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1.
Lymphat Res Biol ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38699876

RESUMO

Background: Lymphedema is chronic limb swelling resulting from lymphatic dysfunction. It affects an estimated five million Americans. There is no cure for this disease. Assessing lymphatic growth is essential in developing novel therapeutics. Intravital microscopy (IVM) is a powerful imaging tool for investigating various biological processes in live animals. Tissue nanotransfection technology (TNT) facilitates a direct, transcutaneous nonviral vector gene delivery using a chip with nanochannel poration in a rapid (<100 ms) focused electric field. TNT was used in this study to deliver the genetic cargo in the murine tail lymphedema to assess the lymphangiogenesis. The purpose of this study is to experimentally evaluate the applicability of IVM to visualize and quantify lymphatics in the live mice model. Methods and Results: The murine tail model of lymphedema was utilized. TNT was applied to the murine tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: TNTpCMV6 group receives pCMV6 (expression vector backbone alone) (n = 6); TNTProx1 group receives pCMV6-Prox1 (n = 6). Lymphatic vessels (fluorescein isothiocyanate [FITC]-dextran stained) and lymphatic branch points (indicating lymphangiogenesis) were analyzed with the confocal/multiphoton microscope. The experimental group TNTProx1 exhibited reduced postsurgical tail lymphedema and increased lymphatic distribution compared to TNTpCMV6 group. More lymphatic branching points (>3-fold) were observed at the TNT site in TNTProx1 group. Conclusions: This study demonstrates a novel, powerful imaging tool for investigating lymphatic vessels in live murine tail model of lymphedema. IVM can be utilized for functional assessment of lymphatics and visualization of lymphangiogenesis following gene-based therapy.

2.
FASEB J ; 38(11): e23709, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38809700

RESUMO

Brown adipose tissue (BAT) is correlated to cardiovascular health in rodents and humans, but the physiological role of BAT in the initial cardiac remodeling at the onset of stress is unknown. Activation of BAT via 48 h cold (16°C) in mice following transverse aortic constriction (TAC) reduced cardiac gene expression for LCFA uptake and oxidation in male mice and accelerated the onset of cardiac metabolic remodeling, with an early isoform shift of carnitine palmitoyltransferase 1 (CPT1) toward increased CPT1a, reduced entry of long chain fatty acid (LCFA) into oxidative metabolism (0.59 ± 0.02 vs. 0.72 ± 0.02 in RT TAC hearts, p < .05) and increased carbohydrate oxidation with altered glucose transporter content. BAT activation with TAC reduced early hypertrophic expression of ß-MHC by 61% versus RT-TAC and reduced pro-fibrotic TGF-ß1 and COL3α1 expression. While cardiac natriuretic peptide expression was yet to increase at only 3 days TAC, Nppa and Nppb expression were elevated in Cold TAC versus RT TAC hearts 2.7- and 2.4-fold, respectively. Eliminating BAT thermogenic activation with UCP1 KO mice eliminated differences between Cold TAC and RT TAC hearts, confirming effects of BAT activation rather than autonomous cardiac responses to cold. Female responses to BAT activation were blunted, with limited UCP1 changes with cold, partly due to already activated BAT in females at RT compared to thermoneutrality. These data reveal a previously unknown physiological mechanism of UCP1-dependent BAT activation in attenuating early cardiac hypertrophic and profibrotic signaling and accelerating remodeled metabolic activity in the heart at the onset of cardiac stress.


Assuntos
Tecido Adiposo Marrom , Fibrose , Proteína Desacopladora 1 , Animais , Tecido Adiposo Marrom/metabolismo , Camundongos , Masculino , Proteína Desacopladora 1/metabolismo , Fibrose/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/genética , Camundongos Endogâmicos C57BL , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Fisiológico , Remodelação Ventricular/fisiologia , Camundongos Knockout , Temperatura Baixa
3.
J Clin Exp Hepatol ; 14(5): 101397, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595988

