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.     

Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery

Aminoacyl-tRNA synthetases (aaRSs) catalyze the esterification of tRNA with a cognate amino acid and are essential enzymes in all three kingdoms of life. Due to their important role in the translation of the genetic code, aaRSs have been recognized as suitable targets for the development of small molecule anti-infectives. In this review, following a concise discussion of aaRS catalytic and proof-reading activities, the various inhibitory mechanisms of reported natural and synthetic aaRS inhibitors are discussed. Using the expanding repository of ligand-bound X-ray crystal structures, we classified these compounds based on their binding sites, focusing on their ability to compete with the association of one, or more of the canonical aaRS substrates. In parallel, we examined the determinants of species-selectivity and discuss potential resistance mechanisms of some of the inhibitor classes. Combined, this structural perspective highlights the opportunities for further exploration of the aaRS enzyme family as antimicrobial targets.     

应用膨胀算法提取目标的直接定位算法

为了解决被动雷达系统中的多发射源定位问题，提出了一种基于多重信号分类(MUSIC)算法和图像膨胀(IE)算法的直接定位方法。该方法结合了谱分析中的MUSIC思想，通过对接收量测协方差矩阵进行特征分析求解目标的位置。首先，在目标个数未知的前提下，利用Akaike信息准则(AIC)来确定模型阶数；然后，推导了基于MUSIC的定位代价函数；之后，利用图像膨胀算法处理得到的代价函数平面；最后，膨胀处理后的输出为目标个数及目标位置的估计值。提出的算法有效地解决了目标检测及提取的问题，能够确定多个目标的位置坐标，为后续的定位性能分析提供可能性，也保证了算法的完整性。进一步地分析了多个临近目标情况下影响目标提取性能的主要因素。     

The location and sizing of urban freight loading/unloading lay-by areas

The volume of freight vehicles operating within city boundaries is steadily increasing, which contributes to road congestion, especially in urban areas with a parking deficit. The proper identification of the location and size of commercial parking lay-by areas, where delivery vehicles can park for a limited time to perform loading/unloading operations, can relieve road congestion. Compared to the existing literature, this paper presents an improved two-stage approach, which includes a mathematical programme and a simulation model for determining the location and sizing of lay-by areas. The robustness and soundness of the results from a methodological and practical point of view are discussed using an example application.     

黔北桑木场背斜铅锌矿深部找矿实例分析*#br#

黔北桑木场背斜位于上扬子地块黔北隆起区毕节弧形褶皱带与赤水克拉通盆地的交汇部位，属于有利的铅锌成矿区带。区内铅锌矿的赋矿层位主要有震旦系灯影组、寒武系清虚洞组、高台组及石冷水组，矿体多产于背斜核部并受断层或裂隙控制。通过对地层岩性特征、地表矿化特征、控容矿构造特征、化探异常特征、物探异常特征等进行综合研究，选择在成矿有利地段进行了工程验证，为进一步开展桑木场背斜铅锌矿深部找矿工作提供了思路。     

城镇化进程中农村集体资产管理问题探究

农村集体资产管理关系着农村经济的发展,对于社会的稳定和谐也有着重要影响,乡镇政府应加强对集体资产的重视,平衡乡镇改革与资产管理之间的关系,分析农村集体资产管理中存在的一些问题,结合自身的特点,采取有效的措施来促进其发展,加快城镇化农村集体资产管理显得尤为重要。     

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.