No miRNA were found in Plasmodium and the ones identified in erythrocytes could not be correlated with infection

<p>Abstract</p> <p>Background</p> <p>The transcriptional regulation of <it>Plasmodium </it>during its complex life cycle requires sequential activation and/or repression of different genetic programmes. MicroRNAs (miRNAs) are a highly conserved class of non-coding RNAs that are important in regulating diverse cellular functions by sequence-specific inhibition of gene expression. What is know about double-stranded RNA-mediated gene silencing (RNAi) and posttranscriptional gene silencing (PTGS) in <it>Plasmodium </it>parasites entice us to speculate whether miRNAs can also function in <it>Plasmodium</it>-infected RBCs.</p> <p>Results</p> <p>Of 132 small RNA sequences, no <it>Plasmodium</it>-specific miRNAs have been found. However, a human miRNA, miR-451, was highly expressed, comprising approximately one third of the total identified miRNAs. Further analysis of miR-451 expression and malaria infection showed no association between the accumulation of miR-451 in <it>Plasmodium falciparum</it>-iRBCs, the life cycle stage of <it>P. falciparum </it>in the erythrocyte, or of <it>P. berghei </it>in mice. Moreover, treatment with an antisense oligonucleotide to miR-451 had no significant effect on the growth of the erythrocytic-stage <it>P. falciparum</it>.</p> <p>Methods</p> <p>Short RNAs from a mixed-stage of <it>P. falciparum</it>-iRBC were separated in a denaturing polyacrylamide gel and cloned into T vectors to create a cDNA library. Individual clones were then sequenced and further analysed by bioinformatics prediction to discover probable miRNAs in <it>P. falciparum</it>-iRBC. The association between miR-451 expression and the parasite were analysed by Northern blotting and antisense oligonucleotide (ASO) of miR-451.</p> <p>Conclusion</p> <p>These results contribute to eliminate the probability of miRNAs in <it>P. falciparum</it>. The absence of miRNA in <it>P. falciparum </it>could be correlated with absence of argonaute/dicer genes. In addition, the miR-451 accumulation in <it>Plasmodium</it>-infected RBCs is independent of parasite infection. Its accumulation might be only the residual of erythroid differentiation or a component to maintain the normal function of mature RBCs.</p

Research on the role of SOX9 in regulating metabolic reprogramming in diffuse large B cell lymphoma

Objective·To explore the role played by the differentially expressed SRY-box transcription factor 9 (SOX9) gene in diffuse large B cell lymphoma (DLBCL), particularly in the regulation of metabolic reprogramming in the germinal center B-cell (GCB) like subtype.Methods·The clinical information and gene expression profile data of 481 DLBCL patients retrieved from the NCICCR-DLBCL database were included. Data analysis and visualisation were performed by using R language version 4.1.3. The classification was performed by using a cell of origin subtype (COO) classification algorithm based on RNA-seq sequencing of expression. ABC/GCB features were used to annotate gene sets, and the classification was verified by gene set enrichment analysis. The ABC and GCB subgroup was dichotomised based on the mean expression of SOX9. Differential analysis was performed by using the DEseq2 package. The relationship between SOX9 and ABC-DLBCL metabolism was analysed by using KEGG (Kyoto Encyclopedia of Genes and Genomes) with the Hallmark annotation set. The survival curves were plotted by using the Kaplan-Meier method. The pan-cancer analysis was performed by using GEPIA2. The microenvironmental scoring analysis was performed by the ESTIMATE package.Results·Of the 481 DLBCL patient samples, all the patients had RNA-seq expression data, 421 had clinical staging, 335 had international prognostic index (IPI) scores and 234 had survival data. The classification yielded 232 (48.2%) ABC subtypes, 173 (36.0%) GCB subtypes and 76 (15.8%) unclassified, consistent with the proportions declared in the database, and the enrichment analysis was verified to be consistent with the ABC/GCB expression profile. Compared to the high SOX9 expression group, the overall survival was shorter in the low SOX9 expression group and the prognostic score was worse. The pan-cancer analysis showed that this phenomenon was also seen in other tumor types. The differential analysis showed that there were 156 upregulated genes and 1 826 downregulated genes in the GCB subtype in the low SOX9 expression group, compared to the high SOX9 expression group. For metabolic processes, down-regulated genes were enriched in glycolysis.Conclusion·In the ABC subtype of DLBCL, the SOX9 gene affects the biological features of ABC-DLBCL by regulating metabolic reprogramming, and low expression of SOX9 in DLBCL, possibly caused by high methylation, predicts decreased glycolysis in tumors. The proportion of tumor stromal cells decreases, showing a worse prognosis