RESUMO

Introduction: Diagnosis of wall-thickening type gallbladder cancer (GBC) is challenging. Computed tomography (CT) and magnetic resonance imaging (MRI) are commonly utilized to evaluate gallbladder wall thickening. However, there is a lack of data comparing the performance of CT and MRI for the detection of wall-thickening type GBC. Aim: We aim to compare the diagnostic accuracy of CT and MRI in diagnosis of wall-thickening type GBC. Materials and methods: This prospective study comprised consecutive patients suspected of wall-thickening type GBC who underwent preoperative contrast-enhanced CT and MRI. The final diagnosis was based on the histopathology of the resected gallbladder lesion. Two radiologists independently reviewed the characteristics of gallbladder wall thickening at CT and MRI. The association of CT and MRI findings with histological diagnosis and the interobserver agreement of CT and MRI findings were assessed. Results: Thirty-three patients (malignancy, 13 and benign, 20) were included. None of the CT findings were significantly associated with GBC. However, at MRI, heterogeneous enhancement, indistinct interface with the liver, and diffusion restriction were significantly associated with malignancy (P = 0.006, <0.001, and 0.005, respectively), and intramural cysts were significantly associated with benign lesions (P = 0.012). For all MRI findings, the interobserver agreement was substantial to perfect (kappa = 0.697-1.000). At CT, the interobserver agreement was substantial to perfect (k = 0.631-1.000). Conclusion: These findings suggest that MRI may be preferred over CT in patients with suspected wall thickening type GBC. However, larger multicenter studies must confirm our findings.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38624244

RESUMO

Significant knowledge gaps exist regarding the responses of cells, tissues, and organs to organismal death. Examining the survival mechanisms influenced by metabolism and environment, this research has the potential to transform regenerative medicine, redefine legal death, and provide insights into life's physiological limits, paralleling inquiries in embryogenesis.

5.
Sci Rep ; 14(1): 7045, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528081

RESUMO

Fins are widely used in many industrial applications, including heat exchangers. They benefit from a relatively economical design cost, are lightweight, and are quite miniature. Thus, this study investigates the influence of a wavy fin structure subjected to convective effects with internal heat generation. The thermal distribution, considered a steady condition in one dimension, is described by a unique implementation of a physics-informed neural network (PINN) as part of machine-learning intelligent strategies for analyzing heat transfer in a convective wavy fin. This novel research explores the use of PINNs to examine the effect of the nonlinearity of temperature equation and boundary conditions by altering the hyperparameters of the architecture. The non-linear ordinary differential equation (ODE) involved with heat transfer is reduced into a dimensionless form utilizing the non-dimensional variables to simplify the problem. Furthermore, Runge-Kutta Fehlberg's fourth-fifth order (RKF-45) approach is implemented to evaluate the simplified equations numerically. To predict the wavy fin's heat transfer properties, an advanced neural network model is created without using a traditional data-driven approach, the ability to solve ODEs explicitly by incorporating a mean squared error-based loss function. The obtained results divulge that an increase in the thermal conductivity variable upsurges the thermal distribution. In contrast, a decrease in temperature profile is caused due to the augmentation in the convective-conductive variable values.

6.
J Mol Model ; 30(4): 111, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536551

RESUMO

CONTEXT: Gallium, renowned for its notably low melting point and unique property of becoming liquid at room temperature, is a valuable constituent in phase change materials. In this study, we investigate the solid-liquid phase transition of gallium using the modified embedded atom method (MEAM) potential. It addresses the technique to compute the free energy difference between the solid and liquid without using a reference state. We examine various thermodynamic and dynamic properties, including density, specific heat capacity, diffusivity, and radial distribution functions. We compute the coexistence temperature of the solid-liquid phase transitions of gallium from free energy analysis. This information is crucial for understanding the behavior of the material under different pressure conditions and can be valuable for various applications, such as materials processing and high-pressure studies. The analysis, findings, and insights of the present work will be of great significance to the broad scientific and engineering communities in the field of phase transformation of materials. METHODS: A series of molecular dynamics(MD) simulations were conducted using the LAMMPS software packages. The gallium atoms are modeled using the modified embedded atom method (MEAM) potential. To accurately predict the solid-liquid phase transitions of gallium, we calculated free energy by employing the "constrained λ integration" method, coupled with multiple histogram reweighting (MHR). The solid-liquid coexistence line is determined through the Gibbs-Duhem integration technique.

