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Abstract The consumption of unrefined vegetable oil poses acute and chronic health issues, yet improper disposal of waste plantain peels is not environmentally sustainable. This research investigates the feasibility, mechanism and thermodynamics of waste plantain peels, and commercial bentonite clay for soybean oil refining. Experiment was carried out using masses (1–4 g) of commercial bentonite clay, and unripe plantain peel ash (UPPA) to degummed and neutralized free fatty acid (FFA) contents in crude soybean oil at varying temperatures (50–120 °C), and time (15–35 min) for treatment of soybean oil. FTIR spectroscopy, SEM, and XRF techniques were applied to characterize the sample. The results established that at optimum 4.0 g dosage, the UPPA (97.73%) was more effective in the removal of FFA from oil at 50 °C and 20 min, while the clay (90%) was more effective in the removal of colour pigment from the vegetable oil 100 °C, and 25 min. The optimum efficiency of Clay-Ash-composite (70:30) in adsorbing pigment from soybean oil corresponds to 80%. The impact of changing viscosities, densities, and acid values on the performance of UPPA, clay, and clay-UPPA composite was investigated. Mechanistic studies confirmed the pseudo-second-order kinetics at 5 × 10–2 g/mg min−1 and 1.87 × 10–1 g/mg min−1, with corresponding adsorption capacity of 30.40 mg/g and 4.91 mg/g, at R2 ≤ 0.9982. The UPPA-driven sorption of FFA occurred as a physisorption and exothermic process (− 620.60 kJ/mol), while colour pigment removal occurred by chemisorption and endothermic process (22.40 kJ/mol). The finding recommends UPPA and composite as economically feasible for refining soybean oil.

Abstract Inflammatory cytokine mediated responses are important in the development of many diseases that are associated with angiogenesis. Targeting angiogenesis as a prominent strategy has shown limited effects in many contexts such as cardiovascular diseases and cancer. One potential reason for the unsuccessful outcome is the mutual dependent role between inflammation and angiogenesis. Inflammation-based therapies primarily target inflammatory cytokines such as interleukin-6 (IL-6) in T cells, macrophages, cancer cells, and muscle cells, and there is a limited understanding of how these cytokines act on endothelial cells. Thus, we focus on one of the major inflammatory cytokines, IL-6, mediated intracellular signaling in endothelial cells by developing a detailed computational model. Our model quantitatively characterized the effects of IL-6 classic and trans-signaling in activating the signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and mitogen-activated protein kinase (MAPK) signaling to phosphorylate STAT3, extracellular regulated kinase (ERK) and Akt, respectively. We applied the trained and validated experiment-based computational model to characterize the dynamics of phosphorylated STAT3 (pSTAT3), Akt (pAkt), and ERK (pERK) in response to IL-6 classic and/or trans-signaling. The model predicts that IL-6 classic and trans-signaling induced responses are IL-6 and soluble IL-6 receptor (sIL-6R) dose-dependent. Also, IL-6 classic and trans-signaling showed similar potency in inducing downstream signaling; however, trans-signaling induces stronger downstream responses and plays a dominant role in the overall effects from IL-6 due to the in vitro experimental setting of abundant sIL-6R. In addition, both IL-6 and sIL-6R levels regulate signaling strength. Moreover, our model identifies the influential species and kinetic parameters that specifically modulate the downstream inflammatory and/or angiogenic signals, pSTAT3, pAkt, and pERK responses. Overall, the model predicts the effects of IL-6 classic and/or trans-signaling stimulation quantitatively and provides a framework for analyzing and integrating experimental data. More broadly, this model can be utilized to identify potential targets that influence IL-6 mediated signaling in endothelial cells and to study their effects quantitatively in modulating STAT3, Akt, and ERK activation.

