Emerging Immunotherapy for Acute Myeloid Leukemia

Several immune checkpoint molecules and immune targets in leukemic cells have been investigated. Recent studies have suggested the potential clinical benefits of immuno-oncology (IO) therapy against acute myeloid leukemia (AML), especially targeting CD33, CD123, and CLL-1, as well as immune checkpoint inhibitors (e.g., anti-PD (programmed cell death)-1 and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) antibodies) with or without conventional chemotherapy. Early-phase clinical trials of chimeric antigen receptor (CAR)-T or natural killer (NK) cells for relapsed/refractory AML showed complete remission (CR) or marked reduction of marrow blasts in a few enrolled patients. Bi-/tri-specific antibodies (e.g., bispecific T-cell engager (BiTE) and dual-affinity retargeting (DART)) exhibited 11–67% CR rates with 13–78% risk of cytokine-releasing syndrome (CRS). Conventional chemotherapy in combination with anti-PD-1/anti-CTLA4 antibody for relapsed/refractory AML showed 10–36% CR rates with 7–24 month-long median survival. The current advantages of IO therapy in the field of AML are summarized herein. However, although cancer vaccination should be included in the concept of IO therapy, it is not mentioned in this review because of the paucity of relevant evidence.     

一种植物油中苯并（a）芘含量测定的固相萃取前处理方法

为了建立一种准确性高、成本低的植物油中苯并(a)芘测定的样品前处理方法，基于GB 5009.7—2016以自制氧化铝柱为固相萃取柱，采用单因素试验对称样量、洗脱剂量、洗脱流速、吸附剂存放时间、吸附剂量这5个影响植物油中苯并（a）芘洗脱的因素进行研究，优化前处理条件，并对测定方法进行考察。结果表明：优化的前处理条件为称样量0.100 0 g、洗脱剂量120 mL、吸附剂（氧化铝）量22 g、洗脱流速1滴/2 s、吸附剂存放时间少于12周；方法检出限为0.2 μg/L，样品加标回收率为94.23%～100.00%，RSD为1.20%～7.36%；同一样品测定结果与SGS测定值接近，相对平均偏差为2.36%～3.50%。说明本试验方法测定结果准确，可应用于油脂企业植物油中痕量苯并（a）芘的测定。     

4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene,a Major Active Metabolite of Bisphenol A,Triggers Pancreatic β-Cell Death via a JNK/AMPKα Activation-Regulated Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway

4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway.     

农药沉积利用率喷雾指示剂诱惑红的酶标仪测定方法

诱惑红是一种水溶性染料,近年来被用作农药沉积利用率测定的指示剂。诱惑红的检测方法为高效液相色谱法和分光光度法。高效液相色谱法需要专门的分析仪器,且价格昂贵,可见分光光度计法操作繁琐,试剂用量大,耗时长,均不适宜田间快速高效测定。笔者发展了诱惑红的酶标仪测定方法,简单高效,可批量检测多个样品,且准确度和精密度高,线性关系良好,514 nm检测波长下不受其他农药影响,并应用于玉米无人飞机喷雾场景下农药雾滴在玉米冠层的沉积利用率测定。     

Effect of the thicknesses of the Al2SiO5 ion conductor on the opto-electrical properties for all-solid electrochromic devices

In this study, an all-solid-state electrochromic device (ECD) with the structure of ITO/WO₃/Al₂SiO₅/NiO_x/ITO was prepared, and the effect of the Al₂SiO₅ solid electrolyte thicknesses on the opto-electrical performance was investigated. The microstructure and surface morphology were characterized using XRD, SEM and AFM, and the surface morphology and degree of surface looseness demonstrate a significant influence on the opto-electrical properties of ECDs. The charge transfer dynamics at the solid-solid interface were characterized using EIS to obtain an ionic conductivity of 4.637 × 10^-8 S/cm. CV, CA and UV–Visible spectra were employed to record the in situ electrochemical and optical properties. The results revealed that the highest optical modulation was 44.58%, the coloring and bleaching times were 14.8 s and 3.7 s, and the highest coloring efficiency was 98.17 cm²/C, which indicates that excellent opto-electrical properties were obtained. When the thickness increases, the degree of surface dense morphology transforms, and the loose morphology is more favorable for ion conductivity, which improves the opto-electrical properties. The results in this study provide insights into the understanding of Al³⁺-based all-solid-state ECDs, which promote the exploration of new types of Al³⁺ ionic conductors for all-solid-state ECDs.     

Weighted regularized extreme learning machine to model the discharge coefficient of side slots

In the current research, a modern learning machine algorithm named “Weighted Regularized Extreme Learning Machine (WRELM)" is implemented for the first time for the simulation of the coefficient of discharge of side slots. For this purpose, an effective variable on the coefficient of discharge of side slots is firstly introduced, then five distinctive WRELM models are produced by it for the estimation of the coefficient. In the next stage, a database is created for verification of WRELM results. it should be mentioned that 70% of the data are utilized for training the WRELM models, while the rest (i.e. 30%) for testing them. After that, the optimal number of hidden layer neurons as well as the best activation function of the WRELM algorithm are chosen. In addition, the best regularization parameter and also the weight function of the WRELM are achieved. By conducting a sensitivity analysis, the most effective variable for the simulation of the coefficient of discharge along with the WRELM superior model is introduced. The WRELM superior model estimates values of the coefficient of discharge with the maximum exactness and the highest correlation. For instance, the estimations of the correlation coefficient and scatter index for this model are computed to be 0.930 and 0.051, respectively. The sensitivity analysis shows that the ratio of the side slot crest height to its length and the Froude number should be considered as the most important input variables. A comparison between the WRELM with the ELM displays that the former works much better. Furthermore, an uncertainty analysis is executed for both models. Eventually, an equation is suggested for the estimation of the coefficient of discharge and a partial derivative sensitivity analysis is performed on it.     

改进的CAGAN在虚拟试衣中的应用

针对CAGAN（Conditional Analogy GAN）换衣后效果模糊，在目标衣服与原始衣服长短不一致时效果一般，相对目标衣服保留过少的细节等问题做了相关研究并对CAGAN进行了改进，提出了新的虚拟试衣方式。经过改进的CAGAN生成一个粗糙的结果，由该结果得到目标衣服穿在模特身上改变形状后的mask，接下来利用mask对目标衣服进行变形，综合变形的衣服和第一步的结果便得到最终的试衣图像。实验结果表明，该方法解决了前面存在的问题，而且取得了非常好的效果。