7.
Surgery ; 175(6): 1539-1546, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38508920

RESUMO

BACKGROUND: Ischemia-reperfusion injury is a common problem in liver surgery and transplantation. Although ischemia-reperfusion injury is known to be more pronounced in fatty livers, the underlying mechanisms for this difference remain poorly understood. We hypothesized that ferroptosis plays a significant role in fatty liver ischemia-reperfusion injury due to increased lipid peroxidation in the presence of stored iron in the fatty liver. To test this hypothesis, the ferroptosis pathway was evaluated in a murine fatty liver ischemia-reperfusion injury model. METHODS: C57BL6 mice were fed with a normal diet or a high fat, high sucrose diet for 12 weeks. At 22 weeks of age, liver ischemia-reperfusion injury was induced through partial (70%) hepatic pedicle clamping for 60 minutes, followed by 24 hours of reperfusion before tissue harvest. Acyl-coenzyme A synthetase long-chain family member 4 and 4-hydroxynonenal were quantified in the liver tissues. In separate experiments, liproxstatin-1 or vehicle control was administered for 7 consecutive days before liver ischemia-reperfusion injury. RESULTS: Exacerbated ischemia-reperfusion injury was observed in the livers of high fat, high sucrose diet fed mice. High fat, high sucrose diet + ischemia-reperfusion injury (HDF+IRI) livers had a significantly greater abundance of acyl-coenzyme A synthetase long-chain family member 4 and 4-hydroxynonenal compared with normal diet + ischemia-reperfusion injury (ND+IRI) livers or sham fatty livers, which indicated an increase of ferroptosis. HFD fed animals receiving liproxstatin-1 injections had a significant reduction in serum aspartate transaminase and alanine transaminase after ischemia-reperfusion injury, consistent with attenuation of ischemia-reperfusion injury in the liver. CONCLUSION: Ferroptosis plays a significant role in ischemia-reperfusion injury in fatty livers. Inhibiting ferroptotic pathways in the liver may serve as a novel therapeutic strategy to protect the fatty liver in the setting of ischemia-reperfusion injury.


Assuntos
Ferroptose , Peroxidação de Lipídeos , Fígado , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Camundongos , Masculino , Fígado/metabolismo , Fígado/irrigação sanguínea , Fígado/patologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Modelos Animais de Doenças , Aldeídos/metabolismo , Coenzima A Ligases/metabolismo , Dieta Hiperlipídica/efeitos adversos , Quinoxalinas , Compostos de Espiro
8.
Mol Ther Nucleic Acids ; 35(1): 102121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38333673

RESUMO

Lymphedema is chronic limb swelling resulting from lymphatic dysfunction. There is no cure for the disease. Clinically, a preventive surgical approach called immediate lymphatic reconstruction (ILR) has gained traction. Experimental gene-based therapeutic approaches (e.g., using viral vectors) have had limited translational applicability. Tissue nanotransfection (TNT) technology uses a direct, transcutaneous nonviral vector, gene delivery using a chip with nanochannel poration in response to a rapid (<100 ms) focused electric field. The purpose of this study was to experimentally prevent lymphedema using focal delivery of a specific gene Prox1 (a master regulator of lymphangiogenesis). TNT was applied to the previously optimized lymphedematous mice tail (day 0) directly at the surgical site with genetic cargo loaded into the TNT reservoir: group I (sham) was given pCMV6 (expression vector backbone alone) and group II was treated with pCMV6-Prox1. Group II mice had decreased tail volume (47.8%) compared to sham and greater lymphatic clearance on lymphangiography. Immunohistochemistry showed greater lymphatic vessel density and RNA sequencing exhibited reduced inflammatory markers in group II compared to group I. Prox1 prophylactically delivered using TNT to the surgical site on the day of injury decreased the manifestations of lymphedema in the murine tail model compared to control.