Abstract We reassessed several orbital topographic data sets for the Perseverance rover landing site at Jezero Crater, Mars to better understand its floor units. Tens‐of‐meters deep topographic anomalies occur in the volcanic floor of Jezero crater and are not a result of impact cratering. Eight km‐scale steep escarpment‐bounded depressions may be locations of paleotopographic highs that were embayed by the volcanic floor lava flows, forming inverted topography from either contemporaneous upward inflation of embaying lavas or later deep scour due to differential erosion over 107−9 years. Five multi km‐scale shallow‐sloped depressions linked by channel‐like forms may record locations of buried paleolakes and channels that predate the volcanic floor units or a drained magma system. These results indicate Jezero experienced multiple closed‐basin or dry phases, allowing erosion of the crater floor and creation of topography, which provides new geologic context for the samples gathered by Perseverance.

Introduction: Several signaling pathways are activated during hypoxia to promote angiogenesis, leading to endothelial cell patterning, interaction, and downstream signaling. Understanding the mechanistic signaling differences between endothelial cells under normoxia and hypoxia and their response to different stimuli can guide therapies to modulate angiogenesis. We present a novel mechanistic model of interacting endothelial cells, including the main pathways involved in angiogenesis.Methods: We calibrate and fit the model parameters based on well-established modeling techniques that include structural and practical parameter identifiability, uncertainty quantification, and global sensitivity.Results: Our results indicate that the main pathways involved in patterning tip and stalk endothelial cells under hypoxia differ, and the time under hypoxia interferes with how different stimuli affect patterning. Additionally, our simulations indicate that Notch signaling might regulate vascular permeability and establish different Nitric Oxide release patterns for tip/stalk cells. Following simulations with various stimuli, our model suggests that factors such as time under hypoxia and oxygen availability must be considered for EC pattern control.Discussion: This project provides insights into the signaling and patterning of endothelial cells under various oxygen levels and stimulation by VEGFA and is our first integrative approach toward achieving EC control as a method for improving angiogenesis. Overall, our model provides a computational framework that can be built on to test angiogenesis-related therapies by modulation of different pathways, such as the Notch pathway.

IntroductionAlthough both COVID-19 and non-COVID-19 ARDS can be accompanied by significantly increased levels of circulating cytokines, the former significantly differs from the latter by its higher vasculopathy, characterized by increased oxidative stress and coagulopathy in lung capillaries. This points towards the existence of SARS-CoV2-specific factors and mechanisms that can sensitize the endothelium towards becoming dysfunctional. Although the virus is rarely detected within endothelial cells or in the circulation, the S1 subunit of its spike protein, which contains the receptor binding domain (RBD) for human ACE2 (hACE2), can be detected in plasma from COVID-19 patients and its levels correlate with disease severity. It remains obscure how the SARS-CoV2 RBD exerts its deleterious actions in lung endothelium and whether there are mechanisms to mitigate this.MethodsIn this study, we use a combination of in vitro studies in RBD-treated human lung microvascular endothelial cells (HL-MVEC), including electrophysiology, barrier function, oxidative stress and human ACE2 (hACE2) surface protein expression measurements with in vivo studies in transgenic mice globally expressing human ACE2 and injected with RBD.ResultsWe show that SARS-CoV2 RBD impairs endothelial ENaC activity, reduces surface hACE2 expression and increases reactive oxygen species (ROS) and tissue factor (TF) generation in monolayers of HL-MVEC, as such promoting barrier dysfunction and coagulopathy. The TNF-derived TIP peptide (a.k.a. solnatide, AP301) -which directly activates ENaC upon binding to its a subunit- can override RBD-induced impairment of ENaC function and hACE2 expression, mitigates ROS and TF generation and restores barrier function in HL-MVEC monolayers. In correlation with the increased mortality observed in COVID-19 patients co-infected with S. pneumoniae, compared to subjects solely infected with SARS-CoV2, we observe that prior intraperitoneal RBD treatment in transgenic mice globally expressing hACE2 significantly increases fibrin deposition and capillary leak upon intratracheal instillation of S. pneumoniae and that this is mitigated by TIP peptide treatment.

