Insight into Amyloid Formation Using Congo Red as the Electrochemical Probe

The amyloid‐β (Aβ) aggregation pathway is an important target for the discovery of drugs that can prevent or delay the onset of Alzheimer’s disease (AD). The electrochemistry of Congo Red (CR) represents a particularly promising tool for screening of Aβ‐binding therapeutics in a rapid and cost‐effective format. The results of the differential pulse voltammetry (DPV) measurements were confirmed using simultaneous UV‐vis analysis of the same incubated Aβ samples. The early changes in the electrochemical signals were attributed to the interaction of the Aβ oligomers with CR. The electrochemical approach, in principle, allowed monitoring small molecule‐Aβ interactions on the time scale of aggregation.     

Generalized Markov Models of Infectious Disease Spread: A Novel Framework for Developing Dynamic Health Policies

We propose a class of mathematical models for the transmission of infectious diseases in large populations. This class of models, which generalizes the existing discrete-time Markov chain models of infectious diseases, is compatible with efficient dynamic optimization techniques to assist real-time selection and modification of public health interventions in response to evolving epidemiological situations and changing availability of information and medical resources. While retaining the strength of existing classes of mathematical models in their ability to represent the within-host natural history of disease and between-host transmission dynamics, the proposed models possess two advantages over previous models: (1) these models can be used to generate optimal dynamic health policies for controlling spreads of infectious diseases, and (2) these models are able to approximate the spread of the disease in relatively large populations with a limited state space size and computation time.     

Highly sensitive detection of S-nitrosylated proteins by capillary gel electrophoresis with laser induced fluorescence

S-nitrosylated proteins are biomarkers of oxidative damage in aging and Alzheimer's disease (AD). Here, we report a new method for detecting and quantifying nitrosylated proteins by capillary gel electrophoresis with laser induced fluorescence detection (CGE-LIF). Dylight 488 maleimide was used to specifically label thiol group (SH) after switching the S-nitrosothiol (S-NO) to SH in cysteine using the "fluorescence switch" assay. In vitro nitrosylation model-BSA subjected to S-nitrosoglutathione (GSNO) optimized the labeling reactions and characterized the response of the LIF detector. The method proves to be highly sensitive, detecting 1.3 picomolar (pM) concentration of nitrosothiols in nanograms of proteins, which is the lowest limit of detection of nitrosothiols reported to date. We further demonstrated the direct application of this method in monitoring protein nitrosylation damage in MQ mediated human colon adenocarcinoma cells. The nitrosothiol amounts in MQ treated and untreated cells are 14.8±0.2 and 10.4±0.5 pmol/mg of proteins, respectively. We also depicted nitrosylated protein electrophoretic profiles of brain cerebrum of 5-month-old AD transgenic (Tg) mice model. In Tg mice brain, 15.5±0.4 pmol of nitrosothiols/mg of proteins was quantified while wild type contained 11.7±0.3 pmol/mg proteins. The methodology is validated to quantify low levels of S-nitrosylated protein in complex protein mixtures from both physiological and pathological conditions.     

一类传染病模型

利用稳定性理论和齐次向量场的性质对一类传染病模型的一般情形进行研究,通过对R2中相应系统的平衡点的存在性和稳定性的分析,得出该类传染病持续生存和最终消亡的阈值,而且它与治愈者的死亡率以及治愈者向易感者的转化率无关.     

Feedback control variables to restrain the Babesiosis disease

In this paper, we complete the study of the dynamics of a recognized continuous‐time model for the Babesiosis disease. The local and global asymptotic stability of the endemic state are established theoretically and experimentally. In addition, to restrain the disease in the original model when the endemic state exists, we propose and study the continuous model with feedback controls. The global stability of the boundary‐equilibrium point of this model is analyzed by means of rigorous mathematical methods. As an important consequence of this result, we propose a strategy to select feedback control variables in order to restrain the disease in the original model. This strategy allows us to make the disease vanish completely. In other words, the feedback controls are specially effective for restraining disease in the model. The validity of the established theoretical result is supported by a set of numerical simulations.     

Modeling of Lone Star Ticks with Deer Migration to Canada

Due to climate change and an increase of favourable habitat, ticks and tick-borne diseases are reported to expand to northern areas in north America. One main factor for lone star ticks to be established in Canada is due to the migration of white-tailed deers from US. In this work, we formulate a compartmental model to study the dynamics of lone star ticks and white-tailed deers, with a focus on migration effect of white-tailed deers. The tickhost interaction and the effect of deer migration are explored analytically and numerically. The positivity of the populations in the model is proved, and the unique positive equilibrium is proved to be asymptotically stable. We conduct sensitivity analysis on a set of parameters, revealing the correlation between the parameters and equilibrium populations. Numerical results show that migration rate of white-tailed deer is one crucial parameter that increases the populations of (infected) ticks and (infected) hosts.     

