 /CH 4 selectivity was attained by MMMs incorporated with 2 wt% of zeolite NH 2 -RHO compared to a pristine PSf membrane. Besides, all MMMs incorporated with zeolite NH 2 -RHO displayed higher ideal CO 2 /CH 4 selectivity than that of the MMMs incorporated with zeolite RHO. By incorporating 1-3 wt% zeolite NH 2 -RHO into PSf matrix, MMMs without interfacial voids were successfully fabricated. Consequently, significant enhancement in ideal CO 2 /CH 4 selectivity was enabled by the incorporation of zeolite NH 2 -RHO into MMMs.

The use of pore forming agents has been notable for improving the water flux in a water-based separation membrane but are rarely being studied as a methodology to influence the substrate's surface architectures for composite membrane fabrication in gas separation. In this study, the influence of lithium chloride (LiCl) on the surface pore architectures and hence, the gas permeance, has been studied in both bare and composite forms with poly(dimethylsiloxane) (PDMS). 1-4 wt% of LiCl was mixed with the dope solution of PES/NMP in the ratio 0.19 and was casted via the dry-wet phase inversion method. Bare substrates were noted to possess increasingly larger surface pore sizes but at a diminishing surface pore density with maximum surface porosity at 2 wt% LiCl. The permeances were, however, significantly reduced with the increase in the LiCl content from 105 300 to 4300 GPU for N 2 gas, presumably due to the thicker skin layer. Nevertheless, the porous surface morphology was confirmed and exhibited Knudsen selectivity with a CO 2 /N 2 selectivity of about 0.8, signifying minimal gas flow resistance by the substrates. Upon coating with a similar amount of thin PDMS layer, the composite permeances retain the same trend with values from 361.9 GPU for 0 wt% LiCl substrates to 68.8 GPU for 4 wt% LiCl substrates for CO 2 gas at a consistent selectivity of about 14. As the PDMS layer of the same volumes were used and no significant difference in the coating thickness was noted, the mixed influence of pore intrusion and lateral diffusion is hypothesised at the substrate-coating interface owing to the different surface pore architectures of the substrates., Competing Interests: The authors have no other competing interests., (This journal is © The Royal Society of Chemistry.)

Objectives: Myoblast transfer therapy (MTT) is a technique to replace muscle satellite cells with genetically repaired or healthy myoblasts, to treat muscular dystrophies. However, clinical trials with human myoblasts were ineffective, showing almost no benefit with MTT. One important obstacle is the rapid senescence of human myoblasts. The main purpose of our study was to compare the various methods for scalable generation of proliferative human myoblasts., Methods: We compared the immortalization of primary myoblasts with hTERT, cyclin D1 and CDK4 R24C , two chemically defined methods for deriving myoblasts from pluripotent human embryonic stem cells (hESCs), and introduction of viral MyoD into hESC-myoblasts., Results: Our results show that, while all the strategies above are suboptimal at generating bona fide human myoblasts that can both proliferate and differentiate robustly, chemically defined hESC-monolayer-myoblasts show the most promise in differentiation potential., Conclusions: Further efforts to optimize the chemically defined differentiation of hESC-monolayer-myoblasts would be the most promising strategy for the scalable generation of human myoblasts, for applications in MTT and high-throughput drug screening., (© 2019 John Wiley & Sons Ltd.)

Many hippocampal cell types are characterized by a progressive increase in scale along the dorsal-to-ventral axis, such as in the cases of head-direction, grid and place cells. Also located in the medial entorhinal cortex (MEC), border cells would be expected to benefit from such scale modulations. However, this phenomenon has not been experimentally observed. Grid cells in the MEC of mammals integrate velocity related signals to map the environment with characteristic hexagonal tessellation patterns. Due to the noisy nature of these input signals, path integration processes tend to accumulate errors as animals explore the environment, leading to a loss of grid-like activity. It has been suggested that border-to-grid cells' associations minimize the accumulated grid cells' error when rodents explore enclosures. Thus, the border-grid interaction for error minimization is a suitable scenario to study the effects of border cell scaling within the context of spatial representation. In this study, we computationally address the question of (i) border cells' scale from the perspective of their role in maintaining the regularity of grid cells' firing fields, as well as (ii) what are the underlying mechanisms of grid-border associations relative to the scales of both grid and border cells. Our results suggest that for optimal contribution to grid cells' error minimization, border cells should express smaller firing fields relative to those of the associated grid cells, which is consistent with the hypothesis of border cells functioning as spatial anchoring signals.

