Mannose‐Modified Multi‐Walled Carbon Nanotubes as a Delivery Nanovector Optimizing the Antigen Presentation of Dendritic Cells

Dendritic cells (DCs) based cancer immunotherapy is largely dependent on adequate antigen delivery and efficient induction of DCs maturation to produce sufficient antigen presentation and ultimately lead to substantial activation of tumor‐specific CD8+ T cells. Carbon nanotubes (CNTs) have attracted great attention in biomedicine because of their unique physicochemical properties. In order to effectively deliver tumor antigens to DCs and trigger a strong anti‐tumor immune response, herein, a specific DCs target delivery system was assembled by using multi‐walled carbon nanotubes modified with mannose which can specifically bind to the mannose receptor on DCs membrane. Ovalbumin (OVA) as a model antigen, could be adsorbed on the surface of mannose modified multi‐walled carbon nanotubes (Man‐MWCNTs) with a large drug loading content. This nanotube‐antigen complex showed low cytotoxicity to DCs and was efficiently engulfed by DCs to induce DCs maturation and cytokine release in vitro, indicating that it could be a potent antigen‐adjuvant nanovector of efficient antigen delivery for therapeutic purpose.Perfectly delivered! Mannose‐modified multi‐walled carbon nanotubes (Man‐MWCNTs) could efficiently deliver a large amount of antigen to bone marrow derived dendritic cells (DCs) through ligand/receptor interactions of mannose, inducing enhanced BMDCs maturation and cytokines secretion.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/1/open201900126-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/2/open201900126.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/3/open201900126_am.pd

Visual characterization of associative quasitrivial nondecreasing operations on finite chains

In this paper we provide visual characterization of associative quasitrivial nondecreasing operations on finite chains. We also provide a characterization of bisymmetric quasitrivial nondecreasing binary operations on finite chains. Finally, we estimate the number of functions belonging to the previous classes.Comment: 25 pages, 18 Figure

IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients

ObjectiveTo investigate the role of IL-2 in the balance of Th17 and Tregs and elucidate the underlying mechanisms of enhanced Th17 differentiation in primary Sjögren’s syndrome (pSS) patients.MethodsThis study involved 31 pSS patients, 7 Sicca patients, and 31 healthy subjects. Th17 and Treg cells were determined by flow cytometry, and IL-17A was detected by immunohistochemistry. IL-2 and IL-6 levels were assessed by ELISA and qPCR. p-STAT5 and p-STAT3 in salivary glands (SGs) were evaluated by immunohistochemistry and flow cytometry. The binding of STAT5 and STAT3 to the Il17a gene locus was measured by chromatin immunoprecipitation.ResultsWe found that the percentage of Th17 cells was increased in the periphery and SG of pSS patients when compared with healthy subjects, but the Treg cells was unchanged. Meanwhile, the IL-2 level was reduced, and the IL-6 and IL-17A level was increased in the plasma of pSS patients. The ratio of IL-2 and IL-6 level was also decreased and IL-2 level was negatively correlated with the level of IL-17A. The expression of Il6 and Il17a mRNA was significantly increased, whereas Foxp3, Tgfb1, Tnfa, and Ifng mRNA were comparable. Furthermore, the level of STAT5 phosphorylation (p-STAT5) was reduced and p-STAT3 was enhanced in the SGs and in peripheral CD4+ T cells of pSS patients. In vitro IL-2 treatment-induced STAT5 competed with STAT3 binding in human Il17a locus, leading to decreased Th17 differentiation, which was associated with the reduced transcription activation marker H3K4me3.ConclusionOur findings demonstrated a Treg-independent upregulation of Th17 generation in pSS, which is likely due to a lack of IL-2-mediated suppression of Th17 differentiation. This study identified a novel mechanism of IL-2-mediated immune suppression in pSS

Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia

Abstract Background Elderly patients with relapsed and refractory acute lymphoblastic leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor-modified T (CAR-T) cells have potentials to cure patients with B cell ALL; however, safety and efficacy of allogeneic CD19 CAR-T cells are still undetermined. Case presentation We treated a 71-year-old female with relapsed and refractory ALL who received co-infusion of haplo-identical donor-derived CD19-directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following induction chemotherapy. Undetectable minimal residual disease by flow cytometry was achieved, and full donor cell engraftment was established. The transient release of cytokines and mild fever were detected. Significantly elevated serum lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic transaminase were observed from days 14 to 18, all of which were reversible after immunosuppressive therapy. Conclusions Our preliminary results suggest that co-infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may induce full donor engraftment in relapsed and refractory ALL including elderly patients, but complications related to donor cell infusions should still be cautioned. Trial registration Allogeneic CART-19 for Elderly Relapsed/Refractory CD19+ ALL. NCT0279955

Supplementary document for Nonlinear photonic crystals for completely independent asymmetric holographic imaging - 6638576.pdf

Supporting Informatio

Grouping Neural Network-Based Smith PID Temperature Controller for Multi-Channel Interaction System

