Urine-derived stem/progenitor cells:A focus on their characterization and potential

Cell therapy,i.e.,the use of cells to repair an affected tissue or organ,is at the forefront of regenerative and personalized medicine.Among the multiple cell types that have been used for this purpose[including adult stem cells such as mesenchymal stem cells or pluripotent stem cells],urine-derived stem cells(USCs)have aroused interest in the past years.USCs display classical features of mesenchymal stem cells such as differentiation capacity and immunomodulation.Importantly,they have the main advantage of being isolable from one sample of voided urine with a cheap and unpainful procedure,which is broadly applicable,whereas most adult stem cell types require invasive procedure.Moreover,USCs can be differentiated into renal cell types.This is of high interest for renal cell therapy-based regenerative approaches.This review will firstly describe the isolation and characterization of USCs.We will specifically present USC phenotype,which is not an object of consensus in the literature,as well as detail their differentiation capacity.In the second part of this review,we will present and discuss the main applications of USCs.These include use as a substrate to generate human induced pluripotent stem cells,but we will deeply focus on the use of USCs for cell therapy approaches with a detailed analysis depending on the targeted organ or system.Importantly,we will also focus on the applications that rely on the use of USC-derived products such as microvesicles including exosomes,which is a strategy being increasingly employed.In the last section,we will discuss the remaining barriers and challenges in the field of USC-based regenerative medicine.

WNT/β-catenin pathway and circadian rhythms in obsessive-compulsive disorder

The neuropsychiatric disease named obsessive-compulsive disorder is composed by obsessions and/or compulsions.Obsessive-compulsive disorder etiologies are undefined.However,numerous mechanisms in several localizations are implicated.Some studies showed that both glutamate,inflammatory factors and oxidative stress could have main functions in obsessive-compulsive disorder.Glycogen synthase kinase-3β,the major negative controller of the WNT/β-catenin pathway is upregulated in obsessive-compulsive disorder.In obsessive-compulsive disorder,some studies presented the actions of the different circadian clock genes.WNT/β-catenin pathway and circadian clock genes appear to be intricate.Thus,this review focuses on the interaction between circadian clock genes and the WNT/β-catenin pathway in obsessive-compulsive disorder.

Thermal Degradation Products of α-Pinene in a Tubular Furnace in the Temperature Range from 300°C to 900°C: Contribution to Wildfire Flashovers

Induced BVOC emissions from pyrolyzed plants that may accumulate in confined topographies have been a controversy for their role in wildfire eruptions or flashovers. α-pinene (C10H16) is one of the most abundant monoterpenes emitted from pyrolyzed Mediterranean vegetation in wildfires. Its thermal degradation under fire thermal stresses produces a range of highly flammable gases. In order to identify these products, thermal degradation experiments were performed on α-pinene in a tubular furnace in an inert atmosphere and a high-temperature range (300°C - 900°C). The pyrolysis products were identified using gas chromatography (GC) linked to a tubular furnace outlet by which their retention times were compared with those of reference standards. The degradation products were mainly terpenoids, aliphatic hydrocarbons (methane, ethane, ethene, propane, propene, 1,3-butadiene, isoprene), and aromatics (benzene, toluene) in addition to hydrogen. The radical mechanisms of the chemical reactions associated with the formation of the products at different experimental temperatures were addressed and compared with the literature. Monoterpenes, butadiene, isoprene, aliphatic hydrocarbons, and aromatics formations from α-pinene were consistent with the literature. However, even if benzene has been identified in our experiments, we cannot support with certainty the mechanisms of its formation described in the literature since acetylene was not observed.

Designing Discrete Predictor-Based Controllers for Networked Control Systems with Time-varying Delays:Application to A Visual Servo Inverted Pendulum System

A discrete predictor-based control method is developed for a class of linear time-invariant networked control systems with a sensor-to-controller time-varying delay and a controller-to-actuator uncertain constant delay,which can be potentially applied to vision-based control systems.The control scheme is composed of a state prediction and a discrete predictor-based controller.The state prediction is used to compensate for the effect of the sensor-to-controller delay,and the system can be stabilized by the discrete predictor-based controller.Moreover,it is shown that the control scheme is also robust with respect to slight message rejections.Finally,the main theoretical results are illustrated by simulation results and experimental results based on a networked visual servo inverted pendulum system.