Purpose: First-in-human phase I trial to determine the safety, pharmacokinetics, and antitumor activity of BIND-014, a novel, tumor prostate-specific membrane antigen (PSMA)-targeted nanoparticle, containing docetaxel., Experimental Design: Patients with advanced solid tumors received BIND-014 every three weeks (n = 28) or weekly (n = 27), with dose levels ranging from 3.5 to 75 mg/m(2) and 15 to 45 mg/m(2), respectively., Results: BIND-014 was generally well tolerated, with no unexpected toxicities. The most common drug-related toxicities (>20% of patients) on either schedule included neutropenia, fatigue, anemia, alopecia, and diarrhea. BIND-014 demonstrated a dose-linear pharmacokinetic profile, distinct from docetaxel, with prolonged persistence of docetaxel-encapsulated circulating nanoparticles. Of the 52 patients evaluable for response, one had a complete response (cervical cancer on the every three week schedule) and five had partial responses (ampullary adenocarcinoma, non-small cell lung, and prostate cancers on the every-three-week schedule, and breast and gastroesophageal cancers on the weekly schedule). Responses were noted in both PSMA-detectable and -undetectable tumors., Conclusions: BIND-014 was generally well tolerated, with predictable and manageable toxicity and a unique pharmacokinetic profile compared with conventional docetaxel. Clinical activity was noted in multiple tumor types. The recommended phase II dose of BIND-014 is 60 mg/m(2) every three weeks or 40 mg/m(2) weekly. Clin Cancer Res; 22(13); 3157-63. ©2016 AACR., (©2016 American Association for Cancer Research.)

Molecular imprinting is an emerging technique to create imprinted polymers that can be applied in affinity-based separation, in particular, biomimetic sensors. In this study, the matrix of siloxane bonds prepared from the polycondensation of hydrolyzed tetraethoxysilane (TEOS) was employed as the inorganic monomer for the formation of a creatinine (Cre)-based molecularly imprinted polymer (MIP). Doped aluminium ion (Al(3+)) was used as the functional cross-linker that generated Lewis acid sites in the confined silica matrix to interact with Cre via sharing of lone pair electrons. Surface morphologies and pore characteristics of the synthesized MIP were determined by field emission scanning electron microscopy (FESEM) and Brunauer-Emmet-Teller (BET) analyses, respectively. The imprinting efficiency of MIPs was then evaluated through the adsorption of Cre with regard to molar ratios of Al(3+). A Cre adsorption capacity of up to 17.40 mg Cre g(-1) MIP was obtained and adsorption selectivity of Cre to its analogues creatine (Cr) and N-hydroxysuccinimide (N-hyd) were found to be 3.90 ± 0.61 and 4.17 ± 3.09, respectively. Of all the studied MIP systems, chemisorption was predicted as the rate-limiting step in the binding of Cre. The pseudo-second-order chemical reaction kinetic provides the best correlation of the experimental data. Furthermore, the equilibrium adsorption capacity of MIP fit well with a Freundlich isotherm (R (2) = 0.98) in which the heterogeneous surface was defined.

Magnetophoresis of iron oxide magnetic nanoparticle (IOMNP) under low magnetic field gradient (<100 T/m) is significantly enhanced by particle shape anisotropy. This unique feature of magnetophoresis is influenced by the particle concentration and applied magnetic field gradient. By comparing the nanosphere and nanorod magnetophoresis at different concentration, we revealed the ability for these two species of particles to achieve the same separation rate by adjusting the field gradient. Under cooperative magnetophoresis, the nanorods would first go through self- and magnetic field induced aggregation followed by the alignment of the particle clusters formed with magnetic field. Time scale associated to these two processes is investigated to understand the kinetic behavior of nanorod separation under low field gradient. Surface functionalization of nanoparticles can be employed as an effective strategy to vary the temporal evolution of these two aggregation processes which subsequently influence the magnetophoretic separation time and rate., (Copyright © 2014 Elsevier Inc. All rights reserved.)

