Genomic insights into selection for heterozygous alleles and woody traits in Populus tomentosa

Heterozygous alleles are widespread in outcrossing and clonally propagated woody plants. The variation in heterozygosity that underlies population adaptive evolution and phenotypic variation, however, remains largely unknown. Here, we describe a de novo chromosome-level genome assembly of Populus tomentosa, an economic and ecologically important native tree in northern China. By resequencing 302 natural accessions, we determined that the South subpopulation (Pop_S) encompasses the ancestral strains of P. tomentosa, while the Northwest subpopulation (Pop_NW) and Northeast subpopulation (Pop_NE) experienced different selection pressures during population evolution, resulting in significant population differentiation and a decrease in the extent of heterozygosity. Analysis of heterozygous selective sweep regions (HSSR) suggested that selection for lower heterozygosity contributed to the local adaptation of P. tomentosa by dwindling gene expression and genetic load in the Pop_NW and Pop_NE subpopulations. Genome-wide association studies (GWAS) revealed that 88 single nucleotide polymorphisms (SNPs) within 63 genes are associated with nine wood composition traits. Among them, the selection for the homozygous AA allele in PtoARF8 is associated with reductions in cellulose and hemicellulose contents by attenuating PtoARF8 expression, and the increase in lignin content is attributable to the selection for decreases in exon heterozygosity in PtoLOX3 during adaptive evolution of natural populations. This study provides novel insights into allelic variations in heterozygosity associated with adaptive evolution of P. tomentosa in response to the local environment and identifies a series of key genes for wood component traits, thereby facilitating genomic-based breeding of important traits in perennial woody plants.     

Self-assembly of molecular beacons through metal ion coordination for fluorescence imaging of miRNA in living cells

Fluorescence nanosensors based on functional nucleic acids have been explored as a powerful sensing platform for disease-relevant miRNAs. This work developed a new hybrid nanosensor (Zr-B) through coordination-driven self-assembly of Zr ions and beacons. The prepared nanosensor exhibited high loading efficiency of beacons and could achieve sensitive and specific detection for miRNAs. The hybrid nanosensor could transfer beacons into living cells efficiently and maintain high stability and biocompatibility in the biological environment, achieving effective miRNA fluorescence imaging in living cells. Therefore, the resultant nanosensor holds potential for applications in disease diagnostics.     

Multistimuli-responsive fluorescence behaviours of aggregation-induced emission small-molecule and electrospun nanofibre films for acid–base vapour sensing

Multistimuli-responsive fluorescent materials have garnered great research interest benefited from their practical applications. Two twisted-structure compounds containing tetraphenylethylene (TPE) as the aggregation-induced emission (AIE) group and a pyridine unit as the acid reaction site to obtain new multistimuli-responsive fluorescent compounds (namely, TPECNPy: TPECNPy-2 and TPECNPy-3) were successfully synthesized through a one-step Knoevenagel condensation reaction. The multiple-stimuli response process of TPECNPy was investigated by means of photoluminescence (PL) spectra and emission colour. The results showed that both TPECNPy compounds with excellent AIE abilities displayed reversible emission wavelength and colour changes in response to multiple external stimuli, including grinding–fuming by CH₂Cl₂ or annealing and HCl-NH₃ vapour fuming. More importantly, fluorescent nanofibre films were prepared by electrospinning a solution of TPECNPy mixed with cellulose acetate (CA), and these exhibited reversible acid-induced discolouration, even with only 1 wt% TPECNPy. The results of this study may inspire strategies for designing multistimuli-responsive materials and preparing fluorescent sensing nanofibre films.     

Duvelisib attenuates bleomycin-induced pulmonary fibrosis via inhibiting the PI3K/Akt/mTOR signalling pathway

