Development of a potent and orally active activator of adenosine monophosphate-activated protein kinase (AMPK), ASP4132, as a clinical candidate for the treatment of human cancer

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a key role in maintaining cellular metabolism. AMP or adenosine diphosphate (ADP) levels rise during metabolic stress, such as during nutrient starvation, hypoxia and muscle contraction, and bind to AMPK to induce activity. Recently, activation of AMPK has been considered an attractive therapeutic strategy in the field of human oncology. Structural optimization of lead compound 2, a new type of AMPK activator with potent AMPK activation activity and attractive selective growth inhibition against human cancer cells, improved aqueous solubility, metabolic stability and animal pharmacokinetics (PK) and culminated in the identification of (5-{1-[(6-methoxypyridin-3-yl)methyl]piperidin-4-yl}-1H-benzimidazol-2-yl)(4-{[4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)methanone ditosylate, ASP4132 (28). Studies on ASP4132 had advanced to clinical trials for the treatment of cancer.     

河西走廊水生植物多样性格局、群落特征及影响因素

水生植物是湿地生态系统重要组成部分,研究水生植物多样性分布格局及其影响因素对地区水生植物资源保护具有重要意义。通过野外调查并结合气候等环境因素,研究了河西走廊主要水生植物群落类型、数量特征、水生植物多样性分布格局及影响因素,并对中域效应假说进行了验证。研究结果表明:(1)河西走廊地区共有水生植物29科42属84种,群落的聚类分析可将河西走廊水生植物群落划分为15个主要群落类型;(2)河西走廊水生植物群落类型主要受到水温、海拔、经纬度等环境因子影响,群落物种多样性指数与盐度以及溶解性固体总量呈显著性相关;(3)河西走廊水生植物多样性空间格局呈现出"∩"型的单峰格局,中域效应模型能较好地解释该地区水生植物多样性水平的纬度格局及海拔垂直分布格局,对该区域水生植物物种丰富度在纬度和海拔梯度上的变异解释率分别为57.56%、63.5%。分析表明,河西走廊水生植物物种丰富度格局由几何(边界)限制和随机过程及其他未知因素共同控制,且几何(边界)限制和随机过程贡献率较大;同时本研究中未考虑的环境异质性、气候、人为干扰等因素也对河西走廊水生植物多样性空间分布产生重要影响。     

火干扰强度对亚热带四种森林类型土壤理化性质的影响

火干扰是通过改变土壤理化性质而影响土壤生态系统功能的重要因素之一。探讨火干扰强度对不同森林类型下土壤理化性质的影响,为利用火干扰促进林分更新及经营提供理论指导。2014年在湖南省株洲市和湘潭市4种次生林(枫香次生林、马尾松-木荷混交林、杉木-木荷混交林及檫木-杉木混交林)内设置16块20 m×20 m样地进行试验,研究了火干扰强度(对照、低强度、中强度、高强度火烧)和林分类型对土壤容重(BD)、土壤斥水性(SWR)、有机质(SOM)、pH、全氮(TN)、全磷(TP)和全钾(TK)的影响。通过描述性统计分析、单因素方差分析和Fisher LSD检验研究各土壤性质在同一林分不同火干扰间,以及同一火干扰下不同林分间的显著性差异和变化趋势(P0.05)。研究发现BD、SWR、pH、TK都随火强度的增大呈上升的趋势,而SOM、TP随火强度增大而减少,TN则随火强度增大没有规律性变化。在同一林分内与对照组相比,低强度火烧对BD、SWR、pH和SOM的影响不显著,中强度有一定影响,而高强度火烧影响显著;而TN、TP、TK在火烧前后均无显著性差异。火干扰后,TN和TP在同一火强度下不同林分间均存在显著性差异(P0.05),而BD、pH值和TP在同一林分内不同火强度间均存在显著性差异(P0.05)。BD、SOM、pH、TK在枫香次生林内普遍显著大于其他林分。结果说明火干扰强度和林分类型在影响土壤理化性质方面起着重要作用。高强度火干扰对土壤性质影响最大,枫香次生林中土壤理化性质与其他混交林相比普遍存在显著性差异。BD、pH和TP受火强度影响显著,BD、SOM、pH、TN、TK和TP受林分类型影响显著。     