PLS-DA优化模型的马铃薯黑心病可见近红外透射光谱检测

马铃薯黑心病是一种马铃薯主要内部缺陷,严重损害薯条、薯片、全粉等加工制品的质量和产率。目前对马铃薯的分级主要侧重于外部品质检测,针对内部缺陷检测的研究很少。旨在开发一种马铃薯黑心病的快速无损检测技术,为此搭建了马铃薯可见近红外透射光谱分析平台,分析健康与黑心病马铃薯的透射光谱特性并优化光谱判别模型参数。基于现有马铃薯分级线和复享PG2000高速光谱仪,采用左右透射方式（光源与光纤探头位于分级线果盘左右两侧）,采集470个马铃薯（其中健康薯234个、黑心薯236个）的透射光谱图,建立偏最小二乘判别模型（PLS-DA）,并利用主成分分析（PCA）与光谱形态特征相结合的方法选择特征波长,优化模型。分析发现,健康薯与黑心薯的可见近红外透射光谱在吸光度值和光谱形态特征方面均存在明显区别。黑心薯的平均光谱吸光度值高于健康薯（650～900 nm范围内）,但黑心薯的平均光谱曲线较为平缓,无明显吸收峰,而健康薯平均光谱曲线在665,732和839 nm附近有明显吸收峰,并且健康薯与黑心薯的平均光谱差值在705 nm处达到最大值。基于PLS-DA法建立了马铃薯黑心病判别模型,对黑心病的判别效果显著,分类器特性曲线（ROC）下面积（AUC）值为0.994 2,黑心薯识别总正确率能够达到97.16%,RMSE_CV和RMSE_P分别为0.28和0.26。此外,成功利用PCA与光谱形态特征相结合的方法对模型进行简化,最终得到由6个波长（658,705,716,800,816和839 nm）组成的特征波长组合,简化后的模型总正确率能够达到96.73%,接近全波段模型判别水平。研究表明,左右透射的方式能够准确识别黑心马铃薯,实现对马铃薯内部缺陷的快速无损检测。对我国马铃薯产业的发展起到一定的促进作用,为马铃薯内部缺陷在线检测技术的提高提供了重要的理论基础和实践依据。     

Neuroprotective Activities of Crossyne flava Bulbs and Amaryllidaceae Alkaloids: Implications for Parkinson’s Disease

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and affects approximately 6.3 million people worldwide. To date, the treatment of PD remains a challenge, as available treatment options are known to be associated with serious side effects; hence, the search for new treatment strategies is critical. Extracts from the Amaryllidaceae plant family as well as their alkaloids have been reported to have neuroprotective potentials. This study, therefore, investigated the biological activities of Crossyne flava and its isolated alkaloids in an in vitro MPP⁺ (1-methyl-4-phenylpyridinium) PD model using SH-SY5Y cells. The effects of the total extract as well as the four compounds isolated from Crossyne flava (i.e., pancratinine B (1), bufanidrine (2), buphanisine (3), and epibuphanisine (4)) were evaluated for cell viability, neuroprotection, levels of reactive oxygen species (ROS), adenosine triphosphate activity (ATP), and caspase 3/7 activity in SH-SY5Y cells. The results obtained showed that pre-treatment with both the extract and the isolated compounds was effective in protecting the SH-SY5Y cells from MPP⁺-induced neurotoxicity and inhibited ROS generation, ATP depletion as well as apoptosis induction in the SH-SY5Y cells. The results of this study show that the Amaryllidaceae plant family may be a source of novel compounds for the treatment of neurodegenerative diseases, which validates the reported traditional uses.     

The Parkinson larynx: Tremor and videostroboscopic findings

Patients with Parkinson's disease have a high incidence of speech, voice, and laryngeal abnormalities. To characterize laryngeal abnormalities, visual-perceptual ratings of endoscopic and stroboscopic examinations of 22 patients diagnosed with idiopathic Parkinson's disease and 7 patients with Parkinson's-plus syndromes were carried out by four trained viewers. Incidence of tremor, tremor location, phase closure, phase symmetry, amplitude, and mucosal waveform were scored. Tremor was observed in one or more of these conditions—rest, normal pitch and loudness, or loud phonation—for most of the 29 patients. Fifty-five percent of the idiopathic Parkinson's disease patients had tremor, with the primary location being vertical laryngeal tremor. Sixty-four percent of the Parkinson's-plus patients had tremor, with the arytenoid cartilages being the primary location. Laryngeal tremor was observed early in the disease in these Parkinson's disease patients. The most striking stroboscopic findings for the idiopathic Parkinson's disease patients were abnormal phase closure and phase asymmetry. Amplitude and mucosal wave-form were essentially within normal limits in the majority of the idiopathic Parkinson patients.     

Episodic paroxysmal laryngospasm: Voice and pulmonary function assessment and management

Episodic paroxysmal laryngospasm (EPL) is a sign of laryngeal dysfunction, often without a specific organic etiology, which can masquerade as asthma, vocal fold paralysis, or a functional voice disorder. The intermittent respiratory distress of EPL may precipitate an apparent upper airway obstructive emergency, resulting in unnecessary endotracheal intubation, cardiopulmonary resuscitation, or tracheostomy. During 27 months, seven women and three men, ages 30–76 years, were assessed by a high diagnostic index of suspicion, an intensive history including psychosocial factors, physical examination of the airways, provocative asthma testing, and swallowing studies. Videolaryngoscopy, stroboscopy, and pulmonary flow-volume loop testing were definitive. The classic appearance was paradoxic inspiratory adduction of the anterior vocal folds with a posterior diamond-shaped glottic gap. During an attack of stridor or wheezing, attenuation of the inspiratory flow rate as depicted by the flow-volume loop suggested partial extrathoracic upper airway obstruction. Swallowing evaluation by videolaryngoscopy and videoesophagography may uncover gastroesophageal reflux disease. Hallmarks of management include patient and family education by observation of laryngoscopic videos, a specific speech therapy program, psychotherapy, and medical treatment of associated disorders. Electromyography may become a valuable future adjunct. Unlike laryngeal dystonia, patients with EPL do not benefit from botulinum toxin type A.