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The migration of photoinitiators (PIs): benzophenone (BP), ethyl 4-dimethylaminobenzoate (EDAB), and 4-chlorobenzophenone (CBP), from polyethylene (PE)-coated paper to 4% (v/v) acetic acid and 10% (v/v) salt-simulated food solution was quantitatively analyzed using gas chromatography–mass spectrometry. The migration behavior of the three PIs was studied under three specific working conditions: conventional heating, microwave power, and random vibration level. The migration rate of the three PIs in acidic food simulants was ranked from BP > EDAB > CBP under the specific working conditions. The mobility of the three PIs increased with increasing temperature, microwave power, and random vibration acceleration in 4% (v/v) acetic acid by 10, 10, and 15%, respectively. The experimental migration data of three PIs in PE-coated paper under different temperatures and microwave powers were used to establish the Crank monolayer migration model according to Fick’s second law. The diffusion coefficient D increased with an increase in experimental conditions. According to the migration data under the condition of random vibration level, a mathematical model conforming to the Fick model was established, fitting the migration process. These results showed that conventional heating, microwave heating, and vibration could affect the food safety of PE-coated paper.

Elton's biotic resistance hypothesis, which posits that diverse communities should be more resistant to biological invasions, has received considerable experimental support. However, it remains unclear whether such a negative diversity-invasibility relationship would persist under anthropogenic environmental change. By using the common ragweed (Ambrosia artemisiifolia) as a model invader, our 4-year grassland experiment demonstrated consistently negative relationships between resident species diversity and community invasibility, irrespective of nitrogen addition, a result further supported by a meta-analysis. Importantly, our experiment showed that plant diversity consistently resisted invasion simultaneously through increased resident biomass, increased trait dissimilarity among residents, and increased community-weighted means of resource-conservative traits that strongly resist invasion, pointing to the importance of both trait complementarity and sampling effects for invasion resistance even under resource enrichment. Our study provides unique evidence that considering species' functional traits can help further our understanding of biotic resistance to biological invasions in a changing environment.

Many groups of vertebrates produce distress calls when attacked by predators as a last attempt to survive. However, few studies investigate whether recognition of distress calls involves learning or acoustic similarity to familiar calls. This study assesses the importance of these two factors as well as phylogenetic relatedness in distress call recognition by tropical rainforest birds. We measured the avian community responses to familiar and unfamiliar distress calls in a lowland tropical rainforest in Costa Rica using playbacks of a sympatric species, the orange-billed sparrow, Arremon aurantiirostris, and a closely related allopatric species, the white-eared ground-sparrow, Melozone leucotis. In addition, to test whether recognition is driven by phylogenetic relatedness to the call sender, we compared the phylogenetic distance of approaching individuals to A. aurantiirostris when using different playback stimuli. We found that individuals called back to sympatric and allopatric calls within similar amounts of time, supporting the role of acoustic similarity in distress call recognition. We also found that individuals approached faster and spent more time inside the observation zone for sympatric distress calls than for allopatric distress calls, and both responses were stronger than the response to white noise (control), which supports the roles of acoustic similarity and learning in distress call recognition. Sympatric distress calls elicited approaching reactions from species that were more closely related to the sympatric species than did white noise, which suggests that phylogenetically related species are more likely to identify and respond to the sympatric distress signaller, while white noise elicited responses from a random subset of species that were on average more distantly related to the sympatric signaller. We conclude that learning, acoustic similarity and phylogenetic relatedness play important roles in the response to distress calls.