C-5-bromo-2-hydroxyphenylcalix[4]-2-methylresorcinarene (I) was synthesized by cyclocondensation of 5-bromo-2-hydroxybenzaldehyde and 2-methylresorcinol in the presence of concentrated HCl. Compound I was characterized by infrared and nuclear magnetic resonance spectroscopic data. X-ray analysis showed that this compound crystallized in a triclinic system with space group of Pī, a = 15.9592(16)Å, b = 16.9417(17)Å, c = 17.0974(17)Å, α = 68.656(3)°, β = 85.689(3)°, γ = 81.631(3)°, Z = 2 and V = 4258.6(7)Å3. The molecule adopts a chair (C2h) conformation. The thermal properties and antioxidant activity were also investigated. It was strongly antiviral against HSV-1 and weakly antibacterial against Gram-positive bacteria. Cytotoxicity testing on Vero cells showed that it is non-toxic, with a CC50 of more than 0.4 mg/mL.

Protein adsorption onto membrane surfaces is important in fields related to separation science and biomedical research. This study explored the molecular interactions between protein, bovine serum albumin (BSA), and nitrocellulose films (NC) using electrokinetic phenomena and the effects of these interactions on the streaming potential measurements for different membrane pore morphologies and pH conditions. The data were used to calculate the streaming ratios of membranes-to-proteins and to compare these values to the electrostatic or hydrophobic attachment of the protein molecules onto the NC membranes. The results showed that different pH and membrane pore morphologies contributes to different protein adsorption mechanisms. The protein adsorption was significantly reduced under conditions where the membrane and protein have like-charges due to electrostatic repulsion. At the isoelectric point (IEP) of the protein, the repulsion between the BSA and the NC membrane was at the lowest; thus, the BSA could be easily attached onto the membrane/solution interface. In this case, the protein was considered to be in a compact layer without intermolecular protein repulsions., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Here we provide a complete review on the use of dynamic light scattering (DLS) to study the size distribution and colloidal stability of magnetic nanoparticles (MNPs). The mathematical analysis involved in obtaining size information from the correlation function and the calculation of Z-average are introduced. Contributions from various variables, such as surface coating, size differences, and concentration of particles, are elaborated within the context of measurement data. Comparison with other sizing techniques, such as transmission electron microscopy and dark-field microscopy, revealed both the advantages and disadvantages of DLS in measuring the size of magnetic nanoparticles. The self-assembly process of MNP with anisotropic structure can also be monitored effectively by DLS.

Background: Hemophilia A results from a deficiency in factor VIII activity. Current treatment regimens require frequent dosing, owing to the short half-life of FVIII. A recombinant FVIII-Fc fusion protein (rFVIIIFc) was molecularly engineered to increase the half-life of FVIII, by 1.5-2-fold, in several preclinical animal models and humans., Objective: To perform a biochemical and functional in vitro characterization of rFVIIIFc, with existing FVIII products as comparators., Methods:  rFVIIIFc was examined by utilizing a series of structural and analytic assays, including mass spectrometry following lysyl endopeptidase or thrombin digestion. rFVIIIFc activity was determined in both one-stage clotting (activated partial thromboplastin time) and chromogenic activity assays, in the context of the FXase complex with purified components, and in both in vitro and ex vivo rotational thromboelastometry (ROTEM) assays performed in whole blood., Results:  rFVIIIFc contained the predicted primary structure and post-translational modifications, with an FVIII moiety that was similar to other recombinant FVIII products. The von Willebrand factor-binding and specific activity of rFVIIIFc were also found to be similar to those of other recombinant FVIII molecules. Both chromogenic and one-stage assays of rFVIIIFc gave similar results. Ex vivo ROTEM studies demonstrated that circulating rFVIIIFc activity was prolonged in mice with hemophilia A in comparison with B-domain-deleted or full-length FVIII. Clot parameters at early time points were similar to those for FVIII, whereas rFVIIIFc showed prolonged improvement of clot formation., Conclusions:  rFVIIIFc maintains normal FVIII interactions with other proteins necessary for its activity, with prolonged in vivo activity, owing to fusion with the Fc region of IgG(1) ., (© 2012 International Society on Thrombosis and Haemostasis.)

Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an ∼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation.

Hepatocellular carcinoma (HCC) is increasingly being detected at an earlier stage, owing to the screening programs and regular imaging follow-up in high-risk populations. Small HCCs still pose diagnostic challenges on imaging due to decreased sensitivity and increased frequency of atypical features. Differentiating early HCC from premalignant or benign nodules is important as management differs and has implications on both the quality of life and the overall survival for the patients. Gadoxetate acid (Gd-EOB-DTPA, Primovist(®), Bayer Schering Pharma) is a relatively new, safe and well-tolerated liver-specific contrast agent for magnetic resonance (MR) imaging of the liver that has combined perfusion- and hepatocyte-specific properties, allowing for the acquisition of both dynamic and hepatobiliary phase images. Its high biliary uptake and excretion improves lesion detection and characterization by increasing liver-to-lesion conspicuity in the added hepatobiliary phase imaging. To date, gadoxetate acid-enhanced MRI has been mostly shown to be superior to unenhanced MRI, computed tomography, and other types of contrast agents in the detection and characterization of liver lesions. This review article focuses on the evolving role of gadoxetate acid in the characterization of HCC, differentiating it from other mimickers of HCC.

Consensus guidelines for radiological diagnosis of hepatocellular carcinoma (HCC) have been drafted by several large international working groups. This article reviews the similarities and differences between the most recent guidelines proposed by the American Association for Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver. Current evidence for the various imaging modalities for diagnosis of HCC and their relevance to the consensus guidelines are reviewed.

Treatment of hemophilia B requires frequent infusions of factor IX (FIX) to prophylax against bleeding episodes. Hemophilia B management would benefit from a FIX protein with an extended half-life. A recombinant fusion protein (rFIXFc) containing a single FIX molecule attached to the Fc region of immunoglobulin G was administered intravenously and found to have an extended half-life, compared with recombinant FIX (rFIX) in normal mice, rats, monkeys, and FIX-deficient mice and dogs. Recombinant FIXFc protein concentration was determined in all species, and rFIXFc activity was measured in FIX-deficient animals. The half-life of rFIXFc was approximately 3- to 4-fold longer than that of rFIX in all species. In contrast, in mice in which the neonatal Fc receptor (FcRn) was deleted, the half-life of rFIXFc was similar to rFIX, confirming the increased circulatory time was due to protection of the rFIXFc via the Fc/FcRn interaction. Whole blood clotting time in FIX-deficient mice was corrected through 144 hours for rFIXFc, compared with 72 hours for rFIX; similar results were observed in FIX-deficient dogs. Taken together, these studies show the enhanced pharmacodynamic and pharmacokinetic properties of the rFIXFc fusion protein and provide the basis for evaluating rFIXFc in patients with hemophilia B.

A 71-year-old man presented to our hospital with 3-week history of fever in the background of loss of both weight and appetite over the past 3 months. He was found to have a large 10-cm mass in the right lobe of the liver on a triple-phase computed tomographic scan. The tumor showed a distinct fatty component, with areas of arterial enhancement and venous washout suggestive of hepatocellular carcinoma (HCC), another component showing progressive and late enhancement suggestive of cholangiocarcinoma (CC), and a third component showing persistent hypoenhancement relative to the liver parenchyma. He underwent surgical resection. This was histopathologically a biphasic tumor composed of areas showing hepatocytic differentiation, in contiguity with areas showing infiltrative glands set within fibrous stroma in keeping with combined hepatocellular and cholangiocarcinoma (cHCC-CC). A third component of pleomorphic spindle and epithelioid appearance in keeping with sarcomatous transformation was also found intimately related to the CC component. The patient developed extensive thoracic and abdominal metastases 2 months after surgery and died shortly after.

The neonatal Fc receptor, FcRn, is responsible for controlling the half-life of IgG antibodies. As a result, inhibitors of FcRn have been investigated as a possible way to modulate IgG half-lives. Such inhibitors could have possible applications in reducing autoantibody levels in autoimmune disease states. To date, monoclonal antibodies, engineered Fc domains, and short peptides have been reported to inhibit FcRn function and modulate IgG half-lives in vivo.