Background In endothelial cells (ECs), glycolysis, regulated by PFKFB3 (6‐phosphofructo‐2‐kinase/fructose‐2,6‐biphosphatase, isoform‐3), is the major metabolic pathway for ATP generation. In preclinical peripheral artery disease models, VEGF165a (vascular endothelial growth factor165a) and microRNA‐93 both promote angiogenesis. Methods and Results Mice following hind‐limb ischemia (HLI) and ECs with, and without, hypoxia and serum starvation were examined with, and without, microRNA‐93 and VEGF165a. Post‐HLI perfusion recovery was monitored. EC metabolism was studied using seahorse assay, and the expression and activity of major metabolism genes were assessed. Reactive oxygen species levels and EC permeability were evaluated. C57Bl/6J mice generated a robust angiogenic response to HLI, with ECs from ischemic versus nonischemic muscle demonstrating no increase in glycolysis. Balb/CJ mice generated a poor angiogenic response post‐HLI; ischemic versus nonischemic ECs demonstrated significant increase in glycolysis. MicroRNA‐93‐treated Balb/CJ mice post‐HLI showed better perfusion recovery, with ischemic versus nonischemic ECs showing no increase in glycolysis. VEGF165a‐treated Balb/CJ mice post‐HLI showed no improvement in perfusion recovery with ischemic versus nonischemic ECs showing significant increase in glycolysis. ECs under hypoxia and serum starvation upregulated PFKFB3. In ECs under hypoxia and serum starvation, VEGF165a versus control significantly upregulated PFKFB3 and glycolysis, whereas miR‐93 versus control demonstrated no increase in PFKFB3 or glycolysis. MicroRNA‐93 versus VEGF165a upregulated glucose‐6‐phosphate dehydrogenase expression and activity, activating the pentose phosphate pathway. MicroRNA‐93 versus control increased reduced nicotinamide adenine dinucleotide phosphate and virtually eliminated the increase in reactive oxygen species. In ECs under hypoxia and serum starvation, VEGF165a significantly increased and miR‐93 decreased EC permeability. Conclusions In peripheral artery disease, activation of the pentose phosphate pathway to promote angiogenesis may offer potential therapeutic advantages.

IntroductionPatients with systemic lupus erythematosus (SLE) are at elevated risk for Q10 cardiovascular disease (CVD) due to accelerated atherosclerosis. Compared to heathy control subjects, lupus patients have higher volumes and densities of thoracic aortic perivascular adipose tissue (PVAT), which independently associates with vascular calcification, a marker of subclinical atherosclerosis. However, the biological and functional role of PVAT in SLE has not been directly investigated.MethodsUsing mouse models of lupus, we studied the phenotype and function of PVAT, and the mechanisms linking PVAT and vascular dysfunction in lupus disease. Results and discussionLupus mice were hypermetabolic and exhibited partial lipodystrophy, with sparing of thoracic aortic PVAT. Using wire myography, we found that mice with active lupus exhibited impaired endothelium-dependent relaxation of thoracic aorta, which was further exacerbated in the presence of thoracic aortic PVAT. Interestingly, PVAT from lupus mice exhibited phenotypic switching, as evidenced by “whitening” and hypertrophy of perivascular adipocytes along with immune cell infiltration, in association with adventitial hyperplasia. In addition, expression of UCP1, a brown/beige adipose marker, was dramatically decreased, while CD45-positive leukocyte infiltration was increased, in PVAT from lupus mice. Furthermore, PVAT from lupus mice exhibited a marked decrease in adipogenic gene expression, concomitant with increased pro-inflammatory adipocytokine and leukocyte marker expression. Taken together, these results suggest that dysfunctional, inflamed PVAT may contribute to vascular disease in lupus.

