Human papillomavirus (HPV) positive head and neck cancer displayed specific transcription landscape but the underlying molecular mechanisms are not fully determined. Here, we interestingly found that HPV infection could globally elongate the 3'-untranslated regions (3'UTRs) in the majority of alternative polyadenylation (APA)-containing genes. Counterintuitively, the 3'UTR elongation does not affect their resident gene expression. Rather, they significantly increase the number of binding sites for RNA-binding proteins (RBPs) and subsequently upregulate a group of oncogenic genes by absorbing RBPs. A significant fraction of HPV affected genes are regulated through such mechanism that is 3'UTR-mediated recruitment of RBPs. As an example, we observed that HPV infection increases the length of 3'UTR of RBM25 transcript and hence recruits much more RNA binding protein including FUS and DGCR8. Consequently, in the absence of FUS and DGCR8 regulation, PD-1 was rescued and up-regulated after HPV infection. Taken together, our findings not only suggest a novel paradigm of how oncogenic viruses shape tumor transcriptome by modifying the 3'UTR, but also present a previously unrecognized layer of APA-RBP interplay in this molecular hierarchy. Modification of the pool of RBP-binding motif might expand our understandings into virus-associated carcinogenesis.
With peptides increasingly favored as drugs, natural product motifs, namely the tryptathionine staple, found in amatoxins and phallotoxins, and the 2,2'-bis-indole found in staurosporine represent unexplored staples for unnatural peptide macrocycles. We disclose the efficient condensation of a 5-hydroxypyrroloindoline with either a cysteine-thiol or a tryptophan-indole to form a tryptathionine or 2-2'-bis-indole staple. Judicious use of protecting groups provides for chemoselective stapling using α-MSH, which provides a basis for investigating both chemoselectivity and affinity. Both classes of stapled peptides show nanomolar K
Abstract Biological hair is widely found in nature, and they are responsible for sensing and responding to environmental stimuli in living organisms. By simulating biological hair characteristics, they develop hair flow sensor to achieve high sensitivity detection of environmental factors such as small motion and fluid flow field. Output signal is the key indicator of hair flow sensor, and the improvement of output signal is important to the design of hair flow sensor. The existing hair flow sensor sensing structure is generally straight hair, and the output signal is limited by the structure, and the response is small. Using the direct piezoelectric fiber as the initial configuration, we form a new piezoelectric curved fiber by modeling the secondary spline curve and control point. We propose an optimization model for piezoelectric functional hair design using axial strain as a target function. At 100Hz and 500Hz, the output voltage of the optimized model is much higher than that of straight, 10 times and 7 times that of straight, respectively; An optimized curved hair configuration is obtained in a specific frequency band from 1 Hz to 500 Hz, whose average voltage magnitude of 3.1×10 −3 V is 4 times greater than that of the straight hair of 7.8×10 −4 V with the same size. The curved hair flow sensor breaks the output limitation of traditional straight hair configuration.
Introduction: Gut microbiota alterations cause inflammation in patients with ulcerative colitis (UC). Fecal microbiota transplantation (FMT) enables manipulating the microbiota’s composition, but the mechanisms underlying colonization of the posttransplantation microbiota are poorly understood. Methods: In this open-label, nonrandomized study, the FMT efficacy and changes in the gut microbiota were evaluated in 8 UC patients with mild-to-moderately active endoscopic colonic lesions. Compositional changes in the fecal and mucosal microbiotas between donors and recipients were examined via 16S rRNA-based sequencing. To investigate the effects of oral corticosteroids on microbiota colonization, FMT was performed in germ-free prednisolone (PSL)-administered mice to examine the factors determining colonization. Results: Four UC patients achieved clinical remission (CR) after FMT, and 3 also achieved endoscopic remission. The fecal microbiotas of the CR patients changed similar to those of the donors after FMT. The mucin-coding gene, MUC2, was less expressed in the colons of the PSL-dependent patients than in the PSL-free patients. In the mice, PSL treatment decreased the fecal mucin production and altered the posttransplantation fecal microbiota composition. Adding either exogenous mucin or the mucin secretagogue, rebamipide, partially alleviated the PSL-induced dysbiosis of the gut microbiota. Administering rebamipide with FMT from healthy donors relieved inflammation in mice with Enterococcus faecium-induced colitis. Conclusion: Colonic mucin controlled the gut microbiota composition, and oral corticosteroid treatment modified the gut microbiota partly by reducing the colonic mucin.
Abstract Dye contamination in printing and dyeing wastewater has long been a major concern due to its serious impact on both the environment and human health. Recently, biological processes have emerged as a promising approach for the treatment of dye pollutants. In this study, a triphenylmethane transporter gene (tmt) was identified from 6 distinct clones screening from a metagenomics library of the printing and dyeing wastewater treatment syste. Escherichia coli expressing tmt revealed 98.1% decolorization efficiency of triphenylmethane dye malachite green within 24 h under shaking culture condition. The tolerance to malachite green was improved over eight-fold in the Tmt strain compared of the none-Tmt expressed strain. Similarly, the tolerance of Tmt strain to other triphenylmethane dyes like crystal violet and brilliant green, was improved by at least four-fold. Site-directed mutations, including A75G, A75S and V100G, were found to reinforce the tolerance of malachite green, and double mutations of these even further improve the tolerance. Therefore, the tmt has been demonstrated to be a specific efflux pump for triphenylmethane dyes, particularly the malachite green. By actively pumping out toxic triphenylmethane dyes, it significantly extends the cells tolerance in a triphenylmethane dye–rich environment, which may provide a promising strategy for bioremediation of triphenylmethane dye pollutants in the environments.
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