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Purpose: We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma-COPD overlap (ACO) and explored their relationships with airflow limitation. Patients and Methods: Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of -860 HU to -950 HU (RVC-860 to-950) and the expiration-to-inspiration ratio of the mean lung density (MLDE/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structureâfunction relationships. Results: The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC-860 to -950 levels decreased in the following order: ACO, COPD, and asthma. RVC-860 to -950 independently predicted FEV1% in asthmatic patients; LAA% and MLDE/I in COPD patients; and LAA%, WA% and RVC-860 to -950 in ACO patients. Conclusion: Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.
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Remodelación de las Vías Aéreas (Respiratorias) , Síndrome de Superposición de la Enfermedad Pulmonar Obstructiva Crónica-Asmática , Asma , Pulmón , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Masculino , Femenino , Persona de Mediana Edad , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Estudios Retrospectivos , Asma/fisiopatología , Asma/diagnóstico por imagen , Asma/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Anciano , Enfisema Pulmonar/fisiopatología , Enfisema Pulmonar/diagnóstico por imagen , Volumen Espiratorio Forzado , Síndrome de Superposición de la Enfermedad Pulmonar Obstructiva Crónica-Asmática/fisiopatología , Síndrome de Superposición de la Enfermedad Pulmonar Obstructiva Crónica-Asmática/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Capacidad Vital , Pruebas de Función Respiratoria , Tomografía Computarizada MultidetectorRESUMEN
Coffee is one of the most consumed beverages worldwide, recognized for its unique taste and aroma and for its social and health impacts. Coffee contains a plethora of nutritional and bioactive components, whose content can vary depending on their origin, processing, and extraction methods. Gathered evidence in literature shows that the regular coffee consumption containing functional compounds (e.g., polysaccharides, phenolic compounds, and melanoidins) can have potential beneficial effects on cardiometabolic risk factors such as abdominal adiposity, hyperglycemia, and lipogenesis. On the other hand, coffee compounds, such as caffeine, diterpenes, and advanced glycation end products, may be considered a risk for cardiometabolic health. The present comprehensive review provides up-to-date knowledge on the structure-function relationships between different chemical compounds present in coffee, one of the most prevalent beverages present in human diet, and cardiometabolic health.
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Café , Café/química , Humanos , Enfermedades Cardiovasculares/prevención & control , Cafeína/análisis , Cafeína/química , Valor Nutritivo , Fenoles/análisis , Fenoles/químicaRESUMEN
Cancer has emerged as a formidable global health challenge, with treatment methods like chemotherapy and radiation often exacerbating the situation due to their associated side effects. Opting for natural sources like plants as a safer and environmentally friendly alternative seems promising. Historically, plants have served as valuable sources for treating diverse health conditions, attributable to their rich composition of therapeutic phytochemicals. Within this array of phytochemicals, alkaloids, especially those found in the Solanaceae plant family, are notably prominent. Alkaloids from Solanaceae plant family called Solanum alkaloids demonstrate noteworthy anti-tumour characteristics and exert a potent inhibitory influence on cancer cell proliferation. They trigger programmed cell death in cancerous cells through various molecular pathways, whether administered alone or combined with other medications. Solanum alkaloids act upon cancer cells via multiple mechanisms, including apoptosis induction, suppression of cell growth and migration, as well as inhibition of angiogenesis. This review provides insights into the anti-cancer attributes of Solanum alkaloids found in various Solanum plant species, along with a brief overview of their other medicinal properties.
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Alcaloides , Antineoplásicos Fitogénicos , Neoplasias , Solanum , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Solanum/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Alcaloides/farmacología , Alcaloides/química , Alcaloides/uso terapéutico , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , AnimalesRESUMEN
Lipase with unique regioselectivity is an attractive biocatalyst for elaborate lipid modification. However, the excavation of novel sn-2 regioselective lipases is difficult due to their scarcity in nature, with Candida antarctica lipase A (CALA) being the pronouncedly reported one. Here, we identified a novel CALA-like lipase from Cordyceps militaris (CACML7) via in silico mining. Through chiral-phase high-performance liquid chromatography, we determined that CACML7 displays sn-2 regioselectivity (>68 %) as does CALA, but exhibits distinctive chain length selectivity and bias against unsaturated fats. Notably, the curvature of the acyl-binding tunnel was expected to contribute to the 2.2-fold higher preference for cis-fatty acid (C18:1, cis-Δ9) over trans-fatty acid (C18:1, trans-Δ9) unlike trans-active CALA. Random pose docking of trioleoylglycerol (TOG) into the active site of a lid-truncated mutant of CACML7 revealed that TOG accepts a tuning fork conformation, of which the precise positioning of the reactive ester group towards the catalytic center was only favorable via sn-2 binding mode. The unique active site morphology, which we refer to as an "acyl-binding tunnel with a narrow entrance," may contribute to the sn-2 regioselectivity of CACML7. Our data provide an attractive model to better understand the mechanism underlying sn-2 regioselectivity.
