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Dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) has been found to be beneficial in rodent rheumatoid arthritis models and human trials. However, the molecular targets of n-3 PUFAs and their beneficial effects on rheumatoid arthritis are under-researched. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor for n-3 PUFA. We aim to investigate whether FFA4 activation reduces collagen-induced rheumatoid arthritis (CIA) by using an FFA4 agonist, compound A (CpdA), in combination with DBA-1J Ffa4 gene wild-type (WT) and Ffa4 gene knock-out (KO) mice. CIA induced an increase in the arthritis score, foot edema, synovial hyperplasia, pannus formation, proteoglycan loss, cartilage damage, and bone erosion, whereas the administration of CpdA significantly suppressed those increases in Ffa4 WT mice but not Ffa4 gene KO mice. CIA increased mRNA expression levels of pro-inflammatory Th1/Th17 cytokines, whereas CpdA significantly suppressed those increases in Ffa4 WT mice but not Ffa4 gene KO mice. CIA induced an imbalance between Th1/Th17 and Treg cells, whereas CpdA rebalanced them in spleens from Ffa4 WT mice but not Ffa4 gene KO mice. In SW982 synovial cells, CpdA reduced the LPS-induced increase in pro-inflammatory cytokine levels. In summary, the present results suggest that the activation of FFA4 in immune and synovial cells could suppress the characteristics of rheumatoid arthritis and be an adjuvant therapy. [ABSTRACT FROM AUTHOR]

In traditional Korean medicines, Magnolia officinalis is commonly included for the remedy of atopic dermatitis, and magnolol is a major constituent of Magnolia officinalis. Its pharmacological effects include anti-inflammatory, hepatoprotective, and antioxidant effects. Using BALB/c mice repeatedly exposed to 1-chloro-2,4-dinitrobenzene (DNCB), magnolol was evaluated in atopic dermatitis-like lesions. Administration of magnolol (10 mg/kg, intraperitoneal injection) markedly relieved the skin lesion severity including cracking, edema, erythema, and excoriation, and significantly inhibited the increase in IgE levels in the peripheral blood. A DNCB-induced increase in mast cell accumulation in atopic dermatitis skin lesions was reversed by magnolol administration, as well as a rise in expression levels of pro-inflammatory Th2/Th17/Th1 cytokines' (IL-4, IL-13, IL-17A, IFN-γ, IL-12A, TARC, IL-8, and IL-6) mRNAs in the lymph nodes and skin (n = 5 per group). In lymph nodes, magnolol reversed DNCB's increase in CD4+RORγt+ Th17 cell fraction and decrease in CD4+FoxP3+ regulatory T cell fraction. The results also showed that magnolol suppressed T cell differentiation into Th17 and Th2 cells, but not Th1 cells. Magnolol suppresses atopic dermatitis-like responses in the lymph nodes and skin, suggesting that it may be feasible to use it as a treatment for atopic dermatitis through its suppression of Th2/Th17 differentiation. [ABSTRACT FROM AUTHOR]

Although a large number of databases are available for regulatory elements, a bottleneck has been created by the lack of bioinformatics tools to predict the interaction modes of regulatory elements. To reduce this gap, we developed the Arabidopsis Transcription Regulatory Factor Domain/Domain Interaction Analysis Tool–liquid/liquid phase separation (LLPS), oligomerization, GO analysis (ART FOUNDATION-LOG), a useful toolkit for protein–nucleic acid interaction (PNI) and protein–protein interaction (PPI) analysis based on domain–domain interactions (DDIs). LLPS, protein oligomerization, the structural properties of protein domains, and protein modifications are major components in the orchestration of the spatiotemporal dynamics of PPIs and PNIs. Our goal is to integrate PPI/PNI information into the development of a prediction model for identifying important genetic variants in peaches. Our program unified interdatabase relational keys based on protein domains to facilitate inference from the model species. A key advantage of this program lies in the integrated information of related features, such as protein oligomerization, LOG analysis, structural characterizations of domains (e.g., domain linkers, intrinsically disordered regions, DDIs, domain–motif (peptide) interactions, beta sheets, and transmembrane helices), and post-translational modification. We provided simple tests to demonstrate how to use this program, which can be applied to other eukaryotic organisms. [ABSTRACT FROM AUTHOR]

