Targets (Metabolic Mediators) of Therapeutic Importance in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC), an extremely aggressive invasive cancer, is the fourth most common cause of cancer-related death in the United States. The higher mortality in PDAC is often attributed to the inability to detect it until it has reached advanced stages. The major challenge in tackling PDAC is due to its elusive pathology, minimal effectiveness, and resistance to existing therapeutics. The aggressiveness of PDAC is due to the capacity of tumor cells to alter their metabolism, utilize the diverse available fuel sources to adapt and grow in a hypoxic and harsh environment. Therapeutic resistance is due to the presence of thick stroma with poor angiogenesis, thus making drug delivery to tumor cells difficult. Investigating the metabolic mediators and enzymes involved in metabolic reprogramming may lead to the identification of novel therapeutic targets. The metabolic mediators of glucose, glutamine, lipids, nucleotides, amino acids and mitochondrial metabolism have emerged as novel therapeutic targets. Additionally, the role of autophagy, macropinocytosis, lysosomal transport, recycling, amino acid transport, lipid transport, and the role of reactive oxygen species has also been discussed. The role of various pro-inflammatory cytokines and immune cells in the pathogenesis of PDAC and the metabolites involved in the signaling pathways as therapeutic targets have been previously discussed. This review focuses on the therapeutic potential of metabolic mediators in PDAC along with stemness due to metabolic alterations and their therapeutic importance.     

Xanthohumol for Human Malignancies: Chemistry,Pharmacokinetics and Molecular Targets

Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of Humulus lupulus L. (Hop plant). XH is an important ingredient in beer and is considered a significant bioactive agent due to its diverse medicinal applications, which include anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, antiviral, antifungal, antigenotoxic, antiangiogenic, and antimalarial effects as well as strong anticancer activity towards various types of cancer cells. XH acts as a wide ranging chemopreventive and anticancer agent, and its isomer, 8-prenylnaringenin, is a phytoestrogen with strong estrogenic activity. The present review focuses on the bioactivity of XH on various types of cancers and its pharmacokinetics. In this paper, we first highlight, in brief, the history and use of hops and then the chemistry and structure–activity relationship of XH. Lastly, we focus on its prominent effects and mechanisms of action on various cancers and its possible use in cancer prevention and treatment. Considering the limited number of available reviews on this subject, our goal is to provide a complete and detailed understanding of the anticancer effects of XH against different cancers.     

Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.     

The (Poly)Pharmacology of Cannabidiol in Neurological and Neuropsychiatric Disorders: Molecular Mechanisms and Targets

Cannabidiol (CBD), the major nonpsychoactive Cannabis constituent, has been proposed for the treatment of a wide panel of neurological and neuropsychiatric disorders, including anxiety, schizophrenia, epilepsy and drug addiction due to the ability of its versatile scaffold to interact with diverse molecular targets that are not restricted to the endocannabinoid system. Albeit the molecular mechanisms responsible for the therapeutic effects of CBD have yet to be fully elucidated, many efforts have been devoted in the last decades to shed light on its complex pharmacological profile. In particular, an ever-increasing number of molecular targets linked to those disorders have been identified for this phytocannabinoid, along with the modulatory effects of CBD on their cascade signaling. In this view, here we will try to provide a comprehensive and up-to-date overview of the molecular basis underlying the therapeutic effects of CBD involved in the treatment of neurological and neuropsychiatric disorders.     

晋煤集团煤层气开发利用和近期规划

本文回顾和总结了晋煤集团煤层气的开发历程和煤层气利用情况，分析了晋煤集团煤层气开发利用的方向和市场，详细阐明了晋煤集团的近期规划和发展前景。     

浮选指标预测与判断神经网络专家系统的研究

将神经网络与传统专家系统有机地结合，建立了用于浮选过程中浮选指标预测与判断的神经网络专家系统，该系统适应性强，且具有良好的自学习功能。     

基于集对分析和AHP 的炮兵远程精确打击目标排序

针对传统目标排序方法忽略了现实中不确定因素和对立因素的缺点,基于集对分析理论建立了炮兵远程精确打击目标排序指标体系。从同、异、反3个方面研究打击目标的确定性与不确定性,运用联系度的概念从全局角度对目标排序问题进行集对分析,并以实例进行目标排序。结果表明,该方法简单易行、思路新颖、易于编程,适合处理大量数据,能较好解决定性分析时认识判读偏差的问题。     

反舰导弹末端机动弹道的实现研究

为了适应未来海战的特点和要求,如何提高反舰导弹的突防能力,已经成为各国研究的一项重点。本文在采用过载控制方案的基础上,采用非线性控制方法,设计了反舰导弹线性自适应变结构复合控制器。在过载稳定回路的基础上,通过对导弹高度和侧向偏移的控制实现了导弹的飞行控制系统设计。通过对导弹的末端机动信号的设计,实现了导弹纵向跃升和航向...     

一种机动目标调频步进雷达成像算法

针对低信噪比下机动目标的调频步进雷达成像问题,提出基于Radon-分数阶模糊函数(RFRAF)的方法进行积累成像的方法.在分析了机动目标的调频步进雷达回波信号特征的基础上,将目标回波信号在RFRAF域进行匹配和积累,通过峰值搜索出目标的运动参数,并构建补偿函数实现机动目标运动补偿,从而获得目标精确ISAR像.计算机仿真结果进一步表明了该方法能在低信噪比下稳健成像.