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that seriously threatens the health of patients. The pathogenesis of IPF is still unclear, and there is a lack of effective therapeutic drugs. Myofibroblasts are the main effector cells of IPF, leading to excessive deposition of extracellular matrix (ECM) and promoting the progression of fibrosis. Inhibiting the excessive activation and relieving autophagy blockage of myofibroblasts is the key to treat IPF. PI3K/Akt/mTOR pathway plays a key regulatory role in promoting fibroblast activation and autophagy inhibition in lung fibrosis. Duvelisib is a PI3K inhibitor that can simultaneously inhibit the activities of PI3K-δ and PI3K-γ, and is mainly used for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma tumour (SLL). In this study, we aimed to examine the effects of Duvelisib on pulmonary fibrosis. We used a mouse model of bleomycin-induced pulmonary fibrosis to evaluate the effects of Duvelisib on pulmonary fibrosis in vivo and further explored the potential pharmacological mechanisms of Duvelisib in lung fibroblasts in vitro. The in vivo experiments showed that Duvelisib significantly alleviated bleomycin-induced collagen deposition and improved pulmonary function. In vitro and in vivo pharmacological experiments showed that Duvelisib dose-dependently suppressed lung fibroblast activation and improved autophagy inhibition by inhibiting the phosphorylation of PI3K, Akt and mTOR. Our results indicate that Duvelisib can alleviate the severity of pulmonary fibrosis and provide potential drugs for the treatment of pulmonary fibrosis.     

RNF7 promotes glioma growth via the PI3K/AKT signalling axis

RNF7 has been reported to play critical roles in various cancers. However, the underlying mechanisms of RNF7 in glioma development remain largely unknown. Herein, the expression level of RNF7 was examined in tissues by quantitative real-time PCR, Western blotting and immunohistochemistry. The effect of RNF7 on glioma progression was measured by performing CCK-8 and apoptosis assays, cell cycle-related experiments and animal experiments. The effect of RNF7 on PI3K/AKT signalling pathway was tested by Western blotting. First, we found that RNF7 was upregulated in tumour tissue compared with normal brain tissue, especially in high-grade glioma, and the high expression of RNF7 was significantly related to tumour size, Karnofsky Performance Scale score and a poor prognosis. Second, RNF7 overexpression facilitated tumour cell cycle progression and cell proliferation and suppressed apoptosis. Conversely, RNF7 knockdown suppressed tumour cell cycle progression and cell proliferation and facilitated apoptosis. Furthermore, follow-up mechanistic studies indicated that RNF7 could facilitate glioma cell proliferation and cell cycle progression and inhibit apoptosis by activating the PI3K/AKT signalling pathway. This study shows that RNF7 can clearly promote glioma cell proliferation by facilitating cell cycle progression and inhibiting apoptosis by activating the PI3K/AKT signalling pathway. Targeting the RNF7/PI3K/AKT axis may provide a new perspective on the prevention or treatment of glioma.     

胶质母细胞瘤外泌体的作用机制研究进展

胶质母细胞瘤(glioblastoma,GBM)因组织学异质性、侵袭能力强、术后复发快等问题,致使患者经手术治疗、化疗和放疗后的预后差,总体生存期短。GBM细胞来源外泌体(GBM cell-derived exosome,GBM-exo)能够通过其携带的细胞因子、miRNA、DNA和蛋白质等调节GBM细胞的增殖和迁移,通过血管生成蛋白和非编码RNA促进肿瘤血管生成,通过调节因子、蛋白质和药物靶向免疫检查点等介导肿瘤免疫逃逸,以及通过非编码RNA对抗GBM细胞的耐药性,有望成为个性化治疗GBM的重要靶标,且可以作为GBM的诊断和预后标志物。本文阐述了GBM-exo的制备方法和生物学特征,及其在GBM细胞增殖、血管生成、免疫逃逸和耐药性方面的作用和分子机制,为研发诊治GBM的新策略提供参考。     

广西荔浦晚泥盆世法门期竹节石

本文研究了广西荔浦上泥盆统榴江组上部扁豆状灰岩中所含的法门期竹节石2属3种,其产出层位分别为牙形刺化石带的 Palmatolepis crepida带和 Pa.marginifera带。     

Inhibition of the HIV-1 and HIV-2 proteases by curcumin and curcumin boron complexes

Curcumin, a relatively non-toxic natural product isolated from Curcuma longa, is a modest inhibitor of the HIV-1 (1050 = 100 μM) and HIV-2 (IC₅₀ = 250 μM) proteases. Simple modifications of the curcumin structure raise the IC₅₀ value but complexes of the central dihydroxy groups of curcumin with boron lower the IC₅₀ to a value as low as 6 μM. The boron complexes are also time-dependent inactivators of the HIV proteases. The increased affinity of the boron complexes may reflect binding of the orthogonal domains of the inhibitor in intersecting sites within the substrate-binding cavity of the enzyme, while activation of the ,β-unsaturated carbonyl group of curcumin by chelation to boron probably accounts for time-dependent inhibition of the enzyme.