Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway

Long non-coding RNAs (lncRNA) have an extensive role in the progression and chemoresistance of gastric cancer (GC). Deeply study the regulatory role of lncRNAs could provide potential therapeutic targets. The aim of this study is to explore the regulatory role of HOTAIR in the progression and oxaliplatin resistance of GC. The expression of HOTAIR in GC and cell lines were detected by using qRT-PCR. Cell proliferation and apoptosis were analysed by CCK-8, EdU incorporation and flow cytometry. Luciferase reporter assay was used to identify the interaction between HOTAIR and ABCG2 (ATP-binding cassette (ABC) superfamily G member 2, ABCG2) via miR-195-5p. The regulatory functions were verified by using molecular biology experiments. HOTAIR was significantly overexpressed in GC and associated with poor prognosis. Knock-down of HOTAIR inhibited the GC cells proliferation and oxaliplatin resistance, while overexpression of HOTAIR showed opposite functions. Further studies found that HOTAIR acted as a competing endogenous RNA (ceRNA) to absorb miR-195-5p and elevated the expression of ABCG2, which leads to resistance of GC cells to oxaliplatin. Taken together, our findings demonstrated that HOTAIR regulates ABCG2 induced resistance of GC to oxaliplatin through miR-195-5p signalling and illustrate the great potential of developing new therapeutic targets for GC patients.     

Pan-Cancer analyses of Necroptosis-Related genes as a potential target to predict immunotherapeutic outcome

Necroptosis is a unique programmed death mechanism of necrotic cells. However, its role and specific mechanism in cancer remain unclear, and a systematic pan-cancer analysis of necroptosis is yet to be conducted. Thus, we performed a specific pan-cancer analysis using The Cancer Genome Atlas and Genotype-Tissue Expression databases to analyse necroptosis expression in terms of cancer prognosis, DNA methylation status, tumour mutative burden, microsatellite instability, immune cell infiltration in different types of cancer and molecular mechanisms. For the first time, we explored the correlation between necroptosis and immunotherapy prognosis. Thus, our study provides a relatively comprehensive understanding of the carcinogenicity of necroptosis in different types of cancer. It is suggested that necroptosis can be used to evaluate the sensitivity of different patients to immunotherapy and may become a potential target for tumour immunotherapy.     

Transmembrane kinase 1-mediated auxin signal regulates membrane-associated clathrin in Arabidopsis roots

Clathrin-mediated endocytosis (CME) is the major endocytic pathway in eukaryotic cells that directly regulates abundance of plasma membrane proteins. Clathrin triskelia are composed of clathrin heavy chains (CHCs) and light chains (CLCs), and the phytohormone auxin differentially regulates membrane-associated CLCs and CHCs, modulating the endocytosis and therefore the distribution of auxin efflux transporter PIN-FORMED2 (PIN2). However, the molecular mechanisms by which auxin regulates clathrin are still poorly understood. Transmembrane kinase (TMKs) family proteins are considered to contribute to auxin signaling and plant development; it remains unclear whether they are involved in PIN transport by CME. We assessed TMKs involvement in the regulation of clathrin by auxin, using genetic, pharmacological, and cytological approaches including live-cell imaging and immunofluorescence. In tmk1 mutant seedlings, auxin failed to rapidly regulate abundance of both CHC and CLC and to inhibit PIN2 endocytosis, leading to an impaired asymmetric distribution of PIN2 and therefore auxin. Furthermore, TMK3 and TMK4 were shown not to be involved in regulation of clathrin by auxin. In summary, TMK1 is essential for auxin-regulated clathrin recruitment and CME. TMK1 therefore plays a critical role in the establishment of an asymmetric distribution of PIN2 and an auxin gradient during root gravitropism.     

