Soft Character of Star-Like Polymer Melts: From Linear-Like Chains to Impenetrable Nanoparticles.

The importance of microscopic details in the description of the behavior of polymeric nanostructured systems, such as hairy nanoparticles, has been lately discussed via experimental and theoretical approaches. Here we focus on star polymers, which represent well-defined soft nano-objects. By means of atomistic molecular dynamics simulations, we provide a quantitative study about the effect of chemistry on the penetrability of star polymers in a melt, which cannot be considered by generic coarse-grained models. The "effective softness" estimated for two dissimilar polymers is confronted with available literature data. A consistent picture about the star penetrability can be drawn when the star internal packing is taken into consideration besides the number and the length of the star arms. These findings, together with the recently introduced two-layer model, represent a step forward in providing a fundamental understanding of the soft character of stars and guiding their design toward advanced applications, such as in all-polymer nanocomposites.

ROOT PENETRATION INDEX 3, a major quantitative trait locus associated with root system penetrability in Arabidopsis.

Soil mechanical impedance precludes root penetration, confining root system development to shallow soil horizons where mobile nutrients are scarce. Using a two-phase-agar system, we characterized Arabidopsis responses to low and high mechanical impedance at three root penetration stages. We found that seedlings whose roots fail to penetrate agar barriers show a significant reduction in leaf area, root length, and elongation zone and an increment in root diameter, while those capable of penetrating show only minor morphological effects. Analyses using different auxin-responsive reporter lines, exogenous auxins, and inhibitor treatments suggest that auxin responsiveness and PIN-mediated auxin distribution play an important role in regulating root responses to mechanical impedance. The assessment of 21 Arabidopsis accessions revealed that primary root penetrability varies widely among accessions. To search for quantitative trait loci (QTLs) associated to root system penetrability, we evaluated a recombinant inbred population derived from Landsberg erecta (Ler-0, with a high primary root penetrability) and Shahdara (Sha, with a low primary root penetrability) accessions. QTL analysis revealed a major-effect QTL localized in chromosome 3, ROOT PENETRATION INDEX 3 (q-RPI3), which accounted for 29.98% (logarithm of odds=8.82) of the total phenotypic variation. Employing an introgression line (IL-321) with a homozygous q-RPI3 region from Sha in the Ler-0 genetic background, we demonstrated that q-RPI3 plays a crucial role in root penetrability. This multiscale study reveals new insights into root plasticity during the penetration process in hard agar layers, natural variation, and genetic architecture behind primary root penetrability in Arabidopsis.

Low cerebrospinal fluid-to-plasma ratios of orally administered lenalidomide mediated by its low cell membrane permeability in patients with hematologic malignancies.

Lenalidomide is a synthetic analog of thalidomide formed by the removal of one keto group (plus the addition of an amino group); it has anti-tumor activities beneficial for the treatment of hematologic malignancies. However, lenalidomide distribution to brain in animal models is reportedly low compared with that of thalidomide. The aim of this study was to evaluate plasma and cerebrospinal fluid concentrations of lenalidomide in three patients with malignant hematologic malignancies. Lenalidomide was detected in plasma from the three Japanese patients 1.5 h following oral administration of 20 mg lenalidomide using liquid chromatography/mass spectrometry, despite the in vitro gastrointestinal permeability of lenalidomide being low. Clinically observed cerebrospinal fluid-to-plasma ratios of lenalidomide were low (1.3-2.4%). Observed influx permeability values for lenalidomide in monkey blood-brain barrier model and human placental cell systems were one order of magnitude lower than those of thalidomide and another second-generation drug, pomalidomide along with a positive permeability control, caffeine. Because of the low cell-barrier permeability of lenalidomide demonstrated in in vitro assays, clinically relevant pharmacokinetic profiles of lenalidomide resulted in low penetrability from plasma into cerebrospinal fluid in patients with hematologic malignancies. Lenalidomide is conclusively suggested to expert its favorable immunomodulatory effects via systemic exposures in the patients.

Dual counterstream architecture may support separation between vision and predictions.