A Schistosoma japonicum chimeric protein with a novel adjuvant induced a polarized Th1 immune response and protection against liver egg burdens

<p>Abstract</p> <p>Background</p> <p>Schitosomiasis japonica is still a significant public health problem in China. A protective vaccine for human or animal use represents an important strategy for long-term control of this disease. Due to the complex life cycle of schistosomes, different vaccine design approaches may be necessary, including polyvalent subunit vaccines. In this study, we constructed four chimeric proteins (designated SjGP-1~4) via fusion of Sj26GST and four individual paramyosin fragments. We tested these four proteins as vaccine candidates, and investigated the effect of deviating immune response on protection roles in mice.</p> <p>Methods</p> <p>The immunogencity and protection efficacy of chimeric proteins were evaluated in mice. Next, the chimeric protein SjGP-3 was selected and formulated in various adjuvants, including CFA, ISA 206, IMS 1312 and ISA 70M. The titers of antigen-specific IgG, IgE and IgG subclass were measured. The effect of adjuvant on cytokine production and percentages of CD3⁺CD8^-IFN-γ⁺cells and CD3⁺CD8^-IL-4⁺cells were analyzed at different time points. Worm burdens and liver egg counts in different adjuvant groups were counted to evaluate the protection efficacy against cercarial challenge.</p> <p>Results</p> <p>Immunization of mice with chimeric proteins provided various levels of protection. Among the four proteins, SjGP-3 induced the highest level of protection, and showed enhanced protective efficacy compared with its individual component Sj26GST. Because of this, SjGP-3 was further formulated in various adjuvants to investigate the effect of adjuvant on immune deviation. The results revealed that SjGP-3 formulated in veterinary adjuvant ISA 70M induced a lasting polarized Th1 immune response, whereas the other adjuvants, including CFA, ISA 206 and IMS 1312, generated a moderate mixed Th1/Th2 response after immunization but all except for IMS 1312 shifted to Th2 response after onset of eggs. More importantly, the SjGP-3/70M formulation induced a significant reduction in liver egg deposition at 47.0–50.3% and the number of liver eggs per female at 34.5–37.2% but less effect on worm burdens at only 17.3–23.1%, whereas no effect of the formulations with other adjuvants on the number of liver eggs per female was observed.</p> <p>Conclusion</p> <p>Construction of polyvalent subunit vaccine was capable to enhance immunogenicity and protection efficacy against schistosomiasis. There was correlation of the polarized Th1 response with reduction of liver egg burdens, supporting the immune deviation strategy for schistosomiasis japonica vaccine development.</p

Polarized electron-beam acceleration driven by vortex laser pulses

We propose a new approach based on an all-optical set-up for generating relativistic polarized electron beams via vortex Laguerre-Gaussian (LG) laser-driven wakefield acceleration. Using a pre-polarized gas target, we find that the topology of the vortex wakefield resolves the depolarization issue of the injected electrons. In full three-dimensional particle-in-cell simulations, incorporating the spin dynamics via the Thomas-Bargmann Michel Telegdi equation, the LG laser preserves the electron spin polarization by more than 80% at high beam charge and flux. The method releases the limit on beam flux for polarized electron acceleration and promises more than an order of magnitude boost in peak flux, as compared to Gaussian beams. These results suggest a promising table-top method to produce energetic polarized electron beams.Comment: We replace some results and revise some description

Review of confidence factor in EC8-part3: a european code for seismic assessment of existing buildings

The built environment, both historic and of recent construction, is exposed to high level of seismic risk due to increasing level of seismicity around the world. Thus, it is necessary to assess the existing building performance to current level of seismicity in order to perform the cost-effective interventions. EC8-Part 3 is devoted to seismic assessment/retrofitting of existing buildings. This document introduces an adjustment factor to account for epistemic uncertainty, called “confidence factor (CF)”. CF is based on the level of knowledge of the structural properties such as geometry, reinforcement layout and detailing, and materials. This solution, plausible from a logical point of view, cannot yet profit from the experience of use in practice, hence its soundness needs to be investigated in real applications. This paper proposes a probabilistic based method to calibrate CF, which can simulate the entire assessment procedure conditional on the acquired knowledge. The method is then applied to six-storey three-bay reinforced concrete frame to assess the role of CF. The obtained CF's values are then critically examined and compared with code-specified ones. The critical problems of using a single factor in seismic assessment of existing buildings are pinpointed

