The Hidden Hydroxide in BaNiO3 Single Crystals Grown from a KOH Flux

Hexagonal oxide perovskites with one-dimensional chains of face-sharing MO6 octahedra are of enduring interest. Specifically, the hexagonal perovskite BaNiO3, prepared via non-ceramic approaches, acts as a highly functional catalyst for the oxygen-evolution reaction (OER) in alkaline media, with numerous studies focusing on this behavior, while its fundamental structural and physical properties have been somewhat overlooked. The current work is intiated by the observation of contrasting magnetic properties of BaNiO3 synthesized via KOH flux growth and high O2 pressure ceramic synthesis. To shed light on this difference, we have performed a series of rigorous analyses and found that the KOH flux-grown crystals made in open-air are actually a wet form of BaNiO3 that can be dried upon annealing in O2 flow but will then slowly degrade if stored under a condition where the O2 partial pressure is not high enough. Therefore, the present work not only provides insightful information to unveil a previously unknown aspect of the OER catalyst BaNiO3, but also rings a bell that the hidden hydroxide principle described here may also be applied to other hexagonal perovskite oxides prepared in wet conditions.Comment: 21 pages, 6 figure

Proteomic Analysis on Neuroblastoma Cell Line SH-SY5Y Treated with β–Amyloid

澱粉樣蛋白與人類衰弱疾病有關，包括阿茲海默症 (Alzheimer’s disease, AD) 、杭廷頓氏舞蹈症 (Huntington’s disease)、普利昂 (Prion) 相關的疾病，並且可能與白內障的形成有關。這種與老化相關的神經疾病，例如AD，肇於平常循環性可溶的β-澱粉樣蛋白胜肽 (Aβ)，其構形轉變為β-澱粉樣蛋白纖維，後者分別形成老年斑或是神經纖維糾結。一些神經纖維糾結顯示其成份亦包含過度磷酸化的 tau 蛋白質。細胞外Aβ的累積和細胞內tau 蛋白纏結會刺激一系列不正常的訊號和反應，例如細胞內離子衡定的破壞， 不尋常的訊息傳導和長期的發炎反應，都會逐漸導致神經細胞的死亡。 由於人體腦部切片樣品多是病患死亡之後才能取得，樣品稀少，且此時往往已是病症末期。初期的細胞生理變化往往不容易觀察，然而這也許是闡明這一類神經失調疾病機制的重要關鍵。因此這篇論文以人類神經母細胞瘤細胞株 SH-SY5Y作為研究的系統，透過蛋白質體學的方法來研究細胞外的Aβ對於細胞內蛋白質表現所造成的影響。 我們以Aβ處理了神經母細胞瘤細胞，並分別利用二維電泳 (2D-PAGE)以及逆轉錄-聚合酶鏈反應 (RT-PCR)發現了一些蛋白質與基因表現上的變化。同時也利用了能夠辨認磷酸化酪胺酸 (tyrosine)的抗體，進行免疫轉漬 (immunoblotting)的實驗，偵測到蛋白質磷酸化的現象。另外，透過暫時表現基因的方式，發現SH-SY5Y細胞表現正常人類水晶體蛋白αB或其突變序列 (R120G)時，對於Aβ的忍受力會有所不同。由於阿茲海默症與蛋白質摺疊錯誤息息相關，而水晶體蛋白αB為一種小熱休克蛋白質，具有蛋白質分子保護者活性，因此水晶體蛋白αB可能參與了訊息傳導與細胞骨架的調控。從而水晶體蛋白αB本身的性質及其在阿茲海默症病理上扮演的角色，有必要進行更深入詳盡的研究。Amyloid is associated with debilitating human ailments including prominently Alzheimer's disease (AD), Huntington's disease, Prion-related diseases and possibly cataract formation. A central event in this kind of aging-related neurological diseases such as Alzheimer's disease is the conformational change from normally circulating soluble amyloid beta peptides (Aβ) into amyloid fibrils, in the form of senile plaques and neurofibrillary tangles respectively. Some neurofibrillary tangles were also shown to consist of hyperphosphorylated tau proteins. Extracellular Aβ accumulation and intracellular tau tangling would stimulate a series of abnormal signaling and response such as disruption of intracellular ion homeostasis, irregular signal transduction and long-term inflammatory response, all progressively leading to neuronal cell death of neurons. Because brain dissections are often available only after patients' death, sporadic samples obtained usually belong to the diseased state of a very late stage. Generally it is difficult to observe cellular changes in the early stage, which may play a critical role to unravel the mechanism underlying this group of neurological disorders. In this study we have therefore resorted to using the neuroblastoma cell line SH-SY5Y as a model system to study the effects of extracellular Aβ on the protein expression profiles of neuronal cells by a proteomic approach. We treated neuroblastoma cells with Aβ and found some changes in protein and gene expressions as judged by 2D-PAGE and RT-PCR, respectively. Additionally, some proteins modified by phosphorylation were detected by immunoblotting with antibodies against phosphotyrosine. We also found cells transfected for temporary expression of human αB-crystallin or its mutant, αB-crystallin R120G, showed different tolerance to the toxic effects of Aβ. Since AD is concerned with protein misfolding and αB-crystallin is a small heat-shock protein with chaperone activity, this protein might be involved in signal transduction and cell skeleton regulation. Detailed study of αB-crystallin and its role in the pathogenesis of amyloid formation and Alzheimer's disease is warranted for future studies.目錄…………………………………………………………I 縮寫表………………………………………………………II 中文摘要……………………………………………………III 英文摘要……………………………………………………VI 壹、背景介紹………………………………………………1 貳、研究動機………………………………………………5 參、實驗設計………………………………………………6 肆、材料與方法……………………………………………7 一、實驗材料……………………………………………7 二、實驗方法……………………………………………9 伍、實驗結果與討論………………………………………19 陸、未來展望………………………………………………23 柒、圖表……………………………………………………24 圖1……………………………………………………24 圖2……………………………………………………25 圖3……………………………………………………26 表1……………………………………………………28 圖4……………………………………………………29 圖5……………………………………………………30 表2……………………………………………………31 圖6……………………………………………………32 圖7……………………………………………………33 捌、附錄……………………………………………………34 玖、參考文獻………………………………………………3

