Significance Previously we demonstrated that IL-15 by continuous infusion at 2 μg/kg/d for 10 days induced a 38-fold increase in circulating natural killer (NK) cells and a 358-fold increase in CD56 bright NK cells. In the present study we demonstrated that IL-15 enhanced antibody-dependent cellular cytotoxicity (ADCC) of tumor-directed monoclonal antibodies in two systems. Both NK cells and macrophages were required for optimal therapeutic responses. These studies support clinical trials of IL-15 combined with tumor-directed monoclonal antibodies. In translation of this study, a phase I trial of IL-15 combined with alemtuzumab has been opened for patients with adult T cell leukemia (ATL) NCT02689453.
Abstract Despite significant advancements in the power conversion efficiency (PCE) of perovskite/silicon tandem solar cells, improving carrier management in top cells remains challenging due to the defective dual interfaces of wide-bandgap perovskite, particularly on textured silicon surfaces. Herein, a series of halide ions (Cl − , Br − , I − ) substituted piperazinium salts are designed and synthesized as post-treatment modifiers for perovskite surfaces. Notably, piperazinium chloride induces an asymmetric bidirectional ions distribution from the top to the bottom surface, with large piperazinium cations concentrating at the perovskite surface and small chloride anions migrating downward to accumulate at the buried interface. This results in effective dual-interface defect passivation and energy band modulation, enabling wide-bandgap (1.68 eV) perovskite solar cells to achieve a PCE of 22.3% and a record product of open-circuit voltage × fill factor (84.4% relative to the Shockley–Queisser limit). Furthermore, the device retains 91.3% of its initial efficiency after 1200 h of maximum power point tracking without encapsulation. When integrated with double-textured silicon heterojunction solar cells, a remarkable PCE of 31.5% is achieved for a 1.04 cm 2 monolithic perovskite/silicon tandem solar cell, exhibiting excellent long-term operational stability ( T 80 = 755 h) without encapsulation in ambient air. This work provides a convenient strategy on dual-interface engineering for making high-efficiency and stable perovskite platforms.
Abstract Inverted perovskite solar cells (IPSCs) suffer from significant non‐radiative recombination losses at the defective perovskite/C 60 interface, limiting the efficiency and stability of perovskite/silicon tandem solar cells. Despite silicon oxide (SiO X ) being a common passivation material in the silicon industry with higher electron selectivity than conventional atomic layer‐deposited alumina, its application in IPSCs is limited by its tendency to damage sensitive perovskite during processing. Here, an oblique angle evaporation method is developed to deposit a conformal, ultra‐thin SiO X layer without damaging the underlying perovskite. This SiO X interlayer not only chemically passivates under‐coordinated Pb 2+ defects but also forms an n/n+ homojunction that provides effective field‐effect passivation, concurrently reducing recombination and enhancing electron selectivity. As a result, extending this strategy to two‐terminal monolithic perovskite/tunnel oxide passivating contact silicon tandem solar cells achieves a stabilized power conversion efficiency of 30.2%, representing one of the highest efficiencies reported for such tandems. More importantly, the robust inorganic nature of SiO X enables it to serve as a dense inner encapsulation, enhancing both light (ISOS‐L‐1) and thermal (ISOS‐D‐2I) device stabilities.
Abstract Background Glyoxalase I (GLYI) and glyoxalase II (GLYII), two enzymes of the glyoxalase pathway, are responsible for the detoxification of a cytotoxic metabolite methylglyoxal (MG) into the nontoxic S-D-lactoylglutathione, which play crucial roles in stress tolerance in various plant species. Considering the roles of glyoxalases, the GLY gene families have been analyzed in higher plant, such as rice, soybean and Chinese cabbage; however, little is known about them in rapeseed ( Brassica napus L.). The B. napus glyoxalase pathway is worth an in-depth investigation about the presence, distribution, localizations, and expression of glyoxalase genes. Result In this study, a total of 35 BnaGLYI and 30 BnaGLYII genes were identified in the B. napus genome, and they were clustered into six and eight subfamilies, respectively. The classifications, chromosomal distributions, gene structures, and conserved motifs were predicted and analyzed. Importantly, these genes were mainly localized in chloroplast and cytoplasm. Moreover, their expression profiles varied among different tissues. For example, BnaGLY genes are expressed in most organs but tend to be highly expressed in a single organ, such as BnaGLYI27 and BnaGLYII19 ; while some members are only expressed in specific tissues, e.g., BnaGLYI32 only expressed in silique pericarps. Some genes were induced at different germination stages. Notably, a number of BnaGLY genes showed responses to Plasmodiophora brassicae infection. Conclusion This study systematically identifies BnaGLYI and BnaGLYII gene families in B. napus . The different sub-cellular organelles and expression analysis offer insight into their biological roles and function in plant development and stress resistance.
