Neurovascular unit on a chip:the relevance and maturity as an advanced in vitro model

The brain is a high-energy demanding organ,consuming around 20%of the metabolic energy generated.To fulfill this demand,cerebral blood flow(CBF)supplies oxygen and glucose continuously through the intricate network of cerebral blood vessels.Although for many years brain activity and blood flow were conceived as independent processes,MRI-based functional brain imaging demonstrated that there is a coupling between them.

Identification of SARS-CoV-2 by gold nanoparticles

The SARS-CoV-2 outbreaks highlighted the need for effective,reliable,fast,easy-to-do and cheap diagnostics procedures.We pragmatically experienced that an early positive-case detection,inevitably coupled with a mass vaccination campaign,is a milestone to control the COVID-19 pandemic.Gold nanoparticles(AuNPs)can indeed play a crucial role in this context,as their physicochemical,optics and electronics properties are being extensively used in photothermal therapy(PTT),radiation therapy(RT),drug delivery and diagnostic.AuNPs can be synthesized by several approaches to obtain different sizes and shapes that can be easily functionalized with many kinds of molecules such as antibodies,proteins,probes,and lipids.In addition,AuNPs showed high biocompatibility making them useful tool in medicine field.We thus reviewed here the most relevant evidence on AuNPs as effective way to detect the presence of SARS-CoV-2 antigens.We trust future diagnostic efforts must take this‘old-fashioned’nanotechnology tool into consideration for the development and commercialization of reliable and feasible detection kits.

Neuronal chemokines:new insights into neuronal communication after injury

Classically,chemokines were described as small proteins driving leukocyte migration.Nonetheless,more and more studies are showing the great variety of cell functions and tissues in which they participate,including neural cells.During the last years,research has highlighted the importance of chemokines in the nervous system,governing a wide range of processes (MesquidaVeny et al.,2021).This is evidenced for example by the crucial role played by CXCL12 during cortical development,or the homeostatic role of neuronal CX3CL1,preventing microglial activation.We are now certain that many chemokines and their receptors are widely expressed in neurons,and growing evidence has shown them as fundamental players in direct neuronal communication,both during homeostasis and after insult.

A 40-year evaluation of drivers of African rainforest change

Background:Tropical forests are repositories of much of the world’s biodiversity and are critical for mitigation of climate change.Yet,the drivers of forest dynamics are poorly understood.This is in large part due to the lack of long-term data on forest change and changes in drivers.Methodology:We quantify changes in tree abundance,diversity,and stand structure along transects first enumerated in 1978 and resampled 2019 in Kibale National Park,Uganda.We tested five predictions.First,based on the purported role of seed dispersal and herbivory and our quantification of changes in the abundance of frugivores and herbivores,we tested two predictions of how faunal change could have influenced forest composition.Second,based on an evaluation of life history strategies,we tested two predictions concerning how the forest could have changed following disturbance that happened prior to written history.Finally,based on a 50-year climate record,we evaluate the possible influence of climate change on forest dynamics.Results:More trees were present on the assessed transects in 2019(508)than in 1978(436),species richness remained similar,but diversity declined as the number of dominant species increased.Rainfall increased by only 3 mm over the 50 years but this had not significant effect on forest changes measured here.Annual average monthly maximum temperature increased significantly by 1.05℃ over 50 years.The abundance of frugivorous and folivorous primates and elephants increased over the 50 years of monitoring.Neither the prediction that an increase in abundance of seed dispersing frugivores increases the abundance of their preferred fruiting tree species,nor that as an increase in folivore abundance causes a decline in their preferred species were supported.As predicted,light-demanding species decreased in abundance while shade-tolerant species increased as expected from Kibale being disturbed prior to historical records.Finally,while temperature increased over the 50 years,we found no means to predict a priori how individual species would respond.Conclusions:Our study revealed subtle changes in the tree community over 40 years,sizable increases in primate numbers,a substantial increase in the elephant population and an increase in local temperature.Yet,a clear picture of what set of interactions impact the change in the tree community remains elusive.Our data on tree life-history strategies and frugivore/herbivore foraging preferences suggest that trees species are under opposing pressures.

