What influenced the lesion patterns and hemodynamic characteristics in patients with internal carotid artery stenosis? A retrospective study

•Blood perfusion influences ischemic lesions in patients with of ICAS.•Communicating arteries influence intracranial blood flow.•TCD was a convenient and rapid tool to assess cerebral blood flow

Genetic architecture of lodging resistance revealed by genome- wide association study in maize (Zea mays L)

Lodging is one of key factors influencing biomass yield, restricting planting density and reducing mechanical harvesting productivity in maize. Targeted cultivating lodging resistance varieties with screened lines is an eco- nomical and effective approach to improve ability of maize lodging resistance. To accomplish this objective, we performed phenotypic assessment of seven lodging-related traits in a diverse maize population consisting of 290 inbred lines and conducted a genome-wide association study with 201 SSR markers to detected marker-trait as- sociations. Seven lodging-related traits all showed broad phenotypic variations. Through evaluation of stalk push- ing resistance in the field for two years, a number of 32 inbred lines featured with strong lodging resistance were selected out. Correlation analysis indicated that stalk pushing resistance had a significantly positive correlation with third internode diameter and fourth internode diameter and a significantly negative correlation with ear height. Furthermore, a total of 27 and 13 significant associations for lodging-related traits were identified in year 2012 and 2013, respectively. Interestingly, three associations on chromosome 4, 5, and 6 were discovered in both years. Thus, this study provides useful information for understanding genetic architecture of lodging resistance in maize and will benefit maize marker-assistant breeding program with improving lodging resistance

Natural products and dietary interventions on liver enzymes: an umbrella review and evidence map

BackgroundThe association between natural products and dietary interventions on liver enzymes is unclear; therefore, this study aimed to examine their effects on liver enzymes in adults.MethodsPubMed, Embase, and Cochrane Library of Systematic Reviews databases were searched from inception until March 2023. The Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) systems were used to assess the methodological and evidence quality, and the therapeutic effects were summarized in a narrative form.ResultsA total of 40 meta-analyses on natural products (n = 25), dietary supplements (n = 10), and dietary patterns (n = 5) were evaluated, and results were presented in a narrative form. The overall methodological quality of the included studies was relatively poor. The results indicated that positive effects were observed for nigella sativa, garlic, artichoke, curcumin, silymarin, vitamin E, vitamin D, L-carnitine, propolis, and polyunsaturated fatty acids on certain liver enzymes. The dietary patterns, including high-protein, Mediterranean, and calorie-restriction diets and evening snacks, may reduce liver enzymes; however, other supplements and herbs did not reduce liver enzyme levels or have minimal effects. The evidence quality was generally weak given the risk of bias, heterogeneity, and imprecision.ConclusionThis umbrella review suggests that natural products and dietary interventions have beneficial therapeutic effects on liver enzymes levels. Further clinical trials are necessary to establish the effectiveness of supplements that reduce liver enzymes

Nickel pyrithione induces apoptosis in chronic myeloid leukemia cells resistant to imatinib via both Bcr/Abl-dependent and Bcr/Abl-independent mechanisms

Abstract Background Acquired imatinib (IM) resistance is frequently characterized by Bcr-Abl mutations that affect IM binding and kinase inhibition in patients with chronic myelogenous leukemia (CML). Bcr-Abl-T315I mutation is the predominant mechanism of the acquired resistance to IM. Therefore, it is urgent to search for additional approaches and targeting strategies to overcome IM resistance. We recently reported that nickel pyrithione (NiPT) potently inhibits the ubiquitin proteasome system via targeting the 19S proteasome-associated deubiquitinases (UCHL5 and USP14), without effecting on the 20S proteasome. In this present study, we investigated the effect of NiPT, a novel proteasomal deubiquitinase inhibitor, on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl. Methods Cell viability was examined by MTS assay and trypan blue exclusion staining assay in KBM5, KBM5R, K562, BaF3-p210-WT, BaF3-p210-T315I cells, and CML patients’ bone marrow samples treated with NiPT. Cell apoptosis in CML cells was detected with Annexin V-FITC/PI and rhodamine-123 staining followed by fluorescence microscopy and flow cytometry and with western blot analyses for apoptosis-associated proteins. Expression levels of Bcr-Abl in CML cells were analyzed by using western blotting and real-time PCR. The 20S proteasome peptidase activity was measured using specific fluorogenic substrate. Active-site-directed labeling of proteasomal DUBs, as well as the phosphorylation of USP14 was used for evaluating the inhibition of the DUBs activity by NiPT. Mouse xenograft models of KBM5 and KBM5R cells were analyzed, and Bcr-Abl-related proteins and protein biomarkers related to proliferation, differentiation, and adhesion in tumor tissues were detected by western blots and/or immunohistological analyses. Results NiPT induced apoptosis in CML cells and inhibited the growth of IM-resistant Bcr-Abl-T315I xenografts in nude mice. Mechanistically, NiPT induced decreases in Bcr-Abl proteins, which were associated with downregulation of Bcr-Abl transcription and with the cleavage of Bcr-Abl protein by activated caspases. NiPT-induced ubiquitin proteasome system inhibition induced caspase activation in both IM-resistant and IM-sensitive CML cells, and the caspase activation was required for NiPT-induced Bcr-Abl downregulation and apoptotic cell death. Conclusions These findings support that NiPT can overcome IM resistance through both Bcr-Abl-dependent and Bcr-Abl-independent mechanisms, providing potentially a new option for CML treatment

