Hydrogen: A Novel Treatment Strategy in Kidney Disease

<b><i>Background:</i></b> Hydrogen is a chemical substance that has yet to be widely used in medicine. However, recent evidence indicates that hydrogen has multi-faceted pharmacological effects such as antioxidant, anti-inflammatory, and antiapoptotic properties. An increased number of studies are being conducted on the application of hydrogen in various diseases, especially those affecting the renal system. <b><i>Summary:</i></b> Hydrogen can be inhaled, as a gas or liquid, and can be administered orally, intravenously, or locally. Hydrogen can rapidly enter suborganelles such as mitochondria and nucleus by simple diffusion, producing reactive oxygen species (ROS) and triggering DNA damage. Hydrogen can selectively scavenge hydroxyl radical (•OH) and peroxynitrite (ONOO⁻), but not other reactive oxygen radicals with physiological functions, such as peroxyanion (O₂⁻) and hydrogen peroxide (H₂O₂). Although the regulatory effect of hydrogen on the signal transduction pathway has been confirmed, the specific mechanism of its influence on signal molecules remains unknown. Although many studies have investigated the therapeutic and preventive effects of H₂ in cellular and animal experiments, clinical trials are few and still far behind. As a result, more clinical trials are required to investigate the role of hydrogen in kidney disease, as well as the effect of its dose, timing, and form on the overall efficacy. Large-scale randomized controlled clinical trials will be required before hydrogen can be used to treat renal illnesses. <b><i>Key Messages:</i></b> This article reviews the mechanisms of hydrogen in the treatment of renal disease and explores the possibilities of its use in clinical practice.

Different solutions of the diffusion equation and its applications

In this report, we solved the advection–diffusion equation under pollutants deposition on the ground surface, taking wind speed and vertical diffusion depend on the vertical height. Also, we estimated a simple diffusion model from point source in an urban atmosphere and the conservative material with downwind was evaluated. Then, we calculated the extreme ground-level concentration as a function of stack height and plume rise in two cases. Comparison between the proposed models and the emission from the Egyptian Atomic Research Reactor at Inshas had been done. Lastly, we discussed the results in this report.

Population density and the SARS-CoV-2 pandemic: comparing the geography of the first and second wave in the Netherlands

The COVID-19 pandemic has boosted public and scholarly debate about the relationship between infectious disease and the urban. Cities are considered contagious because they are hubs in (inter)national networks and contain high densities of people. However, the role of the urban and population density in the spread of pathogens is complex and is mediated by the wider bio-social environment. This paper analsyes the role of population density in the outbreak of COVID-19 in the densely and highly urbanized context of the Netherlands. It compares the geography of the different phases in the epidemic and assesses when and where density plays a role. Using municipal data on the rate of infections and hospitalizations this paper reveals that spatial patterns differ substantially in time, which does not appear to be simple diffusion. Using panel regressions it is demonstrated that population density plays a role in those stages in which containment and mitigation measures were least strict, while in periods of lock down other factors such as household size are associated with higher infection rates. It concludes that lock downs may have greater effect in urban areas as key elements of urbanity are temporarily cancelled out.

Features of photon diffusion in a dispersed medium

Energy transfer by thermal radiation in a dispersed medium with a variable refractive index is discussed. This transfer can be described by a surprisingly simple diffusion equation. The process is naturally to interpret as the photon diffusion. The diffusion equation is free from strict conditions of applicability of the radiation transfer equation, which are usually not satisfied in disperse media with densely packed inhomogeneities. Quantum constraints on the value of the photon diffusion coefficient are derived. These restrictions turn out to be similar to the conditions for the applicability of geometric optics. The lower limit of the thermal conductivity coefficient is obtained, which is easier to verify in the experiment. An independent derivation of this limitation is given from considerations of symmetry and dimension.