Background: Lung cancer has the highest mortality rate among cancers worldwide, with non-small cell lung cancer (NSCLC) the most common type. Increasing evidence shows that PHB2 is highly expressed in other cancer types; however, the effects of PHB2 in NSCLC are currently poorly understood. Method: PHB2 expression and its clinical relevance in NSCLC tumor tissues were analyzed using a tissue microarray. The biological role of PHB2 in NSCLC was investigated in vitro and in vivo using immunohistochemistry and immunofluorescence staining, gene expression knockdown and overexpression, cell proliferation assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, wound healing assay, Transwell assay, western blot analysis, qRT-PCR, coimmunoprecipitation, and mass spectrometry analysis. Results: Our major finding is that PHB2 facilitates tumorigenesis in NSCLC by interacting with and stabilizing RACK1, which further induces activation of downstream tumor-promoting effectors. PHB2 was found to be overexpressed in NSCLC tumor tissues, and its expression was correlated with clinicopathological features. Furthermore, PHB2 overexpression promoted proliferation, migration, and invasion, whereas PHB2 knockdown enhanced apoptosis in NSCLC cells. The stimulating effect of PHB2 on tumorigenesis was also verified in vivo. In addition, PHB2 interacted with RACK1 and increased its expression through posttranslational modification, which further induced activation of the Akt and FAK pathways. Conclusions: Our results reveal the effects of PHB2 on tumorigenesis and its regulation of RACK1 and RACK1-associated proteins and downstream signaling in NSCLC. We believe that the crosstalk between PHB2 and RACK1 provides us with a great opportunity to design and develop novel therapeutic strategies for NSCLC.

Machine learning has been applied to neuroimaging data for estimating brain age and capturing early cognitive impairment in neurodegenerative diseases. Blood parameters like neurofilament light chain are associated with aging. In order to improve brain age predictive accuracy, we constructed a model based on both brain structural magnetic resonance imaging (sMRI) and blood parameters. Healthy subjects (n = 93; 37 males; aged 50-85 years) were recruited. A deep learning network was firstly pretrained on a large set of MRI scans (n = 1,481; 659 males; aged 50-85 years) downloaded from multiple open-source datasets, to provide weights on our recruited dataset. Evaluating the network on the recruited dataset resulted in mean absolute error (MAE) of 4.91 years and a high correlation (r = .67, p.001) against chronological age. The sMRI data were then combined with five blood biochemical indicators including GLU, TG, TC, ApoA1 and ApoB, and 9 dementia-associated biomarkers including ApoE genotype, HCY, NFL, TREM2, Aβ40, Aβ42, T-tau, TIMP1, and VLDLR to construct a bilinear fusion model, which achieved a more accurate prediction of brain age (MAE, 3.96 years; r = .76, p.001). Notably, the fusion model achieved better improvement in the group of older subjects (70-85 years). Extracted attention maps of the network showed that amygdala, pallidum, and olfactory were effective for age estimation. Mediation analysis further showed that brain structural features and blood parameters provided independent and significant impact. The constructed age prediction model may have promising potential in evaluation of brain health based on MRI and blood parameters.

Background: Immunotherapy has dramatically changed the treatment landscape of cancer. Immunotherapies targeting the programmed death 1/programmed death ligand 1 pathway have been shown to lead to durable responses in patients with a variety of cancers. However, combination approaches are required to extend this benefit beyond a subset of patients. Studies have suggested that anti-angiogenic therapy can elicit or enhance tumor immunity response.Therefore, we hypothesised that combining immunotherapy with anti-angiogenic treatment may have a synergistic effect and may enhance the efficacy of both treatments.Methods: We evaluated the combination of bevacizumab (anti-vascular endothelial growth factor monoclonal antibody) and pembrolizumab (anti-programmed death 1 monoclonal antibody) in two mouse models of human non-small cell lung cancer cell lines (H1299 and A549). We monitored tumour growth and examined changes in the tumour vasculature, along with the frequency and phenotype of tumour-infiltrating lymphocytes.Results: The combination of bevacizumab and pembrolizumab synergistically inhibited tumour growth in vivo without overt toxicity in both cell lines. Combination therapy reprogrammed the immune microenvironment by increasing CD8+ cytotoxic T cell infiltration, thereby turning tumours with different phenotypes into inflamed (‘hot’) tumours. This is potentially mediated by vascular normalisation and endothelial cell activation, as demonstrated by a reduction in the number of microvessels and an increase in adhesion molecules.Conclusions: Taken together, our preclinical studies demonstrate that the combination of bevacizumab and pembrolizumab had a synergistic anti-tumour effect and provides a theoretical basis for translating basic research into clinical applications.