During the first century BC, the famous Roman architect, Vitruvius, defined architecture as encompassing three essential properties: I firmitas i (firmness), I utilitas i (utility), and I venustas i (attractiveness or beauty). Contributions This Special Issue comprises 14 articles, with 11 original research articles and one systematic review on the applications of Space Syntax methods and 2 on Shape Grammar research. Lastly, Muslimin [[17]] addresses a combination of Space Syntax and Shape Grammar approaches by incorporating graph and shape computation to generate schematic plan layouts. 1972: 1460-1465 4 Zolfagharkhani M., Ostwald M.J. The Spatial Structure of Yazd Courtyard Houses: A Space Syntax Analysis of the Topological Characteristics of the Courtyard. [Extracted from the article]

Atopic dermatitis is a chronic skin disease that affects millions of people all over the world. The objective of this study was to evaluate the inhibitory effects of the roots of Glycyrrhiza uralensis (GU) and Donkey Hide Gelatin (DHG) water extracts on DNCB-induced NC/Nga mice and TNF-α/IFN-γ treated keratinocytes or LPS-stimulated macrophages. The combined treatment using the water extracts of GU and DHG improved the skin symptom evaluation score and skin histology, with increased expression of the skin barrier proteins Claudin 1 and Sirt 1 in lesion areas. The IFN-γ activity was promoted in PBMCs, ALN, and dorsal skin tissue, while the absolute cell number was reduced for T cells so that the production and expression of serum IgE and cytokines were suppressed. In TNF-α/IFN-γ induced HaCaT cells, IL-6, IL-8, MDC, and RANTES were all inhibited by GU and DHG water extracts, while ICAM-1 and COX-2 levels were similarly downregulated. In addition, GU and DHG water extracts decreased LPS-mediated nitric oxide, IL-6, TNF-α, and PGE2 in RAW 264.7 cells, and the expression of iNOS and COX-2 also decreased. Notably, the DHG:GU ratio of 4:1 was shown to have the best effects of all ratios. In conclusion, GU and DHG have anti-skin inflammatory potentials that can be used as alternative ingredients in the formula of functional foods for people with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Characterising and predicting socio-spatial experience has long been a key research question in space syntax research. Due to the lack of synthesised knowledge about it, this review conducts the first systematic scoping review of space syntax research on the relationships between spatial properties and experiential values. Adopting the "Preferred Reporting Items for Systematic reviews and Meta-Analyses" (PRISMA) framework, this review of space syntax research identifies 38 studies that examine socio-spatial experiences in architectural, medical, and urban spaces. The data arising from this systematic review are used to identify trends in this sub-field of research, including the growth of socio-spatial methods and applications in urban analytics since 2016 and key methodological approaches, characteristics, and factors in space syntax research about socio-spatial experience. The research identified using the systematic framework employs a mixture of descriptive, correlation, and regression methods to examine the dynamic effects of spatial configurations on human experiences. Arising from the results of the review, the article further identifies a collective, predictive model consisting of five syntactic predictors and three categories of experiential values. This article, finally, examines research gaps and limitations in the body of knowledge and suggests future research directions. [ABSTRACT FROM AUTHOR]

In a famous architectural discussion, Colin Rowe links the geometric properties of two sixteenth century villas by Andrea Palladio and two twentieth century villas by the architect Le Corbusier. Rowe observed that different structural systems produced heightened geometric complexity in cross sections through Palladio's villas and in Le Corbusier's plans. Rowe also described a particular type of geometric scaling in portions of the four villas which he partially explains as a type of mathematical 'natural beauty' akin to the golden ratio and Fibonacci sequence. In his writings, Rowe refers to several geometric properties that encapsulate complex, scaled structures, but he lacked a mathematical system to rigorously describe and test his ideas. The present paper utilises the box-counting method for calculating fractal dimensions to analyse 100 images, consisting of architectural plans, sections, and elevations of the four villas and two Fibonacci sequences, to test Rowe's ideas. Ultimately, the results of this research do not support the majority of Rowe's claims about geometric complexity in the villas of Palladio and Le Corbusier, but they do provide insights into Rowe's discussion of geometric scaling and the properties of four famous houses. [ABSTRACT FROM AUTHOR]