Animal Models of Tremor: Relevance to Human Tremor Disorders

ackground: Tremor is the most common movement disorder; however, the pathophysiology of tremor remains elusive. While several neuropathological alterations in tremor disorders have been observed in post-mortem studies of human brains, a full understanding of the relationship between brain circuitry alterations and tremor requires testing in animal models. Additionally, tremor animal models are critical for our understanding of tremor pathophysiology, and/or to serve as a platform for therapy development. Methods: A PubMed search was conducted in May 2018 to identify published papers for review. Results: The methodology used in most studies on animal models of tremor lacks standardized measurement of tremor frequency and amplitude; instead, these studies are based on the visual inspection of phenotypes, which may fail to delineate tremor from other movement disorders such as ataxia. Of the animal models with extensive tremor characterization, harmaline-induced rodent tremor models provide an important framework showing that rhythmic and synchronous neuronal activities within the olivocerebellar circuit can drive action tremor. In addition, dopamine-depleted monkey and mouse models may develop rest tremor, highlighting the role of dopamine in rest tremor generation. Finally, other animal models of tremor have involvement of the cerebellar circuitry, leading to altered Purkinje cell physiology. Discussion: Both the cerebellum and the basal ganglia are likely to play a role in tremor generation. While the cerebellar circuitry can generate rhythmic movements, the nigrostriatal system is likely to modulate the tremor circuit. Tremor disorders are heterogeneous in nature. Therefore, each animal model may represent a subset of tremor disorders, which collectively can advance our understanding of tremor

Nerolidol Suppresses the Inflammatory Response during Lipopolysaccharide-Induced Acute Lung Injury via the Modulation of Antioxidant Enzymes and the AMPK/Nrf-2/HO-1 Pathway

Acute lung injury (ALI) is a life-threatening disease that is characterised by the rapid onset of inflammatory responses. Lipopolysaccharide (LPS) is an endotoxin that plays an important role in triggering ALI via pneumonia and sepsis. However, no effective therapeutic strategies are currently available to treat ALI. Nerolidol is an aliphatic sesquiterpene alcohol that is found in the essential oils of many flowers as well as floral plants. It has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties. Herein, we show that nerolidol pretreatment counteracted the histopathological hallmarks in LPS-induced ALI mice. Indeed, nerolidol pretreatment inhibited LPS-induced alveolar-capillary barrier disruption, lung edema, and lipid peroxidation. Moreover, nerolidol pretreatment prevented the LPS from decreasing the enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase. Importantly, nerolidol treatment enhanced phosphorylation of AMP-activated protein kinase (AMPK) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). Taken together, our study reveals the novel protective effects of nerolidol in LPS-induced ALI via the induction of antioxidant responses and activation of the AMPK/Nrf-2/HO-1 signalling pathway

Tracking motion kinematics and tremor with intrinsic oscillatory property of instrumental mechanics

Abstract Tracking kinematic details of motor behaviors is a foundation to study the neuronal mechanism and biology of motor control. However, most of the physiological motor behaviors and movement disorders, such as gait, balance, tremor, dystonia, and myoclonus, are highly dependent on the overall momentum of the whole‐body movements. Therefore, tracking the targeted movement and overall momentum simultaneously is critical for motor control research, but it remains an unmet need. Here, we introduce the intrinsic oscillatory property (IOP), a fundamental mechanical principle of physics, as a method for motion tracking in a force plate. The overall kinetic energy of animal motions can be transformed into the oscillatory amplitudes at the designed IOP frequency of the force plate, while the target movement has its own frequency features and can be tracked simultaneously. Using action tremor as an example, we reported that force plate‐based IOP approach has superior performance and reliability in detecting both tremor severity and tremor frequency, showing a lower level of coefficient of variation (CV) compared with video‐ and accelerometer‐based motion tracking methods and their combination. Under the locomotor suppression effect of medications, therapeutic effects on tremor severity can still be quantified by dynamically adjusting the overall locomotor activity detected by IOP. We further validated IOP method in optogenetic‐induced movements and natural movements, confirming that IOP can represent the intensity of general rhythmic and nonrhythmic movements, thus it can be generalized as a common approach to study kinematics

