Quantification of Free 2-Furfurylthiol in Coffee Brew Using a Prefabricated Coffee Model

A reliable and sensitive method was developed to quantify the free 2-furfurylthiol (2-FFT) in coffee brew. Using cysteine addition combined with vacuum distillation, a coffee model with trace 2-FFT and similar physicochemical properties as coffee brew was prepared for standard curve construction. During the model preparation, 2-FFT in bound form was released to free 2-FFT and removed from coffee brew through vacuum distillation. The method sensitivity, precision, accuracy and selectivity were evaluated. The limit of quantification (LOQ) was 3.0 μg/L. The coefficient of variation (CV) was 7.1%. The average recovery rates were 86.8–106.2% at spiked concentrations of 22.6, 135.8 and 181 μg/L. Coffee brews prepared using Robusta and Arabica roasted coffee beans were analyzed, and results showed that coffee brew from Robusta coffee beans had a greater amount of free 2-FFT (20.94 μg/L) than Arabica coffee beans from Yunnan (11.34 μg/L) and Columbia (15.33 μg/L), respectively. This method would be beneficial to investigate the free amount of 2-FFT in coffee brew and the sensorial assay based on free 2-FFT concentration.     

A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases

The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs’ adoption. This review discusses the pathological development of some BDs, the NP-targeted components, and the actions exerted on bone remodeling signaling pathways (e.g., Receptor Activator of Nuclear Factor κ B-ligand (RANKL)/monocyte/macrophage colony-stimulating factor (M-CSF)/osteoprotegerin (OPG), mitogen-activated protein kinase (MAPK)s/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1), Bone Morphogenetic Protein 2 (BMP2)-Wnt/β-catenin, PhosphatidylInositol 3-Kinase (PI3K)/protein kinase B (Akt)/Glycogen Synthase Kinase 3 Beta (GSK3β), and other signaling pathways). Although majority of the studies on the osteoprotective properties of NPs against BDs were conducted ex vivo and mostly on animals, the use of NPs for treating human BDs and the prospects for future development remain promising.     

Soft-tissue sarcomas in the adult: news and trends]

The mechanism of growth retardation in Turner's syndrome has not been resolved. It is often referred to as a bone dysplasia, although endocrine derangement has not been ruled out. The present study was undertaken to evaluate the maturation of individual bones of the hand and wrist in girls with Turner's syndrome and thereby obtain information which may aid in elaborating the possible mechanism of the growth retardation in girls with Turner's syndrome. Hand and wrist films of 24 girls with Turner's syndrome, 11 normal girls with short stature and 23 normal controls were evaluated, using the references of Greulich and Pyle. Each bone or epiphysis was given an individual 'age'. During childhood the Turner patients showed the greatest delay in bone age of the phalangeal bones while the least delayed were the radius and ulna (long bones) and metacarpals. The carpal bones showed intermediate retardation. This pattern and extent of maturational retardation was clearly different from that of the short stature normal group, who showed uniform retardation of all bones. During adolescence, the phalangeal bones were further retarded and the carpal bones showed a moderate retardation. The unique profile of bone maturation in Turner's syndrome suggests an insult to chondroplasia, which may be related to estrogen deficiency or to an as yet undetermined endocrine or paracrine derangement.     

Protein Crystals Nucleated and Grown by Means of Porous Materials Display Improved X-ray Diffraction Quality

Well-diffracting protein crystals are indispensable for X-ray diffraction analysis, which is still the most powerful method for structure-function studies of biomolecules. A promising approach to growing such crystals is the use of porous nucleation-inducing materials. However, while protein crystal nucleation in pores has been thoroughly considered, little attention has been paid to the subsequent growth of crystals. Although the nucleation stage is decisive, it is the subsequent growth of crystals outside the pore that determines their diffraction quality. The molecular-scale mechanism of growth of protein crystals in and outside pores is theoretically considered. Due to the low degree of metastability, the crystals that emerge from the pores grow slowly, which is a prerequisite for better diffraction. This expectation has been corroborated by experiments carried out with several types of porous material, such as bioglass (“Naomi’s Nucleant”), buckypaper, porous gold and porous silicon. Protein crystals grown with the aid of bioglass and buckypaper yield significantly better diffraction quality compared with crystals grown conventionally. In all cases, visually superior crystals are usually obtained. Our theoretical conclusion is that heterogeneous nucleation of a crystal outside the pore is an exceptional case. Rather, the protein crystals nucleating inside the pores continue growing outside them.     

Identification of a PEMFC fractional order model

The present paper addresses the important issue of monitoring the operating state of the Polymer Electrolyte Membrane Fuel Cell systems. The monitoring system takes a model based approach. Its originality lies in adopting a fuel cell fractional order impedance model which permits to provide a better insight into the fuel cell physical phenomena without increasing the number of parameters. This article first validates experimentally the accuracy of the suggested model, using a frequency identification method carried out by nonlinear optimization using single fuel cell experimental impedance spectroscopy data. In a second phase, time series identification is achieved using a least square method specifically designed for fractional order models. The latter method is first verified on registered data which represents a basic tool for offline monitoring. Subsequently it is refined as a recursive tool permitting an online monitoring; it is validated on laboratory test bench.     