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The initial adoption of penicillin as an antibiotic marked the start of exploring other compounds essential for pharmaceuticals, yet resistance to penicillins and their side effects has compromised their efficacy. The N-terminal nucleophile (Ntn) amide-hydrolases S45 family plays a key role in catalyzing amide bond hydrolysis in various compounds, including antibiotics like penicillin and cephalosporin. This study comprehensively analyzes the structural and functional traits of the bacterial N-terminal nucleophile (Ntn) amide-hydrolases S45 family, covering penicillin G acylases, cephalosporin acylases, and D-succinylase. Utilizing structural bioinformatics tools and sequence analysis, the investigation delineates structurally conserved regions (SCRs) and substrate binding site variations among these enzymes. Notably, sixteen SCRs crucial for substrate interaction are identified solely through sequence analysis, emphasizing the significance of sequence data in characterizing functionally relevant regions. These findings introduce a novel approach for identifying targets to enhance the biocatalytic properties of N-terminal nucleophile (Ntn) amide-hydrolases, while facilitating the development of more accurate three-dimensional models, particularly for enzymes lacking structural data. Overall, this research advances our understanding of structure-function relationships in bacterial N-terminal nucleophile (Ntn) amide-hydrolases, providing insights into strategies for optimizing their enzymatic capabilities.
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Amidohidrolasas , Amidohidrolasas/química , Amidohidrolasas/metabolismo , Amidohidrolasas/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Sitios de Unión , Relación Estructura-Actividad , Secuencia Conservada , Bacterias/enzimología , Secuencia de Aminoácidos , Modelos Moleculares , Especificidad por SustratoRESUMEN
Skin is the first barrier of body which stands guard for defending aggressive pathogens and environmental pressures all the time. Cutaneous metabolism changes in harmful exposure, following with skin dysfunctions and diseases. Lots of researches have reported that polysaccharides extracted from seaweeds exhibited multidimensional bioactivities in dealing with skin disorder. However, few literature systematically reviews them. The aim of the present paper is to summarize structure, bioactivities and structure-function relationship of algal polysaccharides acting on skin. Algal polysaccharides show antioxidant, immunomodulating, hydration regulating, anti-melanogenesis and extracellular matrix (ECM) regulating abilities via multipath ways in skin. These bioactivities are determined by various parameters, including seaweed species, molecular weight, monosaccharides composition and substitute groups. In addition, potential usages of algae-derived polysaccharides in skin care and therapy are also elaborated. Algal polysaccharides are potential ingredients in formulation that providing anti-aging efficacy for skin.
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Polisacáridos , Algas Marinas , Envejecimiento de la Piel , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Envejecimiento de la Piel/efectos de los fármacos , Humanos , Algas Marinas/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/uso terapéutico , Animales , Piel/efectos de los fármacos , Piel/metabolismo , Cuidados de la Piel/métodos , Relación Estructura-ActividadRESUMEN
Constructing structure-function relationships is critical for the rational design and development of efficient catalysts for CO2 electroreduction reaction (CO2RR). In2O3 is well-known for its specific ability to produce formic acid. However, how the crystal phase and surface affect the CO2RR activity is still unclear, making it difficult to further improve the intrinsic activity and screen for the most active structure. In this work, cubic and hexagonal In2O3 with different stable surfaces ((111) and (110) for cubic, (120) and (104) for hexagonal) are investigated for CO2RR. Theoretical results demonstrate that the adsorption of reactants on cubic In2O3 is stronger than that on hexagonal In2O3, with the cubic (111) surface being the most active for CO2RR. In experiments, synthesized cubic In2O3 nanosheets with predominantly exposed (111) surfaces exhibited a high HCOO- Faradaic efficiency (87.5%) and HCOO- current density (-16.7 mA cm-2) at -0.9 V vs RHE. In addition, an aqueous Zn-CO2 battery based on a cubic In2O3 cathode was assembled. Our work correlates the phases and surfaces with the CO2RR activity, and provides a fundamental understanding of the structure-function relationship of In2O3, thereby contributing to further improvements in its CO2RR activity. Moreover, the results provide a principle for the directional preparation of materials with optimal phases and surfaces for efficient electrocatalysis.