Simulation of receptor triggering by kinetic segregation shows role of oligomers and close-contacts

The activation of T cells, key players of the immune system, involves local evacuation of phosphatase CD45 from a region of the T cell's surface, segregating it from the T cell receptor. What drives this evacuation? In the presence of antigen, what ensures evacuation happens in the sub-second timescales necessary to initiate signaling? In the absence of antigen, what mechanisms ensure evacuation does not happen spontaneously, which could cause signaling errors? Phenomena known to influence spatial organization of CD45 or similar surface molecules include diffusive motion in the lipid bilayer, oligomerization reactions, and mechanical compression against a nearby surface, such as that of the cell presenting antigen. Computer simulations can investigate hypothesized spatiotemporal mechanisms of T cell signaling. The challenge to computational studies of evacuation is that the base process, spontaneous evacuation by simple diffusion, is in the extreme rare event limit, meaning direct stochastic simulation is unfeasible. Here we combine particle-based spatial stochastic simulation with the Weighted Ensemble method for rare events to compute the mean first-passage time for cell surface availability by surface reorganization of CD45. We confirm mathematical estimates that, at physiological concentrations, spontaneous evacuation is extremely rare, roughly 300 years. We find that dimerization decreases the time required for evacuation. A weak bi-molecular interaction (dissociation constant estimate 460 microMolar) is sufficient for an order of magnitude reduction of spontaneous evacuation times, and oligomerization to hexamers reduces times to below 1 second. This introduces a mechanism whereby CD45 oligomerization could be accessible to an engineered therapeutic. For large regions of close-contact, such as those induced by large microvilli, molecular size and compressibility imply a nonzero re-entry probability 60 %, decreasing evacuation times. Simulations show that these reduced evacuation times are still unrealistically long, suggesting that a yet-to-be-described mechanism, besides compressional exclusion at a close contact, drives evacuation.

An integrin αEβ7-dependent mechanism of IgA transcytosis requires direct plasma cell contact with intestinal epithelium

Efficient IgA transcytosis is critical for the maintenance of a homeostatic microbiota. In the canonical model, locally-secreted dimeric (d)IgA reaches the polymeric immunoglobulin receptor (pIgR) on intestinal epithelium via simple diffusion. A role for integrin αE(CD103)β7 during transcytosis has not been described, nor its expression by intestinal B cell lineage cells. We found that αE-deficient (αE−/−) mice have a luminal IgA deficit, despite normal antibody-secreting cells (ASC) recruitment, local IgA production and increased pIgR expression. This deficit was not due to dendritic cell (DC)-derived retinoic acid (RA) nor class-switching defects, as stool from RAG−/− mice reconstituted with αE−/− B cells was also IgA deficient. Flow cytometric, ultrastructural and transcriptional profiling showed that αEβ7-expressing ASC represent an undescribed subset of terminally-differentiated intestinal plasma cells (PC) that establishes direct cell to cell contact with intestinal epithelium. We propose that IgA not only reaches pIgR through diffusion, but that αEβ7+ PC dock with E-cadherin-expressing intestinal epithelium to directly relay IgA for transcytosis into the intestinal lumen.

Hyperspectral and Multispectral Image Fusion by Deep Neural Network in a Self-Supervised Manner

Compared with multispectral sensors, hyperspectral sensors obtain images with high- spectral resolution at the cost of spatial resolution, which constrains the further and precise application of hyperspectral images. An intelligent idea to obtain high-resolution hyperspectral images is hyperspectral and multispectral image fusion. In recent years, many studies have found that deep learning-based fusion methods outperform the traditional fusion methods due to the strong non-linear fitting ability of convolution neural network. However, the function of deep learning-based methods heavily depends on the size and quality of training dataset, constraining the application of deep learning under the situation where training dataset is not available or of low quality. In this paper, we introduce a novel fusion method, which operates in a self-supervised manner, to the task of hyperspectral and multispectral image fusion without training datasets. Our method proposes two constraints constructed by low-resolution hyperspectral images and fake high-resolution hyperspectral images obtained from a simple diffusion method. Several simulation and real-data experiments are conducted with several popular remote sensing hyperspectral data under the condition where training datasets are unavailable. Quantitative and qualitative results indicate that the proposed method outperforms those traditional methods by a large extent.