9.
Microcirculation ; 31(3): e12849, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38354046

RESUMO

OBJECTIVE: An improved understanding of the role of the leptomeningeal collateral circulation in blood flow compensation following middle cerebral artery (MCA) occlusion can contribute to more effective treatment development for ischemic stroke. The present study introduces a model of the cerebral circulation to predict cerebral blood flow and tissue oxygenation following MCA occlusion. METHODS: The model incorporates flow regulation mechanisms based on changes in pressure, shear stress, and metabolic demand. Oxygen saturation in cerebral vessels and tissue is calculated using a Krogh cylinder model. The model is used to assess the effects of changes in oxygen demand and arterial pressure on cerebral blood flow and oxygenation after MCA occlusion. RESULTS: An increase from five to 11 leptomeningeal collateral vessels was shown to increase the oxygen saturation in the region distal to the occlusion by nearly 100%. Post-occlusion, the model also predicted a loss of autoregulation and a decrease in flow to the ischemic territory as oxygen demand was increased; these results were consistent with data from experiments that induced cerebral ischemia. CONCLUSIONS: This study highlights the importance of leptomeningeal collaterals following MCA occlusion and reinforces the idea that lower oxygen demand and higher arterial pressure improve conditions of flow and oxygenation.


Assuntos
Isquemia Encefálica , Hipertensão , Humanos , Infarto da Artéria Cerebral Média , Circulação Colateral/fisiologia , Circulação Cerebrovascular , Oxigênio , Artéria Cerebral Média
10.
ArXiv ; 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38313201

RESUMO

Traumatic Brain Injury (TBI) presents a broad spectrum of clinical presentations and outcomes due to its inherent heterogeneity, leading to diverse recovery trajectories and varied therapeutic responses. While many studies have delved into TBI phenotyping for distinct patient populations, identifying TBI phenotypes that consistently generalize across various settings and populations remains a critical research gap. Our research addresses this by employing multivariate time-series clustering to unveil TBI's dynamic intricates. Utilizing a self-supervised learning-based approach to clustering multivariate time-Series data with missing values (SLAC-Time), we analyzed both the research-centric TRACK-TBI and the real-world MIMIC-IV datasets. Remarkably, the optimal hyperparameters of SLAC-Time and the ideal number of clusters remained consistent across these datasets, underscoring SLAC-Time's stability across heterogeneous datasets. Our analysis revealed three generalizable TBI phenotypes (α, ß, and γ), each exhibiting distinct non-temporal features during emergency department visits, and temporal feature profiles throughout ICU stays. Specifically, phenotype α represents mild TBI with a remarkably consistent clinical presentation. In contrast, phenotype ß signifies severe TBI with diverse clinical manifestations, and phenotype γ represents a moderate TBI profile in terms of severity and clinical diversity. Age is a significant determinant of TBI outcomes, with older cohorts recording higher mortality rates. Importantly, while certain features varied by age, the core characteristics of TBI manifestations tied to each phenotype remain consistent across diverse populations.

11.
Langmuir ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320269

RESUMO

Molybdenum disulfide (MoS2) is a two-dimensional (2D) material that offers molecular transport and sieving properties and might be a potential candidate for membrane technologies for energy and environmental applications. To facilitate the separation application, understanding the structural and dynamic properties of water near the substrate-aqueous solution is essential. Employing the molecular dynamics simulation, we investigate the density, local water network at the solid-liquid interface, and water dynamics in aqueous electrolyte solutions with various chloride salts confined in MoS2 nanochannels with different pore sizes and electrolyte concentrations. Our simulation results confirm that the layering of interfacial water at the hydrophilic MoS2 surface and the water density variation depends on the nature of the ions. The simulation results imply a strong attraction of cations to the surface-liquid interfaces, whereas anions are expelled from the surface due to electrostatic interaction. An examination of the dynamical property of water reveals that the confinement effect is more pronounced on water mobility when the pore width is less than 3 nm, and the salt concentration is below 1 M, whereas the electrolyte concentration greater than 1 M, ions predominantly drive the water mobility as compared to confinement one. These simulation results enhance experimental observations and provide molecular insights into the local ordering mechanism that can be crucial in controlling water dynamics in nanofiltration applications.

