RESUMEN

The present study identified the protective effects of garlic oligo/poly-saccharides of different chain lengths against dextran sulfate sodium (DSS)-induced colitis in mice and elucidated the structure-function relationships. The results showed that oral intake of garlic oligo/poly-saccharides decreased disease activity index, reduced colon shortening and spleen enlargement, and ameliorated pathological damage in the mouse colon. The dysregulation of colonic pro/anti-inflammatory cytokines was significantly alleviated, accompanied by up-regulated antioxidant enzymes, blocked TLR4-MyD88-NF-κB signaling pathway, enhanced intestinal barrier integrity, and restored SCFA production. Garlic oligo/poly-saccharides also reversed gut microbiota dysbiosis in colitic mice by expanding beneficial bacteria and suppressing the growth of harmful bacteria. High-molecular-weight polysaccharides exhibited stronger alleviating effects on DSS-induced colitic symptoms in mice than low-molecular-weight oligo/poly-saccharides did, probably due to their greater ability to be fermented in the colon. Taken together, this study demonstrated the anti-inflammatory effects of garlic oligo/poly-saccharides and revealed that high-molecular-weight polysaccharide fractions were more effective in alleviating DSS-induced colitis.

Asunto(s)

Antiinflamatorios , Colitis , Sulfato de Dextran , Fructanos , Ajo , Microbioma Gastrointestinal , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/patología , Ajo/química , Ratones , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Fructanos/farmacología , Fructanos/química , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo , Relación Estructura-Actividad , Citocinas/metabolismo , Ratones Endogámicos C57BL , Peso Molecular , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos

RESUMEN

A novel artificial peroxidase has been developed for the efficient degradation of the non-steroidal anti-inflammatory drug meloxicam by combining computer simulation and genetic engineering techniques. The results showed that the artificial peroxidase was able to completely degrade meloxicam within 90 s, with a degradation rate of 100 %, which was much higher than that of natural lacquer (46 %). The reaction time of the artificial enzyme was significantly shorter than that of natural peroxidase (10 min) and laccase (48 h). Further studies showed that the amino acid arrangement of the active site of the protein plays an important role in the catalytic performance. The degradation pathway of meloxicam was revealed using UPLC-MS analysis. In vitro toxicity assay showed complete disappearance of toxicity after meloxicam degradation. Therefore, the biocatalytic system proved to be an effective route for the green degradation of meloxicam with important application potential.

RESUMEN

Tendon-bone fibrocartilaginous insertion, or enthesis, is a specialized interfacial region that connects tendon and bone, effectively transferring forces while minimizing stress concentrations. Previous studies have shown that insertion features gradient mineralization and branching fiber structure, which are believed to play critical roles in its excellent function. However, the specific structure-function relationship, particularly the effects of mineralization and structure at the mesoscale fiber level on the properties and function of insertion, remains poorly understood. In this study, we develop mesoscale computational models of the distinct fiber organization at tendon-bone insertions, capturing the branching network from tendon to interface fibers and the different mineralization scales. We specifically analyze three key descriptors: the mineralization scale of interface fibers, the mean, and relative standard deviation of the local branching angles of interface fibers. Tensile test simulations on insertion models with varying mineralization scales of interface fibers and structures are performed to mimic the primary loading condition applied to the insertion. We measure and analyze five representative mechanical properties: Young's modulus, strength, toughness, resilience, and failure strain. Our results reveal that mechanical properties are significantly influenced by the three key descriptors, with tradeoffs observed between mutually exclusive properties. For instance, strength and resilience plateau beyond a certain mineralization scale, while failure strain and Young's modulus exhibit monotonic decreasing and increasing trends, respectively. Consequently, there exists an optimal mineralization scale for toughness due to these tradeoffs. By analyzing the mesoscale deformation and failure mechanisms from simulation trajectories, we identify three fracture regimes closely related to the trends in mechanical properties, supporting the observed tradeoffs. Additionally, we examine in detail the effects of the mean and relative standard deviation of local branching angles on mechanical properties and deformation mechanisms. Overall, our study enhances the fundamental understanding of the composition-structure-function relationships at the tendon-bone insertion, complementing recent experimental studies. The mechanical insights from our work have the potential to guide the future biomimetic design of fibrillar adhesives and interfaces for joining soft and hard materials.