According to a predictive coding framework, visual processing involves the computation of prediction errors between sensory data and a generative model that is supplied via feedback projections. This implies that vision is cognitively penetrable by all sorts of top-down influences. In this paper, we review anatomical and functional data which suggest that feedforward and feedback projections are organized into two parallel processing streams: the supragranular and the infragranular counterstreams. The supragranular counterstream computes surface and motion representation in depth. It represents the best interpretation of what is given in the input image based on physical regularities that are built into this network. By contrast, the infragranular counterstream integrates vision with cognition, because it represents what is likely to be found in the environment based on the predictions derived from learned statistical regularities. The two counterstreams work in parallel, but independently of each other. They compete for dominance, and only one is allowed to deliver its output to higher-order areas at any instance of time. Such an arrangement allows the supragranular counterstream to remain cognitively impenetrable to top-down influences.

Negative affect impedes perceptual filling-in in the uniformity illusion.

The notion of cognitive penetrability, i.e., whether perceptual contents can in principle be influenced by non-perceptual factors, has sparked a significant debate over methodological concerns and the correct interpretation of existing findings. In this study, we combined predictive processing models of visual perception and affective states to investigate influences of affective valence on perceptual filling-in in extrafoveal vision. We tested how experimentally induced affect would influence the probability of perceptual filling-in occurring in the uniformity illusion (N = 50). Negative affect led to reduced occurrence rates and increased onset times of visual uniformity. This effect was selectively observed in illusionary trials, requiring perceptual filling-in, and not in control trials, where uniformity was the veridical percept, ruling out biased motor responses or deliberate judgments as confounding variables. This suggests an influential role of affective status on subsequent perceptual processing, specifically on how much weight is ascribed to priors as opposed to sensory evidence.

Visual Self-Misperception in Eating Disorders.

Many who suffer from eating disorders claim that they see themselves as "fat". Despite decades of research into the phenomenon, behavioural evidence has failed to confirm that eating disorders involve visual misperception of own-body size. I illustrate the importance of this phenomenon for our understanding of perceptual processing, outline the challenges involved in experimentally confirming it, and provide solutions to those challenges.

Thymoquinone Loaded Topical Nanoemulgel for Wound Healing: Formulation Design and In-Vivo Evaluation.

Thymoquinone is a natural bioactive with significant therapeutic activity against multiple ailments including wound healing. The poor aqueous solubility and low skin permeability limit its therapeutic efficacy. The present investigation aimed to improve the biopharmaceutical attributes of thymoquinone to enhance its topical efficacy in wound healing. A nanoemulsion-based hydrogel system was designed and characterized as a nanotechnology-mediated drug delivery approach to improve the therapeutic efficacy of thymoquinone, utilizing a high-energy emulsification technique. The black seed oil, as a natural home of thymoquinone, was utilized to improve the drug loading capacity of the developed nanoemulsion system and reduced the oil droplet size to <100 nm through ultrasonication. The influence of formulation composition, and the ultrasonication process conditions, were investigated on the mean globule size and polydispersity index of the generated nanoemulsion. Irrespective of surfactant/co-surfactant ratio and % concentration of surfactant/co-surfactant mixture, the ultrasonication time had a significant (p < 0.05) influence on the mean droplet size and polydispersity index of the generated nanoemulsion. The developed nanoemulgel system of thymoquinone demonstrated the pseudoplastic behavior with thixotropic properties, and this behavior is desirable for topical application. The nanoemulgel system of thymoquinone exhibited significant enhancement (p < 0.05) in skin penetrability and deposition characteristics after topical administration compared to the conventional hydrogel system. The developed nanoemulgel system of thymoquinone exhibited quicker and early healing in wounded Wistar rats compared to the conventional hydrogel of thymoquinone, while showing comparable healing efficacy with respect to marketed silver sulfadiazine (1%) cream. Furthermore, histopathology analysis of animals treated with a developed formulation system demonstrated the formation of the thick epidermal layer, papillary dermis along with the presence of extensive and organized collagen fibers in newly healed tissues. The outcome of this investigation signifies that topical delivery of thymoquinone through nanoemulgel system is a promising candidate which accelerates the process of wound healing in preclinical study.

The cognitive penetrability of perception: A blocked debate and a tentative solution.

Despite the extensive body of psychological findings suggesting that cognition influences perception, the debate between defenders and detractors of the cognitive penetrability of perception persists. While detractors demand more strictness in psychological experiments, proponents consider that empirical studies show that cognitive penetrability occurs. These considerations have led some theorists to propose that the debate has reached a dead end. The issue about where perception ends and cognition begins is, I argue, one of the reasons why the debate is cornered. Another reason is the inability of psychological studies to present uncontroversial interpretations of the results obtained. To dive into other kinds of empirical sources is, therefore, required to clarify the debate. In this paper, I explain where the debate is blocked, and suggest that neuroscientific evidence together with the predictive coding account, might decant the discussion on the side of the penetrability thesis.