Additional file 2: Table S1. qRT-PCR primer sequences. Table S2. Knockdown sequences. Table S3. Primary antibodies used in this study. Table S4. The SRAMP algorithm was performed on the FBXW7 sequence of non-small cell lung cancer cell lines to predict m6A sites.

Additional file 1: Figure S1. m6A methylation of FBXW7 mRNA by METTL3. Figure S2. Correlation between METTL3 downregulation and unfavorable prognosis in patients with lung adenocarcinoma. Figure S3. FBXW7 overexpression rescued the anti-tumor phenotype impaired by METTL3 knockdown in vitro. Figure S4. m6A-methylated motifs in the coding sequence promote FBXW7 translation. Figure S5. Prediction score of m6A distribution in the non-small cell lung cancer cell line according to the sequence-based RNA adenosine methylation site predictor (SRAMP) algorithm. Figure S6. Histogram showing the differences of each cell group in Fig. 3a.

Background FBXW7 m6A modification plays an important role in lung adenocarcinoma (LUAD) progression; however, the underlying mechanisms remain unclear. Methods The correlation between FBXW7 and various genes related to m6A modification was analyzed using The Cancer Genome Atlas database. The regulatory effects of METTL3 on FBXW7 mRNA m6A modification were examined in a cell model, and the underlying mechanism was determined by methylated RNA immunoprecipitation, RNA immunoprecipitation, luciferase reporter, and mutagenesis assays. In vitro experiments were performed to further explore the biological effects of METTL3-mediated FBXW7 m6A modification on LUAD development. Results Decreased FBXW7 expression was accompanied by downregulated METTL3 expression in human LUAD tissues and was associated with a worse prognosis for LUAD in The Cancer Genome Atlas database. m6A was highly enriched in METTL3-mediated FBXW7 transcripts, and increased m6A modification in the coding sequence region increased its translation. Functionally, METTL3 overexpression or knockdown affected the apoptosis and proliferation phenotype of LUAD cells by regulating FBXW7 m6A modification and expression. Furthermore, FBXW7 overexpression in METTL3-depleted cells partially restored LUAD cell suppression in vitro and in vivo. Conclusions Our findings reveal that METTL3 positively regulates FBXW7 expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in LUAD initiation and development.

Background FBXW7 m6A modification plays an important role in lung adenocarcinoma (LUAD) progression; however, the underlying mechanisms remain unclear. Methods The correlation between FBXW7 and various genes related to m6A modification was analyzed using The Cancer Genome Atlas database. The regulatory effects of METTL3 on FBXW7 mRNA m6A modification were examined in a cell model, and the underlying mechanism was determined by methylated RNA immunoprecipitation, RNA immunoprecipitation, luciferase reporter, and mutagenesis assays. In vitro experiments were performed to further explore the biological effects of METTL3-mediated FBXW7 m6A modification on LUAD development. Results Decreased FBXW7 expression was accompanied by downregulated METTL3 expression in human LUAD tissues and was associated with a worse prognosis for LUAD in The Cancer Genome Atlas database. m6A was highly enriched in METTL3-mediated FBXW7 transcripts, and increased m6A modification in the coding sequence region increased its translation. Functionally, METTL3 overexpression or knockdown affected the apoptosis and proliferation phenotype of LUAD cells by regulating FBXW7 m6A modification and expression. Furthermore, FBXW7 overexpression in METTL3-depleted cells partially restored LUAD cell suppression in vitro and in vivo. Conclusions Our findings reveal that METTL3 positively regulates FBXW7 expression and confirm the tumor-suppressive role of m6A-modified FBXW7, thus providing insight into its epigenetic regulatory mechanisms in LUAD initiation and development. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-01880-3.