RESUMEN

Voltage-gated proton channel (Hv) has activity of proton transport following electrochemical gradient of proton. Hv is expressed in neutrophils and macrophages of which functions are physiologically temperature-sensitive. Hv is also expressed in human sperm cells and regulates their locomotion. H+ transport through Hv is both regulated by membrane potential and pH difference across biological membrane. It is also reported that properties of Hv such as proton conductance and gating are highly temperature-dependent. Hv consists of the N-terminal cytoplasmic domain, the voltage sensor domain (VSD), and the C-terminal coiled-coil domain, and H+ permeates through VSD voltage-dependently. The functional unit of Hv is a dimer via the interaction between C-terminal coiled-coils assembly domain. We have reported that the coiled-coil domain of Hv has the nature of dissociation around our bodily temperature and mutational change of the coiled-coil affected temperature-sensitive gating, especially its temperature threshold. The temperature-sensitive gating is assessed from two separate points: temperature threshold and temperature dependence. In this chapter, I describe physiological roles and molecular structure mechanisms of Hv by mainly focusing on thermosensitive properties.

Asunto(s)

Activación del Canal Iónico , Canales Iónicos , Protones , Temperatura , Humanos , Canales Iónicos/metabolismo , Canales Iónicos/química , Canales Iónicos/genética , Animales , Potenciales de la Membrana/fisiología , Concentración de Iones de Hidrógeno , Dominios Proteicos

RESUMEN

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.

Asunto(s)

Café , Café/química , Humanos , Enfermedades Cardiovasculares/prevención & control , Cafeína/análisis , Cafeína/química , Valor Nutritivo , Fenoles/análisis , Fenoles/química

RESUMEN

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 structure‒function 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.

Asunto(s)

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 Multidetector

RESUMEN

Voltage-gated sodium (Nav) channels sense membrane potential and drive cellular electrical activity. The deathstalker scorpion α-toxin LqhαIT exerts a strong action potential prolonging effect on Nav channels. To elucidate the mechanism of action of LqhαIT, we determined a 3.9 Å cryoelectron microscopy (cryo-EM) structure of LqhαIT in complex with the Nav channel from Periplaneta americana (NavPas). We found that LqhαIT binds to voltage sensor domain 4 and traps it in an "S4 down" conformation. The functionally essential C-terminal epitope of LqhαIT forms an extensive interface with the glycan scaffold linked to Asn330 of NavPas that augments a small protein-protein interface between NavPas and LqhαIT. A combination of molecular dynamics simulations, structural comparisons, and prior mutagenesis experiments demonstrates the functional importance of this toxin-glycan interaction. These findings establish a structural basis for the specificity achieved by scorpion α-toxins and reveal the conserved glycan as an essential component of the toxin-binding epitope.

RESUMEN

Flavobacterium strains exert a substantial influence on roots and leaves of plants. However, there is still limited understanding of how the specific interactions between Flavobacterium and their plant hosts are and how these bacteria thrive in this competitive environment. A crucial step in understanding Flavobacterium - plant interactions is to unravel the structure of bacterial envelope components and the molecular features that facilitate initial contact with the host environment. Here, we have revealed structure and properties of the exopolysaccharides (EPS) produced by Flavobacterium sp. Root935. Chemical analyses revealed a complex and interesting branched heptasaccharidic repeating unit, containing a variety of sugar moieties, including Rha, Fuc, GlcN, Fuc4N, Gal, Man and QuiN and an important and extended substitution pattern, including acetyl and lactyl groups. Additionally, conformational analysis using molecular dynamics simulation showed an extended hydrophobic interface and a distinctly elongated, left-handed helicoidal arrangement. Furthermore, properties of the saccharide chain, and likely the huge substitution pattern prevented interaction and recognition by host lectins and possessed a low immunogenic potential, highlighting a potential role of Flavobacterium sp. Root935 in plant-microbial crosstalk.

Asunto(s)

Flavobacterium , Polisacáridos Bacterianos , Flavobacterium/química , Polisacáridos Bacterianos/química , Polisacáridos Bacterianos/aislamiento & purificación , Simulación de Dinámica Molecular , Raíces de Plantas/microbiología , Raíces de Plantas/química