Après-ski: The spread of coronavirus from Ischgl through Germany

The Austrian ski resort of Ischgl is commonly claimed to be ground zero for the diffusion of the SARS-CoV-2 virus in the first wave of infections experienced by Germany. Drawing on data for 401 German counties, we find that conditional on geographical latitude and testing behavior by health authorities, road distance to Ischgl is indeed an important predictor of infection cases, but – in line with expectations – not of fatality rates. Were all German counties located as far from Ischgl as the most distant county of Vorpommern-Rügen, Germany would have seen about 45 % fewer COVID-19 cases. A simple diffusion model predicts that the absolute value of the distance-to-Ischgl elasticity should fall over time when inter- and intra-county mobility are unrestricted. We test this hypothesis and conclude that the German lockdown measures have halted the spread of the virus.

Investigating the Role Intestinal-Specific FXR and SHP in Regulating Lipid Metabolism in Mice

Dysregulation of lipid metabolism is a causal factor that can lead to a variety of disorders, such as obesity and metabolic syndrome. Dietary fats are digested in the small intestine by the physiological detergents known as bile acids. They emulsify the fats and break them down into smaller molecules in order for the enterocytes to absorb the nutrients through simple diffusion or through the utilization of specific lipid transporters. Interestingly, the nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) not only regulates bile acid synthesis and circulation, but also lipid metabolism. Although many studies have examined the role of FXR in hepatic and intestinal lipid metabolism, studies investigating the role of SHP in the intestine are still lacking. Although FXR and SHP cooperate to regulate many metabolic pathways, FXR or SHP knockout models exhibit different lipid phenotypes. These data indicate there are FXR-dependent and -independent pathways of SHP that controls lipid metabolism. To delineate these two interconnecting yet separate pathways, we will utilize intestine-specific Shp knockout (IShpKO) and intestine-specific Fxr knockout (IFxrKO) mice model and place them on high fat diet to investigate their intestinal intestinal absorption and transportation of lipids. We will also monitor the bile acid pool in the intestine, serum, and liver in these knockouts to evaluate the consequence of intestinal deletion of Fxr as well as Shp on bile acid homeostasis and how this may affect lipid absorption. These experiments will identify how FXR and/or SHP regulates intestinal fat digestion and absorption and if this is secondary to the alterations in bile acid concentration and lipid transporters. In addition, we will also investigate the intestinal Fxr-Shp double knockout (IDKO) mice model to determine their combined contribution in intestinal lipid metabolism. Overall, the results obtained from this research will elucidate if intestinal FXR and SHP cooperate or can independently regulate lipid metabolism and homeostasis.

Teaching Membrane Transport Concepts Using Flipped Teaching & Dramatizations

Cell membrane transport is an important topic discussed in the biology classroom from the middle school to the graduate level. Membrane transport is complex, and students are often confused between different types of transport mechanisms. Dramatization is an active-learning strategy to engage students in learning. The flipped teaching method is designed to introduce lecture content prior to class meeting, thus creating time during class to adapt active-learning strategies such as dramatization. In this work, students were given a pretest prior to the dramatization activity. As each type of membrane transport was discussed, which included simple diffusion, osmosis, facilitated diffusion, and active transport, students were assigned specific roles to demonstrate the movement. The dramatization activity triggered many questions related to the topic, and these questions were addressed immediately. A posttest was conducted at the end of the dramatization activity. Our results demonstrated increases in the students’ understanding, engagement, and confidence level. The combination of flipped teaching and dramatization thus serves as a student-centered active-learning strategy for teaching difficult biological concepts.