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With the surge in protein demand, the application of plant proteins has ushered in a new wave of research. Mung bean is a potential source of protein due to its high protein content (20-30 %). The nutrition, structure, function, and application of mung bean protein have always been a focus of attention. In this paper, these highlighted points have been reviewed to explore the potential application value of mung bean protein. Mung bean protein contains a higher content of essential amino acids than soybean protein, which can meet the amino acid values recommended by FAO/WHO for adults. Mung bean protein also can promote human health due to its bioactivity, such as the antioxidant, and anti-cancer activity. Meanwhile, mung bean protein also has well solubility, foaming, emulsification and gelation properties. Therefore, mung bean protein can be used as an antioxidant edible film additive, emulsion-based food, active substance carrier, and meat analogue in the food industry. It is understood there are still relatively few commercial applications of mung bean protein. This paper highlights the potential application of mung bean proteins, and aims to provide a reference for future commercial applications of mung bean proteins.
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Antioxidantes , Proteínas de Plantas , Vigna , Vigna/química , Proteínas de Plantas/química , Antioxidantes/química , Humanos , SolubilidadRESUMEN
The various connective tissues of the body have different functions, which result from their specific structure and composition. The identification of this structure-function relationship is of great importance for various disciplines such as medicine, biology or tissue engineering. Connective tissue consists mainly of an extracellular matrix (ECM) and a limited number of cells. It is extremely adaptable because the activity of the cells remodels the composition and structure of the ECM in order to adapt the mechanical properties (functions) to the new demands (e.g. an increased mechanical stimulus).
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Tejido Conectivo , Matriz Extracelular , Tejido Conectivo/fisiología , Humanos , Matriz Extracelular/fisiología , Matriz Extracelular/química , Fenómenos Biomecánicos/fisiología , Modelos Biológicos , Animales , Ingeniería de Tejidos/métodosRESUMEN
Brain function is substantially linked to the highly organized modular structure of neuronal networks. However, the structure of in vitro assembled neuronal circuits often exhibits variability, complicating the consistent recording of network functional output and its correlation to network structure. Therefore, engineering neuronal structures with predefined geometry and reproducible functional features is essential to precisely model in vivo neuronal circuits. Here, we engineered microchannel devices to assemble 2D and 3D modular networks. The microchannel devices were coupled with a multi-electrode array (MEA) electrophysiology system to enable recordings from circuits. Each network consisted of 64 modules connected to their adjacent modules by micron-sized channels. Modular circuits within microchannel devices showed enhanced activity and functional connectivity traits. This includes metrics such as connection weights, clustering coefficient, global efficiency, and the number of hub neurons with higher betweenness centrality. In addition, modular networks demonstrated an increased functional modularity score compared to the randomly formed circuits. Neurons within individual modules displayed uniform network characteristics and predominantly participated in their respective functional communities within the same or neighboring physical modules. These observations highlight that the modular network structure promotes the development of segregated functional connectivity traits while simultaneously enhancing the efficiency of overall network connectivity. Our findings emphasize the significant impact of physical constraints on the activity patterns and functional organization within engineered modular networks. These circuits, characterized by stable modular architecture and intricate functional dynamics-key features of the brain networks-offer a robust in vitro model for advancing neuroscience research.