Abstract The Mars 2020 Mastcam‐Z stereo camera investigation enables the generation of three dimension (3D) data products needed to visualize and analyze rocks, outcrops, and other geological and aeolian features. The Planetary Robotics Vision Processing framework “PRoViP” as well as the Instrument Data System on a tactical—sol‐by‐sol—timeframe generate 3D vision products, such as panoramas, distance maps, and textured meshes. Structure‐from‐motion used by the Advanced Science Targeting Toolkit for Robotic Operations (ASTTRO) “Landform” tool and long baseline stereo pipelines add to the 3D vision products' suite on various scales. Data fusion with textured meshes from satellite imagery and 3D data analysis and interpretation of the resulting large 3D data sets is realized by visualization assets like the Planetary Robotics Vision 3D Viewer PRo3D, the 3D Geographical Information System GIS CAMP (Campaign Analysis Mapping and Planning tool), the ASTTRO 3D data presentation and targeting tool, and the Mastcam‐Z planning tool Viewpoint. The pipelines' workflows and the user‐oriented features of the visualization assets, shared across the Mars 2020 mission, are reported. The individual role and interplay, complements and synergies of the individual frameworks are explained. Emphasis is laid on publicly available 3D vision data products and tools. A representative set of scientific use cases from planetary geology, aeolian activity, soil analysis and impact science illustrates the scientific workflow, and public data deployment modes are briefly outlined, demonstrating that 3D vision processing and visualization is an essential mission‐wide asset to solve important planetary science questions such as prevailing wind direction, soil composition, or geologic origin.

Background Peripheral artery disease (PAD) affects >10 million people in the United States. PAD is associated with poor outcomes, including premature death. Machine learning (ML) has been increasingly used on big data to predict clinical outcomes. This study aims to develop ML models to predict in‐hospital mortality in patients hospitalized for PAD based on a national database. Methods and Results Inpatient hospitalization data were obtained from the 2016 to 2019 National Inpatient Sample. A total of 150 921 inpatients were identified with a primary diagnosis of PAD and PAD‐related procedures using codes of the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD‐10‐CM) and International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD‐10‐PCS). Four ML models, including logistic regression, random forest, light gradient boosting, and extreme gradient boosting models, were trained to predict the risk of in‐hospital death based on a selection of variables, including patient characteristics, comorbidities, procedures, and hospital‐related factors. In‐hospital mortality occurred in 1.8% of patients. The performance of the 4 models was comparable, with the area under the receiver operating characteristic curve ranging from 0.83 to 0.85, sensitivity of 77% to 82%, and specificity of 72% to 75%. These results suggest adequate predictability for clinical decision‐making. In all 4 models, the total number of diagnoses and procedures, age, endovascular revascularization procedure, congestive heart failure, diabetes, and diabetes with complications were critical predictors of in‐hospital mortality. Conclusions This study demonstrates the feasibility of ML in predicting in‐hospital mortality in patients with a primary PAD diagnosis. Findings highlight the potential of ML models in identifying high‐risk patients for poor outcomes and guiding personalized intervention.

Abstract The Ang–Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases that involve abnormal vascular permeability and endothelial cell inflammation. The understanding of the molecular mechanisms of the Ang–Tie pathway has been limited due to the complex reaction network formed by the ligands, receptors, and molecular regulatory mechanisms. In this study, we developed a mechanistic computational model of the Ang–Tie signaling pathway validated against experimental data. The model captures and reproduces the experimentally observed junctional localization and downstream signaling of the Ang–Tie signaling axis, as well as the time-dependent role of receptor Tie1. The model predicts that Tie1 modulates Tie2’s response to the context-dependent agonist Ang2 by junctional interactions. Furthermore, modulation of Tie1’s junctional localization, inhibition of Tie2 extracellular domain cleavage, and inhibition of VE-PTP are identified as potential molecular strategies for potentiating Ang2’s agonistic activity and rescuing Tie2 signaling in inflammatory endothelial cells.