Pyroelectric energy harvesting for water splitting

Hydrogen fuel cells are a promising energy conversion technology due to its high energy density and zero greenhouse gas emission. As a result, the production of hydrogen from renewable and alternative resources has gained significant interest in recent decades. This paper demonstrates a new approach which uses a pyroelectric energy harvester for water splitting and represents a novel alternative hydrogen source. Pyroelectrics are attractive for harvesting waste heat due to their ability to convert temperature fluctuations into electrical energy. A range of pyroelectric materials and geometries for water electrolysis are analysed to determine, (i) the minimum material thickness to generate a critical potential to initialise water decomposition and, (ii) to maximize the charge and hydrogen mass production. We then successfully demonstrate that an appropriate pyroelectric material, when combined with rectification of the alternating current, can harvest heat fluctuations and generate a sufficient electric potential difference and current for water splitting. By harvesting the pyroelectric electrical energy, a continuous hydrogen bubble production was observed during thermal cycling. Practical routes to maximize the level of hydrogen production for this new concept are also explored.     

Phosphodiesterase-4 Inhibition Reduces Cutaneous Inflammation and IL-1β Expression in a Psoriasiform Mouse Model but Does Not Inhibit Inflammasome Activation

Apremilast (Otezla^®) is an oral small molecule phosphodiesterase 4 (PDE4) inhibitor approved for the treatment of psoriasis, psoriatic arthritis, and oral ulcers associated with Behçet’s disease. While PDE4 inhibition overall is mechanistically understood, the effect of apremilast on the innate immune response, particularly inflammasome activation, remains unknown. Here, we assessed the effect of apremilast in a psoriasis mouse model and primary human cells. Psoriatic lesion development in vivo was studied in K5.Stat3C transgenic mice treated with apremilast for 2 weeks, resulting in a moderate (2 mg/kg/day) to significant (6 mg/kg/day) resolution of inflamed plaques after 2-week treatment. Concomitantly, epidermal thickness dramatically decreased, the cutaneous immune cell infiltrate was reduced, and proinflammatory cytokines were significantly downregulated. Additionally, apremilast significantly inhibited lipopolysaccharide- or anti-CD3-induced expression of proinflammatory cytokines in peripheral mononuclear cells (PBMCs). Notably, inflammasome activation and secretion of IL-1β were not inhibited by apremilast in PBMCs and in human primary keratinocytes. Collectively, apremilast effectively alleviated the psoriatic phenotype of K5.Stat3 transgenic mice, further substantiating PDE4 inhibitor-efficiency in targeting key clinical, histopathological and inflammatory features of psoriasis. Despite lacking direct effect on inflammasome activation, reduced priming of inflammasome components upon apremilast treatment reflected the indirect benefit of PDE4 inhibition in reducing inflammation.     

PROBABILITY-ONE HOMOTOPY ALGORITHMS FOR ROBUST CONTROLLER SYNTHESIS WITH FIXED-STRUCTURE MULTIPLIERS

Continuation algorithms that avoid multiplier–controller iteration have been developed earlier for fixed-architecture, mixed structured singular value controller synthesis. These algorithms have only been formulated for the special case of Popov multipliers and rely on an ad hoc initialization scheme. In addition, the algorithms have not used the prediction capabilities obtained by computing the Jacobian matrix of the continuation (or homotopy) map, and have assumed that the homotopy zero curve is monotonic. This paper develops probability-one homotopy algorithms based on the use of general fixed-structure multipliers. These algorithms can be initialized using an arbitrary (admissible) multiplier and a stabilizing compensator. In addition, as with all probability-one algorithms, the homotopy zero curve is not assumed to be monotonic and prediction is accomplished by using the homotopy Jacobian matrix. This approach also appears to have some advantages over the bilinear matrix inequality (BMI) approaches resulting from extensions of the LMI framework for robustness analysis. © 1997 by John Wiley & Sons, Ltd.     

Intranasal Administration of Forskolin and Noopept Reverses Parkinsonian Pathology in PINK1 Knockout Rats

Parkinson’s Disease (PD) is a brain-degenerative disorder characterized by a progressive loss of midbrain dopamine neurons. Current standard-of-care includes oral administration of Levodopa to address motor symptoms, but this treatment is not disease-modifying. A reduction in Protein Kinase A (PKA) signaling and neurotrophic support contributes to PD pathology. We previously showed that enhancing PKA activity in the brain via intraperitoneal administration of Forskolin in Parkinsonian rats (PINK1 knockout) abrogate motor symptoms and loss of midbrain dopamine neurons. Given that intraperitoneal administration is invasive, we hypothesized that intranasal administration of Forskolin and a second nootropic agent (Noopept) could reverse PD pathology efficiently. Results show that intranasal administration of a formulation (CNS/CT-001) containing Forskolin (10 µM) and Noopept (20 nM) significantly reversed motor symptoms, loss of hind limb strength, and neurodegeneration of midbrain dopamine neurons in PINK1-KO rats and is indistinguishable from wild-type (WT) rats; therapeutic effects associated with increased PKA activity and levels of BDNF and NGF in the brain. Intranasal administration of CNS/CT-001, but not Forskolin, significantly decreased the number of α-synuclein aggregates in the cortex of PINK1-KO rats, and is indistinguishable from WT rats. Overall, we show proof of concept that intranasal administration of CNS/CT-001 is a non-invasive, disease-modifying formulation for PD.