Stem cells therapy for regenerative medicine:Principles of present and future practice

The characterization and isolation of various stem cell populations, from embryonic to tissue-derived stem cells and induced pluripotent stem cells (iPSCs), have led to a rapid growth in the field of stem cell research and its potentially clinical application in the field of regenerative medicine and tissue repair. Stem cell therapy has recently progressed from the preclinical to the early clinical trial arena for a variety of diseases states, although further knowledge on action mechanisms, long-term safety issues, and standardization and characterization of the therapeutic cell products remains to be thoroughly elucidated. In this paper we summarize the current state of the art of basic and clinical research that were highlighted at the 2012 meeting of the Spanish Cell Therapy Network. This includes the current research involving in genomic and transcriptomic characterization of selected stem cell populations, studies of the role of resident and transplanted stem cells during tissue regeneration and their mechanism of action, improved new strategies of tissue engineering, transplantation of mesenchymal stem cells (MSCs) in different animal models of disease, disease correction by iPSCs, and preliminary results of cell therapy in human clinical trials.

Processed Radio Frequency towards Pancreas Enhancing the Deadly Diabetes Worldwide

Diabetes is a chronic and debilitating disease,which is associated with a range of complications putting tremendous burden on medical,economic and socio-technological infrastructure globally.Yet the higher authorities of health services are facing the excruciating cumulative reasons of diabetes as a very imperative worldwide issue in the 21st century.The study aims to relook at the misapplication of the processed radio frequency that frailties in the pancreas within and around the personal body boundary area.The administered sensor data were obtained at laboratory experiments from the selected specimens on dogs and cats in light and dark environments.The study shows the frequent urine flow speed varies with sudden infection due to treated wireless sensor networks in active open eyes.The overweight and obese persons are increasingly affected in diabetes with comprehensive urinary pressure due to continuous staying at dark environment.The findings replicate the increasing tide of diabetes globally.The study also represents the difficulties of physicians to provide adequate diabetic management according to their expectancy due to insecure personal area network control unit.Dynamic sensor network is indispensable for healthcare but such network is at risk to health security due to digitalized poisoning within GPS positions.The study recommends the anti-radiation integrated system policy with user’s security alternative approach to inspire dealing with National Health Policy and Sustainable Development Goals 2030.

Zn-Mg and Zn-Cu alloys for stenting applications:From nanoscale mechanical characterization to in vitro degradation and biocompatibility

In the recent decades,zinc(Zn)and its alloys have been drawing attention as promising candidates for bioresorbable cardiovascular stents due to its degradation rate more suitable than magnesium(Mg)and iron(Fe)alloys.However,its mechanical properties need to be improved in order to meet the criteria for vascular stents.This work investigates the mechanical properties,biodegradability and biocompatibility of Zn-Mg and Zn-Cu alloys in order to determine a proper alloy composition for optimal stent performance.Nanoindentation measurements are performed to characterize the mechanical properties at the nanoscale as a function of the Zn microstructure variations induced by alloying.The biodegradation mechanisms are discussed and correlated to microstructure,mechanical performance and bacterial/cell response.Addition of Mg or Cu alloying elements refined the microstructure of Zn and enhanced yield strength(YS)and ultimate tensile strength(UTS)proportional to the volume fraction of secondary phases.Zn-1Mg showed the higher YS and UTS and better performance in terms of degradation stability in Hanks’solution.Zn-Cu alloys presented an antibacterial effect for S.aureus controlled by diffusion mechanisms and by contact.Biocompatibility was dependent on the degradation rate and the nature of the corrosion products.

Biomolecular functionalization for enhanced cell–material interactions of poly(methyl methacrylate)surfaces 5th China-Europe Symposium on Biomaterials in Regenerative Medicine(CESB 2015)Hangzhou,China April 7–10,2015

The integration of implants or medical devices into the body tissues requires of good cell–material interactions.However,most polymeric materials used for these applications lack on biological cues,which enhanced mid-and long-term implant failure due to weak integration with the surrounding tissue.Commonly used strategies for tissue–material integration focus on functionalization of the material surface by means of natural proteins or short peptides.However,the use of these biomolecules involves major drawbacks such as immunogenic problems and oversimplification of the constructs.Here,designed elastin-like recombinamers(ELRs)are used to enhance poly(methyl methacrylate)surface properties and compared against the use of short peptides.In this study,cell response has been analysed for different functionalization conditions in the presence and absence of a competing protein,which interferes on surface–cell interaction by unspecific adsorption on the interface.The study has shown that ELRs can induce higher rates of cell attachment and stronger cell anchorages than short peptides,being a better choice for surface functionalization.