Crater counting is a widely applied methodology for dating large areas of planetary surfaces, but is difficult to apply the method to constrain the durations of stratigraphic unconformities. Unconformities with exhumed craters are thought to indicate long hiatuses that can only be indirectly dated through stratigraphic relationships with other surfaces with uniform exposure ages. On Mars, sedimentary deposits with prominent unconformities with exhumed craters are found in layered deposits in the Arabia Terra region as well as Gale crater within Mount Sharp. In this work, we present a Linear Crater Counting methodology and apply it to constrain these unconformities observed in Arabia Terra and in Mount Sharp. The method applies a linear sampling domain correction to conventional two‐dimensional crater size frequency distributions and Bayesian Poisson process statistics in order to constrain the likely durations of these unconformities. We found that unconformities in Arabia Terra were on the order of 0.1–1 Gyr in length and that the unconformity preserved at Mount Sharp is at least 0.2 Gyr in length given estimates of the ages of the host craters. Hiatuses of these lengths constrain the age of the overlying deposits to be Late Hesperian or Amazonian in age. Two utility plots are also provided, along with the derivation, for researchers to apply this method to dating arbitrary geologic contacts on Mars and to adapt it to other bodies. Plain Language Summary: The crater counting method is a widely used method to date planetary surfaces. Crater counting works by comparing the number of craters in an area to the expected number of craters that should be observed for that area using a model of how many craters form and their expected size through time. On Mars, geologic contacts of sedimentary deposits with exhumed craters are seen in Arabia Terra and in Gale crater in Mount Sharp. Craters exhumed in these geologic contacts are thought to indicate long gaps in time between the formation dates of the upper and lower rock layers. However, dating these time gaps directly is not possible with conventional crater counting. To solve this problem, we developed a new linear crater counting method which describes the likely number of craters for a given age that could be found along a line on the surface of Mars. We apply this method to the geologic contacts seen in Arabia Terra and in Gale crater, and find that the time gaps are hundreds of millions of years in length to over a billion years in length. Our results confirm predictions that these deposits are geologically younger than previously thought. Key Points: We describe a novel linear crater counting method to date stratigraphic unconformities using partially exhumed craters along unit boundariesWe found that layered deposits in Arabia Terra and the Upper mound unit in Gale crater could be Amazonian in Age from applying our methodOur methodology can be applied broadly to better understand chronostratigraphy across the solar system [ABSTRACT FROM AUTHOR]

Cassini and many investigators reported whistler chorus near Saturn equatorial plane moving outwards. Whistler can propagate when going to high latitude and can alter its characteristics while interacting resonantly with available energetic electrons. Here investigating wave for a relativistic beam of the electron. It is observed and reported by Cassini Magnetospheric Imaging Instrument (MIMI) that inward radial injection of highly energetic particles is most dominant in Saturn intrinsic magnetosphere. Within this paradigm, an empirical energy dispersion relation for propagated whistler-mode oscillations in quasi Saturn magnetospheric plasma from such a non-monotonous ringed distribution function has been established. The kinetic approach and method of characteristics methodologies were used in the computations, which have been shown to be the best for building perturbed plasma states. The perturbed distribution function was estimated using the unperturbed particle routes. The ring distribution function was used to construct an unexpected growth rate expression for relativistic plasma in the inner magnetosphere. The results from the Saturn magnetosphere have been calculated and interpreted using a range of parameters. Temperature heterogeneity was shown to be a significant source of free energy that aided the propagation of a whistler-mode wave. By raising the peak value, the bulk injection of energetic hot electron injection impacts the growth rate. Growth was also demonstrated to be accelerated when the propagation angle increased. The research contributes to a better understanding of the relationship between wave and particle emissions and VLF emissions on a large scale.