12.
Sci Rep ; 14(1): 3257, 2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331988

RESUMO

Macrophages assume diverse phenotypes and functions in response to cues from the microenvironment. Earlier we reported an anti-inflammatory effect of Collagenase Santyl® Ointment (CSO) and the active constituent of CSO (CS-API) on wound macrophages in resolving wound inflammation indicating roles beyond debridement in wound healing. Building upon our prior finding, this study aimed to understand the phenotypes and subsets of macrophages following treatment with CS-API. scRNA-sequencing was performed on human blood monocyte-derived macrophages (MDM) following treatment with CS-API for 24 h. Unbiased data analysis resulted in the identification of discrete macrophage subsets based on their gene expression profiles. Following CS-API treatment, clusters 3 and 4 displayed enrichment of macrophages with high expression of genes supporting extracellular matrix (ECM) function. IPA analysis identified the TGFß-1 pathway as a key hub for the CS-API-mediated ECM-supportive phenotype of macrophages. Earlier we reported the physiological conversion of wound-site macrophages to fibroblasts in granulation tissue and impairment of such response in diabetic wounds, leading to compromised ECM and tensile strength. The findings that CSO can augment the physiological conversion of macrophages to fibroblast-like cells carry significant clinical implications. This existing clinical intervention, already employed for wound care, can be readily repurposed to improve the ECM response in chronic wounds.


Assuntos
Colagenases , Macrófagos , Humanos , Desbridamento , Colagenases/metabolismo , Macrófagos/metabolismo , Matriz Extracelular/metabolismo , Fenótipo
13.
J Diabetes Complications ; 38(2): 108666, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38266570

RESUMO

AIMS: To evaluate the long-term effects of behavioral treatments on glycemic and psychological outcomes for patients with major depressive disorder (MDD) and type 2 diabetes (T2D). METHODS: Program ACTIVE II was a multicenter randomized controlled comparative effectiveness trial of cognitive behavioral therapy (CBT), exercise (EXER), combination treatment (CBT + EXER) and usual care (UC) for adults with MDD and T2D. RESULTS: Primary outcomes: change in A1c and depressive symptoms at 6- (N = 87) and 12-months (N = 75) from baseline. In those with a baseline A1c ≥7.0 %, CBT + EXER showed lasting A1c benefit at 6- (-1.2 %; SE: 0.6; p = 0.032) and 12-months (-1.4 %; SE: 0.6; p = 0.025) compared to UC. All groups had clinically significant improvements in depressive symptoms. At 6 months, CBT + EXER had significant improvements in diabetes-related distress regimen burden (p = 0.005); and social support (CIRS, p = 0.043) compared to UC. CONCLUSIONS: The Program ACTIVE II CBT + EXER intervention demonstrated a sustained improvement in A1c for a subgroup of study participants with a baseline A1c ≥7.0 %. However, this finding should be considered preliminary because of small sample size. All 3 behavioral intervention groups demonstrated improvements in psychosocial outcomes one-year post-intervention. These findings point to the enduring benefits of community-based interventions to extend the availability of depression treatment for T2D patients.


Assuntos
Terapia Cognitivo-Comportamental , Transtorno Depressivo Maior , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/psicologia , Hemoglobinas Glicadas , Terapia Combinada , Resultado do Tratamento
14.
Nanomaterials (Basel) ; 14(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38276735

RESUMO

Tissue nanotransfection (TNT), a cutting-edge technique of in vivo gene therapy, has gained substantial attention in various applications ranging from in vivo tissue reprogramming in regenerative medicine, and wound healing to cancer treatment. This technique harnesses the advancements in the semiconductor processes, facilitating the integration of conventional transdermal gene delivery methods-nanoelectroporation and microneedle technologies. TNT silicon chips have demonstrated considerable promise in reprogramming fibroblast cells of skin in vivo into vascular or neural cells in preclinical studies to assist in the recovery of injured limbs and damaged brain tissue. More recently, the application of TNT chips has been extended to the area of exosomes, which are vital for intracellular communication to track their functionality during the wound healing process. In this review, we provide an in-depth examination of the design, fabrication, and applications of TNT silicon chips, alongside a critical analysis of the electroporation-based gene transfer mechanisms. Additionally, the review discussed the existing limitations and challenges in the current technique, which may project future trajectories in the landscape of gene therapy. Through this exploration, the review aims to shed light on the prospects of TNT in the broader context of gene therapy and tissue regeneration.

