68 research outputs found

    A Meta-Analysis of Survival Outcomes Following Reoperation in Recurrent Glioblastoma: Time to Consider the Timing of Reoperation

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    Background: Glioblastoma multiforme (GBM) inevitably recurs, but no standard regimen has been established for recurrent patients. Reoperation at recurrence alleviates mass effects, and the survival benefit has been reported in many studies. However, in most studies, the effect of reoperation timing on survival benefit was ignored. The aim of this meta-analysis was to investigate whether reoperation provided similar survival benefits in recurrent GBM patients when it was analyzed as a fixed or time-dependent covariate.Methods: A systematic literature search of PubMed, EMBASE, and Cochrane databases was performed to identify original articles that evaluated the associations between reoperation and prognosis in recurrent GBM patients.Results: Twenty-one articles involving 8,630 patients were included. When reoperation was considered as a fixed covariate, it was associated with better overall survival (OS) and post-progression survival (PPS) (OS: HR = 0.66, 95% CI 0.61-0.71, p < 0.001, I2 = 0%; PPS: HR = 0.70, 95% CI 0.57–0.88, p < 0.01, I2 = 70.2%). However, such a survival benefit was not observed when reoperation was considered as a time-dependent covariate (OS: HR = 2.19, 95% CI 1.47–3.27, p < 0.001; PPS: HR = 0.95, 95% CI 0.82–1.10, p = 0.51, I2 = 0%). The estimate bias caused by ignoring the time-dependent nature of reoperation was further demonstrated by the re-analysis of survival data in three included studies.Conclusions: The timing of reoperation may have an impact on the survival outcome in recurrent GBM patients, and survival benefits of reoperation in recurrent GBM may be overestimated when analyzed as fixed covariates. Proper analysis methodology should be used in future work to confirm the clinical benefits of reoperation

    The complete mitochondrial genomes of Dactylella tenuis, a fungus phylogenetically close to nematode-trapping fungus

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    In our study, we sequenced the complete mitochondrial genome of Dactylella tenuis and obtained the complete mitochondrial DNA sequence. This mitogenome is a typical circular molecule of 186,056 bp in length, which is rich in AT (73.79%), including 14 protein-coding genes, 24 transfer RNA genes, and 2 ribosomal RNA genes. Phylogenetic analysis showed the evolutionary relationship between D. tenuis and other species of nematode-trapping fungus

    detection and extraction method for plaintext sequential lsb steganography

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    By using the statistical properties of the top bits of plaintext, a detection and extraction method for the plaintext sequential least significant bit(LSB) steganography is proposed. The LSBs of the image is obtained by sequentially scanning, and 8 sequences are gained with every bit of the first byte as the beginning and 7 sampling interval. The appropriate window length and the threshold R are chosen, the 8 sequences with the window are sectioned and advantage values of the window are calculated. If one of advantage values is greater than R, the image is judged to be a stego image. After the biggest advantage sequence is found out from 8 sequences, the beginning and the end of the secret message are estimated and the plaintext is recovered. The theoretical analysis and experimental results show that the proposed method is effective. When only 200 bytes English plaintext is embedded in an image, the proposed method can detect and extract the plaintext successfully.By using the statistical properties of the top bits of plaintext, a detection and extraction method for the plaintext sequential least significant bit(LSB) steganography is proposed. The LSBs of the image is obtained by sequentially scanning, and 8 sequences are gained with every bit of the first byte as the beginning and 7 sampling interval. The appropriate window length and the threshold R are chosen, the 8 sequences with the window are sectioned and advantage values of the window are calculated. If one of advantage values is greater than R, the image is judged to be a stego image. After the biggest advantage sequence is found out from 8 sequences, the beginning and the end of the secret message are estimated and the plaintext is recovered. The theoretical analysis and experimental results show that the proposed method is effective. When only 200 bytes English plaintext is embedded in an image, the proposed method can detect and extract the plaintext successfully

    Antimicrobial resistance crisis: could artificial intelligence be the solution?