Analysis of the in vitro degradation and the in vivo tissue response to bi-layered 3D-printed scaffolds combining PLA and biphasic PLA/bioglass components--Guidance of the inflammatory response as basis for osteochondral regeneration

The aim of the present study was the in vitro and in vivo analysis of a bi-layered 3D-printed scaffold combining a PLA layer and a biphasic PLA/bioglass G5 layer for regeneration of osteochondral defects in vivo Focus of the in vitro analysis was on the(molecular)weight loss and the morphological and mechanical variations after immersion in SBF.The in vivo study focused on analysis of the tissue reactions and differences in the implant bed vascularization using an established subcutaneous implantation model in CD-1 mice and established histological and histomorphometrical methods.Both scaffold parts kept their structural integrity,while changes in morphology were observed,especially for the PLA/G5 scaffold.Mechanical properties decreased with progressive degradation,while the PLA/G5 scaffolds presented higher compressive modulus than PLA scaffolds.The tissue reaction to PLA included low numbers of BMGCs and minimal vascularization of its implant beds,while the addition of G5 lead to higher numbers of BMGCs and a higher implant bed vascularization.Analysis revealed that the use of a bi-layered scaffold shows the ability to observe distinct in vivo response despite the physical proximity of PLA and PLA/G5 layers.Altogether,the results showed that the addition of G5 enables to reduce scaffold weight loss and to increase mechanical strength.Furthermore,the addition of G5 lead to a higher vascularization of the implant bed required as basis for bone tissue regeneration mediated by higher numbers of BMGCs,while within the PLA parts a significantly lower vascularization was found optimally for chondral regeneration.Thus,this data show that the analyzed bi-layered scaffold may serve as an ideal basis for the regeneration of osteochondral tissue defects.Additionally,the results show that it might be able to reduce the number of experimental animals required as it may be possible to analyze the tissue response to more than one implant in one experimental animal.

Junctional epithelium and hemidesmosomes:Tape and rivets for solving the“percutaneous device dilemma”in dental and other permanent implants

The percutaneous device dilemma describes etiological factors, centered around the disrupted epithelial tissue surrounding non-remodelable devices, that contribute to rampant percutaneous device infection. Natural percutaneous organs, in particular their extracellular matrix mediating the “device”/epithelium interface, serve as exquisite examples to inspire longer lasting long-term percutaneous device design. For example, the tooth’s imperviousness to infection is mediated by the epithelium directly surrounding it, the junctional epithelium (JE). The hallmark feature of JE is formation of hemidesmosomes, cell/matrix adhesive structures that attach surrounding oral gingiva to the tooth’s enamel through a basement membrane. Here, the authors survey the multifaceted functions of the JE, emphasizing the role of the matrix, with a particular focus on hemidesmosomes and their five main components. The authors highlight the known (and unknown) effects dental implant - as a model percutaneous device - placement has on JE regeneration and synthesize this information for application to other percutaneous devices. The authors conclude with a summary of bioengineering strategies aimed at solving the percutaneous device dilemma and invigorating greater collaboration between clinicians, bioengineers, and matrix biologists.

Ionic Species Affect the Self-Propulsion of Urease-Powered Micromotors

Enzyme-powered motors self-propel through the catalysis of in situ bioavailable fuels,which makes them excellent candidates for biomedical applications.However,fundamental issues like their motion in biological fluids and the understanding of the propulsion mechanism are critical aspects to be tackled before a future application in biomedicine.Herein,we investigated the physicochemical effects of ionic species on the self-propulsion of urease-powered micromotors.Results showed that the presence of PBS,NaOH,NaCl,and HEPES reduced self-propulsion of urease-powered micromotors pointing towards iondependent mechanisms of motion.We studied the 3D motion of urease micromotors using digital holographic microscopy to rule out any motor-surface interaction as the cause of motion decay when salts are present in the media.In order to protect and minimize the negative effect of ionic species on micromotors’performance,we coated the motors with methoxypolyethylene glycol amine(mPEG)showing higher speed compared to noncoated motors at intermediate ionic concentrations.These results provide new insights into the mechanism of urease-powered micromotors,study the effect of ionic media,and contribute with potential solutions to mitigate the reduction of mobility of enzyme-powered micromotors.