15.
AJP Rep ; 14(1): e11-e15, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38269127

RESUMO

Objective To assess and correlate sleep quality and depressed mood symptoms in the late pregnancy and early postpartum periods. Study Design In a prospective pilot observational study, participants completed the Pittsburgh Sleep Quality Index (PSQI) and the Edinburgh Postnatal Depression Scale (EPDS) questionnaires at delivery, 1, and 2 months postpartum. Pearson's correlation coefficients and PROC MIXED function estimated overall correlation for repeated measures. Results Twenty-six women were enrolled with a mean gestational age at delivery of 38.4 (± 2.4) weeks. Sleep quality and mood data were available at the three time points for 24, 16, and 11 participants, respectively. Poor sleep scores were noted by 75.0, 87.5, and 72.7% of women at the three time points. An elevated EPDS score of 10 or higher was claimed by 20.8, 12.5, and 18.2% of women, respectively. Higher PSQI scores were positively associated with higher EPDS scores overall ( r = 0.71, p < 0.001) and at each of the individual time points ( r = 0.79, p < 0.0001; r = 0.52, p = 0.04; and r = 0.70, p = 0.016, respectively). None of the women reporting good sleep quality had elevated EPDS scores. Conclusion Poor sleep is commonly reported around delivery, and at 1 and 2 months postpartum, and there is an association between poor sleep and depression symptoms.

16.
ChemSusChem ; 17(3): e202301365, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-37830175

RESUMO

[FeFe]-hydrogenases are capable of reducing protons at a high rate. However, molecular oxygen (O2 ) induces the degradation of their catalytic cofactor, the H-cluster, which consists of a cubane [4Fe4S] subcluster (4FeH ) and a unique diiron moiety (2FeH ). Previous attempts to prevent O2 -induced damage have focused on enhancing the protein's sieving effect for O2 by blocking the hydrophobic gas channels that connect the protein surface and the 2FeH . In this study, we aimed to block an O2 diffusion pathway and shield 4FeH instead. Molecular dynamics (MD) simulations identified a novel water channel (WH ) surrounding the H-cluster. As this hydrophilic path may be accessible for O2 molecules we applied site-directed mutagenesis targeting amino acids along WH in proximity to 4FeH to block O2 diffusion. Protein film electrochemistry experiments demonstrate increased O2 stabilities for variants G302S and S357T, and MD simulations based on high-resolution crystal structures confirmed an enhanced local sieving effect for O2 in the environment of the 4FeH in both cases. The results strongly suggest that, in wild type proteins, O2 diffuses from the 4FeH to the 2FeH . These results reveal new strategies for improving the O2 stability of [FeFe]-hydrogenases by focusing on the O2 diffusion network near the active site.


Assuntos
Aquaporinas , Hidrogenase , Proteínas Ferro-Enxofre , Hidrogênio/química , Hidrogenase/química , Prótons , Oxigênio/química , Proteínas Ferro-Enxofre/química , Proteínas Ferro-Enxofre/metabolismo
17.
Adv Wound Care (New Rochelle) ; 13(2): 70-82, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37534840

RESUMO

Objective: Hydrolyzed collagen-based matrices are widely used as wound care dressings. Information on the mechanism of action of such dressings is scanty. The objective of this study was to test the effect of a specific hydrolyzed collagen powder (HCP), which is extensively used for wound care management in the United States. Approach: The effects of HCP on resolution of wound inflammation, perfusion, closure, and breaking strength of the repaired skin were studied in an experimental murine model. Results: In early (day 7) inflammatory phase of wound macrophages, HCP treatment boosted phagocytosis and efferocytosis of wound-site macrophages. In these cells, inducible reactive oxygen species were also higher on day (d) 7. HCP treatment potentiated the expression of anti-inflammatory interleukin (IL)-10 cytokine and proangiogenic vascular endothelial growth factor (VEGF) production. Excisional wounds dressed with HCP showed complete closure on day 21, while the control wounds remained open. HCP treatment also demonstrated improved quality of wound healing as marked by the improved breaking strength of the closed wound tissue/repaired skin. Innovation: These data represent first evidence on the mechanism of action of clinically used HCP. Conclusion: HCP dressing favorably influenced both wound inflammation and vascularization. Improved breaking strength of HCP-treated repaired skin lays the rationale for future studies testing the hypothesis that HCP-treated closed wounds would show fewer recurrences.