Qualitative Determination of Photodegradation Products of Progesterone and Testosterone in Aqueous Solution

Direct photochemical degradations of progesterone (PR) and testosterone (TR), two naturally produced hormones, have been conducted in non-buffered aqueous solution (pH ranging between 5.5 and 6.0). The irradiation experiments were carried out in a batch reactor upon monochromatic (254 nm) and polychromatic (λ > 290 nm) at 25°C. GLC/MS and LC/UV-DAD/MS analyses were performed to investigate phototransformation products after a solid phase extraction (SPE) step for analytes concentration. For each compound several by-products have been identified and are the same ones under both irradiation conditions. Because of the presence of the same chromophore (α, β-unsaturated group) absorbing UV radiations in both hormones, the majority of chromatographic peaks correspond to by-products formed according to identical mechanisms involving isomerization, enolization, oxidation and hydration to lead to the generation of lumiketone, cyclopentenone, spiro-hydration, oxidation and hydroxylation photoproducts.

High resolution nuclear magnetic resonance investigation of metabolic disturbances induced by focal traumatic brain injury in a rat model:a pilot study

Experimental models of traumatic brain injury (TBI) provide a useful tool for understanding the cerebral metabolic changes induced by this pathological condition. Here, we report on the time course of changes in cerebral metabolites after TBI using high-resolution proton magnetic resonance spectroscopy (NMR). Extracts from adult male Sprague-Dawley rats were subjected to fluid lateral percussion and were then examined by NMR at 3, 24 and 48 h after the injury. A metabolomic approach was carried out to identify the cerebral metabolites impacted by the TBI and their quantitative temporal changes. Lactate, valine and ascorbate were the three first metabolites to be significantly modified after TBI. The quantitative elevation for these compounds last for the entire experimental time explored. Within 24 hours post-TBI, a significant elevation in choline-derivates, alanine and glucose were also measured. On the other hand, N-acetyl aspartate, a neuronal marker, and myo- inositol, an important organic osmolyte in the mammalian brain, were not significantly impacted in the chronic phase of TBI.

Stem cell therapy in retinal diseases

Alteration of the outer retina leads to various diseases such as age-related macular degeneration or retinitis pigmentosa characterized by decreased visual acuity and ultimately blindness.Despite intensive research in the field of retinal disorders,there is currently no curative treatment.Several therapeutic approaches such as cell-based replacement and gene therapies are currently in development.In the context of cell-based therapies,different cell sources such as embryonic stem cells,induced pluripotent stem cells,or multipotent stem cells can be used for transplantation.In the vast majority of human clinical trials,retinal pigment epithelial cells and photoreceptors are the cell types considered for replacement cell therapies.In this review,we summarize the progress made in stem cell therapies ranging from the pre-clinical studies to clinical trials for retinal disease.

Myelinosome organelles in pathological retinas: ubiquitous presence and dual role in ocular proteostasis maintenance

The timely and efficient elimination of aberrant proteins and damaged organelles, formed in response to various genetic and environmental stressors, is a vital need for all cells of the body. Recent lines of evidence point out several non-classical strategies employed by ocular tissues to cope with aberrant constituents generated in the retina and in the retinal pigmented epithelium cells exposed to various stressors. Along with conventional strategies relying upon the intracellular degradation of aberrant constituents through ubiquitin-proteasome and/or lysosome-dependent autophagy proteolysis, two non-conventional mechanisms also contribute to proteostasis maintenance in ocular tissues. An exosome-mediated clearing and a myelinosome-driven secretion mechanism do not require intracellular degradation but provide the export of aberrant constituents and “waste proteins” outside of the cells. The current review is centered on the non-degradative myelinosome-driven secretion mechanism, which operates in the retina of transgenic Huntington’s disease R6/1 model mice. Myelinosome-driven secretion is supported by rare organelles myelinosomes that are detected not only in degenerative Huntington’s disease R6/1 retina but also in various pathological states of the retina and of the retinal pigmented epithelium. The intra-retinal traffic and inter-cellular exchange of myelinosomes was discussed in the context of a dual role of the myelinosome-driven secretion mechanism for proteostasis maintenance in different ocular compartments. Special focus was made on the interplay between degradative and non-degradative strategies in ocular pathophysiology, to delineate potential therapeutic approaches to counteract several vision diseases.

