Kinetics of IL-23 and IL-12 Secretion in Response to Toxoplasma gondii Antigens from THP-1 Monocytic Cells

IL-23 and IL-12 are structurally similar and critical for the generation of efficient cellular immune responses. Toxoplasma gondii induces a strong cell-mediated immune response. However, little is known about IL-23 secretion profiles in T. gondii-infected immune cells in connection with IL-12. We compared the patterns of IL-23 and IL-12 production by THP-1 human monocytic cells in response to stimulation with live or heat-killed T. gondii tachyzoites, or with equivalent quantities of either T. gondii excretory/secretory proteins (ESP) or soluble tachyzoite antigen (STAg). IL-23 and IL-12 were significantly increased from 6 hr after stimulation with T. gondii antigens, and their secretions were increased with parasite dose-dependent manner. IL-23 concentrations were significantly higher than those of IL-12 at the same multiplicity of infection. IL-23 secretion induced by live parasites was significantly higher than that by heat-killed parasites, ESP, or STAg, whereas IL-12 secretion by live parasite was similar to those of ESP or STAg. However, the lowest levels of both cytokines were at stimulation with heat-killed parasites. These data indicate that IL-23 secretion patterns by stimulation with various kinds of T. gondii antigens at THP-1 monocytic cells are similar to those of IL-12, even though the levels of IL-23 induction were significantly higher than those of IL-12. The detailed kinetics induced by each T. gondii antigen were different from each other.     

Toll‐like receptor‐mediated IRE1α activation as a therapeutic target for inflammatory arthritis

In rheumatoid arthritis (RA), macrophage is one of the major sources of inflammatory mediators. Macrophages produce inflammatory cytokines through toll‐like receptor (TLR)‐mediated signalling during RA. Herein, we studied macrophages from the synovial fluid of RA patients and observed a significant increase in activation of inositol‐requiring enzyme 1α (IRE1α), a primary unfolded protein response (UPR) transducer. Myeloid‐specific deletion of the IRE1α gene protected mice from inflammatory arthritis, and treatment with the IRE1α‐specific inhibitor 4U8C attenuated joint inflammation in mice. IRE1α was required for optimal production of pro‐inflammatory cytokines as evidenced by impaired TLR‐induced cytokine production in IRE1α‐null macrophages and neutrophils. Further analyses demonstrated that tumour necrosis factor (TNF) receptor‐associated factor 6 (TRAF6) plays a key role in TLR‐mediated IRE1α activation by catalysing IRE1α ubiquitination and blocking the recruitment of protein phosphatase 2A (PP2A), a phosphatase that inhibits IRE1α phosphorylation. In summary, we discovered a novel regulatory axis through TRAF6‐mediated IRE1α ubiquitination in regulating TLR‐induced IRE1α activation in pro‐inflammatory cytokine production, and demonstrated that IRE1α is a potential therapeutic target for inflammatory arthritis.     

Herceptin, a recombinant humanized anti-ERBB2 monoclonal antibody, induces cardiomyocyte death

P53 protein levels are elevated by trastuzumab and the biologically similar rat ERBB2/HER2/NEU antibody; and that this coincides with enhanced apoptosis, increased cleaved caspase-3 levels and diminished cardiac function. We also demonstrate that MDM2 may be a regulatory target of anti-ERBB2 thereby implicating the MDM2/p53 axis as a potential molecular component for the undesirable cardiac outcomes noted with trastuzumab. Finally, we show that these MDM2/p53-mediated events are independent of both the ERK1/2 and Akt systems. In conclusion, our findings suggest that the adverse cardiac events observed with trastuzumab may stem from its negative regulation of MDM2 events which impairs p53 degradation resultantly promoting apoptosis leading to cardiac dysfunction. These observations may have important therapeutic implications since they suggest that anticancer agents that inhibit MDM2 and its downstream actions may curb tumor progression at the expense of increasing cardiac stress.     

The preparation and characterization of chitosan rods modified with Fe3+ by a chelation mechanism

Chitosan composite rods (CS-Fe(3+)) were prepared via an in situ precipitation method. The relationships among the preparation, structures, and properties of the CS-Fe(3+) composite rods have been investigated. The results of Fourier-transform infrared spectroscopy (FTIR) and core electron X-ray photoelectron spectroscopy (XPS) indicate that the CS and Fe(3+) are coordinated via a chelation mechanism. The content of Fe(3+) in the complex was determined by atomic absorption spectrometry (AAS) and elemental analysis (EA), the results of which suggested that the content of Fe(3+) in the complex can be controlled by the concentration of the ferric salts during coordination. The changes in thermal stability and crystallization properties were measured by thermogravimetric analysis (TGA) and X-ray diffraction (XRD) patterns, respectively. Scanning electron microscopy (SEM) was used to observe the morphological change of the CS-Fe(3+) complex rod. After coordination with Fe(3+), the CS rod had a denser, layered structure. However, the layered structure cannot remain intact when the ratios of -NH(2)/Fe(3+) are 100/15 and 100/20. Moreover, its thermal stability decreased, and its bending strength was improved significantly (from 86 MPa to more than 210 MPa), despite the remarkable decrease in the degree of crystallinity.     