水电开发对鱼类种群分布及生态类型变化的影响——以溪洛渡至向家坝河段为例

梯级水库修建后自然河流形成了河相段和湖相段,而河流生境的改变对鱼类种群空间分布和生态类型变化产生了重要影响。为探究金沙江梯级水电开发对鱼类资源的影响,结合2018年5月渔获物和文献记载水库修建前后的渔获物数据,分析了鱼类群落组成及变化,优势物种及群落多样性特点,以及鱼类在河相、湖相段生态类型的变化。结果表明,梯级水库建设后溪洛渡至向家坝鱼类的种类数减少,随着水库的运行该减少趋势放缓,而大型鱼的种类数占比呈增长趋势。受生境变化的影响,鱼类优势物种发生变化,水库河相段和湖相段生态类型差异较大。生态类型组成上以缓流型、生活于水流中下层、产卵初始水温高于18℃等生态类型占优。研究表明,高坝大库的运行会造成鱼类种群以生态需求为目标,形成明显的空间分布和群落结构特征,而梯级水库建设导致的水动力条件差异是鱼类群落生态类型差异的内在驱动力。     

Common plasma protein marker LCAT in aggressive human breast cancer and canine mammary tumor

Breast cancer is one of the most frequently diagnosed cancers. Although biomarkers are continuously being discovered, few specific markers, rather than classification markers, representing the aggressiveness and invasiveness of breast cancer are known. In this study, we used samples from canine mammary tumors in a comparative approach. We subjected 36 fractions of both canine normal and mammary tumor plasmas to high-performance quantitative proteomics analysis. Among the identified proteins, LCAT was selectively expressed in mixed tumor samples. With further MRM and Western blot validation, we discovered that the LCAT protein is an indicator of aggressive mammary tumors, an advanced stage of cancer, possibly highly metastatic. Interestingly, we also found that LCAT is overexpressed in high-grade and lymphnode-positive breast cancer in silico data. We also demonstrated that LCAT is highly expressed in the sera of advanced-stage human breast cancers within the same classification. In conclusion, we identified a possible common plasma protein biomarker, LCAT, that is highly expressed in aggressive human breast cancer and canine mammary tumor.     

Aidi injection,a traditional Chinese biomedical preparation for gynecologic tumors: a systematic review and PRISMA-compliant meta-analysis

Aidi injection (ADI), a traditional Chinese biomedical preparation, is a promising adjuvant therapy for gynecologic tumors (GTs), including cervical cancer (CC), endometrial cancer (EC), and ovarian cancer (OC). Although studies have reported positively on ADI therapy, its exact effects and safety in GT patients remain controversial. Therefore, a wide-ranging systematic search of electronic databases was performed for this meta-analysis. Data from 38 trials including 3309 GT patients were analyzed. The results indicated that the combination of conventional treatment and ADI markedly improved the patients’ overall response rate (P<0.00001), disease control rate (P<0.00001), and quality of life (P<0.05) compared with conventional treatment alone. Furthermore, patient immunity was enhanced with combined treatment, as indicated by significantly increased percentages of CD3⁺ (P=0.005) and CD4⁺ (P<0.00001) and increased CD4⁺/CD8⁺ ratio (P=0.001). Most of the adverse events caused by radiochemotherapy such as gastrointestinal issues, leukopenia, thrombocytopenia, and hepatotoxicity, (P<0.05 for all) were significantly alleviated when ADI was used in the GT patients. However, other adverse events such as nephrotoxicity, diarrhea, alopecia, and neurotoxicity did not significantly differ between the two groups. Overall, these results suggest that the combination of conventional and ADI treatment is more effective than conventional treatment alone.     

