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

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

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

Aerodynamic Enhancement of Vertical-Axis Wind Turbines Using Plain and Serrated Gurney Flaps

In light of the escalating demand for renewable energy sources, vertical-axis wind turbines have emerged as a pivotal technical solution for addressing the challenge of clean energy supply in residential and urban areas. As a simple and feasible passive control method, the plain Gurney flap (PGF) is widely applied to improve turbine aerodynamic performance. In this paper, the influence of a novel serrated gurney flap (SGF) with different flap heights is studied on the NACA0021 airfoil by numerical simulations. The findings demonstrate that, compared with the PGF, the SGF reduces the trailing edge reverse vortices from a pair to a single vortex and possesses lower drag. When the flap height reaches 6% of the chord (6%c), the lift-to-drag ratio of SGF surpasses that of PGF. A turbine rotor is equipped with an SGF and a PGF to compare their performances. The result confirms the flap effect depending on the rotor’s tip speed. At a low tip speed ratio (TSR), the PGF works better than the SGF. The SGF is preferred over the PGF for a higher tip speed ratio (TSR > 2.5). With the 6%c flap height, the performance of the SGF rotor surpasses the PGF by 13.9% at TSR = 2.62

A Comprehensive Analysis of Inorganic Ions and Their Selective Removal from the Reconstituted Tobacco Extract Using Electrodialysis

Many tobacco stalks, dust, and fines are discharged in the tobacco industry, rich in inorganic minerals ions and nicotine salts. The high salinity and nicotine salts are challenging to be addressed by traditional treatment and are a severe threat that ought to be overcome. Thus, proper techniques can regenerate the tobacco stalks into reconstituted tobacco flakes used as cigarette filler. The electrodialysis process has been a viable approach to removing the inorganic ingredients in wastewater. We studied concentration, pH, and co-related influences with the nicotine and sugar/nicotine contents on the desalination performance. The results show that the inorganic ions such as Cl−, K+, Ca2+, and Mg2+ ions were successfully removed. When the feed concentration ranges from 3 to 15%, the removal ratio of the K+ ions is higher than Ca2+ and Mg2+ ions. As we reported previously, the K+ and Ca2+ ions are unfavorable for the total particulate matter emission but beneficial to decreasing the HCN delivery in mainstream cigarette smoke. Selective ED is a robust technology to reduce the harmful component delivery in cigarette smoke

MOF-Derived Formation of Ni₂P–CoP Bimetallic Phosphides with Strong Interfacial Effect toward Electrocatalytic Water Splitting

Bimetallic phosphides have attracted research interest for their synergistic effect and superior electrocatalytic activities for electrocatalytic water splitting. Herein, a MOF-derived phosphorization approach was developed to produce Ni₂P–CoP bimetallic phosphides as bifunctional electrocatalysts for both hydrogen and oxygen evolution reactions (HER and OER). Ni₂P–CoP shows superior electrocatalytic activities to both pure Ni₂P and CoP toward HER and OER, revealing a strong synergistic effect. High-resolution transmission electron microscopy and energy dispersive X-ray spectroscopy elemental mapping analysis show that, in the sample Ni₂P–CoP, the Ni₂P and CoP nanoparticles with an average particle size 10–20 nm were mixed closely on the nanoscale, creating numerous Ni₂P/CoP interfaces. By comparison with the sample Ni₂P+CoP, in which seldom Ni₂P/CoP interfaces exist, we documented that the Ni₂P/CoP interface is an essential prerequisite to realize the synergistic effect and to achieve the enhanced electrocatalytic activities in Ni₂P–CoP bimetallic phosphides. This finding is meaningful for designing and developing bicomponent and even multicomponent electrocatalysts

Origin and tectonic implications of Early Cretaceous high- and low-Mg series rocks and mafic enclaves in the Bomi-Chayu Fold Belt, SE Tibet

Early Cretaceous granitoids are widespread on the Tibetan Plateau and record the tectonic evolution of several Tethyan oceans. We describe Early Cretaceous high-Mg (Mg-# > 50) and low-Mg (Mg-# < 50) granitoids, minor diorites, and mafic enclaves from the Bomi-Chayu Fold Belt, SE Tibet. Zircon U-Pb dating reveals two episodes of granitoid emplacement at similar to 122 and similar to 117 Ma. High-Mg series rocks have higher Mg-# and compatible element concentrations (e.g., Cr and Ni) than low-Mg series samples. Their Mg-# and compatible element abundances are also elevated relative to an experimental melt generated under the conditions of a thickened lower crustal. Enriched whole-rock Nd and zircon Hf isotopic signatures, coupled with low Y (<18 ppm) and Yb (<1.9 ppm) concentrations in some samples, indicate that the high-Mg series was derived from thickened lower crust and underwent minor mixing with cumulate pyroxenite in the lower crust. In contrast, low-Mg series rocks record a purely crustal origin, although differences are noted between Na-rich (subgroup 1) and K-rich (subgroup 2) compositions. Mafic enclaves hosted in the granitoids yield identical formation ages and isotopic compositions to their host rocks, suggesting a common origin. The spatial-temporal distribution of Early Cretaceous granitoids in the Bomi-Chayu Fold Belt indicates that magmatism occurred in an analogous tectonic regime to that of similar rocks in the Tengchong Terrane. The Bomi-Chayu granitoids are therefore distinct from those in the northern and central Lhasa subterranes and are related to the evolution of the Myitkyina Tethys Ocean in eastern Myanmar. (C) 2019 Elsevier B.V. All rights reserved

Chemo-drugs in cell microparticles reset antitumor activity of macrophages by activating lysosomal P450 and nuclear hnRNPA2B1

Abstract Macrophages in tumors (tumor-associated macrophages, TAMs), a major population within most tumors, play key homeostatic functions by stimulating angiogenesis, enhancing tumor cell growth, and suppressing antitumor immunity. Resetting TAMs by simple, efficacious and safe approach(s) is highly desirable to enhance antitumor immunity and attenuate tumor cell malignancy. Previously, we used tumor cell-derived microparticles to package chemotherapeutic drugs (drug-MPs), which resulted in a significant treatment outcome in human malignant pleural effusions via neutrophil recruitments, implicating that drug-MPs might reset TAMs, considering the inhibitory effects of M2 macrophages on neutrophil recruitment and activation. Here, we show that drug-MPs can function as an antitumor immunomodulator by resetting TAMs with M1 phenotype and IFN-β release. Mechanistically, drug molecules in tumor MPs activate macrophage lysosomal P450 monooxygenases, resulting in superoxide anion formation, which further amplifies lysosomal ROS production and pH value by activating lysosomal NOX2. Consequently, lysosomal Ca2+ signaling is activated, thus polarizing macrophages towards M1. Meanwhile, the drug molecules are delivered from lysosomes into the nucleus where they activate DNA sensor hnRNPA2B1 for IFN-β production. This lysosomal-nuclear machinery fully arouses the antitumor activity of macrophages by targeting both lysosomal pH and the nuclear innate immunity. These findings highlight that drug-MPs can act as a new immunotherapeutic approach by revitalizing antitumor activity of macrophages. This mechanistic elucidation can be translated to treat malignant ascites by drug-MPs combined with PD-1 blockade