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Técnicas Biosensibles , Dispositivos Laboratorio en un Chip , Red Nerviosa , Neuronas , Neuronas/fisiología , Red Nerviosa/fisiología , Animales , Técnicas Biosensibles/instrumentación , Diseño de Equipo , Células Cultivadas , Encéfalo/fisiologíaRESUMEN
Purpose: To establish generalizable pointwise spatial relationship between structure and function through occlusion analysis of a deep-learning (DL) model for predicting the visual field (VF) sensitivities from 3-dimensional (3D) OCT scan. Design: Retrospective cross-sectional study. Participants: A total of 2151 eyes from 1129 patients. Methods: A DL model was trained to predict 52 VF sensitivities of 24-2 standard automated perimetry from 3D spectral-domain OCT images of the optic nerve head (ONH) with 12 915 OCT-VF pairs. Using occlusion analysis, the contribution of each individual cube covering a 240 × 240 × 31.25 µm region of the ONH to the model's prediction was systematically evaluated for each OCT-VF pair in a separate test set that consisted of 996 OCT-VF pairs. After simple translation (shifting in x- and y-axes to match the ONH center), group t-statistic maps were derived to visualize statistically significant ONH regions for each VF test point within a group. This analysis allowed for understanding the importance of each super voxel (240 × 240 × 31.25 µm covering the entire 4.32 × 4.32 × 1.125 mm ONH cube) in predicting VF test points for specific patient groups. Main Outcome Measures: The region at the ONH corresponding to each VF test point and the effect of the former on the latter. Results: The test set was divided to 2 groups, the healthy-to-early-glaucoma group (792 OCT-VF pairs, VF mean deviation [MD]: -1.32 ± 1.90 decibels [dB]) and the moderate-to-advanced-glaucoma group (204 OCT-VF pairs, VF MD: -17.93 ± 7.68 dB). Two-dimensional group t-statistic maps (x, y projection) were generated for both groups, assigning related ONH regions to visual field test points. The identified influential structural locations for VF sensitivity prediction at each test point aligned well with existing knowledge and understanding of structure-function spatial relationships. Conclusions: This study successfully visualized the global trend of point-by-point spatial relationships between OCT-based structure and VF-based function without the need for prior knowledge or segmentation of OCTs. The revealed spatial correlations were consistent with previously published mappings. This presents possibilities of learning from trained machine learning models without applying any prior knowledge, potentially robust, and free from bias. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Cytotoxins (CTs) are three-finger membrane-active toxins present mainly in cobra venom. Our analysis of the available CT amino acid sequences, literature data on their membrane activity, and conformational equilibria in aqueous solution and detergent micelles allowed us to identify specific amino acid residues which interfere with CT incorporation into membranes. They include Pro9, Ser28, and Asn/Asp45 within the N-terminal, central, and C-terminal loops, respectively. There is a hierarchy in the effect of these residues on membrane activity: Pro9 > Ser28 > Asn/Asp45. Taking into account all the possible combinations of special residues, we propose to divide CTs into eight groups. Group 1 includes toxins containing all of the above residues. Their representatives demonstrated the lowest membrane activity. Group 8 combines CTs that lack these residues. For the toxins from this group, the greatest membrane activity was observed. We predict that when solely membrane activity determines the cytotoxic effects, the activity of CTs from a group with a higher number should exceed that of CTs from a group with a lower number. This classification is supported by the available data on the cytotoxicity and membranotropic properties of CTs. We hypothesize that the special amino acid residues within the loops of the CT molecule may indicate their involvement in the interaction with non-lipid targets.
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Membrana Celular , Citotoxinas , Membrana Celular/efectos de los fármacos , Animales , Citotoxinas/química , Citotoxinas/toxicidad , Venenos Elapídicos/química , Venenos Elapídicos/toxicidad , Aminoácidos/química , Secuencia de Aminoácidos , HumanosRESUMEN
Dictyophora indusiata is a common edible mushroom with great potential in the field of medicine against metabolic disorders, inflammation, and immunodeficiency. Our previous studies have shown that different fractions of the polysaccharide from Dictyophora indusiata (DIP) have various structural characteristics and morphology. However, the impact of the structural features on the protective effects of DIP against metabolic syndrome remains unclear. In this study, three distinct polysaccharide fractions have been extracted from Dictyophora indusiata and a high-fat diet-induced metabolic syndrome (MetS) was constructed in mice. The effects of these fractions on a range of MetS-associated endpoints, including abnormal blood glucose, lipid profiles, body fat content, liver function, intestinal microbiota and their metabolites were investigated. Through correlation analysis, the potential link between the monosaccharide composition of the polysaccharides and their biological activities was determined. The study aimed to explore the potential mechanisms and ameliorative effects of these polysaccharide fractions on MetS, thereby providing statistical evidence for understanding the relationship between monosaccharides composition of Dictyophora indusiata polysaccharides and their potential utility in treating metabolic disorders.