Anthropogenic nitrogen (N) and sulfur (S) deposition can change above- and belowground biodiversity, including root-associated fungi that are tightly linked to plant fitness. We investigated the effect of eleven years of N and S addition on the diversity of root-associated fungal pathogens and mutualists, including ectomycorrhizal fungi (EMF), dark septate endophytes (DSEs), and ericoid mycorrhizal fungi (ERM), in a broadleaf tree-dominated boreal forest using HiSeq sequencing of ITS2 amplicons of root fungal DNA. Long-term N and S addition increased the diversity of root-associated pathogens, notably the abundance of Venturia macularis, which causes aspen leaf and shoot blight, in the forest floor. Nitrogen addition increased the abundance of several N-sensitive EMF taxa and of EMF related to organic-N uptake from the soil, but had little effect on the overall abundance and diversity of EMF. Nitrogen and S addition did not affect the abundance and diversity of DSEs, but N addition decreased the Shannon diversity and evenness of ERM communities in the mineral soil. The changed diversity of root-associated fungal pathogens and mutualists suggests that long-term N and S addition will impact the host plant's capacity for nutrient acquisition and defense against pathogens in the broadleaf-dominated boreal forest.

African swine fever virus (ASFV) is a highly pathogenic large DNA virus that causes African swine fever (ASF) in domestic pigs and European wild boars with mortality rate up to 100%. The DP96R gene of ASFV encodes one of the viral virulence factors, yet its action mechanism remains unknown. In this study, we report that DP96R of ASFV China 2018/1 strain subverts type I IFN production in cGAS sensing pathway. DP96R inhibited the cGAS/STING, and TBK1 but not IRF3-5D mediated IFN-β and ISRE promoters activation. Furthermore, DP96R selectively blocked the activation of NF-κB promoter induced by cGAS/STING, TBK1, and IKKβ, but not by overexpression of p65. Moreover, DP96R inhibited phosphorylation of TBK1 stimulated by cGAS/STING activation, and TBK1-induced antiviral response. Finally, truncated mutation analysis demonstrated that the region spanning amino acids 30 to 96 of DP96R was responsible for the inhibitory activity. To our knowledge, this is for the first time that DP96R of ASFV China 2018/1 is reported to negatively regulate type I IFN expression and NF-κB signaling by inhibiting both TBK1 and IKKβ, which plays an important role in virus immune evasion.

Cancer cells exhibit extreme sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) over normal cells, highlighting TRAIL's potential as a novel and effective cancer drug. However, the therapeutic effect of TRAIL is limited due to drug resistance. In the present study, we sought to investigate the potential effects of luteolin as a TRAIL sensitizer in non-small cell lung cancer (NSCLC) cells. A549 and H1975 cells had low sensitivity or were resistant to TRAIL. Luteolin alone or in combination with TRAIL decreased cell viability and increased apoptosis. Furthermore, luteolin alone or in combination with TRAIL enhanced death receptor 5 (DR5) expression and dynamin-related protein 1 (Drp1)-dependent mitochondrial fission. However, the synergistic effect of luteolin on cell viability and apoptosis was reversed by DR5 and Drp1 inhibition, suggesting that DR5 upregulation and mitochondrial dynamics may be essential for luteolin as a sensitizer of TRAIL-based therapy in NSCLC. Moreover, luteolin treatment alone or in combination with TRAIL increased the phosphorylation of c-Jun N-terminal kinase (JNK), while SP600125 (the JNK inhibitor) significantly abolished the synergistic effect on DR5 expression and Drp1 translocation, indicating that JNK signaling activation was greatly associated with the synergistic effect exerted by luteolin in NSCLC cells. Therefore, TRAIL combined with luteolin could be as an effective chemotherapeutic strategy for NSCLC.

With the development of economy, the issue of investment environment on regional economy has become a major topic for the theory research of decision-making