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    Abstract Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed. The discovery and introduction of novel antibiotics are time-consuming and expensive. According to WHO’s report of antibacterial agents in clinical development, only 18 novel antibiotics have been approved since 2014. Therefore, novel antibiotics are critically needed. Artificial intelligence (AI) has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics. Here, we first summarized recently marketed novel antibiotics, and antibiotic candidates in clinical development. In addition, we systematically reviewed the involvement of AI in antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction, and antibiotic stewardship

    Recent Advances in Small Peptides of Marine Origin in Cancer Therapy

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    Cancer is one of the leading causes of death in the world, and antineoplastic drug research continues to be a major field in medicine development. The marine milieu has thousands of biological species that are a valuable source of novel functional proteins and peptides, which have been used in the treatment of many diseases, including cancer. In contrast with proteins and polypeptides, small peptides (with a molecular weight of less than 1000 Da) have overwhelming advantages, such as preferential and fast absorption, which can decrease the burden on human gastrointestinal function. Besides, these peptides are only connected by a few peptide bonds, and their small molecular weight makes it easy to modify and synthesize them. Specifically, small peptides can deliver nutrients and drugs to cells and tissues in the body. These characteristics make them stand out in relation to targeted drug therapy. Nowadays, the anticancer mechanisms of the small marine peptides are still largely not well understood; however, several marine peptides have been applied in preclinical treatment. This paper highlights the anticancer linear and cyclic small peptides in marine resources and presents a review of peptides and the derivatives and their mechanisms

    YKL-40 in high-grade glioma: Prognostic value of protein versus mRNA expression

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    Background: YKL-40 has been reported to be associated with the prognosis of glioma patients. However, expression of YKL-40 was detected at protein or mRNA level in different studies. This may result in conclusion bias. This study is to investigate the prognostic value of increased YKL-40 protein versus mRNA expression in glioma patients. Methods: A comprehensive systematic search and review were performed using PubMed, EMBASE, and NKI databases to identify literature (published before May 1, 2018) that evaluated the association between YKL-40 and survival in glioma patients. Results: Thirteen relevant studies, involving 2139 patients, were included in this study. Elevated YKL-40 expression was associated with worse overall survival (OS) in glioma patients (hazard ratio [HR] = 1.44, 95% confidence interval [CI]: 1.27–1.63, P < 0.001), especially in high-grade glioma (anaplastic glioma: HR = 1.37, 95% CI: 1.09–1.74, P = 0.008; glioblastoma multiform: HR = 1.52, 95% CI: 1.33–1.73, P < 0.001). The increased YKL-40 protein level in serum (detected by ELISA) or in tumor tissues (detected by immunohistochemistry) was associated with worse OS (ELISA: HR = 1.43, 95% CI: 1.29–1.59, P < 0.001; immunohistochemistry: HR = 1.52, 95% CI: 1.20–1.93, P = 0.001). However, the association between elevated YKL-40 mRNA level (detected by real-time PCR) with worse OS was not significant (HR = 1.44, 95% CI: 0.73–2.83, P = 0.29, I2 = 68.3%). In addition when status of IDH1 mutation or/and O6-methylguanine-DNA methyltransferase promoter was incorporated as multivariate, increased expression level of YKL-40 was not associated with poorer survival (HR = 1.39, 95% CI: 0.99–1.93, P = 0.055). Conclusion: YKL-40 protein level, rather than mRNA level, may be a valuable biomarker to assess the prognosis in glioma patients

    Identification of and Mechanistic Insights into SARS-CoV-2 Main Protease Non-Covalent Inhibitors: An In-Silico Study

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    The indispensable role of the SARS-CoV-2 main protease (Mpro) in the viral replication cycle and its dissimilarity to human proteases make Mpro a promising drug target. In order to identify the non-covalent Mpro inhibitors, we performed a comprehensive study using a combined computational strategy. We first screened the ZINC purchasable compound database using the pharmacophore model generated from the reference crystal structure of Mpro complexed with the inhibitor ML188. The hit compounds were then filtered by molecular docking and predicted parameters of drug-likeness and pharmacokinetics. The final molecular dynamics (MD) simulations identified three effective candidate inhibitors (ECIs) capable of maintaining binding within the substrate-binding cavity of Mpro. We further performed comparative analyses of the reference and effective complexes in terms of dynamics, thermodynamics, binding free energy (BFE), and interaction energies and modes. The results reveal that, when compared to the inter-molecular electrostatic forces/interactions, the inter-molecular van der Waals (vdW) forces/interactions are far more important in maintaining the association and determining the high affinity. Given the un-favorable effects of the inter-molecular electrostatic interactions—association destabilization by the competitive hydrogen bond (HB) interactions and the reduced binding affinity arising from the un-compensable increase in the electrostatic desolvation penalty—we suggest that enhancing the inter-molecular vdW interactions while avoiding introducing the deeply buried HBs may be a promising strategy in future inhibitor optimization