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Dieta Alta en Grasa , Síndrome Metabólico , Animales , Síndrome Metabólico/tratamiento farmacológico , Ratones , Dieta Alta en Grasa/efectos adversos , Polisacáridos Fúngicos/farmacología , Polisacáridos Fúngicos/química , Masculino , Monosacáridos/análisis , Polisacáridos/farmacología , Polisacáridos/química , Microbioma Gastrointestinal/efectos de los fármacos , Basidiomycota/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Modelos Animales de Enfermedad , Agaricales/químicaRESUMEN
This study aimed to investigate the chemical composition, structural properties, and biological properties of pectin polysaccharides (AP-FS, AP-QG, and AP-HG) isolated from different varieties of apple pomace. Based on the methylation and nuclear magnetic resonance analyses, the structure of AP-FS was determined to be composed of an α-1,4-linked homogalacturonan backbone that exhibited high levels of O-6 methylation. All pectins exhibit potent inhibitory activity against human colon cancer and human liver cancer cells, along with immunostimulatory effects. Among them, AP-FS exhibited the highest activity level. Finally, we further investigated the underlying mechanism behind the effect of AP-FS on RAW 264.7 cells using proteomics analysis. Our findings revealed that AP-FS triggers RAW 264.7 macrophage activation via NOD-like receptor (NLR), NF-κB, and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, our research contributes to a better understanding of the structure-function relationship among apple pectins, and AP-FS has the potential to be applied to dietary supplements targeting immunomodulation.
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Malus , Pectinas , Pectinas/química , Pectinas/farmacología , Malus/química , Ratones , Animales , Células RAW 264.7 , Humanos , Relación Estructura-Actividad , Metilación , FN-kappa B/metabolismoRESUMEN
CONTEXT: The osteopathic tenets may serve as a useful guideline for an interprofessional program. There is an alignment between the osteopathic tenets and the concept of interprofessional education (IPE). IPE occurs when students from two or more professions work with each other to collaborate or improve healthcare outcomes. Holistic treatment is fundamental in both instances, and the interrelatedness of structure and function requires acknowledgment of all healthcare professionals' roles in treating a patient. IPE allows students to gain a better understanding of their own professional roles and the roles of their fellow healthcare providers in treating patients more effectively. OBJECTIVES: The objectives of this analysis are to evaluate the ability of an interprofessional summer workshop/lecture utilizing an osteopathic focus to educate students from different healthcare colleges about the interconnectedness of the systems of the human body and how working with a team-based approach will ultimately benefit their collective patients. A secondary objective was to determine the students' perceptions before and after the lecture/workshop to see if there were any perceived differences among students in different healthcare professions at either time. METHODS: This was a retrospective data analysis conducted on pretest/posttest surveys completed by 73 incoming students from six different healthcare colleges participating in the Summer Preparedness and Readiness Course (SPaRC), held annually at Western University of Health Sciences (WUHS) in Pomona, California. Analysis was conducted on responses collected during the SPaRC programs of 2013, 2016, and 2019. Participants were given surveys containing five questions scored on a five-point Likert scale. The surveys were given before and after an integrated lecture/hands-on workshop presented at SPaRC that reviewed multiple studies showing the utility of connecting the healthcare professions to best treat a patient. RESULTS: A total of 73 students responded to both the prelecture and postlecture surveys. When the number of positive scores were totaled from students from all colleges, there was an increase in positive responses from 190 (52.2â¯%) in prelecture surveys when compared to 336 (92.3â¯%) in postlecture surveys. A Wilcoxon signed-rank test suggested that the lecture workshop elicited a significant improvement in scores from prelecture to postlecture for all students (Z=-6.976, p=0.000). Median scores improved from 3.60â¯at baseline to 4.40 after the lecture/workshop. Secondary analysis conducted utilizing Kruskal-Wallis H to examine the differences between the responses of the different colleges prelecture and postlecture showed no significant differences prelecture (H [6]=7.58, p=0.271) and a significant difference between postlecture answers (H [6]=14.04, p=0.029). A series of post hoc independent Kruskal-Wallis H analyses was conducted to identify where differences were, and the only identifiable difference after Bonferroni corrections was between students from the Doctor of Osteopathic Medicine college and the Physician Assistant's college after the lecture/survey (p=0.041). CONCLUSIONS: An interprofessional program with the osteopathic principles of focusing on body unity and relatedness of structure and function may serve as a helpful tool for uniting healthcare professionals in their ultimate goal of better serving their patients.
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Porous starch (PS), a modified form of starch with unique properties, is attracting substantial attention for its diverse advantages and applications. Its intricate porous structure, crystalline and amorphous characteristics, and hydrophilic-hydrophobic properties stem from pore formation via physical, chemical, enzymatic, and combined synergistic methods. Porous starch offers benefits like improved gelatinization temperature, water absorption, increased surface area, tunable crystallinity, and enhanced functional properties, making it appealing for diverse food industry applications. To optimize its properties, determining the parameters governing porous structure formation is crucial. Factors such as processing conditions, starch source, and modification methods substantially impact porosity and the overall characteristics of the material. Understanding and controlling these parameters allows customization for specific applications, from pharmaceutical drug delivery systems to enhancing texture and moisture retention in food products. To date, studies shedding light on how porosity formation can be fine-tuned for specific applications are fewer. This review critically assesses the existing reports on porous starch, focusing on how preparation methods affect porosity formation, thereby influencing the product's crystallinity/hydrophilic-hydrophobic nature and overall applicability.