Past historical research on Iranian educational architecture has highlighted three socio-spatial characteristics: (i) the topological variance of spatial properties, (ii) the flexibility of spatial configuration, and (ii) the centrality of outdoor spaces, which remain under scrutiny. This paper aims to quantitatively examine the topological changes in the spatial configurations of Yazd schools over time. The study entails the application of a Justified Plan Graph (JPG) method to quantify and compare the morphological properties of three historical sets of 20 Yazd schools (traditional, transitional and modern, and contemporary). The results confirm the historical changes in the Yazd schools' flexibility and their outdoor spaces' centrality, although the variance of spatial properties over time is not clearly observed. In particular, due to the relatively higher centrality values of outdoor spaces, the traditional schools, regardless of their rigid spatial logics, developed more integrated and interactive spatial configurations. As a first historical study on the socio-spatial configuration of Yazd schools, this paper precisely demonstrates the JPG method for this longitudinal spatial analysis. [ABSTRACT FROM AUTHOR]

The objective of this study was to design and evaluate an orodispersible film (ODF) composed of aripiprazole (ARP), prepared using a conventional solvent casting technique, and to fuse a three-dimensional (3D) printing technique with a hot-melt extrusion (HME) filament. Klucel® LF (hydroxypropyl cellulose, HPC) and PE-05JPS® (polyvinyl alcohol, PVA) were used as backbone polymers for 3D printing and solvent casting. HPC-, PVA-, and ARP-loaded filaments were applied for 3D printing using HME. The physicochemical and mechanical properties of the 3D printing filaments and films were optimized based on the composition of the polymers and the processing parameters. The crystalline states of drug and drug-loaded formulations were investigated using differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). The dissolution and disintegration of the 3D-printed films were faster than those of solvent-cast films. HPC-3D printed film was fully disintegrated within 45 ± 3.5 s. The dissolution rate of HPC films reached 80% within 30 min at pH 1.2 and pH 4.0 USP buffer. There was a difference in the dissolution rate of about 5 to 10% compared to PVA films at the same sampling time. The root mean square of the roughness (Rq) values of each sample were evaluated using atomic force microscopy. The higher the Rq value, the rougher the surface, and the larger the surface area, the more salivary fluid penetrated the film, resulting in faster drug release and disintegration. Specifically, The HPC 3D-printed film showed the highest Rq value (102.868 nm) and average surface roughness (85.007 nm). The puncture strength of 3D-printed films had desirable strength with HPC (0.65 ± 0.27 N/mm2) and PVA (0.93 ± 0.15 N/mm2) to prevent deformation compared to those of marketed film products (over 0.34 N/mm2). In conclusion, combining polymer selection and 3D printing technology could innovatively design ODFs composed of ARP to solve the unmet medical needs of psychiatric patients. [ABSTRACT FROM AUTHOR]

Itraconazole (ITZ) is a class II drug according to the biopharmaceutical classification system. Its solubility is pH 3-dependent, and it is poorly water-soluble. Its pKa is 3.7, which makes it a weak base drug. The aim of this study was to prepare solid dispersion (SD) pellets to enhance the release of ITZ into the gastrointestinal environment using hot-melt extrusion (HME) technology and a pelletizer. The pellets were then filled into capsules and evaluated in vitro and in vivo. The ITZ changed from a crystalline state to an amorphous state during the HME process, as determined using DSC and PXRD. In addition, its release into the gastrointestinal tract was enhanced, as was the level of ITZ recrystallization, which was lower than the marketed drug (Sporanox®), as assessed using an in vitro method. In the in vivo study that was carried out in rats, the AUC0–48h of the commercial formulation, Sporanox®, was 1073.9 ± 314.7 ng·h·mL−1, and the bioavailability of the SD pellet (2969.7 ± 720.6 ng·h·mL−1) was three-fold higher than that of Sporanox® (*** p < 0.001). The results of the in vivo test in beagle dogs revealed that the AUC0–24h of the SD-1 pellet (which was designed to enhance drug release into gastric fluids) was 3.37 ± 3.28 μg·h·mL−1 and that of the SD-2 pellet (which was designed to enhance drug release in intestinal fluids) was 7.50 ± 4.50 μg·h·mL−1. The AUC of the SD-2 pellet was 2.2 times higher than that of the SD-1 pellet. Based on pharmacokinetic data, ITZ would exist in a supersaturated state in the area of drug absorption. These results indicated that the absorption area is critical for improving the bioavailability of ITZ. Consequently, the bioavailability of ITZ could be improved by inhibiting precipitation in the absorption area. [ABSTRACT FROM AUTHOR]