ABSTRACT The vascular endothelial injury occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but the mechanisms are poorly understood. We sought to determine the frequency and type of cytokine elevations and their relationship to endothelial injury induced by plasma from patients with SARS-CoV-2 versus controls. Plasma from eight consecutively enrolled patients hospitalized with acute SARS-CoV-2 infection was compared to controls. Endothelial cell (EC) barrier integrity was evaluated using ECIS (electric cell-substrate impedance sensing) on human lung microvascular EC. Plasma from all SARS-CoV-2 but none from controls decreased transendothelial resistance to a greater degree than that produced by tumor necrosis factor-alpha (TNF-α), the positive control for the assay. Thrombin, angiopoietin 2 (Ang2), and vascular endothelial growth factor (VEGF), complement factor C3a and C5a, and spike protein increased endothelial permeability, but to a lesser extent and a shorter duration when compared to SARS-CoV-2 plasma. Analysis of Ang2, VEGF, and 15 cytokines measured in plasma revealed striking patient-to-patient variability within the SARS-CoV-2 patients. Pretreatment with thrombin inhibitors, single, or combinations of neutralizing antibodies against cytokines, Ca3 and C5a receptor antagonists, or with ACE2 antibody failed to lessen the SARS-CoV-2 plasma-induced EC permeability. The EC barrier destructive effects of plasma from patients with SARS-CoV-2 were susceptible to heat inactivation. Plasma from patients hospitalized with acute SARS-CoV-2 infection uniformly disrupts lung microvascular integrity. No predicted single, or set of, cytokine(s) accounted for the enhanced vascular permeability, although the factor(s) were heat-labile. A still unidentified but potent circulating factor(s) appears to cause the EC disruption in SARS-CoV-2 infected patients. IMPORTANCE Lung vascular endothelial injury in SARS-CoV-2 patients is one of the most important causes of morbidity and mortality and has been linked to more severe complications including acute respiratory distress syndrome (ARDS) and subsequent death due to multiorgan failure. We have demonstrated that in eight consecutive patients with SARS-CoV-2, who were not selected for evidence of endothelial injury, the diluted plasma-induced intense lung microvascular damage, in vitro. Known endothelial barrier-disruptive agents and proposed mediators of increased endothelial permeability in SARS-CoV-2, induced changes in permeability that were smaller in magnitude and shorter in duration than plasma from patients with SARS-CoV-2. The effect on endothelial cell permeability of plasma from patients with SARS-CoV-2 was heat-labile. The main plasma factor that causes the increased endothelial permeability remains to be identified. Our study provides a possible approach for future studies to understand the underlying mechanisms leading to vascular injury in SARS-CoV-2 infections.

ObjectiveThe successful scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has led to increasing life expectancy, and thus increased risk of hypertension. We aimed to describe the incidence and predictors of hypertension in HIV patients receiving ART at a publicly funded clinic in rural Uganda.MethodsWe abstracted data from medical records of adult patients who initiated ART at an HIV clinic in south-western Uganda during 2010-2012. We defined hypertension as at least two consecutive clinical visits, with a SBP at least 140 mmHg and/or SBP of at least 90 mmHg, or prescription for an antihypertensive medication. We calculated the incidence of hypertension and fit multivariable Cox proportional-hazards models to identify predictors of hypertension.ResultsA total of 3389 patients initiated ART without a prior diagnosis of hypertension during the observation period. Over 3990 person-years of follow-up, 445 patients developed hypertension, for a crude incidence of 111.5/1000 (95% confidence interval 101.9-121.7) person-years. Rates were highest among men aged at least 40 years (158.8 per/1000 person-years) and lowest in women aged 30-39 years (80/1000 person-years). Lower CD4 cell count at ART initiation, as well as traditional risk factors including male sex, increasing age, and obesity, were independently associated with hypertension.ConclusionWe observed a high incidence of hypertension in HIV-infected persons on ART in rural Uganda, and increased risk with lower nadir CD4 cell counts. Our findings call for increased attention to screening of and treatment for hypertension, along with continued prioritization of early ART initiation.