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Chronic wounds such as diabetic ulcers are a major complication in diabetes caused by hyperglycemia, prolonged inflammation, high oxidative stress, and bacterial bioburden. Bioactive biopolymers have been found to have a biological response in wound tissue microenvironments and are used for developing advanced tissue engineering strategies to enhance wound healing. These biopolymers possess innate bioactivity and are biodegradable, with favourable mechanical properties. However, their bioactivity is highly dependent on their structural properties, which need to be carefully considered while developing wound healing strategies. Biopolymers such as alginate, chitosan, hyaluronic acid, and collagen have previously been used in wound healing solutions but the modulation of structural/physico-chemical properties for differential bioactivity have not been the prime focus. Factors such as molecular weight, degree of polymerization, amino acid sequences, and hierarchical structures can have a spectrum of immunomodulatory, anti-bacterial, and anti-oxidant properties that could determine the fate of the wound. The current narrative review addresses the structure-function relationship in bioactive biopolymers for promoting healing in chronic wounds with emphasis on diabetic ulcers. This review highlights the need for characterization of the biopolymers under research while designing biomaterials to maximize the inherent bioactive potency for better tissue regeneration outcomes, especially in the context of diabetic ulcers.
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A group of bacterial proteases, the Pro-Pro endopeptidases (PPEPs), possess the unique ability to hydrolyze proline-proline bonds in proteins. Since a protease's function is largely determined by its substrate specificity, methods that can extensively characterize substrate specificity are valuable tools for protease research. Previously, we achieved an in-depth characterization of PPEP prime-side specificity. However, PPEP specificity is also determined by the non-prime-side residues in the substrate. To gain a more complete insight into the determinants of PPEP specificity, we characterized the non-prime- and prime-side specificity of various PPEPs using a combination of synthetic combinatorial peptide libraries and mass spectrometry. With this approach, we deepened our understanding of the P3-P3' specificities of PPEP-1 and PPEP-2, while identifying the endogenous substrate of PPEP-2 as the most optimal substrate in our library data. Furthermore, by employing the library approach, we investigated the altered specificity of mutants of PPEP-1 and PPEP-2. Additionally, we characterized a novel PPEP from Anoxybacillus tepidamans, which we termed PPEP-4. Based on structural comparisons, we hypothesized that PPEP-4 displays a PPEP-1-like prime-side specificity, which was substantiated by the experimental data. Intriguingly, another putative PPEP from Clostridioides difficile, CD1597, did not display Pro-Pro endoproteolytic activity. Collectively, we characterized PPEP specificity in detail using our robust peptide library method and, together with additional structural information, provide more insight into the intricate mechanisms that govern protease specificity.
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The construction of high-performance n-type semiconductors is crucial for the advancement of organic electronics. As an attractive n-type semiconductor, molecular systems based on perylene diimide derivatives (PDIs) have been extensively investigated over recent years. Owing to the fascinating aggregated structure and high performance, S-heterocyclic annulated PDIs (SPDIs) are receiving increasing attention. However, the relationship between the structure and the electrical properties of SPDIs has not been deeply revealed, restricting the progress of PDI-based organic electronics. Here, we developed two novel SPDIs with linear and dendronized substituents in the imide position, named linear SPDI and dendronized SPDI, respectively. A series of structural and property characterizations indicated that linear SPDI formed a long-range-ordered crystalline structure based on helical supramolecular columns, while dendronized SPDI, with longer alkyl side chains, formed a 3D-ordered crystalline structure at a low temperature, which transformed into a hexagonal columnar liquid crystal structure at a high temperature. Moreover, no significant charge carrier transport signal was examined for linear SPDI, while dendronized SPDI had a charge carrier mobility of 3.5 × 10-3 cm2 V-1 s-1 and 2.1 × 10-3 cm2 V-1 s-1 in the crystalline and liquid crystalline state, respectively. These findings highlight the importance of the structure-function relationship in PDIs, and also offer useful roadmaps for the design of high-performance organic electronics for down-to-earth applications.