Synthesis,Biological Evaluation,and Docking Study of Ring-Opening Amide Analogs of Matrine as Antitumor Agents

In this article, we designed and synthesized two series of matrine analogs with ring-opening in the lactam portion of the molecule. Our in vitro cytotoxicity study showed that analog N-(3-bromophenyl)-4-[(1R,3aS,10aR,10bS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl]butanamide ( B11 ) with a meta-bromide on the phenyl ring displayed the best antiproliferative activity. Moreover, B11 induced cell cycle arrest in G1 phase and cell apoptosis in a dose-dependent manner in A549 cells. Molecular modeling revealed that B11 achieved a higher docking score compared to its precursor tert-butyl (1R,3aS,10aR,10bS)-1-[4-(3-bromoanilino)-4-oxobutyl]octahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridine-2(3H)-carboxylate ( A11 , an analog of B11 with a Boc group) and parent compound matrine, possibly because B11 formed a hydrogen bond with SER91 and a halogen bond with GLN320 on the binding site of annexin A2. Overall, we discovered the potential anticancer lead compound B11 , which can be used for further study both in vitro and in vivo.     

The landscape and prognostic value of immune characteristics in uterine corpus endometrial cancer

In the present study, we explored the clinical and immunological characteristics of 575 uterine corpus endometrial carcinoma (UCEC) samples obtained from The Cancer Genome Atlas (TCGA) using the ESTIMATE and CIBERSORT algorithms. First, Kaplan–Meier and univariate Cox regression analyses indicated that the immune cell score was a prognostic factor for overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox regression analysis further revealed that the immune cell score was an independent prognostic factor for UCEC patients. Second, we investigated the correlation between the infiltration levels of 22 types of immune cells and the immune score. Survival analysis based on the 22 immune cell types showed that higher levels of regulatory T cell, activated NK cell, and follicular helper T-cell infiltration were associated with longer OS, while higher levels of CD8+ T cell and naive B-cell infiltration were associated with longer RFS. Next, we performed differential expression and prognosis analyses on 1534 immune-related genes and selected five from 14 candidate genes to construct a prognostic prediction model. The area under the receiver-operating characteristic (ROC) curve (AUC) for 3- and 5-year survival were 0.711 and 0.728, respectively. Further validation using a stage I–II subgroup showed similar results, presenting AUC values for 3- and five-year survival of 0.677 and 0.692, respectively. Taken together, the present study provides not only a deeper understanding of the relationship between UCEC and the immune landscape but also guidance for the future development of UCEC immunotherapy.     

miR-194-5p negatively regulates the proliferation and differentiation of rabbit skeletal muscle satellite cells

Molecular and Cellular Biochemistry - Skeletal muscle satellite cells (SMSCs), also known as a multipotential stem cell population, play a crucial role during muscle growth and regeneration. In...     

研究生病理学实验带教的探索与实践

医学研究生教育的目的是培养高素质创新型医学人才,创新离不开科研,病理学是多学科科研究工作的基础。建立科研平台提高科研能力是研究生教育十分关注的问题。如何培养研究生病理学实验能力,使学到知识技术在今后的科研活动中得以运用,本文就近几年我们在研究生病理学实验带教实践过程中的一些方法作一介绍。     

Plastome phylogeny and lineage diversification of Salicaceae with focus on poplars and willows

Phylogenetic relationships and lineage diversification of the family Salicaceae sensu lato (s.l.) remain poorly understood. In this study, we examined phylogenetic relationships between 42 species from six genera based on the complete plastomes. Phylogenetic analyses of 77 protein coding genes of the plastomes produced good resolution of the interrelationships among most sampled species and the recovered clades. Of the sampled genera from the family, Flacourtia was identified as the most basal and the successive clades comprised both Itoa and Poliothyrsis, Idesia, two genera of the Salicaceae sensu stricto (s.s.) (Populus and Salix). Five major subclades were recovered within the Populus clade. These subclades and their interrelationships are largely inconsistent with morphological classifications and molecular phylogeny based on nuclear internal transcribed spacer sequence variations. Two major subclades were identified for the Salix clade. Molecular dating suggested that species diversification of the major subclades in the Populus and Salix clades occurred mainly within the recent Pliocene. In addition, we found that the rpl32 gene was lost and the rps7 gene evolved into a pseudogene multiple times in the sampled genera of the Salicaceae s.l. Compared with previous studies, our results provide a well‐resolved phylogeny from the perspective of the plastomes.     

绿化植物的生活型对边坡植被物种多样性及护坡性能的影响

为了探讨绿化植物生活型构成对边坡植被物种多样性及护坡性能的影响, 揭示生活型构成-群落特征-物种多样性-生态系统功能间的内在联系, 借助三物种组装实验, 分别构建以草本、灌木或乔木为主体的草本型(HHX_i)、灌木型(SSX_i)、乔木型(AAX_i)或草-灌-乔混合型(HSA)配置模式的实验小区, 对实验区内边坡植被的群落特征、护坡性能进行持续4年的生态监测。结果表明: (1)边坡植被的物种丰富度与绿化植物生活型构成有关, AAX_i的物种丰富度总体高于其他模式, 呈AAX_i > SSX_i > HSA > HHX_i趋势。(2)不同配置模式边坡植被的群落盖度不一样, 年际间差异显著: 建坪初期(2010-2011年), HHX_i的群落盖度远高于其他模式, HSA次之, AAX_i最低; 2012-2013年间, HSA的群落盖度最高, HHX_i次之, AAX_i最低。(3)边坡植被的Shannon-Wiener指数、Pielou指数与绿化植物生活型构成有关, 其变化规律与群落盖度类似: 建坪初期, HHX_i的多样性水平远高于其他模式, 呈HHX_i > HSA > SSX_i > AAX_i趋势; 之后, 呈HSA > HHX_i > SSX_i > AAX_i趋势。(4)边坡植被的护坡性能与群落内的物种多样性密切相关: 多样性水平越高, 护坡性能越强。可见, 在生态护坡过程中, 绿化植物生活型构成对提高边坡植被物种多样性、改善护坡性能至关重要。     

小麦新材料“J—11”与黑麦可杂交性的遗传研究

新材料“J－11”比众所周知的高亲和性品系“中国春”具有明显更高的与黑麦的可杂交性,遗传分析表明,“J－11”与“中国春”的可杂交性基因一样表现为完全隐性,但控制“J－11”和“中国春”与黑麦可杂交性的基因型确实不相同,“J－11”除具有“中国春”的3对可杂交性基因,即5B上的kr1,5A上的kr2和5D上的kr3,外,还具有1个新的可杂交性基因kr4,位于1A染色体上,新基因kr4表现为强效,其效应比kr1的弱,但在kr2和kr3的强。小麦可杂交性基因间存在互作,表现为纯合隐性等位基因对其它显性等位基因的抑制作用,而纯合隐性等位基因的效应可加性。