The thermal vacuum test (TVT) is an important verification process in the development of spacecraft and load. There are often multiple temperature points on the device under test (DUT) that require control. The interaction among multiple channels poses a challenge for temperature control in the TVT. To solve this problem, a multi-channel Smith proportional–integral–derivative (PID) controller based on a grouping neural network (Grouping-NN) is proposed. Firstly, the mathematical derivation for a typical multi-channel temperature control model of the TVT is carried out. Then, the multi-channel interaction system is identified using a Grouping-NN to predict the output temperature of each channel by grouping the hidden layer neurons according to the number of channels. Finally, two Grouping-NNs are utilized to update the Smith predictor, and the time-delay error is fed back to the PID controller, which is used to optimize the control effect of the multi-channel interaction system under high time delay. The proposal is compared with the traditional PID controller and Smith predictor-based PID controller through simulation. The simulation results show that the proposed method has better suppression of overshooting. In addition, the algorithm is verified by controlling the temperature of six channels in a practical thermal vacuum test

An FGFR1-Binding Peptide Modified Liposome for siRNA Delivery in Lung Cancer

Liposome modification by targeting ligands has been used to mediate specific interactions and drug delivery to target cells. In this study, a new peptide ligand, CP7, was found to be able to effectively bind to FGFR1 through reverse molecular docking and could cooperate with VEGFR3 to achieve targeting of A549 cells. CP7 was modified on the surface of the liposome to construct a targeted and safe nanovehicle for the delivery of a therapeutic gene, Mcl-1 siRNA. Due to the specific binding between CP7 and A549 cells, siRNA-loaded liposome-PEG-CP7 showed increased cellular uptake in vitro, resulting in significant apoptosis of tumor cells through silencing of the Mcl-1 gene, which is associated with apoptosis and angiogenesis. This gene delivery system also showed significantly better antitumor activity in tumor-bearing mice in vivo. All of these suggested that siRNA-loaded liposome-PEG-CP7 could be a promising gene drug delivery system with good bioavailability and minimal side effects for treatment

Disentangling the formation and evolvement mechanism of plants-induced dried soil layers on China's Loess Plateau

The extent of the effect of China's Loess Plateau on global climate change partially depends on the achievements of the Grain for Green Program (GFGP). This region is prone to drought problems, especially the widespread creation of dried soil layer (DSL), which is intensified by the revegetation from GFGP initiatives. A DSL is the result of soil desiccation in deep soil profiles. The occurrence and expansion of DSLs are strengthened by the high risk of the Loess Plateau to climate change. On the basis of the 14-year data of soil water content (SWC) of four revegetation types on a loessial slope, we investigated the evolution processes and recovery possibility of DSL. Results showed that both variation trends and abrupt changes in the SWC time series were distinctly affected by revegetation. The 40 cm thickness of the DSL was triggered when Medicago sativa and Caragana korshinskii grew for 2 and 4 years, respectively. The downward extension depth of DSL reached 580 cm under the two plants above within 7 and 8 years of planting. However, the results suggested the possibility of DSL disappearance as shown by the formation depth dynamics of DSL, the fluctuation of DSL-SWC, and the phenomenon of sandwiched DSL. During deep moisture recharge and DSL recovery, although the SWC sensitivity to textural variation was present in the vertical profile, the effects of soil texture on SWC were decreased. Wet climate was linked to both DSL thinning and thickening. Thus, the effect of wet climate is bidirectional for DSL development, thereby highlighting the important role of revegetation. The results of this work enhance our understanding of DSL and may help alleviate the risk of drought in the Loess Plateau

Spatial and temporal variability of 0‐ to 5‐m soil–water storageat the watershed scale

Dynamic relationships among rainfall patterns, soil water distribution, and plant growth are crucial for sustainable conservation of soil and water resources in water-limited ecosystems. Spatial and temporal variation in deep soil water content at a watershed scale have not yet been characterized adequately due to the lack of deep soil water data. Deep soil-water storage (SWS) up to a depth of 5m (n=73) was measured at 19 sampling occasions at the LaoYeManQu watershed on the Chinese Loess Plateau (CLP). At a depth of 0-1.5m, the annual mean SWS was highly correlated with rain intensity, and the correlation decreased with depth, but within the layers at 1.5-5.0m, the changes in SWS indicated a lag between precipitation and the replenishment of soil water. Geostatistical parameters of SWS were also highly dependent on depth, and the mean SWS presented similar spatial structures in two adjacent layers. Temporal stability of SWS as indicated by mean relative difference, standard deviation of the relative difference (SDRD), and mean absolute bias error (MABE) was significantly weaker at the shallow than at deeper layers. Soil separates and organic carbon content controlled the spatial pattern of SWS at the watershed scale. One representative location (Site 57) was identified to estimate the mean SWS in the 1- to 5-m layer of the watershed. Semivariograms of the SDRD and MABE were best fitted by an isotropic spherical model, and their spatial distributions were depth-dependent. Both temporal stability and spatial variability of SWS increased over depth. This study is helpful for deep SWS estimation and sustainable management of soil and water on the CLP, and for other similar regions around the world