Comments on Debra Hull's concept of rationality.

D. B. Hull (1988) misinterprets "rationality" as used in rational-emotive therapy (RET) in her critique of the present author's (1987) article. As used in RET, rational not only means derived from reason, but also means efficiently aiding human happiness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

提高计算机软件课程教学效果的思考

在信息技术时代的今天,伴随着计算机技术的迅猛发展以及在日常生活和工作中的普及,我们如何掌握常用的计算机应用软件成为每个人工作学习中不可缺少的课程。在该课程的教学过程中,教师应选择合适的版本,以培养学生的动手能力、自学能力和创新意识为出发点,综合运用实例教学法、任务驱动教学法等方法,同时给学生创造一个自主的学习环境,并建立灵活的评价体系,以增强教学效果。     

美国大学教学评估及其对中国高等教育的启示

美国大学和学院，学生对教师教学进行有效性评估。不同大学对教学有不同要求和标准；美国学术界对教学评估体系利与弊展开过辩论，而学生和老师的背景特征可能引起偏见。美国学生对老师进行教学评估的体系，对中国高等教育教学可能有一定的他石意义，但是，评估体系的现实条件有差异，中国不应当照抄或照搬美国教学评估，尤其应该摒弃将教与学关系扭曲为买方和卖方关系的观念。取其精华而弃其糟粕，建立适应中国的教学评估体系才能提高高等教育质量。     

Treatment of Oxidative Stress with Exosomes in Myocardial Ischemia

A thrombus in a coronary artery causes ischemia, which eventually leads to myocardial infarction (MI) if not removed. However, removal generates reactive oxygen species (ROS), which causes ischemia–reperfusion (I/R) injury that damages the tissue and exacerbates the resulting MI. The mechanism of I/R injury is currently extensively understood. However, supplementation of exogenous antioxidants is ineffective against oxidative stress (OS). Enhancing the ability of endogenous antioxidants may be a more effective way to treat OS, and exosomes may play a role as targeted carriers. Exosomes are nanosized vesicles wrapped in biofilms which contain various complex RNAs and proteins. They are important intermediate carriers of intercellular communication and material exchange. In recent years, diagnosis and treatment with exosomes in cardiovascular diseases have gained considerable attention. Herein, we review the new findings of exosomes in the regulation of OS in coronary heart disease, discuss the possibility of exosomes as carriers for the targeted regulation of endogenous ROS generation, and compare the advantages of exosome therapy with those of stem-cell therapy. Finally, we explore several miRNAs found in exosomes against OS.     

Dehydropeptide Supramolecular Hydrogels and Nanostructures as Potential Peptidomimetic Biomedical Materials

Supramolecular peptide hydrogels are gaining increased attention, owing to their potential in a variety of biomedical applications. Their physical properties are similar to those of the extracellular matrix (ECM), which is key to their applications in the cell culture of specialized cells, tissue engineering, skin regeneration, and wound healing. The structure of these hydrogels usually consists of a di- or tripeptide capped on the N-terminus with a hydrophobic aromatic group, such as Fmoc or naphthalene. Although these peptide conjugates can offer advantages over other types of gelators such as cross-linked polymers, they usually possess the limitation of being particularly sensitive to proteolysis by endogenous proteases. One of the strategies reported that can overcome this barrier is to use a peptidomimetic strategy, in which natural amino acids are switched for non-proteinogenic analogues, such as D-amino acids, β-amino acids, or dehydroamino acids. Such peptides usually possess much greater resistance to enzymatic hydrolysis. Peptides containing dehydroamino acids, i.e., dehydropeptides, are particularly interesting, as the presence of the double bond also introduces a conformational restraint to the peptide backbone, resulting in (often predictable) changes to the secondary structure of the peptide. This review focuses on peptide hydrogels and related nanostructures, where α,β-didehydro-α-amino acids have been successfully incorporated into the structure of peptide hydrogelators, and the resulting properties are discussed in terms of their potential biomedical applications. Where appropriate, their properties are compared with those of the corresponding peptide hydrogelator composed of canonical amino acids. In a wider context, we consider the presence of dehydroamino acids in natural compounds and medicinally important compounds as well as their limitations, and we consider some of the synthetic strategies for obtaining dehydropeptides. Finally, we consider the future direction for this research area.     