Variation of Helicoverpa armigera symbionts across developmental stages and geographic locations

Cotton bollworm (Helicoverpa armigera) poses a global problem, causing substantial economic and ecological losses. Endosymbionts in insects play crucial roles in multiple insect biological processes. However, the interactions between H. armigera and its symbionts have not been well characterized to date. We investigated the symbionts of H. armigera in the whole life cycle from different geographical locations. In the whole life cycle of H. armigera, Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria were the dominant bacteria at the phylum level, while Enterococcus, Enterobacter, Glutamicibacter, and Bacillus were the four dominant bacteria at the genus level. Furthermore, high similarity in symbiotic bacterial community was observed in different stages of H. armigera, which were dominated by Enterococcus and Enterobacter. In fields, the dominant bacteria were Proteobacteria and Bacteroidetes, whereas, in the laboratory, the dominant bacteria were Proteobacteria. At the genus level, the dominant bacteria in cotton bollworm eggs of wild populations were Enterobacter, Morganella, Lactococcus, Asaia, Apibacter, and Enterococcus, and the subdominant bacteria were Bartonella, Pseudomonas, and Orbus. Moreover, the symbionts varied with geographical locations, and the closer the geographical distance, the more similar the microbial composition. Taken together, our study identifies and compares the symbiont variation along with geographical gradients and host development dynamic and reveals the high flexibility of microbiome communities in H. armigera, which probably benefits for the successful survival in a complicated changing environment

Sublethal and intergenerational effects of fipronil on Binodoxys communis larvae based on transcriptome sequencing

Fipronil is widely used in the agricultural world as an efficient phenylpyrazole insecticide to control pests. Binodoxys communis is a key parasitic natural enemy of major homopteran pests and can successfully control the population of pests such as cotton aphids. It has not yet been studied what effects would sublethal doses of fipronil have on Binodoxys communis larvae. Here, this study evaluated the effect of fipronil on Binodoxys communis larvae and analyze the transcriptome results. The results showed that LC10 (1.19 mg/L) and LC25 (1.73 mg/L) had significant negative effects on the survival rate and parasitism rate of F0 generation. Moreover, exposure to high concentrations (LC25) of fipronil still had obvious passive effect on the F1 generation of Binodoxys communis. These results indicated that sublethal doses of fipronil have malignant effects on the biological functions of parasitoids and their offspring. The results of transcriptome analysis showed that differentially expressed genes (DEGs) of Binodoxys communis after LC10 treatment are mainly related to immunity and detoxification. LC25 treatment instead resulted in changes in the expression of genes related to nutrition, energy and metabolism reactions. Seven of the identified DEGs were selected for real-time fluorescence quantitative PCR analysis. To the best of our knowledge, this is the first report to evaluate the sublethal, intergenerational, and transcriptomic side effects of fipronil on larvae of parasitic natural pest enemies. Our findings provide data to accurately assess the risk of fipronil usage on Binodoxys communis larvae, and provide important theoretical support for the comprehensive prevention and control of natural enemies and pesticides

RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy

Prolonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation

Genome-Wide Mapping of DNA Methylation in Chicken

Cytosine DNA methylation is an important epigenetic modification termed as the fifth base that functions in diverse processes. Till now, the genome-wide DNA methylation maps of many organisms has been reported, such as human, Arabidopsis, rice and silkworm, but the methylation pattern of bird remains rarely studied. Here we show the genome-wide DNA methylation map of bird, using the chicken as a model organism and an immunocapturing approach followed by high-throughput sequencing. In both of the red jungle fowl and the avian broiler, DNA methylation was described separately for the liver and muscle tissue. Generally, chicken displays analogous methylation pattern with that of animals and plants. DNA methylation is enriched in the gene body regions and the repetitive sequences, and depleted in the transcription start site (TSS) and the transcription termination site (TTS). Most of the CpG islands in the chicken genome are kept in unmethylated state. Promoter methylation is negatively correlated with the gene expression level, indicating its suppressive role in regulating gene transcription. This work contributes to our understanding of epigenetics in birds