Prednisolone therapy of idiopathic feline lower urinary tract disease: a double-blind clinical study

A double-blind clinical study was performed to evaluate prednisolone as treatment for idiopathic feline lower urinary tract disease. No differences in response were observed in prednisolone- and placebo-treated cats.     

Kinetic modelling of textural changes in ready-to-eat breakfast cereals during soaking in semi-skimmed milk

Summary Ready‐to‐eat breakfast cereals immersed in milk undergo undesirable changes in texture because of sudden moisture uptake. The textural changes are ascribable to a plasticizing effect of water, which modifies the mechanical strength of products by softening the starch/protein matrix. In this work, some textural parameters of different cereal flakes were derived from the force–displacement curves monitored during 300 s of immersion in milk. Hardness loss, deformability increment and changes in the force–displacement curve profile were calculated and plotted against soaking time. The application of a sugar coating process to a model cereal flake increased the initial product hardness and improved the preservation of the textural parameters during immersion. The Peleg model closely fitted the experimental data, with regression coefficients from 0.967 to 0.999.     

Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.     

Influence of temperature on the liver circadian clock in the ruin lizard Podarcis sicula

Reptiles represent an interesting animal model to investigate the influence of temperature on molecular circadian clocks. The ruin lizard Podarcis sicula lives in a continental climate and it is subjected to wide range of environmental temperatures during the course of the year. As consequence, ruin lizard daily activity pattern includes either the hibernation or periods of inactivity determined by hypothermia. Here we showed the rhythmic expression of two clock genes, lPer2 and lClock, in the liver of active lizards exposed to summer photo-thermoperiodic conditions. Interestingly, the exposition of lizards to hypothermic conditions, typical of winter season, induced a strong dampening of clock genes mRNA rhythmicity with a coincident decrease of levels. We also examined the qualitative and quantitative distribution of lPER2 and lCLOCK protein in different cellular compartments during the 24-h cycle. In the liver of active lizards both proteins showed a rhythmic expression profile in all cellular compartments. After 3 days at 6 degrees C, some temporal fluctuations of the lCLOCK and lPER2 are still detectable, although, with some marked modifications in respect to the values detected in the liver of active lizards. Besides demonstrating the influence of low temperature on the lizard liver circadian oscillators, present results could provide new essential information for comparative studies on the influence of temperature on the circadian system across vertebrate classes.     

Effects of freezing and frozen storage on the physicochemical and sensory characteristics of four types of goat's cheese

Summary Physicochemical and organoleptic properties were studied in two batches of four different types of goat's milk cheese: fresh, washed curd, soft with surface flora, and Majorero, frozen for four months prior to ripening and/or chilled storage. Frozen storage did not produce significant changes in the rheological or sensory characteristics of the cheeses, except in the case of fresh cheese, the textural characteristics of which were adversely affected. The level of proteolysis, estimated from the amino-acid nitrogen, was higher in the pre-frozen washed curd, soft with surface flora, and Majorero cheeses. The level of lipolysis was comparable, except in the soft cheese with surface flora, which presented higher levels of free fatty acids when stored frozen before ripening.

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Einfluß des Gefrierens und der Gefrierlagerung auf die physikalisch-chemischen und organoleptischen Eigenschaften von vier Ziegenkäsen

Zusammenfassung Aus Ziegenmilch wurden jeweils zwei Chargen von vier spanischen Käsesorten hergestellt: Frischkäse, gewaschene Käsemasse, Weichkäse mit Oberflächenflora und Majorero -Käse. Von jeder Charge wurde die Hälfte gefroren gelagert und erst nach vier Monaten auf die übliche Weise gereift und/oder gekühlt aufbewahrt. Die physikalisch-chemischen und organoleptischen Eigenschaften wurden danach untersucht. Im Vergleich mit Käsen, die nicht gefroren gewesen waren, ergaben sich keine wesentlichen Unterschiede in den rheologischen und sensorischen Eigenschaften, mit Ausnahme bei den Frischkäsen, bei dem sich die Textur durch die Aufbewahrung in gefrorenem Zustand verschlechtert hatte. Der Gehalt an freien Aminosäuren, ein Maß für die Proteolyse, war höher in der gewaschenen Käsemasse, in dem Weichkäse mit Oberflächenflora und in dem Majorero-Käse, die vier Monate gefroren gewesen waren. Durch die Gefrierlagerung hatte sich der Fettabbau nicht verändert, mit Ausnahme bei dem Käse mit Oberflächenflora, bei dem der Gehalt an freien Fettsäuren erhöht war im Vergleich mit dem Käse, der nicht vier Monate gefriergelagert worden war.

     

Porous Enzymatic Membrane for Nanotextured Glucose Sweat Sensors with High Stability toward Reliable Noninvasive Health Monitoring

Development of reliable glucose sensors for noninvasive monitoring without interruption or limiting users' mobility is highly desirable, especially for diabetes diagnostics, which requires routine/long‐term monitoring. However, their applications are largely limited by the relatively poor stability. Herein, a porous membrane is synthesized for effective enzyme immobilization and it is robustly anchored to the modified nanotextured electrode solid contacts, so as to realize glucose sensors with significantly enhanced sensing stability and mechanical robustness. To the best of our knowledge, this is the first report of utilizing such nanoporous membranes for electrochemical sensor applications, which eliminates enzyme escape and provides a sufficient surface area for molecular/ion diffusion and interactions, thus ensuring the sustainable catalytic activities of the sensors and generating reliable measureable signals during noninvasive monitoring. The as‐assembled nanostructured glucose sensors demonstrate reliable long‐term stable monitoring with a minimal response drift for up to 20 h, which delivers a remarkable enhancement. Moreover, they can be integrated into a microfluidic sensing patch for noninvasive sweat glucose monitoring. The as‐synthesized nanostructured glucose sensors with remarkable stability can inspire developments of various enzymatic biosensors for reliable noninvasive composition analysis and their ultimate applications in predictive clinical diagnostics, personalized health‐care monitoring, and chronic diseases management.     

