Distinct genomic traits of acral and mucosal melanomas revealed by targeted mutational profiling

The incidence of melanoma is rising globally including China. Comparing to Caucasians, the incidence of non‐cutaneous melanomas is significantly higher in Chinese. Herein, we performed genomic profiling of 89 Chinese surgically resected primary melanomas, including acral (n = 54), cutaneous (n = 22), and mucosal (n = 13), by hybrid capture‐based next‐generation sequencing. We show that mucosal melanomas tended to harbor more pathogenic mutations than other types of melanoma, though the biological significance of this finding remains uncertain. Chromosomal arm‐level alterations including 6q, 9p, and 10p/q loss were highly recurrent in all subtypes, but mucosal melanoma was significantly associated with increased genomic instability. Importantly, 7p gain significantly correlated with unfavorable clinical outcomes in non‐cutaneous melanomas, representing an intriguing prognostic biomarker of those subtypes. Furthermore, focal amplification of 4q12 (KIT, KDR, and PDGFRα) and RAD51 deletion were more abundant in mucosal melanoma, while NOTCH2 amplification was enriched in acral melanoma. Additionally, cutaneous melanomas had higher mutation load than acral melanomas, while mucosal melanomas did not differ from other subtypes in mutation burden. Together, our data revealed important features of acral and mucosal melanomas in Chinese including distinctive driver mutation pattern and increased genomic instability. These findings highlight the possibilities of combination therapies in the clinical management of melanoma.     

Some Meaningful Weighted Log-Rank and Weighted Win Loss Statistics

Statistics in Biosciences - Weighted log-rank statistics and recently weighted win loss statistics are often used to test the null hypothesis that the treatment group and the control group have no...     

The effect of intrauterine inflammation on mTOR signaling in mouse fetal brain

Fetuses exposed to an inflammatory environment are predisposed to long‐term adverse neurological outcomes. However, the mechanism by which intrauterine inflammation (IUI) is responsible for abnormal fetal brain development is not fully understood. The mechanistic target of rapamycin (mTOR) signaling pathway is closely associated with fetal brain development. We hypothesized that mTOR signaling might be involved in fetal brain injury and malformation when fetuses are exposed to the IUI environment. A well‐established IUI model was utilized by intrauterine injection of lipopolysaccharide (LPS) to explore the effect of IUI on mTOR signaling in mouse fetal brains. We found that microglia activation in LPS fetal brains was increased, as demonstrated by elevated Iba‐1 protein level and immunofluorescence density. LPS fetal brains also showed reduced neuronal cell counts, decreased cell proliferation demonstrated by low Ki67‐positive density, and elevated neuron apoptosis evidenced by high expression of cleaved Caspase 3. Furthermore, we found that mTOR signaling in LPS fetal brains was elevated at 2 hr after LPS treatment, declined at 6 hr and showed overall inhibition at 24 hr. In summary, our study revealed that LPS‐induced IUI leads to increased activation of microglia cells, neuronal damage, and dynamic alterations in mTOR signaling in the mouse fetal brain. Our findings indicate that abnormal changes in mTOR signaling may underlie the development of future neurological complications in offspring exposed to prenatal IUI.     

Mutation of the chloroplast‐localized phosphate transporter OsPHT2;1 reduces flavonoid accumulation and UV tolerance in rice

Phosphorus (P) is an essential macronutrient required for plant development and production. The mechanisms regulating phosphate (Pi) uptake are well established, but the function of chloroplast Pi homeostasis is poorly understood in Oryza sativa (rice). PHT2;1 is one of the transporters/translocators mediating Pi import into chloroplasts. In this study, to gain insight into the role of OsPHT2;1‐mediated stroma Pi, we analyzed OsPHT2;1 function in Pi utilization and photoprotection. Our results showed that OsPHT2;1 was induced by Pi starvation and light exposure. Cell‐based assays showed that OsPHT2;1 localized to the chloroplast envelope and functioned as a low‐affinity Pi transporter. The ospht2;1 had reduced Pi accumulation, plant growth and photosynthetic rates. Metabolite profiling revealed that 52.6% of the decreased metabolites in ospht2;1 plants were flavonoids, which was further confirmed by 40% lower content of total flavonoids compared with the wild type. As a consequence, ospht2;1 plants were more sensitive to UV‐B irradiation. Moreover, the content of phenylalanine, the precursor of flavonoids, was also reduced, and was largely associated with the repressed expression of ADT1/MTR1. Furthermore, the ospht2;1 plants showed decreased grain yields at relatively high levels of UV‐B irradiance. In summary, OsPHT2;1 functions as a chloroplast‐localized low‐affinity Pi transporter that mediates UV tolerance and rice yields at different latitudes.     

湖南蓝山县端午药市的瑶药调查

中国南方一些少数民族地区民间“端午药市”流传至今,体现了民族医药的独具特色及其深远影响。为了解瑶族端午药市交易现状和发掘民族医药传统知识,采用民族植物学等方法对湖南省蓝山县端午药市进行调查,完成包括基原、地方名、药用部位、用途和用法、出现频度等内容的药用植物编目。结果表明:蓝山县端午药市药用植物种类丰富,共收集鉴定103科 222属262种,药用植物种类广泛分布于各科和各属中,其中种类较多的科有五加科(11种)、茜草科(11种)、菊科(11种)、百合科(10种)、唇形科(9种)、蝶形花科(8种)、芸香科(7种)。药市药浴植物畅销且种类多样,达94种,占总数的35.9%,体现瑶族在治疗疾病上以预防保健为主的理念。经统计药市上均未被国家药典和地方标准收录的药用植物有131种,占总数的50.2%,成为发掘新药源、新用途的潜在资源。对端午药市售药者年龄的调查发现,售药者的年龄主要集中在50～59岁间,占总人数的67%,40岁以下的仅占总人数的3%,可见民族药用传统知识的传承存在传承人老龄化、潜在传承人数量锐减的现象。此外,还对药市交易药用植物的种类组成和民族药用特色进行分析,探讨了端午药市对药用传统知识保护与传承的影响,并对蓝山端午药市的可持续发展提出了建议。     