A case is presented of a life-threatening septicaemia and associated peripheral necrosing microembolic phenomenon, resulting from a dog lick to an insignificant burn wound. The isolated bacterium was Capnocytophaga canimorsus, a slow-growing Gram-negative bacillus commonly found in dog saliva. Any clinician seeing patients with a history of dog bite/saliva contact and progressive illness should consider this bacterium as a possible offender and take special care to elicit an accurate history, specifically including questions regarding animal contact.

The neonatal Fc receptor FcRn provides IgG molecules with their characteristically long half-lives in vivo by protecting them from intracellular catabolism and then returning them to the extracellular space. Other investigators have demonstrated that mice lacking FcRn are protected from induction of various autoimmune diseases, presumably because of the accelerated catabolism of pathogenic IgGs in the animals. Therefore, targeting FcRn with a specific inhibitor may represent a unique approach for the treatment of autoimmune disease or other diseases where the reduction of pathogenic IgG will have a therapeutic benefit. Using phage display peptide libraries, we screened for ligands that bound to human FcRn (hFcRn) and discovered a consensus peptide sequence that binds to hFcRn and inhibits the binding of human IgG (hIgG) in vitro. Chemical optimization of the phage-identified sequences yielded the 26-amino acid peptide dimer SYN1436, which is capable of potent in vitro inhibition of the hIgG-hFcRn interaction. Administration of SYN1436 to mice transgenic for hFcRn induced an increase in the rate of catabolism of hIgG in a dose-dependent manner. Treatment of cynomolgus monkeys with SYN1436 led to a reduction of IgG by up to 80% without reducing serum albumin levels that also binds to FcRn. SYN1436 and related peptides thus represent a previously uncharacterized family of potential therapeutic agents for the treatment of humorally mediated autoimmune and other diseases.

Background: The alpha and beta subunits of FSH were fused to the Fc domain of IgG1 either in a single chain or a heterodimer format. These molecules were absorbed through the epithelium in lung and intestine by neonatal Fc receptor (FcRn)-mediated transcytosis., Methods and Results: Single chain and heterodimer FSH-Fc were made recombinantly in Chinese hamster ovary cells. Treatment of rats with a single s.c. dose of single chain or heterodimer FSH-Fc resulted in greater stimulation of ovarian weight (20.8+/-3.9 and 26.9+/-6.1 mg respectively) compared to those receiving vehicle (12.1+/-1.0 mg) or an equimolar dose of recombinant human FSH (14.3+/-1.7 mg). Both FSH-Fc fusion proteins were absorbed after oral dosing of newborn rats with long terminal half-lives of approximately 60 h, and pulmonary delivery in four cynomolgus monkeys produced maximum serum concentrations between 69 and 131 ng/ml with long terminal half-lives between 55 and 210 h. Serum inhibin levels increased after pulmonary dosing with single chain FSH-Fc (1.3- and 1.4-fold) and heterodimer FSH-Fc (5.9- and 7.1-fold) and remained elevated for >12 days after treatment with heterodimer FSH-Fc., Conclusions: We have shown that FSH-Fc fusion proteins have increased stability in blood and improved bioactivity in vivo, and that heterodimer FSH-Fc is more active in rats and monkeys than single chain FSH-Fc. These data suggest that Fc fusion proteins offer the potential for oral and pulmonary delivery of FSH.

Administration of therapeutic proteins by methods other than injection is limited, in part, by inefficient penetration of epithelial barriers. Therefore, unique approaches to breaching these barriers are needed. The neonatal constant region fragment (Fc) receptor (FcRn), which is responsible for IgG transport across the intestinal epithelium in newborn rodents, is expressed in epithelial cells in adult humans and non-human primates. Here we show that FcRn-mediated transport is functional in the lung of non-human primates and that this transport system can be used to deliver erythropoietin (Epo) when it is conjugated to the Fc domain of IgG1. FcRn-dependent absorption was more efficient when the EpoFc fusion protein was deposited predominantly in the upper and central airways of the lung, where epithelial expression of FcRn was most prominently detected. To optimize fusion protein absorption in the lung, we created a recombinant "monomeric-Epo" Fc fusion protein comprised of a single molecule of Epo conjugated to a dimeric Fc. This fusion protein exhibited enhanced pharmacokinetic and pharmacodynamic properties. The bioavailability of the EpoFc monomer when delivered through the lung was approximately equal to that reported for unconjugated Epo delivered s.c. in humans. These studies show that FcRn can be harnessed to noninvasively deliver bioactive proteins into the systemic circulation in therapeutic quantities.

