Tris[2-(pyrrol-2-ylmethyl­eneamino)eth­yl]amine

The title compound, C21H27N7, was synthesized by reaction of tris­(2-amino­ethyl)amine and pyrrole-2-carbaldehyde in ethanol at room temperature. The structure is stabilized by intra- and inter­molecular C—H⋯N and N—H⋯N hydrogen-bonding inter­actions

Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier

Mesenchymal stem cell (MSC) transplantation has been shown to represent a potential treatment for traumatic spinal cord injury (SCI). However, there are several obstacles that need to be overcome before MSCs can be considered for clinical application, such as failure of MSCs to reach the spinal cord lesion core and possible tumor formation. Recent studies have suggested that MSC treatment is beneficial owing to paracrine-secreted factors. Extracellular vesicles are considered to be some of the most valuable paracrine molecules. However, the therapeutic mechanism of extracellular vesicles on spinal cord injury has not been studied clearly. Therefore, our study investigated the effect of systemic administration of extracellular vesicles on the loss of motor function after SCI and examined the potential mechanisms underlying their effects. Disruption of the blood-spinal cord barrier (BSCB) is a crucial factor that can be detrimental to motor function recovery. Pericytes are an important component of the neurovascular unit, and play a pivotal role in maintaining the structural integrity of the BSCB. Our study demonstrated that administration of bone mesenchymal stem cell-derived extracellular vesicles (BMSC-EV) reduced brain cell death, enhanced neuronal survival and regeneration, and improved motor function compared with the administration of BMSC-EV free culture media (EV-free CM). Besides, the BSCB was attenuated and pericyte coverage was significantly decreased in vivo. Furthermore, we found that exosomes reduced pericyte migration via downregulation of NF-κB p65 signaling, with a consequent decrease in the permeability of the BSCB. In summary, we identified that extracellular vesicles treatment suppressed the migration of pericytes and further improved the integrity of the BSCB via NF-κB p65 signaling in pericytes. Our data suggest that extracellular vesicles may serve as a promising treatment strategy for SCI

Differential early diagnosis of benign versus malignant lung cancer using systematic pathway flux analysis of peripheral blood leukocytes

Early diagnosis of lung cancer is critically important to reduce disease severity and improve overall survival. Newer, minimally invasive biopsy procedures often fail to provide adequate specimens for accurate tumor subtyping or staging which is necessary to inform appropriate use of molecular targeted therapies and immune checkpoint inhibitors. Thus newer approaches to diagnosis and staging in early lung cancer are needed. This exploratory pilot study obtained peripheral blood samples from 139 individuals with clinically evident pulmonary nodules (benign and malignant), as well as ten healthy persons. They were divided into three cohorts: original cohort (n = 99), control cohort (n = 10), and validation cohort (n = 40). Average RNAseq sequencing of leukocytes in these samples were conducted. Subsequently, data was integrated into artificial intelligence (AI)-based computational approach with system-wide gene expression technology to develop a rapid, effective, non-invasive immune index for early diagnosis of lung cancer. An immune-related index system, IM-Index, was defined and validated for the diagnostic application. IM-Index was applied to assess the malignancies of pulmonary nodules of 109 participants (original + control cohorts) with high accuracy (AUC: 0.822 [95% CI: 0.75–0.91, p < 0.001]), and to differentiate between phases of cancer immunoediting concept (odds ratio: 1.17 [95% CI: 1.1–1.25, p < 0.001]). The predictive ability of IM-Index was validated in a validation cohort with a AUC: 0.883 (95% CI: 0.73–1.00, p < 0.001). The difference between molecular mechanisms of adenocarcinoma and squamous carcinoma histology was also determined via the IM-Index (OR: 1.2 [95% CI 1.14–1.35, p = 0.019]). In addition, a structural metabolic behavior pattern and signaling property in host immunity were found (bonferroni correction, p = 1.32e − 16). Taken together our findings indicate that this AI-based approach may be used for “Super Early” cancer diagnosis and amend the current immunotherpay for lung cancer

The alteration of the structure and macroscopic mechanical response of porcine patellar tendon by elastase digestion

Background: The treatment of patellar tendon injury has always been an unsolved problem, and mechanical characterization is very important for its repair and reconstruction. Elastin is a contributor to mechanics, but it is not clear how it affects the elasticity, viscoelastic properties, and structure of patellar tendon.Methods: The patellar tendons from six fresh adult experimental pigs were used in this study and they were made into 77 samples. The patellar tendon was specifically degraded by elastase, and the regional mechanical response and structural changes were investigated by: (1) Based on the previous study of elastase treatment conditions, the biochemical quantification of collagen, glycosaminoglycan and total protein was carried out; (2) The patellar tendon was divided into the proximal, central, and distal regions, and then the axial tensile test and stress relaxation test were performed before and after phosphate-buffered saline (PBS) or elastase treatment; (3) The dynamic constitutive model was established by the obtained mechanical data; (4) The structural relationship between elastin and collagen fibers was analyzed by two-photon microscopy and histology.Results: There was no statistical difference in mechanics between patellar tendon regions. Compared with those before elastase treatment, the low tensile modulus decreased by 75%–80%, the high tensile modulus decreased by 38%–47%, and the transition strain was prolonged after treatment. For viscoelastic behavior, the stress relaxation increased, the initial slope increased by 55%, the saturation slope increased by 44%, and the transition time increased by 25% after enzyme treatment. Elastin degradation made the collagen fibers of patellar tendon become disordered and looser, and the fiber wavelength increased significantly.Conclusion: The results of this study show that elastin plays an important role in the mechanical properties and fiber structure stability of patellar tendon, which supplements the structure-function relationship information of patellar tendon. The established constitutive model is of great significance to the prediction, repair and replacement of patellar tendon injury. In addition, human patellar tendon has a higher elastin content, so the results of this study can provide supporting information on the natural properties of tendon elastin degradation and guide the development of artificial patellar tendon biomaterials

