The protective effects of C16 peptide and angiopoietin-1 compound in lipopolysaccharide-induced acute respiratory distress syndrome

C16 peptide and angiopoietin-1 (Ang-1) have been found to have anti-inflammatory activity in various inflammation-related diseases. However, their combined role in acute respiratory distress syndrome (ARDS) has not been investigated yet. The objective of this study was to investigate the effects of C16 peptide and Ang-1 in combination with lipopolysaccharide (LPS)-induced inflammatory insult in vitro and in vivo. Human pulmonary microvascular endothelial cells and human pulmonary alveolar epithelial cells were used as cell culture systems, and an ARDS rodent model was used for in vivo studies. Our results demonstrated that C16 and Ang-1 in combination significantly suppressed inflammatory cell transmigration by 33% in comparison with the vehicle alone, and decreased the lung tissue wet-to-dry lung weight ratio to a maximum of 1.53, compared to 3.55 in the vehicle group in ARDS rats. Moreover, C  +  A treatment reduced the histology injury score to 60% of the vehicle control, enhanced arterial oxygen saturation (SO₂), decreased arterial carbon dioxide partial pressure (PCO₂), and increased oxygen partial pressure (PO₂) in ARDS rats, while also improving the survival rate from 47% (7/15) to 80% (12/15) and diminishing fibrosis, necrosis, and apoptosis in lung tissue. Furthermore, when C  +  A therapy was administered 4 h following LPS injection, the treatment showed significant alleviating effects on pulmonary inflammatory cell infiltration 24 h postinsult. In conclusion, our in vitro and in vivo studies show that C16 and Ang-1 exert protective effects against LPS-induced inflammatory insult. C16 and Ang-1 hold promise as a novel agent against LPS-induced ARDS. Further studies are needed to determine the potential for C16 and Ang-1 in combination in treating inflammatory lung diseases.     

LncRNA SNHG1 exerts a protective role in cardiomyocytes hypertrophy via targeting miR‐15a‐5p/HMGA1 axis

Heart failure preceded by pathological cardiac hypertrophy is a leading cause of death. Long noncoding RNA small nucleolar RNA host gene 1 (SNHG1) was reported to inhibit cardiomyocytes apoptosis, but the role and underlying mechanism of SNHG1 in pathological cardiac hypertrophy have not yet been understood. This study was designed to investigate the role and molecular mechanism of SNHG1 in regulating cardiac hypertrophy. We found that SNHG1 was upregulated during cardiac hypertrophy both in vivo (transverse aortic constriction treatment) and in vitro (phenylephrine [PE] treatment). SNHG1 overexpression attenuated the cardiomyocytes hypertrophy induced by PE, while SNHG1 inhibition promoted hypertrophic response of cardiomyocytes. Furthermore, SNHG1 and high‐mobility group AT‐hook 1 (HMGA1) were confirmed to be targets of miR‐15a‐5p. SNHG1 promoted HMGA1 expression by sponging miR‐15a‐5p, eventually attenuating cardiomyocytes hypertrophy. There data revealed a novel protective mechanism of SNHG1 in cardiomyocytes hypertrophy. Thus, targeting of SNHG1‐related pathway may be therapeutically harnessed to treat cardiac hypertrophy.     

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.     

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.     

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。     

Signature of sexual conflict is actually conflict resolved

There has been substantial interest of late in using population genetic methods to study sexual conflict, where an allele increases the fitness of one sex at some cost to the other (Mank, 2017). Population genomic scans for sexual conflict offer an important advance given the difficulties of identifying antagonistic alleles from more traditional methods, and could greatly increase our understanding of the extent and loci of sexual conflict. This is particularly true for studies in natural populations, for which obtaining accurate fitness measurements for each sex can be challenging. In this issue of Molecular Ecology, Bissegger, Laurentino, Roesti, and Berner (2019) present a cautionary tale about how to interpret these population genomic data.