    Bark Beetle-Associated Blue-Stain Fungi Increase Antioxidant Enzyme Activities and Monoterpene Concentrations in Pinus yunnanensis

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    <p>Yunnan pine is the most important tree species in SW China in both economical and ecological terms, but it is often killed by pine shoot beetles (Tomicus spp.). Tomicus beetles are secondary pests in temperate regions and the aggressiveness of the beetles in SW China is considered to be due to the warm subtropical climates as well as the beetles’ virulent fungal associates. Here, we assessed the virulence of three blue-stain fungi (Leptographium wushanense, L. sinense and Ophiostoma canum) associated with pine shoot beetles to Yunnan pine (Pinus yunnanensis) in SW China. Following fungal inoculation, we measured necrotic lesion lengths, antioxidant enzyme activities and monoterpene concentrations in the stem phloem of Yunnan pine. Leptographium wushanense induced twice as long lesions as L. sinense and O. canum, and all three fungi induced significantly longer lesions than sterile agar control inoculations. The activity of three tested antioxidant enzymes (peroxidase, polyphenol oxidase, and superoxide dismutase) increased after both fungal inoculation and control inoculation. However, L. wushanense and L. sinense generally caused a greater increase in enzyme activities than O. canum and the control treatment. Fungal inoculation induced stronger increases in six major monoterpenes than the control treatment, but the difference was significant only for some fungus-monoterpene combinations. Overall, our results show that L. wushanense and L. sinense elicit stronger defense responses and thus are more virulent to Yunnan pine than O. canum. The two Leptographium species may thus contribute to the aggressiveness of their beetle vectors and could damage Yunnan pine across SW China if they spread from the restricted geographical area they have been found in so far.</p

    Electrospray ionization mass spectrometry study on dipeptide 4-chlorobutyl ester produced from refluxing of amino acid with phosphoryl chloride in tetrahydrofuran

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    Phosphoryl chloride was able to promote the formation of peptide and the ringopening of tetrahydrofuran (THF) followed by a sequence of successive reactions by simply refluxing. ESI multistage tandem mass spectrometry was applied to trace the reaction and elucidate the product structures, dipeptide 4-chlorobutyl ester. Copyright (c) 2005 John Wiley & Sons, Ltd

    Table_1_A novel necroptosis-related lncRNA signature for predicting prognosis and anti-cancer treatment response in endometrial cancer.docx

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    BackgroundNecroptosis, a form of programmed cell death, underlies tumorigenesis and the progression of cancers. Anti-cancer strategies targeting necroptosis have increasingly been shown to present a potential cancer therapy. However, the predictive utility and anticancer sensitivity value of necroptosis-related lncRNAs (NRLs) for endometrial cancer (EC) are currently unknown.MethodsEC patient gene expression profiles and the corresponding clinical information collected from The Cancer Genome Atlas were used to identify NRLs that constituted a predictive signature for EC. The functional pathways, immune status, clinicopathological correlation, and anticancer drug sensitivity of the patients relative to the NRLs signatures were analyzed.ResultsA signature composed of 7 NRLs (AC019080.5, BOLA3-AS1, AC022144.1, AP000345.2, LEF1-AS1, AC010503.4, and RPARP-AS1) was identified. The high-risk patient group with this signature exhibited a poorer prognosis and lower survival rate than low-risk group lacking this signature. This necroptosis-related lncRNA signature had a higher predictive accuracy compared with other clinicopathological variables (area under the receiver operating characteristic curve of the risk score: 0.717). Additionally, when patients were stratified based on other clinicopathological variables, the overall survival was significantly shorter in the high-risk versus low-risk group across all cohorts. Gene set enrichment analysis (GSEA) revealed that immune- and tumor-related signaling pathways and biological processes were enriched in the high-risk group compared to the low-risk group. Single-sample gene set enrichment analysis (ssGSEA) additionally showed that the resulting risk score was strongly correlated with EC patient immune status. Finally, patients with high-risk scores were more sensitive to the anti-cancer drugs such as Docetaxel, Mitomycin.C, Vinblastine, AZD.2281 (olaparib), AZD6244, and PD.0332991 (Palbociclib).ConclusionThese findings reveal a novel necroptosis-related lncRNA signature for predicting EC patient prognosis and shed new light on anticancer therapy strategies for EC.</p
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