基于叶片干物质的滴灌玉米临界氮稀释曲线构建

建立宁夏引黄灌区滴灌玉米临界氮浓度稀释曲线,采用临界氮浓度模型对滴灌玉米氮营养状况进行分析,探讨基于此模型推导的氮营养指数用于诊断氮营养的可行性,为实现滴灌玉米氮肥精准管理和生态环境保护提供理论参考。试验以‘天赐19’玉米为材料,设置6个氮素水平(0、90、180、270、360和450 kg·hm^-2),在2年田间定位试验的基础上构建基于叶片干物质(LDM)的滴灌玉米临界氮浓度(N_c)稀释曲线和氮营养指数模型。结果表明: 1)滴灌玉米叶片干物质和氮浓度之间呈负幂函数关系,其模型表达式分为2部分: 当LDM<1.15 t·hm^-2时,N_c=3.2%;当LDM≥1.15 t·hm^-2时,N_c=3.29LDM^-0.29;2)拟合模型的评价指标均方根误差(RMSE)和标准化均方根误差(n-RMSE)分别为0.203、8.0%,年度间具有较好的稳定性;3)不同氮素处理下,氮营养指数(NNI)在0.47~1.44。不同生长阶段NNI与产量呈显著正相关,与氮肥农学利用效率呈显著负相关,故NNI可进一步解释滴灌玉米在限氮和非限氮条件下的产量变化。本研究基于叶片干物质构建的临界氮浓度稀释曲线可在滴灌玉米拔节期至吐丝期提供准确的氮素营养状况估测。     

20(S)‐Protopanaxadiol inhibits epithelial‐mesenchymal transition by promoting retinoid X receptor alpha in human colorectal carcinoma cells

Colorectal carcinoma (CRC) recurrence is often accompanied by metastasis. Most metastasis undergo through epithelial‐mesenchymal transition (EMT). Studies showed that retinol X receptor alpha (RXRα) and 20(S)‐Protopanaxadiol (PPD) have anti‐tumour effects. However, the anti‐metastasis effect of 20(S)‐PPD and the effect of RXRα on EMT‐induced metastasis are few studies on. Therefore, the role of RXRα and 20(S)‐PPD in CRC cell metastasis remains to be fully elucidated. RXRα with clinicopathological characteristics and EMT‐related expression in clinical samples were examined. Then, RXRα and EMT level in SW480 and SW620 cells, overexpressed and silenced RXRα in SW620 cells and SW480 cells, respectively, were evaluated. Finally, 20(S)‐PPD effect on SW620 and SW480 cells was evaluated. The results showed that a lower RXRα expression in cancer tissues, and a moderate negative correlation between RXRα and N stage, and tended to higher level of EMT. SW480 and SW620 cells had the highest and lowest RXRα expression among four CRC cell lines. SW480 had lower EMT level than SW620. Furthermore, 20(S)‐PPD increased RXRα and inhibited EMT level in SW620 cell. Finally, 20(S)‐PPD cannot restore SW480 cells EMT level to normal when RXRα silencing. These findings suggest that 20(S)‐PPD may inhibit EMT process in CRC cells by regulating RXRα expression.     

Light Harvesting at Oblique Incidence Decoupled from Transmission in Organic Solar Cells Exhibiting 9.8% Efficiency and 50% Visible Light Transparency

For many years, it has been recognized that potential organic photovoltaic cells must be integrated into elements requiring high transparency. In most of such elements, sunlight is likely to be incident at large angles. Here it is demonstrated that light transmission can be largely decoupled from harvesting by optically tailoring an infrared shifted nonfullerene acceptor based organic cell architecture. A 9.67% power conversion efficiency at 50° incidence is achieved together with an average visual transmission above 50% at normal incidence. The deconstruction of a 1D nanophotonic structure is implemented to conclude that just two λ/4 thick layers are essential to reach, for a wide incidence angle range, a higher than 50% efficiency increase relative to the standard configuration reference. In an outdoor measurement of vertically positioned 50% visible transparent cells, it is demonstrated that 9.80% of sunlight energy can be converted into electricity during the course of 1 day.