Natural polyphenols in preclinical models of epilepsy.

Natural polyphenols are being tested both in preclinical and clinical settings for the treatment of different neurological disorders. The article describes the outcome of three polyphenols, resveratrol, epigallocatechin gallate, and quercetin, in preclinical animal models of epilepsy (both acute and chronic) and epileptogenesis. In theory, the antioxidant and neuroprotective properties of these natural polyphenols might be valuable in the management of acute seizures and the prevention of epileptogenesis. It is fascinating to observe that these polyphenols have a capacity to alter various signaling processes involved in the pathogenesis of epilepsy. The antiepileptic or antiseizure potential with these molecules delivers a mixed outcome. Some studies have demonstrated the usefulness of these molecules in preclinical models of epilepsy; however, contrary to the findings also exist. These molecules have poor bioavailability that may remain as the limiting factor in their clinical effects. The use of nanotechnology and other techniques have been tested to enhance bioavailability and brain penetration. There are no randomized double-blinded clinical studies establishing their antiepileptic effects in humans. It is concluded that more preclinical mechanism-based studies are needed to deliver a more certain picture regarding the use of natural polyphenols in the treatment of epilepsy.

Phaeodactylum tricornutum as a model organism for testing the membrane penetrability of sulphonamide carbonic anhydrase inhibitors.

Carbonic anhydrases (CAs) are ubiquitous metalloenzymes, which started to be investigated in detail in pathogenic, as well as non-pathogenic species since their pivotal role is to accelerate the physiological CO2 hydration/dehydration reaction significantly. Here, we propose the marine unicellular diatom Phaeodactylum tricornutum as a model organism for testing the membrane penetrability of CA inhibitors (CAIs). Seven inhibitors belonging to the sulphonamide type and possessing a diverse scaffold have been explored for their in vitro inhibition of the whole diatom CAs and the in vivo inhibitory effect on the growth of P. tricornutum. Interesting, inhibition of growth was observed, in vivo, demonstrating that this diatom is a good model for testing the cell wall penetrability of this class of pharmacological agents. Considering that many pathogens are difficult and dangerous to grow in the laboratory, the growth inhibition of P. tricornutum with different such CAIs may be subsequently used to design inhibition studies of CAs from pathogenic organisms.

Topically applied hypericin exhibits skin penetrability on nude mice.

Hypericin, a powerful natural photosensitizer in photodynamic therapy (PDT), is suitable for treating skin diseases involving excess capillary proliferation. In the present study, we aimed to evaluate the skin penetrability of topically applied hypericin, expecting a reduced risk of prolonged skin photosensitivity, which often occurs after systemic administration. Firstly, the Franz diffusion cell assays were performed to evaluate the penetration effects of different enhancers, including menthol, propylene glycol, camphanone, azone, and carbamide. In view of above evaluation results, we selected menthol as the enhancer in the subsequent in vivo studies. The setting groups were as follows: the blank control group, the light-exposure control group, the gel-base control group, the hypericin gel group, and a hypericin gel-containing menthol group. Except for the blank control, all other animals were irradiated by a LED light. Then, fluorescence microscopy was performed to examine the distribution of hypericin in the skin of nude mouse. Macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment. Immunohistochemistry was used to determine the expression change of PECAM-1. As shown in the results, menthol facilitated hypericin penetrate the skin of nude mice most. The results of in vivo assays revealed that hypericin penetrated nude mouse skin, spread to the dermis, and resulted in obvious photosensitivity reaction on the dermal capillaries. Moreover, skin injured by the photosensitive reaction induced by hypericin-PDT treatment was replaced by normal skin within 7 days. We concluded that topical applied hypericin could penetrate nude mouse skin well and has a great potential in PDT treatment of skin diseases.

Applicability of Diffuse Ultrasound to Evaluation of the Water Permeability and Chloride Ion Penetrability of Cracked Concrete.