Since architect Nicholas Negroponte first proposed a vision of responsive architecture smart environments have been widely investigated, especially in the fields of computer science and engineering. Despite growing interest in the topic, a comprehensive review of research about smart environments from the architectural perspective is largely missing. In order to provide a formal understanding of smart environments in architecture, this paper conducts a systematic literature review of scholarly sources over the last decade, focusing on four related subjects: (1) responsive architecture, (2) kinetic architecture, (3) adaptive architecture and (4) intelligent buildings. Through this review, the paper identifies and examines interactive and collective behaviors in smart environments, thereby contributing to defining the properties of creative, smart spaces in the contemporary digital ecosystem. In addition, this research offers a means of systematically characterizing and constructing smart environments as interactive and collective platforms, enabling occupants to sense, experience and understand smart spaces. [ABSTRACT FROM AUTHOR]

A vancomycin-intermediate Staphylococcus aureus (VISA) outbreak occurred in an intensive care unit (ICU) in South Korea. We aimed to investigate the condition that led to the VISA outbreak and seek measures to prevent further spread of the multidrug-resistant organism. A total of three VISA isolates were obtained from two patients and a health care worker (HCW) in a newly built 450-bed secondary hospital. Extensive screening of close contacts for VISA in terms of space sharing and physical contact, irrespective of contact time, was performed. Furthermore, multilocus sequence type, staphylococcal cassette chromosome mec type, and spa type profiles were determined for all VISA isolates. The relationship between vancomycin use and the minimum inhibitory concentration (MIC) of S. aureus was also investigated. Molecular typing showed that the strains of the three VISA isolates were identical, indicating horizontal hospital transmission. We assumed that VISA colonised in the HCW could have transmitted to the two patients, which resulted in one infection and one colonisation. The affected HCW was excused from work and was decolonised with mupirocin. Five weeks after the interventions, no additional VISA isolates were identified. No relationship between vancomycin use and MIC of S. aureus was identified. Extensive screening of contacts in addition to decolonisation is crucial in preventing the further spread of VISA. [ABSTRACT FROM AUTHOR]

The design of a building façade has a significant impact on the way people respond to it physiologically and behaviourally. Few methods are available to assist an architect to understand such impacts during the design process. Thus, this paper examines the viability of using two computational methods to examine potential visual stimulus-sensation relationships in facade design. The first method, fractal analysis, is used to holistically measure the visual stimuli of a design. This paper describes both the box counting (density) and differential box counting (intensity) approaches to determining fractal dimension (D) in architecture. The second method, visual attention simulation, is used to explore pre-attentive processing and sensation in vision. Four measures—D-density (Dd), D-intensity (Di), heat map and gaze sequence—are used to provide quantitative and qualitative indicators of the ways people read different design options. Using two façade designs as examples, the results of this application reveal that the D values of a façade image have a relationship with the pre-attentive processing shown in heat map and gaze sequence simulations. The findings are framed as a methodological contribution to the field, but also to the disciplinary knowledge gap about the stimulus-sensation relationship and visual reasoning in design. [ABSTRACT FROM AUTHOR]

Decision-making in design is a cognitive process wherein alternatives are generated and evaluated, potentially enabling a more creative design process. In recent years parametric design's heightened capacity for automatically generating and evaluating options has been celebrated by researchers and designers, but it has also placed an increased emphasis on decision-making activities which have not previously been studied in this context. This paper conducts the first in-depth protocol analysis of the decision-making process (DMP) in parametric design. Using empirical data, it identifies three parametric DMPs at the conceptual design stage: (i) "conclusive" DMP, (ii) "confirmative" DMP, and (iii) "simulative" DMP. The results of this research indicate that while conclusive DMP generates and evaluates design alternatives, its "forward incrementation" approach has only limited potential for creativity. The confirmative DMP develops three creative operation loops in parametric design, suggesting it may be an important creative process. The simulative DMP simultaneously addresses divergent and convergent thinking, also indicating potential creative operations and outcomes. The identification and analysis of these DMPs contributes to developing new knowledge about the processes used in parametric design and their capacity to support creative results. [ABSTRACT FROM AUTHOR]

