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.     

An active balancer with rapid bidirectional charge shuttling and adaptive equalization current control for lithium-ion battery strings

This article proposes an active balancer, which features bidirectional charge shuttling and adaptive equalization current control, to fast counterbalance the state of charge (SOC) of cells in a lithium-ion battery (LIB) string. The power circuit consists of certain bidirectional buck-boost converters to transfer energy among the different cells back and forth. Owing to the characterization of the open-circuit voltage (OCV) vs SOC in LIB being relatively smooth near the SOC middle range, the SOC-inspected balance strategy can achieve more precise and efficient equilibrium than the voltage-based control. Accordingly, a compensated OCV-based SOC estimation is put forward to take into account the discrepancy of SOC estimation. Besides, the varied-duty-cycle (VDC) and curve-fitting modulation (CFM) methods are devised herein to tackle the problems of slow equalization rate and low balance efficacy, which arise from the diminution in balancing current as the SOC difference between the cells decreases in the later duration of equalization especially. The proposed strategies have taken the battery nonlinear characteristic and circuit parameter nonideality into account and can adaptively modulate the duty cycle with the SOC difference to keep balancing current constant throughout the balancing cycle. Simulated and experimental results are given to demonstrate the feasibility and effectiveness of the same prototype constructed. Compared with the fixed duty cycle and the VDC methods, the proposed CFM has the best balancing efficiency of 81.4%, and the balance time is shortened by 27.1% and 18.6%, respectively.     

Optimized Biocatalytic Synthesis of 2-Selenopyrimidine Nucleosides by Transglycosylation**

Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes.     

Decreased CD10-positive granulocytes for the differential diagnosis of myelodysplastic syndrome

Myelodysplastic syndromes (MDS) are highly heterogeneous myeloid neoplasms, and a large number of patients are difficult to diagnose and classify by blood and bone marrow examination. As a surface marker of granulocyte, studies have shown CD10 can be used to define the degree of granulocyte maturation in MDS patients. However, whether it can be used for differential diagnosis of MDS and other hematological diseases remains inconclusive. To explore the value of CD10 for differential diagnosis of MDS, 60 newly diagnosed MDS, 20 aplastic anemia (AA) patients, and 35 iron-deficient anemia (IDA) patients were selected for this study. Bone marrow (BM) specimens were processed for surface marker analysis and labeled with pre-conjugated monoclonal antibodies. Stained cells were detected by flow cytometry. Our results indicated that CD10-positive granulocytes were significantly decreased in BM of MDS patients than AA and IDA patients, and the level of CD10-positive mature granulocytes was not associated with the clinical stages of malignancy. Receiver operating characteristic (ROC) areas under the curve (AUC) of CD10-positive granulocytes was 0.86 and 0.85, respectively, in MDS patients than the IDA group and AA group with good specificity and sensitivity. Further, CD10-positive granulocytes were increased after effective treatment. In conclusion, we found the decrease in CD10-positive granulocytes has a differential diagnostic value of MDS.     

总变差模型在书画打印宣纸印刷质量预测中的应用

为了建立适用于书画打印宣纸印刷质量的预测模型,本研究测量了14种书画打印宣纸的粗糙度、白度、不透明度、定量、光泽度和针对宣纸特别设定的帘纹深浅以及帘纹疏密度等表面物理参量,并在相同条件下,使用喷墨打印设备输出并测量印品色度值,利用总变差模型构建去除帘纹色差的测定方法,得到与人眼视觉特征相符的色差。运用GRNN广义回归神经网络结合书画打印宣纸表面物理参量与宣纸去帘纹后的色差值,建立预测模型。结果表明,该模型能够在仅测量书画打印宣纸表面物理参量的情况下,便能较为准确地预测书画打印宣纸印刷质量,为书画打印宣纸印刷前的选纸工作提供指导依据。     

轻量级电驱水下机械臂设计与运动学分析

设计了一款四功能水下机械臂，并对驱动关节进行了模块化设计和密封测试。为了保证水下机械臂的可靠性，在水下机械臂水下测试前，进行了强度校核和模态分析。为了验证水下机械臂的性能，通过 Ｄ- Ｈ法建立了其运动学模型，在此基础上分别进行了正、逆运动学分析。此外还采用蒙特卡洛法，在正运动学分析的基础上研究了工作空间特点。研究结果将为进一步的运动控制提供有益的帮助。