Epitope-Imprinted Nanoparticles as Transforming Growth Factor-β3 Sequestering Ligands to Modulate Stem Cell Fate

Growth factors (GFs) are biomolecules with potent biological effects but inherent limitations hinder their potential as therapeutic agents and cell culture supplements in tissue engineering and regenerative medicine (TERM). Biomaterials that sequester endogenous GFs by affinity binding might circumvent such limitations and thus are being increasingly investigated. Here, molecularly imprinted nanoparticles (MINPs) are proposed as specific abiotic ligands for GFs. As a proof of concept, a conformational epitope of transforming growth factor-β3 (TGF-β3) is designed and surface imprinted onto polyacrylamide-based nanoparticles by inverse microemulsion polymerization. It is found that, depending on the polymerization mixture composition, MINPs can recognize and preferentially bind TGF-β3, either in noncompetitive assays or from a complex human fluid (platelet lysate). Substrates functionalized with MINPs are then used for 2D culture of adipose-derived stem cells. Remarkably, gene and protein expression profiles show a marked upregulation of SOX-9, suggesting activation of TGF-β3 signaling pathways without requiring supplementation with exogenous GF. Likewise, culturing these cells in pellets incorporating MINPs previously incubated with platelet lysate results in higher collagen II-rich matrix deposition, compared to pellets incorporating non-imprinted nanoparticles. In summary, results suggest MINPs can be used as cost-effective, stable, and scalable alternative abiotic GF ligands to guide cell fate in TERM applications.     

Use of β-hydroxyacyl-CoA-dehydrogenase (HADH) activity to differentiate frozen from unfrozen fish and shellfish

 Further work on an enzymic method to differentiate frozen from unfrozen fish and shellfish is reported. The method is based on the release of the β-hydroxyacyl-CoA-dehydrogenase (HADH) from mitochondria during freezing. Enzymic activity was evaluated in fresh and frozen thawed samples from sole (Solea solea), sea bream (Pagellus centrodontus), hake (Merluccius merluccius), gilt headed bream (Sparus aurata), sea bass (Dicentrarchus labrax), salmon (Salmo salar), prawn (Penaeus japonicus) and Norwegian lobster (Nephrops norvegicus). Changes in the HADH activity of fresh and frozen thawed samples were compared after freezing at –196  °C for 15 min. Two values were obtained: U (by dividing: HADH activity of samples frozen at –196  °C, then thawed/HADH activity of unfrozen samples) and F (by dividing: HADH activity of samples frozen at –18  °C, thawed, then frozen at –196  °C /HADH activity of samples frozen at –18  °C, then thawed). Statistical analysis showed significant differences (P≤0.05) between both quotients for gilt headed bream, salmon, sea bream, sole and prawn, and an arbitrary limit was set at 2 to differentiate frozen thawed from unfrozen samples. The application of this limit made it possible to discriminate the unfrozen from the frozen thawed state of around 90% of the total samples analysed. Best results were obtained for prawn (100% of samples differentiated). In the present paper, a laboratory routine is proposed based on the comparison of the HADH activity of a sample analysed straight away and that of a sample frozen at –196  °C and then thawed. The reported method is simple and fast. The entire laboratory procedure can be performed in 45 min. Received: 20 July 1998 / Revised version: 2 November 1998     

Chiral Excitonic Organic Photodiodes for Direct Detection of Circular Polarized Light

A facile route to soft matter self‐powered bulk heterojunction photodiode detectors sensitive to the circular polarization state of light is shown based on the intrinsic excitonic circular dichroism of the photoactive layer blend. As light detecting materials, enantiopure semiconducting small molecular squaraine derivates of opposite handedness are employed. Via Mueller matrix ellipsometry, the circular dichroism is proven to be of H‐type excitonic nature and not originating from mesoscopic structural ordering. Within the green spectral range, the photodiodes convert circular polarized light into a handedness‐dependent photocurrent with a maximum dissymmetry factor of ±0.1 corresponding to 5% overall efficiency for the polarization discrimination under short circuit conditions. On the basis of transfer matrix optical simulations, it is rationalized that the optical dissymmetry fully translates into a photocurrent dissymmetry for ease of device design. Thereby, the photodiode's ability to efficiently distinguish between left and right circularly polarized light without the use of external optical elements and voltage bias is demonstrated. This allows a straightforward and sustainable future design of flexible, lightweight, and compact integrated platforms for chiroptical imaging and sensing.     

Composite Nanostructures of TiO2 and ZnO for Water Splitting Application: Atomic Layer Deposition Growth and Density Functional Theory Investigation

The commercialization of solar fuel devices requires the development of novel engineered photoelectrodes for water splitting applications which are based on redundant, cheap, and environmentally friendly materials. In the current study, a combination of titanium dioxide (TiO₂) and zinc oxide (ZnO) onto nanotextured silicon is utilized for a composite electrode with the aim to overcome the individual shortcomings of the respective materials. The properties of conformal coverage of TiO₂ and ZnO layers are designed on the atomic scale by the atomic layer deposition technique. The resulting photoanode shows not only promising stability but also nine times higher photocurrents than an equivalent photoanode with a pure TiO₂ encapsulation onto the nanostructured silicon. Density functional theory calculations indicate that segregation of TiO₂ at the ZnO surfaces is favorable and leads to the stabilization of the ZnO layers in water environments. In conclusion, the novel designed composite material constitutes a promising base for a stable and effective photoanode for the water oxidation reaction.