A Legged Small Celestial Body Landing Mechanism: Landing Simulation and Experimental Test

Landing mechanism tends to rebound and turn over, and the stability time is long when landing on the small celestial body. Its landing performance in different conditions is necessary to be evaluated to guide the landing. Here, landing performance evaluation is realized by simulation. Key factors affecting the landing performance including cardan element damping, foot anchors, retro-rocket thrust, landing slope angle, and landing attitude are analyzed. A microgravity platform is built to test the landing mechanism, and the consistency between the simulation and the experiment is compared. On the basis of simulation and experiment, some landing suggestions are proposed to improve the landing performance

Micro- and Nanosatellite Sensorless Electromagnetic Docking Control Based on the High-Frequency Injection Method

This paper proposes a sensorless electromagnetic docking method suitable for micro- and nanosatellites. Based on the circuit model of the electromagnetic docking device, an algorithm for calculating the distance between two satellites on the basis of the high-frequency injection (HFI) method has been developed. In the specific implementation, first, a high-frequency (HF) voltage is injected into one of the two electromagnets; second, the HF currents induced by both electromagnets are measured and their respective root-mean-squares (RMSs) are calculated; third, two RMSs are substituted into a specific formula to obtain a variable carrying distance information; finally, the variable is utilized to calculate the distance estimation using the look-up table interpolation method. This paper presents a closed-loop electromagnetic docking controller which includes an outer distance loop and an inner speed loop and adopts the distance estimation as the feedback. The proposed sensorless electromagnetic docking method is verified by the distance estimation tracking response test and the ground-based docking test. The results indicate that low-impact docking can be achieved under the initial condition that the two satellites have a certain degree of misalignment. The proposed method can be adopted as a primary or as a redundant electromagnetic docking solution for resource-critical micro- and nanosatellites

Production of high-energy 6-Ah-level Li | |LiNi0.83Co0.11Mn0.06O2 multi-layer pouch cells via negative electrode protective layer coating strategy

Abstract Stable lithium metal negative electrodes are desirable to produce high-energy batteries. However, when practical testing conditions are applied, lithium metal is unstable during battery cycling. Here, we propose poly(2-hydroxyethyl acrylate-co-sodium benzenesulfonate) (PHS) as negative electrode protective layer. The PHS contains soft poly (2-hydroxyethyl acrylate) and poly(sodium p-styrene sulfonate), which improve electrode flexibility, connection with the Cu current collector and transport of Li ions. Transmission electron cryomicroscopy measurements reveal that PHS induces the formation of a solid electrolyte interphase with a fluorinated rigid and crystalline internal structure. Furthermore, theoretical calculations suggest that the -SO3 - group of poly(sodium p-styrene sulfonate) promotes Li-ion motion towards interchain migration through cation-dipole interaction, thus, enabling uniform Li-ion diffusion. Electrochemical measurements of Li | |PHS-coated-Cu coin cells demonstrate an average Coulombic efficiency of 99.46% at 1 mA/cm2, 6 mAh/cm2 and 25 °C. Moreover, when the PHS-coated Li metal negative electrode is paired with a high-areal-capacity LiNi0.83Co0.11Mn0.06O2-based positive electrode in multi-layer pouch cell configuration, the battery delivers an initial capacity of 6.86 Ah (corresponding to a specific energy of 489.7 Wh/kg) and, a 91.1% discharge capacity retention after 150 cycles at 2.5 mA/cm2, 25 °C and 172 kPa

MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model

Widespread death of transplanted mesenchymal stem cells (MSCs) hampers the development of stem cell therapy for Alzheimer disease (AD). Cell pre-conditioning might help cope with this challenge. We tested whether let-7f-5p-modified MSCs could prolong the survival of MSCs after transplantation. When exposed to Aβ25−35in vitro, MSCs showed significant early apoptosis with decrease in the let-7f-5p levels and increased caspase-3 expression. Upregulating microRNA let-7f-5p in MSCs alleviated Aβ25−35-induced apoptosis by decreasing the caspase-3 levels. After computerized analysis and the luciferase reporter assay, we identified that caspases-3 was the target gene of let-7f-5p. In vivo, hematoxylin and eosin staining confirmed the success of MSCs transplantation into the lateral ventricles, and the let-7f-5p upregulation group showed the lowest apoptotic rate of MSCs detected by TUNEL immunohistochemistry analysis and immunofluorescence. Similarly, bioluminescent imaging showed that let-7f-5p upregulation moderately prolonged the retention of MSCs in brain. In summary, we identified the anti-apoptotic role of let-7f-5p in Aβ25−35-induced cytotoxicity, as well as the protective effect of let-7f-5p on survival of grafted MSCs by targeting caspase-3 in AD models. These findings show a promising approach of microRNA-modified MSCs transplantation as a therapy for neurodegenerative diseases