This work presents a novel approach for producing gastro-retentive floating tablets (GRFT) by coupling hot-melt extrusion (HME) and fused deposition three-dimensional printing (3DP). Filaments containing theophylline (THEO) within a hydroxypropyl cellulose (HPC) matrix were prepared using HME. 3DP tablets with different infill percentages and shell thickness were developed and evaluated to determine their drug content, floating behavior, dissolution, and physicochemical properties. The dissolution studies revealed a relationship between the infill percentage/shell thickness and the drug release behavior of the 3DP tablets. All the developed GRFTs possessed the ability to float for 10 h and exhibited zero-order release kinetics. The drug release could be described by the Peppas–Sahlin model, as a combination of Fickian diffusion and swelling mechanism. Drug crystallinity was found unaltered throughout the process. 3DP coupled with HME, could be an effective blueprint to produce controlled-release GRFTs, providing the advantage of simplicity and versatility compared to the conventional methods. [ABSTRACT FROM AUTHOR]

The role of conversion surgery in metastatic gastric cancer remains unclear. Cancer dormancy markers might have a role in predicting the survival in patients with conversion surgery. We identified 26 patients who went through conversion surgery, i.e., a curative-intent gastrectomy with metastasectomy after chemotherapy in initially metastatic gastric cancer. As controls, 114 potential candidates for conversion surgery who only received chemotherapy were included for the propensity score matching. Conversion surgery showed a significantly longer overall survival (OS) compared with only palliative chemotherapy (median—43.6 vs. 14.0 months, respectively, p < 0.001). This better survival in the conversion surgery group persisted even after propensity matching (p < 0.001), and also when compared to patients with tumor response over 5.1 months in the chemotherapy only group (p = 0.005). In the conversion surgery group, OS was longer in patients with R0 resection (22/26, 84.6%) than without R0 resection (4/26, 15.4%) (median—not reached vs 22.1 months, respectively, p = 0.005). Although it should be interpreted with caution due to the primitive analysis in a small population, the positive expression of NR2F1 showed a longer duration of disease-free survival (DFS) after conversion surgery (p = 0.016). In conclusion, conversion surgery showed a durable OS even in patients with initially metastatic gastric cancer when R0 resection was achieved after chemotherapy. [ABSTRACT FROM AUTHOR]

The role of conversion surgery in metastatic gastric cancer remains unclear. Cancer dormancy markers might have a role in predicting the survival in patients with conversion surgery. We identified 26 patients who went through conversion surgery, i.e., a curative-intent gastrectomy with metastasectomy after chemotherapy in initially metastatic gastric cancer. As controls, 114 potential candidates for conversion surgery who only received chemotherapy were included for the propensity score matching. Conversion surgery showed a significantly longer overall survival (OS) compared with only palliative chemotherapy (median-43.6 vs. 14.0 months, respectively, p < 0.001). This better survival in the conversion surgery group persisted even after propensity matching ( p < 0.001), and also when compared to patients with tumor response over 5.1 months in the chemotherapy only group ( p = 0.005). In the conversion surgery group, OS was longer in patients with R0 resection (22/26, 84.6%) than without R0 resection (4/26, 15.4%) (median-not reached vs 22.1 months, respectively, p = 0.005). Although it should be interpreted with caution due to the primitive analysis in a small population, the positive expression of NR2F1 showed a longer duration of disease-free survival (DFS) after conversion surgery ( p = 0.016). In conclusion, conversion surgery showed a durable OS even in patients with initially metastatic gastric cancer when R0 resection was achieved after chemotherapy.

Type 2 diabetes is characterized by insulin resistance, which leads to increased blood glucose levels. Adipocytes are involved in the development of insulin resistance, resulting from the dysfunction of the insulin signaling pathway. In this study, we investigated whether meso -dihydroguaiaretic acid (MDGA) may modulate glucose uptake in adipocytes, and examined its mechanism of action. MDGA enhanced adipogenesis through up-regulation of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α in 3T3-L1 adipocytes partially differentiated with sub-optimal concentrations of insulin. MDGA also increased glucose uptake by stimulating expression and translocation of glucose transporter 4 (GLUT4) in adipocytes. These results suggest that MDGA may increase GLUT4 expression and its translocation by promoting insulin sensitivity, leading to enhanced glucose uptake., Competing Interests: The authors declare no conflict of interest.