This study aims to explore the applicability of diffuse ultrasound to the evaluation of water permeability and chloride ion penetrability of cracked concrete. Lab-scale experiments were conducted on disk-shaped concrete specimens, each having a different width of a penetrating crack that was generated by splitting tension along the centerline. The average crack width of each specimen was determined using an image binarization technique. The diffuse ultrasound test employed signals in the frequency range of 200 to 440 kHz. The water flow rate was measured using a constant water-head permeability method, and the chloride diffusion coefficient was determined using a modified steady-state migration method. Then, the effects of crack width on the diffusion characteristics of ultrasound (i.e., diffusivity, dissipation), water flow rate, and chloride diffusion coefficient are investigated. The correlations between the water flow rate and diffuse ultrasound parameters, and between the chloride diffusion coefficient and diffuse ultrasound parameters, are examined. The results suggest that diffuse ultrasound is a promising method for assessing the water permeability and chloride ion penetrability of cracked concrete.

Attention and cognitive penetrability: The epistemic consequences of attention as a form of metacognitive regulation.

A recent approach to the cognitive penetrability of perception, i.e. the possibility that perception is shaped top-down by high-level cognitive states such as beliefs and desires, proposes to understand the phenomenon on the basis of its consequences, among which there is a challenge for the epistemic role of perceptual experience in justifying beliefs (Stokes, 2015). In this paper, I argue that some attentional phenomena qualify as cases of cognitive penetrability under this consequentialist approach. I present a popular theory of attention, the biased-competition theory, on which basis I establish that attention is a form of metacognitive regulation. I argue that attention (as metacognitive regulation) involves the right kind of cognitive-perceptual relation and leads to the same epistemic consequences as other more traditional versions of cognitive penetrability.

Priors in perception: Top-down modulation, Bayesian perceptual learning rate, and prediction error minimization.

I discuss top-down modulation of perception in terms of a variable Bayesian learning rate, revealing a wide range of prior hierarchical expectations that can modulate perception. I then switch to the prediction error minimization framework and seek to conceive cognitive penetration specifically as prediction error minimization deviations from a variable Bayesian learning rate. This approach retains cognitive penetration as a category somewhat distinct from other top-down effects, and carves a reasonable route between penetrability and impenetrability. It prevents rampant, relativistic cognitive penetration of perception and yet is consistent with the continuity of cognition and perception.

Language can boost otherwise unseen objects into visual awareness.

Linguistic labels (e.g., "chair") seem to activate visual properties of the objects to which they refer. Here we investigated whether language-based activation of visual representations can affect the ability to simply detect the presence of an object. We used continuous flash suppression to suppress visual awareness of familiar objects while they were continuously presented to one eye. Participants made simple detection decisions, indicating whether they saw any image. Hearing a verbal label before the simple detection task changed performance relative to an uninformative cue baseline. Valid labels improved performance relative to no-label baseline trials. Invalid labels decreased performance. Labels affected both sensitivity (d') and response times. In addition, we found that the effectiveness of labels varied predictably as a function of the match between the shape of the stimulus and the shape denoted by the label. Together, the findings suggest that facilitated detection of invisible objects due to language occurs at a perceptual rather than semantic locus. We hypothesize that when information associated with verbal labels matches stimulus-driven activity, language can provide a boost to perception, propelling an otherwise invisible image into awareness.

"Top-down" effects where none should be found: the El Greco fallacy in perception research.

A tidal wave of recent research purports to have discovered that higher-level states such as moods, action capabilities, and categorical knowledge can literally and directly affect how things look. Are these truly effects on perception, or might some instead reflect influences on judgment, memory, or response bias? Here, we exploited an infamous art-historical reasoning error (the so-called "El Greco fallacy") to demonstrate that multiple alleged top-down effects (including effects of morality on lightness perception and effects of action capabilities on spatial perception) cannot truly be effects on perception. We suggest that this error may also contaminate several other varieties of top-down effects and that this discovery has implications for debates over the continuity (or lack thereof) of perception and cognition.

A study on the synthesis and performance evaluation of fly ash and alccofine as sustainable cementitious materials.

