Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model

Tissue regeneration is often impaired in patients with metabolic disorders such as diabetes mellitus and obesity, exhibiting reduced wound repair and limited regeneration capacity. We and others have demonstrated that wound healing under normal metabolic conditions is potentiated by the secretome of human endothelial cell-differentiated mesenchymal stem cells (hMSC-EC). However, it is unknown whether this effect is sustained under hyperglycemic conditions. In this study, the wound healing effect of secretomes from undifferentiated human mesenchymal stem cells (hMSC) and hMSC-EC in a type-2 diabetes mouse model was analyzed. hMSC were isolated from human Wharton’s jelly and differentiated into hMSC-EC. hMSC and hMSC-EC secretomes were analyzed and their wound healing capacity in C57Bl/6J mice fed with control (CD) or high fat diet (HFD) was evaluated. Our results showed that hMSC-EC secretome enhanced endothelial cell proliferation and wound healing in vivo when compared with hMSC secretome. Five soluble proteins (angiopoietin-1, angiopoietin-2, Factor de crecimiento fibroblástico, Matrix metallopeptidase 9, and Vascular Endothelial Growth Factor) were enriched in hMSC-EC secretome in comparison to hMSC secretome. Thus, the five recombinant proteins were mixed, and their pro-healing property was evaluated in vitro and in vivo. Functional analysis demonstrated that a cocktail of these proteins enhanced the wound healing process similar to hMSC-EC secretome in HFD mice. Overall, our results show that hMSC-EC secretome or a combination of specific proteins enriched in the hMSC-EC secretome enhanced wound healing process under hyperglycemic conditions.     

Tailoring and structure of PtRu nanoparticles supported on functionalized carbon for DMFC applications: New evidence of the hydrous ruthenium oxide phase

The influence of the structure and morphology of PtRu nanoparticles supported on functionalized carbon black has been investigated for CO and methanol electrooxidation in a half-cell and in a DMFC single cell. Carbon black was treated with HNO₃ to obtain an oxidized surface (Vulcan-N), and PtRu nanoparticles supported on Vulcan-N were prepared via impregnation, Bönnemann's method and the sulfito-complex route. Temperature programmed reduction (TPR) measurements evidence the presence of RuO₂·xH₂O phase in the catalyst obtained by the sulfito-complex route. This phase was stabilized by metal–support interaction, whereas alloy characteristics were estimated for PtRu catalyst obtained by impregnation and Bönnemann's method. The nature of the precursor–support interaction, induced by the nature of the functional groups on the carbon surface, affects the structure of the electrocatalyst and subsequent behavior in electroactivity. When synthesized through Bönnemann's method, the surface oxygen-containing groups of the support seem to be unable to stabilize the anhydrous precursors of platinum and ruthenium, yielding crystalline RuO₂. Methanol electrooxidation performance was clearly different in the three catalysts, whereas only a few negligible differences were observed in CO oxidation. The superior performance in DMFC of the catalysts obtained by the sulfito-complex route accounts for both the presence of RuO₂·xH₂O species and the functionalization of carbon black.     

Physical Reasoning to Synchronize Electrical Signals and Related Diagnostics in Plasma Focus Devices

Plasma Focus (PF) devices as well as other similar pulsed discharge devices requires a variety of diagnostics for their proper control and optimization, including the voltage between electrodes, the time derivative of the discharge current, detection of X-rays and neutron emissions, and pulsed laser images (Shadow, Schlieren, interferograms). This article discusses the problem of the time reference of all these outputs and proposes specific techniques for synchronizing them based on sound physical grounds. The foundations of synchronization criterion are verified in several experiments on PF devices.     

Senescent CD4+CD28− T Lymphocytes as a Potential Driver of Th17/Treg Imbalance and Alveolar Bone Resorption during Periodontitis

Senescent cells express a senescence-associated secretory phenotype (SASP) with a pro-inflammatory bias, which contributes to the chronicity of inflammation. During chronic inflammatory diseases, infiltrating CD4⁺ T lymphocytes can undergo cellular senescence and arrest the surface expression of CD28, have a response biased towards T-helper type-17 (Th17) of immunity, and show a remarkable ability to induce osteoclastogenesis. As a cellular counterpart, T regulatory lymphocytes (Tregs) can also undergo cellular senescence, and CD28⁻ Tregs are able to express an SASP secretome, thus severely altering their immunosuppressive capacities. During periodontitis, the persistent microbial challenge and chronic inflammation favor the induction of cellular senescence. Therefore, senescence of Th17 and Treg lymphocytes could contribute to Th17/Treg imbalance and favor the tooth-supporting alveolar bone loss characteristic of the disease. In the present review, we describe the concept of cellular senescence; particularly, the one produced during chronic inflammation and persistent microbial antigen challenge. In addition, we detail the different markers used to identify senescent cells, proposing those specific to senescent T lymphocytes that can be used for periodontal research purposes. Finally, we discuss the existing literature that allows us to suggest the potential pathogenic role of senescent CD4⁺CD28⁻ T lymphocytes in periodontitis.     