Factors associated with decreased compliance after on-site extracorporeal membrane oxygenation cannulation for acute respiratory distress syndrome:A retrospective,observational cohort study

Background Extracorporeal membrane oxygenation(ECMO)for acute respiratory distress syndrome(ARDS)is systematically associated with decreased respiratory system compliance(CRS).It remains unclear whether transportation to the referral ECMO center,changes in ventilatory mode or settings to achieve ultra-protective ventilation,or the natural evolution of ARDS drives this change in respiratory mechanics.Herein,we assessed the precise moment when CRS decreases after ECMO cannulation and identified factors associated with decreased CRS.Methods To rule out the effect of transportation and the different modes of ventilation on CRS,we conducted a retrospective,single-center,observational cohort study from January 2013 to May 2020,on 22 patients with severe ARDS requiring on-site ECMO and ventilated in pressure-controlled mode to achieve ultra-protective ventilation.CRS was assessed at different time points ranging from 12 h before ECMO cannulation to 72 h after ECMO cannulation.The primary outcome was the relative change in CRS between 3 h before and 3 h after ECMO cannulation.The secondary outcomes included variables associated with the relative changes in CRS within the first 3 h after ECMO cannulation and the relative changes in CRS at each time point.Results CRS decreased within the first 3 h after ECMO cannulation(−28.3%,95%confidence interval[CI]:−38.8 to−17.9,P<0.001),while the decrease was mild before and after these first 3 h after ECMO cannulation.To achieve ultra-protective ventilation,respiratory rate decreased in the mean by–13 breaths/min(95%CI:−15 to−11)and driving pressure by−8.3 cmH2O(95%CI:−11.2 to−5.3),resulting in decreased tidal volume by−3.3 mL/kg of predicted body weight(95%CI:−3.9 to−2.6)as compared to before ECMO cannulation(P<0.001 for all).Plateau pressure reduction,driving pressure reduction,and tidal volume reduction were significantly associated with decreased CRS after ECMO cannulation,whereas neither respiratory rate,positive end-expiratory pressure,inspired fraction of oxygen,fluid balance,nor mean airway pressure was associated with decreased CRS.Conclusions Decreased driving pressure resulting in lower tidal volume to achieve ultra-protective ventilation after ECMO cannulation was associated with a marked decrease in CRS in ARDS patients with on-site ECMO cannulation.

Vanadium mineralization at Los Chihuidos sediment-hosted Cu-V deposit,Neuquén Basin,Argentina:An approach to vanadium ore forming processes

Vanadium mineralization at Los Chihuidos deposit of the Neuquén Basin is linked to the development of a redox front system related to the inflow of hydrocarbons into the red sandstone of the Huincul Formation.Interaction of hydrocarbons with oxidized red beds and connate water generated redox reactions where hematite was dissolved due to iron reduction resulting in the discoloration of the red strata.At the contact between oxidized red sandstone and reduced white sandstone,precipitation of specific mineral phases resulted in the V ore with minor amounts of Cu.With the implementation of the redox interface,abundant V-montmorillonite and V-hematite precipitated at the more oxidizing conditions and Cu-V-corrensite-type at the more reducing conditions of the redox front.As the redox front advanced with fluids constantly migrating into the reservoir,more reducing conditions were stablished,promoting chloritization and minor illitization with V-Cu incorporation and continuous upgrading of the ore.Main ore mineralogy consists of clay minerals including V-bearing montmorillonite,Cu-V-corrensite-type,V-di-trioctahedral chlorite and Cu-tri-trioctahedral chlorite with minor V-illite-smectite mixed-layer minerals and associated secondary V-hematite.Chloritization over illitization was favored due to high amounts of Fe and Mg in detrital clasts and in connate fluids and by low K availability related to low amounts of detrital K-feldspar.The spatial transition of V and/or Cu bearing clay minerals observed through the mineralized redox front at Los Chihuidos deposit(kaolinite→smectite→illite/smectite→corrensite-type→di-trioctahedral-chlorite→tri-trioctahedral-chlorite)and the related variation of V-Cu concentrations in bulk rock are indicative of increasing pH and decreasing Eh of resident solutions from red to white sandstones during the hypogene mineralization process.Late influx of Cu-rich oxidized basinal brines precipitated main copper ore with Cu-sulfides in the white sandstone up to the contact with the redox front in contact with hydrocarbons.During uplift and exhumation,percolation of meteoric water promoted remobilization of V and Cu and the precipitation of oxidized V-Cu ore.