Construction and global infrastructure depend on cement production. It is one of the biggest carbon emitters, making it an aspect of environmental sustainability and climate change mitigation. Each stage of cement production releases CO2 and other greenhouse gasses. About 8% of worldwide CO2 emissions come from the cement sector, making it a major contributor. Different supplementary cementitious materials (SCMs) like fly ash (FA), silica fume (SF), and slag are used to partially replace traditional raw materials like limestone, reducing the environmental impact. This study investigated the use of supplementary cementitious materials, specifically FA and alccofine (AF), as partial replacements for cement in concrete to reduce environmental impact. The study first identified an optimal replacement percentage for FA (20%, 30%, and 40%) by weight of cement. Subsequently, using the optimal FA percentage, AF was added at varying percentages (5%, 10%, and 15%) by weight of cement. The study evaluated the mechanical properties of the concrete mixtures, including workability, compressive strength, split tensile strength, and flexural strength. Durability, measured by water sorptivity and rapid chloride penetrability tests, was also assessed. The microstructural properties of the concrete were analyzed to understand their influence on performance. As a result of the significant environmental implications of producing and using concrete for all activities, an in-depth life cycle assessment (LCA) was conducted. Additionally, artificial neural networks were employed to predict the compressive strength of the concrete. The study concluded that incorporating FA and AF in concrete mixtures is a promising approach to producing more environmentally friendly concrete.

Bifonazole caffeate: The first molecular salt of bifonazole with enhanced biopharmaceutical property based on experiments and quantum chemistry research.

In order to make novel breakthroughs in molecular salt studies of BCS class-IV antifungal medication bifonazole (BIF), a salification-driven strategy towards ameliorating attributes and aiding augment efficiency is raised. This strategy fully harnesses structural characters together attributes and benefits of caffeic acid (CAF) to concurrently enhance dissolvability and permeability of BIF by introducing the two ingredients into the identical molecular salt lattice through the salification reaction, which, coupled with the aroused potential activity of CAF significantly amplifies the antifungal efficacy of BIF. Guided by this route, the first BIF-organic molecular salt, BIF-CAF, is directionally designed and synthesized with satisfactorily structural characterizations and integrated theoretical and experimental explorations on the pharmaceutical properties. Single-crystal X-ray diffraction resolving confirms that there is a lipid-water amphiphilic sandwich structure constructed by robust charge-assistant hydrogen bonds in the salt crystal, endowing the molecular salt with the potential to enhance both dissolvability and permeability relative to the parent drug, which is validated by experimental evaluations. Remarkably, the comprehensive DFT-based theoretical investigations covering frontier molecular orbital, molecular electrostatic potential, Hirshfeld surface analysis, reduced density gradient, topology, sphericity and planarity analysis strongly support these observations, thereby allowing some positive relationships between macroscopic properties and microstructures of the molecular salt can be made. Intriguingly, the optimal properties, together with the stimulated activity of CAF markedly augment in vitro antifungal ability of the molecular salt, with magnifying inhibition zones and reducing minimum inhibitory concentrations. These findings fill in the gaps on researches of BIF-organic molecular salt, and adequately exemplify the feasibility and validity by integrating theoretical and experimental approaches to resolve BIF's problems via the salification-driven tactic.

Developing Plant Exosomes as an Advanced Delivery System for Cosmetic Peptide.

Peptides are a promising skincare ingredient, but due to their inherent instability and the barrier function of the skin's surface, they often have limited skin absorption and penetration, which can significantly hinder their skincare benefits. To address this, a novel technique called NanoGlow has been introduced for encapsulating peptide-based cosmetic raw materials into engineered nanosized plant-derived exosomes (pExo) to achieve the goal of a healthier and more radiant skin state. In this approach, pExo served as carriers for cosmetic peptides across the intact skin barrier, enhancing their biological effectiveness in skin beauty. The NanoGlow strategy combines chemical activation and physical proencapsulation, boasting a high success rate and straightforward and stable operation, making it suitable for large-scale production. Comprehensive analysis using in vitro cellular absorption and skin penetration models has demonstrated that the nanosized pExo carriers significantly improve peptide penetration into the skin compared to free peptides. Furthermore, in vivo tissue slice studies have shown that pExo carriers efficiently deliver acetyl hexapeptide-8 to the skin's dermis, surpassing the performance of free peptides. Cosmetic skincare effect analysis has also indicated that pExo-loaded cosmetic peptides deliver superior results. Therefore, the NanoGlow technique harnesses the natural size and properties of pExo to maximize the bioavailability of cosmetic peptides, holding great promise for developing advanced peptide delivery systems in both the cosmetic and medical drug industries.