The Role of CaMKII and ERK Signaling in Addiction

Nicotine is the predominant addictive compound of tobacco and causes the acquisition of dependence through its interactions with nicotinic acetylcholine receptors and various neurotransmitter releases in the central nervous system. The Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) play a pivotal role in synaptic plasticity in the hippocampus. CaMKII is involved in long-term potentiation induction, which underlies the consolidation of learning and memory; however, the roles of CaMKII in nicotine and other psychostimulant-induced addiction still require further investigation. This article reviews the molecular mechanisms and crucial roles of CaMKII and ERK in nicotine and other stimulant drug-induced addiction. We also discuss dopamine (DA) receptor signaling involved in nicotine-induced addiction in the brain reward circuitry. In the last section, we introduce the association of polyunsaturated fatty acids and cellular chaperones of fatty acid-binding protein 3 in the context of nicotine-induced addiction in the mouse nucleus accumbens and provide a novel target for the treatment of drug abuse affecting dopaminergic systems.     

Chloroquine-Induced Accumulation of Autophagosomes and Lipids in the Endothelium

Chloroquine (CQ) is an antimalarial drug known to inhibit autophagy flux by impairing autophagosome–lysosome fusion. We hypothesized that autophagy flux altered by CQ has a considerable influence on the lipid composition of endothelial cells. Thus, we investigated endothelial responses induced by CQ on human microvascular endothelial cells (HMEC-1). HMEC-1 cells after CQ exposure were measured using a combined methodology based on label-free Raman and fluorescence imaging. Raman spectroscopy was applied to characterize subtle chemical changes in lipid contents and their distribution in the cells, while the fluorescence staining (LipidTox, LysoTracker and LC3) was used as a reference method. The results showed that CQ was not toxic to endothelial cells and did not result in the endothelial inflammation at concentrations of 1–30 µM. Notwithstanding, it yielded an increased intensity of LipidTox, LysoTracker, and LC3 staining, suggesting changes in the content of neutral lipids, lysosomotropism, and autophagy inhibition, respectively. The CQ-induced endothelial response was associated with lipid accumulation and was characterized by Raman spectroscopy. CQ-induced autophagosome accumulation in the endothelium is featured by a pronounced alteration in the lipid profile, but not in the endothelial inflammation. Raman-based assessment of CQ-induced biochemical changes offers a better understanding of the autophagy mechanism in the endothelial cells.     

Achieving High Electroluminescence Efficiency and High Color Rendering Index for All-Fluorescent White OLEDs Based on an Out-of-Phase Sensitizing System

Sensitizing conventional fluorescence (CF) dopants with thermally activated delayed fluorescence (TADF) materials has achieved considerable progress, by which the advantages of TADF materials and CF dopants can be fully harnessed. However, the usually used co-phase configuration of CF dopant-engaged sensitizing systems often encounters exciton loss due to Dexter energy transfer (DET). Herein, an effective out-of-phase configuration is proposed to sensitize CF dopants in the fabrication of white organic light-emitting diodes (WOLEDs). Based on a new efficient sky-blue TADF luminogen DCP-BP-DPAC which has an electroluminescence (EL) peak at 486 nm and an EL efficiency of 26.6%, a green TADF material BDMAC-XT, and a red CF dopant DBP sensitized by BDMAC-XT through an out-of-phase configuration without interlayer, efficient WOLEDs are successfully fabricated. By further adopting orange TBRB or 4CzTPNBu as intermediate sensitizers, more efficient energy transfer to DBP is achieved via Förster energy transfer. Through step-by-step energy transfer and elimination of excess DET process, high-performance all-fluorescent WOLEDs are achieved, providing excellent EL efficiencies over 23.0%, and highly stable white light with a high color rendering index of 87. The outstanding EL performance and high-quality emission color demonstrate the great potential of the proposed out-of-phase design for sensitizing systems of WOLEDs.     

Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

超高效液相色谱-飞行时间质谱法快速分析测定山药中7种常见杀菌剂

目的 建立超高效液相色谱-飞行时间质谱检测山药中7种常见杀菌剂的分析方法。方法 样品经乙腈提取，水浴氮吹至近干，丙酮定容，经超高效液相色谱-飞行时间质谱检测。结果 在正离子模式下，7种杀菌剂在水-甲醇（均含有0.01%甲酸和5 mmol/L甲酸铵）流动相中都具有较好的响应；0.01~0.40 mg/L范围内线性良好，相关系数R均大于0.999。不同温度（50℃、70℃）水浴实验结果表明70℃水浴温度符合实验要求。三个浓度水平的加标回收实验的回收率为70.75％～108.07％，相对标准偏差为 0.02％～5.01％。结论 该方法操作简单、分析准确，满足山药中常见杀菌剂的检测要求。