New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers

Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy,including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin,Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.

An Immersed Method Based on Cut-Cells for the Simulation of 2D Incompressible Fluid Flows Past Solid Structures

We present a cut-cell method for the simulation of 2D incompressible flows past obstacles.It consists in using the MAC scheme on cartesian grids and imposing Dirchlet boundary conditions for the velocity field on the boundary of solid structures following the Shortley-Weller formulation.In order to ensure local conservation properties,viscous and convecting terms are discretized in a finite volume way.The scheme is second order implicit in time for the linear part,the linear systems are solved by the use of the capacitance matrix method for non-moving obstacles.Numerical results of flows around an impulsively started circular cylinder are presented which confirm the efficiency of the method,for Reynolds numbers 1000 and 3000.An example of flows around a moving rigid body at Reynolds number 800 is also shown,a solver using the PETSc-Library has been prefered in this context to solve the linear systems.

Genomic integrity of human induced pluripotent stem cells:Reprogramming, differentiation and applications

Ten years after the initial generation of induced pluripotent stem cells(hiPSCs)from human tissues,their potential is no longer questioned,with over 15000 publications listed on PubMed,covering various fields of research;including disease modeling,cell therapy strategies,pharmacology/toxicology screening and 3D organoid systems.However,despite evidences that the presence of mutations in hiPSCs should be a concern,publications addressing genomic integrity of these cells represent less than 1%of the literature.After a first overview of the mutation types currently reported in hiPSCs,including karyotype abnormalities,copy number variations,single point mutation as well as uniparental disomy,this review will discuss the impact of reprogramming parameters such as starting cell type and reprogramming method on the maintenance of the cellular genomic integrity.Then,a specific focus will be placed on culture conditions and subsequent differentiation protocols and how their may also trigger genomic aberrations within the cell population of interest.Finally,in a last section,the impact of genomic alterations on the possible usages of hiPSCs and their derivatives will also be exemplified and discussed.We will also discuss which techniques or combination of techniques should be used to screen for genomic abnormalities with a particular focus on the necessary quality controls and the potential alternatives.

On the Rayleigh-Plateau instability

In this paper,we study the surface instability of a cylindrical pore in the absence of stress.This instability is called the Rayleigh-Plateau instabilty.We consider the model developed by Spencer et al.[18],Kirill et al.[10]and Boutat et al.[2]in the case without stress.We obtain a nonlinear parabolic PDE of order four.We show the local existence and uniqueness of the solution of this problem by using Faedo-Galerkin method.The main results are the global existence of the solution and the convergence to the mean value of the initial data for long time.Numerical tests are also presented in this study.

Minigene Analysis of the c.743 + 40A >G Intronic Variant in the <i>CFTR</i>Gene

Background: Since the identification of the cystic fibrosis transmembrane regulator (CFTR) gene in 1989, many polymorphisms have been identified in cystic fibrosis (CF) or CFTR-related disorders (CFTR-RDs) patients and still remain to be characterized at the molecular level. These polymorphisms are difficult to classify as pathogenic or non-disease causing because the polymorphisms are either located in the coding region, but are synonymous, or are found in the intronic regions. Here we investigated the potential impact of the c.743 + 40A > G polymorphism within CFTR intron 6 on the alternative splicing. Indeed, this variant has been observed frequently in our examined patients. Moreover, a family carrying this variant exhibited CFTR-RD phenotype. Methods: By denaturing high pressure liquid phase chromatography (DHPLC) and sequencing, thirty of 293 subjects French origin carried the c.743 + 40A > G variant. Of these, 16 patients were affected by CF or CFTR-RD. Wild-type sequences and mutant CFTR intron 6 and its boundaries were inserted into the pTBNdeI hybride minigene and expressed in three different cell lines. After RT-PCR analysis of mRNA using specific primers, sequences of the minigene transcripts were obtained. Results: No aberrant splicing was detected with minigene carrying c.743 + 40A > G variant in all transfected cell lines. However, an alternative splicing in the positive control was detected with a minigene carrying the c.1392G > T + 1G > T mutation: 5 nucleotides were deleted from mRNA sequences, indicating that used cell lines are appropriate for studying the splicing. Conclusion: Transient transfections of a minigene containing the c.743 + 40A > G polymorphism showed no splicing errors, and thus this intronic alteration was finally classified as non-pathogenic. As it is always associated with c.2562T > G and c.4389G > A, or TG12-7T poly-morphisms, further experiments are needed to determine the role of these complex alleles in disease pathogenesis.