Efficient polymer-mediated delivery system for thiocyclam: Nanometerization remarkably improves the bioactivity toward green peach aphids

The unscientific application of synthetic pesticides has brought various negative effects on the environment, hindering the sustainable development of agriculture. Nanoparticles can be applied as carriers to improve pesticide delivery, showing great potential in the development of pesticide formulation in recent years. Herein, a star polymer (SPc) was constructed as an efficient pesticide nanocarrier/adjuvant that could spontaneously assemble with thiocyclam or monosultap into a complex, through hydrophobic association and hydrogen bonding, respectively, with the pesticide-loading contents of 42.54% and 19.3%. This complexation reduced the particle sizes of thiocyclam from 543.54 to 52.74 nm for pure thiocyclam, and 3 814.16 to 1 185.89 nm for commercial preparation (cp) of thiocyclam. Interestingly, the introduction of SPc decreased the contact angles of both pure and cp thiocyclam on plant leaves, and increased the plant uptake of cp thiocyclam to 2.4–1.9 times of that without SPc. Meanwhile, the SPc could promote the bioactivity of pure/cp thiocyclam against green peach aphids through leaf dipping method and root application. For leaf dipping method, the 50% lethal concentration decreased from 0.532 to 0.221 g/L after the complexation of pure thiocyclam with SPc, and that decreased from 0.390 to 0.251 g/L for cp thiocyclam. SPc seems a promising adjuvant for nanometerization of both pure and cp insecticides, which is beneficial for improving the delivery efficiency and utilization rate of pesticides.     

Peptide MSI-1 inhibited MCR-1 and regulated outer membrane vesicles to combat immune evasion of Escherichia coli

Polymyxin resistance is conferred by MCR-1 (mobile colistin resistance 1)-induced lipopolysaccharide (LPS) modification of G⁻ bacteria. However, the peptide MSI-1 exerts potent antimicrobial activity against mcr-1-carrying bacteria. To further investigate the potential role of MCR-1 in improving bacterial virulence and facilitating immune evasion, and the immunomodulatory effect of peptide MSI-1, we first explored outer membrane vesicle (OMV) alterations of mcr-1-carrying bacteria in the presence and absence of sub-MIC MSI-1, and host immune activation during bacterial infection and OMV stimulation. Our results demonstrated that LPS remodelling induced by MCR-1 negatively affected OMV formation and protein cargo by E. coli. In addition, MCR-1 diminished LPS-stimulated pyroptosis but facilitated mitochondrial dysfunction, further aggravating apoptosis in macrophages induced by OMVs of E. coli. Similarly, TLR4-mediated NF-κB activation was markedly alleviated once LPS was modified by MCR-1. However, peptide MSI-1 at the sub-MIC level inhibited the expression of MCR-1, further partly rescuing OMV alteration and attenuation of immune responses in the presence of MCR-1 during both infection and OMV stimulation, which can be exploited for anti-infective therapy.     

Solid-phase microextraction and cuticular hydrocarbon differences related to reproductive activity in juniper bark borer Semanotus bifasciatus Motschulsky

Cuticular hydrocarbons of Cerambycidae species can function as signals for sex recognition. Little is known about the copulatory signals of the juniper bark borer Semanotus bifasciatus, a major economic threat to Platycladus orientalis Franco in China. Here, we investigated the cuticular hydrocarbons of both sexes of S. bifasciatus to determine the chemically mediated mating signals using the solid-phase microextraction (SPME) technique with carbowax/divinylbenzene fibers (CAR/DVB) and then analyzed by coupled gas chromatography-mass spectrometry (GC-MS). A series of aliphatic saturated straight-chain n-alkanes (n-C₂₃ to n-C₂₈), internally branched monomethylalkanes at carbons 3, 11, or 13, and dimethylalkanes were identified, which showed no qualitative differences in either sex and were similar in the samples with SPME fiber extraction and those with hexane extraction. The bioassay showed that 11-methylpentacosane (11-MeC₂₅), 11-methylhexacosane (11-MeC₂₆), and 11-methylheptacosane (11-MeC₂₇) have sex-specific recognition functions that triggered more mating attempts at a female-specific ratio of 100:4:60 than at a male-specific ratio of 100:85:50. In addition, the female-specific ratio of 11-methylalkanes can elicit about 70% of male mating attempts within about 60 s, whereas live females elicit about 98% of male mating attempts within 25 s. The discrepancy in the initiation of mating attempts by synthetic mixtures and live females suggests that the methyl isomers 3-MeC₂₅, 3-MeC₂₇, and/or 11,15-diMeC₂₇ may also be involved in the mating behavior of S. bifasciatus. These results suggest that 11-MeC₂₅, 11-MeC₂₆, and 11-MeC₂₇ constitute the contact sex pheromone of S. bifasciatus, with the presence or absence of 11-MeC₂₆ in particular playing an important role in mate recognition by males.