Structural Analysis of the Black-Legged Tick Saliva Protein Salp15

Salp15 is one of the proteins in the saliva of the tick Ixodes scapularis. Together with other biomolecules injected into the mammalian host at the biting site, it helps the tick to sustain its blood meal for days. Salp15 interferes with the cellular immune response of the mammalian host by inhibiting the activation of CD4⁺ T-lymphocytes. This function is co-opted by pathogens that use the tick as a vector and invade the host when the tick bites, such as Borrelia burgdorferi, the causative agent of Lyme borreliosis. Because of the immunity-suppressing role of Salp15, it has been proposed as a candidate for therapeutic applications in disorders of the immune system. The protein is produced as a 135-residue long polypeptide and secreted without its N-terminal signal 1–21 sequence. Detailed structural studies on Salp15 are lacking because of the difficulty in producing large amounts of the folded protein. We report the production of Salp15 and its structural analysis by NMR. The protein is monomeric and contains a flexible N-terminal region followed by a folded domain with mixed α + β secondary structures. Our results are consistent with a three-dimensional structural model derived from AlphaFold, which predicts the formation of three disulfide bridges and a free C-terminal cysteine.     

Molecular Epidemiology of Enteroaggregative Escherichia coli (EAEC) Isolates of Hospitalized Children from Bolivia Reveal High Heterogeneity and Multidrug-Resistance

Enteroaggregative Escherichia coli (EAEC) is an emerging pathogen frequently associated with acute diarrhea in children and travelers to endemic regions. EAEC was found the most prevalent bacterial diarrheal pathogen from hospitalized Bolivian children less than five years of age with acute diarrhea from 2007 to 2010. Here, we further characterized the epidemiology of EAEC infection, virulence genes, and antimicrobial susceptibility of EAEC isolated from 414 diarrheal and 74 non-diarrheal cases. EAEC isolates were collected and subjected to a PCR-based virulence gene screening of seven virulence genes and a phenotypic resistance test to nine different antimicrobials. Our results showed that atypical EAEC (a-EAEC, AggR-negative) was significantly associated with diarrhea (OR, 1.62, 95% CI, 1.25 to 2.09, p < 0.001) in contrast to typical EAEC (t-EAEC, AggR-positive). EAEC infection was most prevalent among children between 7–12 months of age. The number of cases exhibited a biannual cycle with a major peak during the transition from warm to cold (April–June). Both typical and a-EAEC infections were graded as equally severe; however, t-EAEC harbored more virulence genes. aap, irp2 and pic were the most prevalent genes. Surprisingly, we detected 60% and 52.6% of multidrug resistance (MDR) EAEC among diarrheal and non-diarrheal cases. Resistance to ampicillin, sulfonamides, and tetracyclines was most common, being the corresponding antibiotics, the ones that are frequently used in Bolivia. Our work is the first study that provides comprehensive information on the high heterogenicity of virulence genes in t-EAEC and a- EAEC and the large prevalence of MDR EAEC in Bolivia.     

ARP-P4: deep analysis of a hybrid SDN ARP-Path/P4Runtime switch

Telecommunication Systems - The Software-Defined Networking (SDN) architecture decouples the control plane from the data plane, but it does not explicitly state where the control should be located....     

A WH/GSMT-based full-wave analysis for planar transmission linesembedded in multilayered dielectric substrates

A new full-wave analysis method, referred to as the WH/GSMT, is developed to solve multilayered planar transmission line problems. First, the scattering of an obliquely incident parallel plate mode (PPM) by a PEC half plane embedded in a multilayered isotropic dielectric substrate within a PEC parallel plate region is analyzed via the Wiener-Hopf (WH) technique. The solution is then incorporated into the generalized scattering matrix technique (GSMT) to find the (complex) propagation constant and characteristic impedance of the planar transmission lines. The lateral power leakage is taken into account rigorously in the WH/GSMT. Numerical results including the microstrip line, conductor-backed slotline, coupled microstrip lines, and antipodal finlines are presented along with a discussion of the advantages/disadvantages of this method