Functionalized Reduced Graphene Oxide as a Versatile Tool for Cancer Therapy

Cancer is one of the deadliest diseases in human history with extremely poor prognosis. Although many traditional therapeutic modalities—such as surgery, chemotherapy, and radiation therapy—have proved to be successful in inhibiting the growth of tumor cells, their side effects may vastly limited the actual benefits and patient acceptance. In this context, a nanomedicine approach for cancer therapy using functionalized nanomaterial has been gaining ground recently. Considering the ability to carry various anticancer drugs and to act as a photothermal agent, the use of carbon-based nanomaterials for cancer therapy has advanced rapidly. Within those nanomaterials, reduced graphene oxide (rGO), a graphene family 2D carbon nanomaterial, emerged as a good candidate for cancer photothermal therapy due to its excellent photothermal conversion in the near infrared range, large specific surface area for drug loading, as well as functional groups for functionalization with molecules such as photosensitizers, siRNA, ligands, etc. By unique design, multifunctional nanosystems could be designed based on rGO, which are endowed with promising temperature/pH-dependent drug/gene delivery abilities for multimodal cancer therapy. This could be further augmented by additional advantages offered by functionalized rGO, such as high biocompatibility, targeted delivery, and enhanced photothermal effects. Herewith, we first provide an overview of the most effective reducing agents for rGO synthesis via chemical reduction. This was followed by in-depth review of application of functionalized rGO in different cancer treatment modalities such as chemotherapy, photothermal therapy and/or photodynamic therapy, gene therapy, chemotherapy/phototherapy, and photothermal/immunotherapy.     

Biflavonoid-Induced Disruption of Hydrogen Bonds Leads to Amyloid-β Disaggregation

Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC₅₀ values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease.     

Cell Therapies in Bladder Cancer Management

Currently, bladder cancer (BC) represents a challenging problem in the field of Oncology. The high incidence, prevalence, and progression of BC have led to the exploration of new avenues in its management, in particular in advanced metastatic stages. The recent inclusion of immune checkpoint blockade inhibitors as a therapeutic option for BC represents an unprecedented advance in BC management. However, although some patients show durable responses, the fraction of patients showing benefit is still limited. Notwithstanding, cell-based therapies, initially developed for the management of hematological cancers by infusing immune or trained immune cells or after the engineering of chimeric antigen receptor (CAR) expressing cells, are promising tools to control, or even cure, solid tumors. In this review, we summarize recent cell-based immunotherapy studies, with a special focus on BC.     

Oxytocin Signaling as a Target to Block Social Defeat-Induced Increases in Drug Abuse Reward

There is huge scientific interest in the neuropeptide oxytocin (OXT) due to its putative capacity to modulate a wide spectrum of physiological and cognitive processes including motivation, learning, emotion, and the stress response. The present review seeks to increase the understanding of the role of OXT in an individual’s vulnerability or resilience with regard to developing a substance use disorder. It places specific attention on the role of social stress as a risk factor of addiction, and explores the hypothesis that OXT constitutes a homeostatic response to stress that buffers against its negative impact. For this purpose, the review summarizes preclinical and clinical literature regarding the effects of OXT in different stages of the addiction cycle. The current literature affirms that a well-functioning oxytocinergic system has protective effects such as the modulation of the initial response to drugs of abuse, the attenuation of the development of dependence, the blunting of drug reinstatement and a general anti-stress effect. However, this system is dysregulated if there is continuous drug use or chronic exposure to stress. In this context, OXT is emerging as a promising pharmacotherapy to restore its natural beneficial effects in the organism and to help rebalance the functions of the addicted brain.     

Methamphetamine Blocks Adenosine A2A Receptor Activation via Sigma 1 and Cannabinoid CB1 Receptors

Methamphetamine is, worldwide, one of the most consumed drugs of abuse. One important side effect is neurodegeneration leading to a decrease in life expectancy. The aim of this paper was to check whether the drug affects one of the receptors involved in neurodegeneration/neuroprotection events, namely the adenosine A_2A receptor (A_2AR). First, we noticed that methamphetamine does not affect A_2A functionality if the receptor is expressed in a heterologous system. However, A_2AR becomes sensitive to the drug upon complexes formation with the cannabinoid CB₁ receptor (CB₁R) and the sigma 1 receptor (σ₁R). Signaling via both adenosine A_2AR and cannabinoid CB₁R was affected by methamphetamine in cells co-expressing the two receptors. In striatal primary cultures, the A_2AR–CB₁R heteromer complex was detected and methamphetamine not only altered its expression but completely blocked the A_2AR- and the CB₁R-mediated activation of the mitogen activated protein kinase (MAPK) pathway. In conclusion, methamphetamine, with the participation of σ₁R, alters the expression and function of two interacting receptors, A_2AR, which is a therapeutic target for neuroprotection, and CB₁R, which is the most abundant G protein-coupled receptor (GPCR) in the brain.