Transcriptome-wide identification of altered RNA m6A profiles in cardiac tissue of rats with LPS-induced myocardial injury

PurposeMyocardial injury is a common complication in patients with endotoxaemia/sepsis, especially in children. Moreover, it develops through an unclear pathophysiological mechanism, and effective therapies are lacking. Recently, RNA modification, particularly N6-methyladenosine (m6A) modification, has been found to be involved in various physiological processes and to play important roles in many diseases. However, the role of m6A modification in endotoxaemia/sepsis-induced myocardial injury is still in its infancy. Therefore, we attempted to construct the m6A modification map of myocardial injury in a rat model treated by lipopolysaccharide (LPS) and explore the role of m6A modification in LPS-induced myocardial injury.MethodMyocardial injury adolescent rat model was constructed by intraperitoneal injection of LPS. m6A RNA Methylation Quantification Kit was used to detect overall level of m6A modification in rat cardiac tissue. m6A-specific methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were conducted to identify the altered m6A-modified genes and differentially expressed genes in cardiac tissue of rats treated by LPS and control rats (6 versus. 6). Bioinformatics was used to analyze the functions of differentially m6A modified genes, differentially expressed genes, and genes with both differential m6A modification and differential expression. qPCR was used to detect expression of m6A modification related enzymes.ResultWe found that the overall level of m6A modification in cardiac tissue of the LPS group was up-regulated compared with that of the control group. MeRIP-seq and RNA-seq results showed that genes with differential m6A modification, genes with differential expression and genes with both differential m6A modification and differential expression were closely associated with inflammatory responses and apoptosis. In addition, we found that m6A-related enzymes (Mettl16, Rbm15, Fto, Ythdc2 and Hnrnpg) were differentially expressed in the LPS group versus. the control group.Conclusionm6A modification is involved in the pathogenesis process of LPS-induced myocardial injury, possibly through the regulation of inflammatory response and apoptosis-related pathways. These results provide valuable information regarding the potential pathogenic mechanisms underlying LPS-induced myocardial injury

The Potential Regimen of Target-Controlled Infusion of Propofol in Flexible Bronchoscopy Sedation: A Randomized Controlled Trial

<div><p>Objectives</p><p>Target-controlled infusion (TCI) provides precise pharmacokinetic control of propofol concentration in the effect-site (Ce), eg. brain. This pilot study aims to evaluate the feasibility and optimal TCI regimen for flexible bronchoscopy (FB) sedation.</p><p>Methods</p><p>After alfentanil bolus, initial induction Ce of propofol was targeted at 2 μg/ml. Patients were randomized into three titration groups (i.e., by 0.5, 0.2 and 0.1 μg/ml, respectively) to maintain stable sedation levels and vital signs. Adverse events, frequency of adjustments, drug doses, and induction and recovery times were recorded.</p><p>Results</p><p>The study was closed early due to significantly severe hypoxemia events (oxyhemoglobin saturation <70%) in the group titrated at 0.5 μg/ml. Forty-nine, 49 and 46 patients were enrolled into the 3 respective groups before study closure. The proportion of patients with hypoxemia events differed significantly between groups (67.3 vs. 46.9 vs. 41.3%, <i>p</i> = 0.027). Hypotension events, induction and recovery time and propofol doses were not different. The Ce of induction differed significantly between groups (2.4±0.5 vs. 2.1±0.4 vs. 2.1±0.3 μg/ml, <i>p</i> = 0.005) and the Ce of procedures was higher at 0.5 μg/ml titration (2.4±0.5 vs. 2.1±0.4 vs. 2.2±0.3 μg/ml, <i>p</i> = 0.006). The adjustment frequency tended to be higher for titration at 0.1 μg/ml but was not statistically significant (2 (0∼6) vs. 3 (0∼6) vs. 3 (0∼11)). Subgroup analysis revealed 14% of all patients required no further adjustment during the whole sedation. Comparing patients requiring at least one adjustment with those who did not, they were observed to have a shorter induction time (87.6±34.9 vs. 226.9±147.9 sec, p<0.001), a smaller induction dose and Ce (32.5±4.1 vs. 56.8±22.7 mg, p<0.001; 1.76±0.17 vs. 2.28 ±0.41, p<0.001, respectively), and less hypoxemia and hypotension (15.8 vs.56.9%, p = 0.001; 0 vs. 24.1%, p = 0.008, respectively).</p><p>Conclusion</p><p>Titration at 0.5 μg/ml is risky for FB sedation. A subgroup of patients required no more TCI adjustment with fewer complications. Further studies are warranted to determine the optimal regimen of TCI for FB sedation.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT01101477" target="_blank">NCT01101477</a></p></div