Ionic Liquids Mediated Ionothermal Process for the One-Step Synthesis of High Surface Area Alumina Supported Noble Metals

Aluminas supported noble metal nanoparticles have been synthesized by a new ionothermal process. The method used is easy to implement and allows obtaining catalysts in one step with high specific surface area. In addition, the metallic phase in the composites is highly dispersed and exhibits homogeneous size.

Early identification of acute respiratory distress syndrome in times of the COVID-19 pandemic

Acute respiratory distress syndrome(ARDS)was reported for the first time in 1967 in 12 patients with sudden respiratory failure due to a non-cardiogenic pulmonary edema.[1]Even though these patients had no underlying pulmonary disease,they rapidly developed severe hypoxemia,stiff lungs,and pulmonary bilateral infiltrates within a few days after a precipitating factor.Autopsy revealed a characteristic histological pattern of diffuse alveolar damage involving hyaline membranes,edema,necrosis,and cell proliferation.[2,3]The definition of ARDS evolved markedly over time and the Berlin definition,which was proposed in 2012,is currently the most recent one.[4]First,acute onset of respiratory symptoms appearing or worsening within 7 days of a clinical insult,thereby excluding patients who develop respiratory failure over more prolonged periods due to idiopathic pulmonary fibrosis,non-specific interstitial pneumonitis,organizing pneumonia,or pulmonary vasculitis.

Structural characteristics of electrohydrodynamic jets induced by a blade-plane actuator subjected to highly non-uniform electric fields:Parametric investigation through the particle image velocimetry techniques

This study set out to systematically investigate the structural characteristics of plane electrohydrodynamic jets through the particle image velocimetry(PIV)techniques.Due to the wide range of applied voltages and electrode gaps under various experimental conditions,an assessment of the image quality and a statistical analysis of the velocity fields are first performed to ensure the validity of the PIV measurements,which were originally applied purely to fluid mechanics.The results indicate that the time interval between two consecutive images should be pre-adjusted to reduce the number of uncorrelated vector fields.Moreover,the minimum number of instantaneous fields should be achieved for an accurate calculation of the time-averaged fields.An equivalent electric field criterion adapted to the asymmetric electrode configuration is defined to find similarities in flow structures under different voltage and electrode gap conditions.As the applied electric field increases,three injection regimes are identified and the current increases almost linearly,indicating a large conduction current component.The decrease in charge density due to recombination proves to be relevant in all cases of this study.Analogous to the parametric analysis approach for classical jets and thermal plumes,the evolution of the coefficients of axial velocity,half-width and turbulence intensity are investigated.

Pretreatment of Soil Samples Rich in Short-Range-Order Minerals Before Particle-Size Analysis by the Pipette Method

The possibilities of combining the dissolution of short-range-order minerals (SROMs) like allophane and imogolite, by ammonium oxalate and a particle size distribution analysis performed by the pipette method were investigated by tests on a soil sample from Reunion, a volcanic island located in the Indian Ocean, having a large SROMs content. The need to work with moist soil samples was again emphasized because the microaggregates formed during air-drying are resistant to the reagent. The SROM content increased, but irregularly, with the number of dissolutions by ammonium oxalate: 334 and 470 mg g-1 of SROMs were dissolved after one and three dissolutions respectively. Six successive dissolutions with ammonium oxalate on the same soil sample showed that 89% of the sum of oxides extracted by the 6 dissolutions were extracted by the first dissolution (mean 304 mg g-1 ). A compromise needs to be found between the total removal of SROMs by large quantities of ammonium oxalate and the preservation of clay minerals, which were unexpectedly dissolved by this reagent. These tests enabled a description of the clay assemblage of the soil (gibbsite, smectite, and traces of kaolinite) in an area where such information was lacking due to the difficulties encountered in recuperation of the clay fraction.