Tumor-associated macrophages mediate resistance of EGFR-TKIs in non-small cell lung cancer: mechanisms and prospects

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutation. However, resistance to EGFR-TKIs is inevitable. Currently, most studies on the mechanism of EGFR-TKIs resistance mainly focus on the spontaneous resistance phenotype of NSCLC cells. Studies have shown that the tumor microenvironment (TME) also mediates EGFR-TKIs resistance in NSCLC. Tumor-associated macrophages (TAMs), one of the central immune cells in the TME of NSCLC, play an essential role in mediating EGFR-TKIs resistance. This study aims to comprehensively review the current mechanisms underlying TAM-mediated resistance to EGFR-TKIs and discuss the potential efficacy of combining EGFR-TKIs with targeted TAMs therapy. Combining EGFR-TKIs with TAMs targeting may improve the prognosis of NSCLC with EGFR mutation to some extent

Scattering Field Enhanced Biosensing Based on Sub-wavelength Split-ring Plasmonic Cavity With High Q-factor

Plasmonic structures are widely used in modern biosensor design. various plasmonic resonant cavities could efficiently achieve a high Q-factor, improving the local field intensity to enhance photoluminescence or SERS (Surface-Enhanced Raman Scattering) of small molecules. Also, the combination between virus-like particles and plasmonic structures could significantly influence the scattering spectrum and field, which is utilized as a method for biological particle detection. In this paper, we designed one kind of gold plasmonic cavity with the shape of a split-ring. An edge gap and a bonus center bulge are introduced in the split-ring structure. Our simulation is based on Finite Difference Time Domain (FDTD) method. Polarization Indirect Microscopic Imaging (PIMI) technique is used here to detect far-field mode distribution under the resonant wavelength. The simulation results demonstrate resonant peaks in the visible spectrum at about 600 nm with a Q-factor reaches to 74. Localized hot spots are generated by an edge dipole mode and a cavity hexapole mode at resonant wavelength, which is according to dark points in the PIMI sinδ image. Also, the split-ring cavity shows a sensitivity when combined with biological particles. The scattering distribution is evidently changed as a result of energy exchange between particles and split-ring cavity, indicating a promising possibility for biosensing

AluScan: a method for genome-wide scanning of sequence and structure variations in the human genome

<p>Abstract</p> <p>Background</p> <p>To complement next-generation sequencing technologies, there is a pressing need for efficient pre-sequencing capture methods with reduced costs and DNA requirement. The Alu family of short interspersed nucleotide elements is the most abundant type of transposable elements in the human genome and a recognized source of genome instability. With over one million Alu elements distributed throughout the genome, they are well positioned to facilitate genome-wide sequence amplification and capture of regions likely to harbor genetic variation hotspots of biological relevance.</p> <p>Results</p> <p>Here we report on the use of inter-Alu PCR with an enhanced range of amplicons in conjunction with next-generation sequencing to generate an Alu-anchored scan, or 'AluScan', of DNA sequences between Alu transposons, where Alu consensus sequence-based 'H-type' PCR primers that elongate outward from the head of an Alu element are combined with 'T-type' primers elongating from the poly-A containing tail to achieve huge amplicon range. To illustrate the method, glioma DNA was compared with white blood cell control DNA of the same patient by means of AluScan. The over 10 Mb sequences obtained, derived from more than 8,000 genes spread over all the chromosomes, revealed a highly reproducible capture of genomic sequences enriched in genic sequences and cancer candidate gene regions. Requiring only sub-micrograms of sample DNA, the power of AluScan as a discovery tool for genetic variations was demonstrated by the identification of 357 instances of loss of heterozygosity, 341 somatic indels, 274 somatic SNVs, and seven potential somatic SNV hotspots between control and glioma DNA.</p> <p>Conclusions</p> <p>AluScan, implemented with just a small number of H-type and T-type inter-Alu PCR primers, provides an effective capture of a diversity of genome-wide sequences for analysis. The method, by enabling an examination of gene-enriched regions containing exons, introns, and intergenic sequences with modest capture and sequencing costs, computation workload and DNA sample requirement is particularly well suited for accelerating the discovery of somatic mutations, as well as analysis of disease-predisposing germline polymorphisms, by making possible the comparative genome-wide scanning of DNA sequences from large human cohorts.</p