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Abstract The retrovirus, human T cell lymphotrophic virus-1 (HTLV-1) is the etiologic agent of ATL and the neurological disorder, HAM/TSP. Infection with HTLV-1 results in viral tax protein mediated constitutive activation of the JAK3/STAT5 pathway in patients' T-lymphocytes that is believed to result in malignant transformation or autoimmunity. JAK3 plays a key role in cytokine receptor-mediated signal transduction including the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 that use the common γ- chain. This suggests that inhibitors of JAK3 may be of benefit in HTLV-1-associated diseases. We evaluated the effect of a novel small molecule JAK3 inhibitor, CP690550 on the cytokine-dependent cell line, NK92. CP690550 at 50 or 100 nM effectively inhibited the proliferation of IL-2-stimulated NK92 cells, but not NK92 that were stimulated with IL-12 or the combination of IL-6 and its receptor (IL-6R) that do not utilize the common γ-chain and JAK3 for signaling and proliferation. We also demonstrated the relative specificity of this inhibitor on another cytokine-dependent cell line, 32Dβ where at 50 or 100 nM CP690550 inhibited IL-2 and JAK3 mediated proliferation but did not affect murine IL-3-mediated cell proliferation. The activation mediated phosphorylation of STAT5 in NK92 cells in response to IL-2 stimulation was inhibited by CP690550. We evaluated the action of CP690550 on the ex vivo proliferation of peripheral blood mononuclear cells (PBMC) from selected patients with the smoldering or chronic subtypes of ATL, or HAM/TSP whose PBMC are associated with the production of cytokines, in particular, IL-2, IL-9 and IL-15 that use the common γ-chain and JAK3. CP690550 at 50 nM inhibited the ex vivo spontaneous proliferation of PBMC from 11 patients with ATL and 9 patients with HAM/TSP at 6-day by means of 66% and 86.4%, respectively. CP690550 also inhibited the proliferation of NK92 cells stimulated with the 6-day ex vivo PBMC culture supernatants from ATL and HAM/TSP patients by a mean of 83.9% and 82%, respectively. We also demonstrated that CP690550 effectively inhibited the activation of the JAK3/STAT5 pathway in isolated T-cells from ATL patients. On the basis of this study, the JAK3 inhibitor CP690550 deserve further study as a potential therapeutic agent for select patients with HTLV-1-associated ATL and HAM/TSP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2526.
Objective To explore the feasibility of co-expressing recombinant baculovirus vector with dual promoters as dual-gene delivery vector.Methods After enhanced green fluorescent protein (EGFP) and glial cell line-derived neurotrophic factor (GDNF) respectively under cytomegalovirus (CMV) promoter were cloned into the pFastBac Dual vector,the recombinant plasmid pFastBac Dual-CMV-EGFP-CMV-GDNF was generated,and then transfected into HEK293T cells with Lipofectamine2000.Indirect immunofluorescence was applied to examining the co-expression of EGFP and GDNF in transfected 293T cells.Bac Dual-CMV-EGFP-CMV-GDNF was produced according to Bac-to-Bac Baculovirus Expression System manual,and used to transduce Hela cells at suitable MOI.Then indirect immunofluorescence and western blot analysis were used for detecting the existence of target proteins in Hela cells.Results Plasmid pFastBac DuaI-CMV-EGFP-CMV-GDNF and Bac Dual-CMV-EGFP-CMV-GDNF were successfully generated.EGFP and GDNF were co-expressed in one single 293T cell or Hela cell.Conclusions The pFastBac Dual vector was proved to be an effective dual-gene delivery vector,which supplied a new viral vector for multi-gene therapy.
Key words:
Baculovirus ; Dual-promoter; Co-expression; Dual-gene delivery vector; Multi-gene therapy
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