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Bo Hu Xiaolu Ma Peiyao Fu Qiman Sun Weiguo Tang Haixiang Sun Zhangfu Yang Mincheng Yu Jian Zhou Jia Fan Yang Xu 《基因组蛋白质组与生物信息学报(英文版)》2021,19(6):913
The aim of this study was to identify novel prognostic mRNA and microRNA (miRNA) biomarkers for hepatocellular carcinoma (HCC) using methods in systems biology. Differentially expressed mRNAs, miRNAs, and long non-coding RNAs (lncRNAs) were compared between HCC tumor tissues and normal liver tissues in The Cancer Genome Atlas (TCGA) database. Subsequently, a prognosis-associated mRNA co-expression network, an mRNA–miRNA regulatory network, and an mRNA–miRNA–lncRNA regulatory network were constructed to identify prognostic biomarkers for HCC through Cox survival analysis. Seven prognosis-associated mRNA co-expression modules were obtained by analyzing these differentially expressed mRNAs. An expression module including 120 mRNAs was significantly correlated with HCC patient survival. Combined with patient survival data, several mRNAs and miRNAs, including CHST4, SLC22A8, STC2, hsa-miR-326, and hsa-miR-21 were identified from the network to predict HCC patient prognosis. Clinical significance was investigated using tissue microarray analysis of samples from 258 patients with HCC. Functional annotation of hsa-miR-326 and hsa-miR-21-5p indicated specific associations with several cancer-related pathways. The present study provides a bioinformatics method for biomarker screening, leading to the identification of an integrated mRNA–miRNA–lncRNA regulatory network and their co-expression patterns in relation to predicting HCC patient survival. 相似文献
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Libin Ni Jian Xiao Di Zhang Zhenxuan Shao Chongan Huang Sheng Wang Yaosen Wu Naifeng Tian Liaojun Sun Aimin Wu Yifei Zhou Xiangyang Wang Xiaolei Zhang 《Cell death & disease》2022,13(2)
The pathophysiology of spinal cord injury (SCI) involves primary injury and secondary injury. Secondary injury is a major target for SCI therapy, whereas microglia play an important role in secondary injury. The immunoresponsive gene 1 (Irg-1) has been recorded as one of the most significantly upregulated genes in SCI tissues in gene chip data; however, its role in SCI remains unclear. This study aims to illustrate the role of Irg-1 as well as its regulated metabolite itaconate in SCI. It was demonstrated that the expression of Irg-1 was increased in spinal cord tissues in mice as well as in microglia stimulated by lipopolysaccharides (LPS). It was also shown that overexpression of Irg-1 may suppress LPS-induced inflammation in microglia, while these protective effects were attenuated by Nrf2 silencing. In vivo, overexpression of Irg-1 was shown to suppress neuroinflammation and improve motor function recovery. Furthermore, treatment of microglia with itaconate demonstrated similar inflammation suppressive effects as Irg-1 overexpression in vitro and improved motor function recovery in vivo. In conclusion, the current study shows that Irg-1 and itaconate are involved in the recovery process of SCI, either Irg-1 overexpression or itaconate treatment may provide a promising strategy for the treatment of SCI.Subject terms: Apoptosis, Cell death in the nervous system, Microglia, Trauma 相似文献
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Habitat loss and fragmentation are widely acknowledged as the main driver of the decline of giant panda populations. The Chinese government has made great efforts to protect this charming species and has made remarkable achievements, such as population growth and habitat expansion. However, habitat fragmentation has not been reversed. Protecting giant pandas in a large spatial extent needs to identify core habitat patches and corridors connecting them. This study used an equal‐sampling multiscale random forest habitat model to predict a habitat suitability map for the giant panda. Then, we applied the resistant kernel method and factorial least‐cost path analysis to identify core habitats connected by panda dispersal and corridors among panda occurrences, respectively. Finally, we evaluated the effectiveness of current protected areas in representing core habitats and corridors. Our results showed high scale dependence of giant panda habitat selection. Giant pandas strongly respond to bamboo percentage and elevation at a relatively fine scale (1 km), whereas they respond to anthropogenic factors at a coarse scale (≥2 km). Dispersal ability has significant effects on core habitats extent and population fragmentation evaluation. Under medium and high dispersal ability scenarios (12,000 and 20,000 cost units), most giant panda habitats in the Qionglai mountain are predicted to be well connected by dispersal. The proportion of core habitats covered by protected areas varied between 38% and 43% under different dispersal ability scenarios, highlighting significant gaps in the protected area network. Similarly, only 43% of corridors that connect giant panda occurrences were protected. Our results can provide crucial information for conservation managers to develop wise strategies to safeguard the long‐term viability of the giant panda population. 相似文献
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Signaling by bone morphogenetic proteins (BMPs) plays pivotal roles in embryogenesis, adult tissue homeostasis, and disease. Recent studies revealed that the well-established WNT agonist R-spondin 2 (RSPO2) is also a BMP receptor (BMP receptor type 1A) antagonist, with roles in early Xenopus embryogenesis and human acute myeloid leukemia (AML). To uncouple the BMP antagonist function from the WNT agonist function and to promote development of AML therapeutics, here we identified a 10-mer peptide (RW) derived from the thrombospondin 1 domain of RSPO2, which specifically prevents binding between RSPO2 and BMP receptor type 1A without altering WNT signaling. We also show that a corresponding RW dendrimer (RWd) exhibiting improved half-life relieves inhibition of BMP receptor signaling by RSPO2 in human AML cells, reduces cell growth, and induces differentiation. Moreover, microinjection of RWd in Xenopus embryos ventralizes the dorsoventral embryonic patterning by upregulating BMP signaling without affecting WNT signaling. Our study corroborates the function of RSPO2 as a BMP receptor antagonist and provides a proof of concept for pharmacologically uncoupling BMP antagonist from WNT agonist functions of RSPO2 using the inhibitor peptide RWd with enhanced target selectivity and limited side effects. 相似文献
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Zhijing Xie Xin Sun Johannes Lux TingWen Chen Mikhail Potapov Donghui Wu Stefan Scheu 《Ecology and evolution》2022,12(2)
Altitudinal changes in the diversity of plants and animals have been well documented; however, soil animals received little attention in this context and it is unclear whether their diversity follows general altitudinal distribution patterns. Changbai Mountain is one of few well‐conserved mountain regions comprising natural ecosystems on the Eurasian continent. Here, we present a comprehensive analysis of the diversity and community composition of Collembola along ten altitudinal sites representing five vegetation types from forest to alpine tundra. Among 7834 Collembola individuals, 84 morphospecies were identified. Species richness varied marginally significant with altitude and generally followed a unimodal relationship with altitude. By contrast, the density of Collembola did not change in a consistent way with altitude. Collembola communities changed gradually with altitude, with local habitat‐related factors (soil and litter carbon‐to‐nitrogen ratio, litter carbon content, and soil pH) and climatic variables (precipitation seasonality) identified as major drivers of changes in Collembola community composition. Notably, local habitat‐related factors explained more variation in Collembola assemblages than climatic variables. The results suggest that local habitat‐related factors including precipitation and temperature are the main drivers of changes in Collembola communities with altitude. Specifically, soil and litter carbon‐to‐nitrogen ratio correlated positively with Collembola communities at high altitudes, whereas soil pH correlated positively at low altitudes. This documents that altitudinal gradients provide unique opportunities for identifying factors driving the community composition of not only above‐ but also belowground invertebrates. 相似文献