RESUMEN

The meniscus tissue is crucial for knee joint biomechanics and is frequently susceptible to injuries resulting in early-onset osteoarthritis. Consequently, the need for meniscal substitutes spurs ongoing development. The meniscus is a composite tissue reinforced with circumferential and radial collagenous fibers; the mechanical role of the latter has yet to be fully unveiled. Here, we investigated the role of radial fibers using a synergistic methodology combining meniscal tissue structure imaging, a computational knee joint model, and the fabrication of simple biomimetic composite laminates. These laminates mimic the basic structural units of the meniscus, utilizing longitudinal and transverse fibers equivalent to the circumferential and radial fibers in meniscal tissue. In the computational model, the absence of radial fibers resulted in stress concentration within the meniscus matrix and up to 800 % greater area at the same stress level. Furthermore, the contact pressure on the tibial cartilage increased drastically, affecting up to 322 % larger areas. Conversely, in models with radial fibers, we observed up to 25 % lower peak contact pressures and width changes of less than 0.1 %. Correspondingly, biomimetic composite laminates containing transverse fibers exhibited minor transverse deformations and smaller Poisson's ratios. They demonstrated structural shielding ability, maintaining their mechanical performance with the reduced amount of fibers in the loading direction, similar to the ability of the torn meniscus to carry and transfer loads to some extent. These results indicate that radial fibers are essential to distribute contact pressure and tensile stresses and prevent excessive deformations, suggesting the importance of incorporating them in novel designs of meniscal substitutes. STATEMENT OF SIGNIFICANCE: The organization of the collagen fibers in the meniscus tissue is crucial to its biomechanical function. Radially oriented fibers are an important structural element of the meniscus and greatly affect its mechanical behavior. However, despite their importance to the meniscus mechanical function, radially oriented fibers receive minor attention in meniscal substitute designs. Here, we used a synergistic methodology that combines imaging of the meniscal tissue structure, a structural computational model of the knee joint, and the fabrication of simplistic biomimetic composite laminates that mimic the basic structural units of the meniscus. Our findings highlight the importance of the radially oriented fibers, their mechanical role in the meniscus tissue, and their importance as a crucial element in engineering novel meniscal substitutes.

RESUMEN

We have approached the construction of an artificial enzyme by employing a robust protein scaffold, lactococcal multidrug resistance regulator, LmrR, providing a structured secondary and outer coordination spheres around a molecular rhodium complex, [RhI(PEt2NglyPEt2)2]-. Previously, we demonstrated a 2-3 fold increase in activity for one Rh-LmrR construct by introducing positive charge in the secondary coordination sphere. In this study, a series of variants was made through site-directed mutagenesis where the negative charge is located in the secondary sphere or outer coordination sphere, with additional variants made with increasingly negative charge in the outer coordination sphere while keeping a positive charge in the secondary sphere. Placing a negative charge in the secondary or outer coordination sphere demonstrates decreased activity by a factor of two compared to the wild-type Rh-LmrR. Interestingly, addition of positive charge in the secondary sphere, with the negatively charged outer coordination sphere restores activity. Vibrational and NMR spectroscopy suggest minimal changes to the electronic density at the rhodium center, regardless of inclusion of a negative or positive charge in the secondary sphere, suggesting another mechanism is impacting catalytic activity, explored in the discussion.

Asunto(s)

Dióxido de Carbono , Rodio , Rodio/química , Hidrogenación , Dióxido de Carbono/química , Dióxido de Carbono/metabolismo , Biocatálisis , Modelos Moleculares , Catálisis , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Complejos de Coordinación/química , Complejos de Coordinación/metabolismo

RESUMEN

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.

Asunto(s)

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 Sustrato

RESUMEN

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.

Asunto(s)

Cordyceps , Ácidos Grasos , Lipasa , Lipasa/química , Lipasa/metabolismo , Lipasa/genética , Cordyceps/enzimología , Cordyceps/química , Cordyceps/metabolismo , Especificidad por Sustrato , Ácidos Grasos/metabolismo , Ácidos Grasos/química , Estereoisomerismo , Simulación del Acoplamiento Molecular , Dominio Catalítico , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética

RESUMEN

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.

Asunto(s)

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 , Animales

RESUMEN

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.

RESUMEN

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).

Asunto(s)

Tejido Conectivo , Matriz Extracelular , Tejido Conectivo/fisiología , Humanos , Matriz Extracelular/fisiología , Matriz Extracelular/química , Fenómenos Biomecánicos/fisiología , Modelos Biológicos , Animales , Ingeniería de Tejidos/métodos

RESUMEN

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.

Asunto(s)

Antioxidantes , Proteínas de Plantas , Vigna , Vigna/química , Proteínas de Plantas/química , Antioxidantes/química , Humanos , Solubilidad

RESUMEN

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.

RESUMEN

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.

Asunto(s)

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 , Humanos

RESUMEN

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.

Asunto(s)

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/fisiología

RESUMEN

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.

Asunto(s)

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-Actividad