Assuntos
Colágeno , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Pós/farmacologia , Colágeno/farmacologia , Cicatrização , Bandagens , Inflamação/metabolismo , Perfusão
18.
Biomimetics (Basel) ; 8(8)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38132513

RESUMO

Evolutionary algorithms are a large class of optimization techniques inspired by the ideas of natural selection, and can be employed to address challenging problems. These algorithms iteratively evolve populations using crossover, which combines genetic information from two parent solutions, and mutation, which adds random changes. This iterative process tends to produce effective solutions. Inspired by this, the current study presents the results of thermal variation on the surface of a wetted wavy fin using a genetic algorithm in the context of parameter estimation for artificial neural network models. The physical features of convective and radiative heat transfer during wet surface conditions are also considered to develop the model. The highly nonlinear governing ordinary differential equation of the proposed fin problem is transmuted into a dimensionless equation. The graphical outcomes of the aspects of the thermal profile are demonstrated for specific non-dimensional variables. The primary observation of the current study is a decrease in temperature profile with a rise in wet parameters and convective-conductive parameters. The implemented genetic algorithm offers a powerful optimization technique that can effectively tune the parameters of the artificial neural network, leading to an enhanced predictive accuracy and convergence with the numerically obtained solution.

19.
J Clin Exp Hepatol ; 13(6): 972-976, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37975041

RESUMO

Background: The differentiation of benign and malignant gallbladder wall thickening is challenging. The purpose of this study is to evaluate a new sonographic sign, "cervix sign" for differentiation of benign and malignant gallbladder neck thickening. Methods: This retrospective study comprised consecutive patients with gallbladder neck thickening who underwent sonography between August 2019 and December 2021. The presence of "cervix sign" was assessed by two radiologists independently. Results: Sixty-five patients had gallbladder neck thickening (28 malignant and 37 benign). The sonographic "cervix sign" was present in 18 (64%) patients with malignant thickening and in only one (2.7%) patient with benign thickening (P = 0.0001). The mean wall thickness was greater, and symmetric wall thickening and liver metastases were more common in malignant thickening with "cervix sign" (without reaching statistical significance). There was substantial agreement (kappa = 0.78) between the two observers for the cervix sign. Conclusion: Sonographic "cervix sign" is a useful ancillary feature of gallbladder neck cancer.

20.
Mil Med ; 188(Suppl 6): 674-681, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37948279

RESUMO

INTRODUCTION: Between 5% and 20% of all combat-related casualties are attributed to burn wounds. A decrease in the mortality rate of burns by about 36% can be achieved with early treatment, but this is contingent upon accurate characterization of the burn. Precise burn injury classification is recognized as a crucial aspect of the medical artificial intelligence (AI) field. An autonomous AI system designed to analyze multiple characteristics of burns using modalities including ultrasound and RGB images is described. MATERIALS AND METHODS: A two-part dataset is created for the training and validation of the AI: in vivo B-mode ultrasound scans collected from porcine subjects (10,085 frames), and RGB images manually collected from web sources (338 images). The framework in use leverages an explanation system to corroborate and integrate burn expert's knowledge, suggesting new features and ensuring the validity of the model. Through the utilization of this framework, it is discovered that B-mode ultrasound classifiers can be enhanced by supplying textural features. More specifically, it is confirmed that statistical texture features extracted from ultrasound frames can increase the accuracy of the burn depth classifier. RESULTS: The system, with all included features selected using explainable AI, is capable of classifying burn depth with accuracy and F1 average above 80%. Additionally, the segmentation module has been found capable of segmenting with a mean global accuracy greater than 84%, and a mean intersection-over-union score over 0.74. CONCLUSIONS: This work demonstrates the feasibility of accurate and automated burn characterization for AI and indicates that these systems can be improved with additional features when a human expert is combined with explainable AI. This is demonstrated on real data (human for segmentation and porcine for depth classification) and establishes the groundwork for further deep-learning thrusts in the area of burn analysis.


Assuntos
Inteligência Artificial , Queimaduras , Humanos , Suínos , Animais , Ultrassonografia
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