Focus: Preventive Medicine: Pre-Participation Screening of Athletes: Primary Health Care Physicians’ Knowledge,Experience, and Approach in Turkey

Pre-participation screening (PPS) is crucial for assessing the competitive athletes since their risk of sudden death is higher than non-athletes. In Turkey, PPS is performed at the primary health care setting by primary care physicians (PCPs) who are family medicine specialists (FMSs) or general practitioners (GPs). Although there are national guidelines, there is no legal regulation for this process. This study aims to evaluate PCPs’ knowledge, experience, and approach about PPS. We prepared an online survey for PCPs and used non-probabilistic sampling. PPS attitudes and practices were analyzed and compared according to factors such as experience, education, and being GP or FMS. Of the 214 PCPs included in the study, 39.3% were female. The mean age was 44.9 years (SD:8.88). The average work experience was 7.9 years. Most participants were aware of their authorization to perform PPS (89.7%) and had previously prepared it (90.2%). However, 6.5% of them felt confident in performing PPS. Only 13.1% were aware of the guidelines. Almost 25% of the participants stated being informed about the subject at some part of their career, but this did not affect the confidence or referral decisions. In addition to medical history and physical examination, further testing was considered necessary by 96.3% of the participants. Significantly more tests were ordered by GPs than FMSs (p=0.026 and p=0.011, respectively). The accurate referral decision ratio was 59.3%, without difference between FMSs and GPs (p=0.216). We found that awareness of the guidelines was low among PCPs who lack confidence in PPS. These factors collectively increased the tendency for unnecessary further testing and referral. Therefore, the PPS implementation into medical school and residency curriculums and national legal regulation for the process is a necessity in Turkey.     

Focus: Preventive Medicine: Leveraging Organizational Health Literacy to Enhance Health Promotion and Risk Prevention: A Narrative and Interpretive Literature Review

Organizational health literacy involves the health care organizations’ ability to establish an empowering and co-creating relationship with patients, engaging them in the design and delivery of health services in collaboration with health professionals. Although scholars agree that organizational health literacy contributes to health promotion and risk prevention via patient empowerment, literature is not consistent in depicting the interplay between organizational health literacy and preventive medicine. The article intends to shed light into this issue, summarizing current knowledge about this topic and advancing avenues for further development. A narrative literature review was performed through a systematic search on PubMed^®, Scopus^®, and Web of Science^™. The review focused on 50 relevant contributions. Organizational health literacy triggers the transition towards a patient-centered approach to care. It complements individual health literacy, enabling patients to actively participate in health promotion and risk prevention as co-producers of health services and co-creators of value. However, many obstacles – including lack of time and limited resources available – prevent the transition towards health literate health care organizations. Two initiatives are required to overcome extant barriers. On the one hand, a health literate workforce should be prepared to increase the institutional ability of health care organizations to empower and engage patients in health co-creation. On the other hand, increased efforts should be made to assess organizational health literacy and to make its contribution to preventive medicine explicit.     

稀有鮈鲫对不同生境的选择性偏好

对不同生境的识别和选择性偏好是保障鱼类生存和繁衍的重要能力之一。以稀有鮈鲫（Gobiocypris rarus）为研究对象,使用沙、水草和石块在观测水缸中进行多种排列组合以构建不同的生境类型,基于在各区域的停留时长和中线跨越次数两项参数,测试稀有鮈鲫对不同生境类型的偏好以及营养状态、生境组成物数量、环境照度对该行为影响。结果表明,稀有鮈鲫对不同的生境类型具有明显的选择性偏好,对仅水草生境偏好程度最高,对仅石块生境的偏好程度最低。该偏好行为在24 h的禁食后变化不显著（P > 0.05）,但生境组成物数量和环境照度对该行为具有显著影响（P < 0.05）,其偏好程度随水草数量和照度的增加而增加,在包含8棵水草及1 000 lx的照度下最高。