大鼠脑缺血/再灌注过程中血流量和脑组织含水量的变化趋势*

目的:研究大鼠脑缺血/再灌注过程中血流量及与脑组织水含量变化的趋势。方法:选取5只成年SD雄性大鼠(n=5),参照改良Zea-Longa线栓法制备大鼠大脑中动脉缺血/再灌注模型,2 h后拔出线栓。利用PeriCam PSI血流灌注成像系统实时监测大鼠在缺血前及缺血5 min、30 min、1 h、2 h、再灌注5 min、30 min、1 h、2 h、4 h、6 h及24 h的血流灌注量,记录在ROI(感兴趣区)测量的数值。再选取15只成年SD雄性大鼠,分为Control组、缺血2 h、再灌注30 min、4 h及24 h组(n=3)。正常组不做任何处理,实验组按上述线栓法制备MCAO模型。取新鲜脑组织用干湿重法测定其左、右半球的水含量。结果:栓塞时缺血侧血流量逐渐下降,缺血2 h下降最低(P＜0.05);再灌注早期血流量恢复较大(P＜0.05),30 min时显著下降(P＜0.05),4 h明显上升(P＜0.05),24 h再次上升(P＜0.05)但低于缺血前血流量(P＞0.05)。脑组织水含量测量,缺血2 h组和再灌注30 min组与正常组无明显差异(P＞0.05);再灌4 h组和再灌24 h组明显增高(P＜0.05),且再灌24 h组明显高于再灌4 h组(P＜0.05)。结论:大鼠脑缺血/再灌注过程中血流量和脑组织中水含量的变化存在一定的规律,且脑组织中水含量与再灌注过程中血流量的变化有一定关系。     

大渡河中游干暖河谷区生境对植物群落分布格局和多样性的影响

大渡河中游干暖河谷区滑坡和泥石流灾害频发, 对该区域坡面植物群落的研究有助于揭示植被演替的方向, 为坡面植被生态恢复提供基本依据。本研究沿大渡河中游河谷区每隔约5 km设置典型样地, 调查了植被的物种组成和分布以及样地的地形、土壤等10个生境因子, 探讨河谷区植被的连续性变化, 并通过多元回归树(multivariate regression trees, MRT)、多样性指数和典范对应分析(canonical correspondence analysis, CCA)等方法对植物群落进行分类、比较和排序。结果表明: 大渡河中游干暖河谷植被以土壤碳含量、pH值和C : N等3个因子为节点, 可划分为多花胡枝子(Lespedeza floribunda)-荩草(Arthraxon hispidus)-香薷(Elsholtzia ciliate)(群落A)、地果(Ficus tikoua)-车桑子(Dodonaea viscosa)-川滇薹草(Carex schneideri)(群落B)、云南松(Pinus yunnanensis)-栓皮栎(Quercus variabilis)(群落C)和荩草-扭黄茅(Heteropogon contortus)(群落D)等4种群落。该区域以灌木和草本为主要植被类型(群落A、B、C), 间或有裸地分布, 易成为泥石流灾害产生的物源区; 以多花胡枝子为主的灌草群落A的物种丰富度、优势度与多样性表现一致, 均高于以乔木和草本为主的群落C和D, 但物种多样性优势并不显著, 灌草群落分布广而结构单一, 外来物种占比为8.33%, 是生态系统脆弱和不稳定的表现。多元回归树和典范对应分析结果表明, pH值、C : N、坡向和土壤容重等4个因子对植物群落组成和分布影响最大, 且土壤因子的影响大于地形因子。     

罗霄山脉翼手目物种多样性及适生区预测

罗霄山脉位于中国大陆东南部, 是一条南北走向的大型山脉, 面积约6.76万km²。该山脉位于欧亚大陆东部季风区, 生物多样性丰富, 是亚洲东部第三纪冰期动物重要的避难所。为了解罗霄山脉翼手目物种多样性状况, 本研究组于2013-2018年, 使用雾网、手网和竖琴网等工具开展了针对性调查与标本采集, 同时运用形态分类学和分子系统发生学方法鉴定物种。根据调查结果并结合文献记载: 罗霄山脉地区现有翼手目物种4科14属40种, 其中罗霄山脉翼手目新记录种25种, 省级翼手目分布新记录种9种。同时, 本研究基于5年的调查采集位点, 使用生物多样 性与气候变化虚拟实验室(the Biodiversity & Climate Change Virtual Laboratory)在线生境预测平台, 对罗霄山脉翼手目物种当前的适生区, 以及3种不同量温室气体排放情景下(representative concentration pathway, RCP 2.6 / 6.0 / 8.5) 2050年的适生区进行预测, 其中随机森林算法(random forest)的模型解释力较优, 其预测结果显示: 影响该区域翼手目分布的主要环境因子为降水季节性和年平均温度; 山脉中部及南部为翼手目的高适生区, 面积约为罗霄山脉的30%; 与当前适生区相比, RCP 2.6情景下2050年该类群适生区有所扩增, RCP 6.0和RCP 8.5情景下均会导致翼手目适生区急剧缩减, 且分布区将迁移至高海拔区域以响应气候变化。而本项目的开展不仅初步掌握了罗霄山脉翼手目物种多样性本底状况, 也为开展后续的翼手目研究和保护管理提供了参考。