Large-scale dendrimer-based uneven nanopatterns for the study of local arginine-glycine-aspartic acid （RGD） density effects on cell adhesion

Cell adhesion processes are governed by the nanoscale arrangement of the extracellular matrix （ECM）, being more affected by local rather than global concentrations of cell adhesive ligands. In many cell-based studies, grafting of dendrimers on surfaces has shown the benefits of the local increase in concentration provided by the dendritic configuration, although the lack of any reported surface characterization has limited any direct correlation between dendrimer disposition and cell response. In order to establish a proper correlation, some control over dendrimer surface deposition is desirable. Here, dendrimer nanopatterning has been employed to address arginine-glycine-aspartic acid （RGD） density effects on cell adhesion. Nanopatterned surfaces were fully characterized by atomic force microscopy （AFM）, scanning tunneling microscopy （STM） and X-ray photoelectron spectroscopy （XPS）, showing that tunable distributions of cell adhesive ligands on the surface are obtained as a function of the initial dendrimer bulk concentration. Cell experiments showed a clear correlation with dendrimer surface layout： Substrates presenting regions of high local ligand density resulted in a higher percentage of adhered cells and a higher degree of maturation of focal adhesions （FAs）. Therefore, dendrimer nano- patterning is presented as a suitable and controlled approach to address the effect of local ligand density on cell response. Moreover, due to the easy modification of dendrimer peripheral groups, dendrimer nanopatterning can be further extended to other ECM ligands having density effects on cells.

Tailoring RGD local surface density at the nanoscale toward adult stem cell chondrogenic commitment

Arginine-glycine-aspartic acid （RGD） dendrimer-based nanopatterns on poly（L- lactic acid） were used as bioactive substrates to evaluate the impact of the RGD local surface density on the chondrogenic induction of adult human mesenchymal stem cells. During chondrogenic commitment, active extracellular matrix （ECM） remodeling takes place, playing an instructive role in the differentiation process. Although three-dimensional environments such as pellet or micromass cultures are commonly used for in vitro chondrogenic differentiation, these cultures are rather limited with respect to their ability to interrogate cells in celI-ECM interactions. In the present study, the nanopatterns of the tunable RGD surface density were obtained as a function of the initial dendrimer concentration. The local RGD surface density was quantified through probability contour plots for the minimum interparticle distance, constructed from the corresponding atomic force microscopy images, and correlated with the cell adhesion and differentiation response. The results revealed that the local RGD surface density at the nanoscale acts as a regulator of chondrogenic commitment, and that intermediate adhesiveness of cells to the substrates favors mesenchymal cell condensation and early chondrogenic differentiation.

Long-term in vivo single-cell lineage tracing of deep structures using three-photon activation

Genetic labeling techniques allow for noninvasive lineage tracing of cells in vivo.Two-photon inducible activators provide spatial resolution for superficial cells,but labeling cells located deep within tissues is precluded by scattering of the far-red illumination required for two-photon photolysis.Three-photon illumination has been shown to overcome the limitations of two-photon microscopy for in vivo imaging of deep structures,but whether it can be used for photoactivation remains to be tested.Here we show,both theoretically and experimentally,that three-photon illumination overcomes scattering problems by combining longer wavelength excitation with high uncaging three-photon cross-section molecules.We prospectively labeled heart muscle cells in zebrafish embryos and found permanent labeling in their progeny in adult animals with negligible tissue damage.This technique allows for a noninvasive genetic manipulation in vivo with spatial,temporal and cell-type specificity,and may have wide applicability in experimental biology.

Cyclophilins A and B oppositely regulate renal tubular epithelial cell phenotype

Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial–mesenchymal transition(pEMT),proliferation,and further redifferentiation into specialized tubule epithelial cells(TECs).Because the immunosuppressant cyclosporine-A produces pEMT in TECs and inhibits the peptidyl-prolyl isomerase(PPIase)activity of cyclophilin(Cyp)proteins,we hypothesized that cyclophilins could regulate TEC phenotype.Here we demonstrate that in cultured TECs,CypA silencing triggers loss of epithelial features and enhances transforming growth factorβ(TGFβ)-induced EMT in association with upregulation of epithelial repressors Slug and Snail.This pro-epithelial action of CypA relies on its PPIase activity.By contrast,CypB emerges as an epithelial repressor,because CypB silencing promotes epithelial differentiation,prevents TGFβ-induced EMT,and induces tubular structures in 3D cultures.In addition,in the kidneys of CypB knockout mice subjected to unilateral ureteral obstruction,inflammatory and pro-fibrotic events were attenuated.CypB silencing/knockout leads to Slug,but not Snail,downregulation.CypB support of Slug expression depends on its endoplasmic reticulum location,where it interacts with calreticulin,a calcium-buffering chaperone related to Slug expression.As CypB silencing reduces ionomycin-induced calcium release and Slug upregulation,we suggest that Slug expression may rely on CypB modulation of calreticulin-dependent calcium signaling.In conclusion,this work uncovers new roles for CypA and CypB in modulating TEC plasticity and identifies CypB as a druggable target potentially relevant in promoting kidney repair.