Selenocysteine incorporation at UGA codons requires cis-acting mRNA secondary structures and several specialized trans-acting factors. The latter include a selenocysteine-specific tRNA, an elongation factor specific for this tRNA and a SECIS-binding protein, SBP2, which recruits the elongation factor to the selenoprotein mRNA. Overexpression of selenoprotein mRNAs in transfected cells results in inefficient selenocysteine incorporation due to limitation of one or more of these factors. Using a transfection-based competition assay employing overexpression of selenoprotein mRNAs to compete for selenoprotein synthesis, we investigated the ability of the trans-acting factors to overcome competition and restore selenocysteine incorporation. We report that co-expression of SBP2 overcomes the limitation produced by selenoprotein mRNA overexpression, whereas selenocysteyl-tRNA and the selenocysteine-specific elongation factor do not. Competition studies indicate that once bound to SECIS elements, SBP2 does not readily exchange between them. Finally, we show that SBP2 preferentially stimulates incorporation directed by the seleno protein P and phospholipid hydroperoxide glutathione peroxidase SECIS elements over those of other selenoproteins. The mechanistic implications of these findings for the hierarchy of selenoprotein synthesis and nonsense-mediated decay are discussed.

Type 3 iodothyronine deiodinase (D3) catalyzes the conversion of T4 and T3 to inactive metabolites. It is highly expressed in placenta and thus can regulate circulating fetal thyroid hormone concentrations throughout gestation. We have cloned and expressed a 2.1-kb human placental D3 cDNA which encodes a 32-kD protein with a Km of 1.2 nM for 5 deiodination of T3 and 340 nM for 5' deiodination of reverse T3. The reaction requires DTT and is not inhibited by 6n-propylthiouracil. We quantitated transiently expressed D3 by specifically labeling the protein with bromoacetyl [125I]T3. The Kcat/Km ratio for 5 deiodination of T3 was over 1,000-fold that for 5' deiodination of reverse T3. Human D3 is a selenoenzyme as evidenced by (a) the presence of an in frame UGA codon at position 144, (b) the synthesis of a 32-kD 75Se-labeled protein in D3 cDNA transfected cells, and (c) the presence of a selenocysteine insertion sequence element in the 3' untranslated region of the mRNA which is required for its expression. The D3 selenocysteine insertion sequence element is more potent than that in the type 1 deiodinase or glutathione peroxidase gene, suggesting a high priority for selenocysteine incorporation into this enzyme. The conservation of this enzyme from Xenopus laevis tadpoles to humans implies an essential role for regulation of thyroid hormone inactivation during embryological development.

Selenocysteine is co-translationally incorporated into prokaryotic and eukaryotic selenoproteins at in-frame UGA codons. However, the only component of the eukaryotic selenocysteine incorporation machinery identified to date is the selenocysteine-specific tRNA(Sec). In prokaryotes, selenocysteine is synthesized from seryl-tRNA(Sec) and the active selenium donor, selenophosphate. Selenophosphate is synthesized from selenide and ATP by the selD gene product, selenophosphate synthetase, and is required for selenocysteine synthesis and incorporation into bacterial selenoproteins. We have now cloned human selD and shown that transfection of the human selD cDNA into mammalian cells results in increased selenium labeling of a mammalian selenoprotein, type 1 iodothyronine deiodinase. Despite significant differences between the mechanisms of selenoprotein synthesis in prokaryotes and eukaryotes, human selD weakly complements a bacterial selD mutation, partially restoring selenium incorporation into bacterial selenoproteins. Human selenophosphate synthetase has only 32% homology with the bacterial protein, although a highly homologous region that has similarity to a consensus ATP/GTP binding domain has been identified. Point mutations within this region result in decreased incorporation of selenium into type 1 iodothyronine deiodinase in all but one case. Further analysis revealed that reduced selenium labeling was due to altered ATP binding properties of the mutant selenophosphate synthetases.