Long nanopore reads are advantageous in de novo genome assembly. However, nanopore reads usually have broad error distribution and high-error-rate subsequences. Existing error correction tools cannot ...correct nanopore reads efficiently and effectively. Most methods trim high-error-rate subsequences during error correction, which reduces both the length of the reads and contiguity of the final assembly. Here, we develop an error correction, and de novo assembly tool designed to overcome complex errors in nanopore reads. We propose an adaptive read selection and two-step progressive method to quickly correct nanopore reads to high accuracy. We introduce a two-stage assembler to utilize the full length of nanopore reads. Our tool achieves superior performance in both error correction and de novo assembling nanopore reads. It requires only 8122 hours to assemble a 35X coverage human genome and achieves a 2.47-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line shows an NG50 of 22 Mbp. The high-quality assembly of nanopore reads can significantly reduce false positives in structure variation detection.
Cell membrane–based nanosystems with desirable characteristics have been studied extensively for many therapeutic applications. However, current research has focused on single cell membrane, and ...multifunctional fused membrane materials from different membrane types are still rare. Herein, a platelet–cancer stem cell (CSC) hybrid membrane‐coated iron oxide magnetic nanoparticle (MN) {CSC‐PMN} is presented for the first time for the enhanced photothermal therapy of head and neck squamous cell carcinoma (HNSCC). Inherited from the original source cells, the platelet membrane shows immune evading ability due to the surface marker comprising a number of “don't eat me” signals, and the CSC membrane has homotypic targeting capabilities due to the specific surface adhesion molecules. The CSC‐PMNs possess superior characteristics for immune evasion, active cancer targeting, magnetic resonance imaging, and photothermal therapy. Compared with single cell membrane–coated MNs, CSC‐PMNs exhibit prolonged circulation times and enhanced targeting abilities. Moreover, the CSC‐PMNs exhibit a superior photothermal ability that provides excellent HNSCC tumor growth inhibition, particularly in an immunocompetent Tgfbr1/Pten conditional double knockout HNSCC mouse model that contains a more complex tumor microenvironment that is similar to the human HNSCC microenvironment. Collectively, this biomimetic multimembrane‐coated nanoplatform may provide enhanced antitumor efficacy in the complex tumor microenvironment.
A natural cancer stem cell‐platelet hybrid mimic membrane is collected from tumor‐bearing mice and further used for magnetic nanoparticle coating. The obtained biomimetic nanoparticles are then injected into the same mice for magnetic resonance imaging and photothermal therapy. The work presents a novel design strategy for personalized cancer theranostics.
A compact dual band-notched ultra-wideband (UWB) multiple-input multiple-output (MIMO) antenna with high isolation is designed on a FR4 substrate (27 × 30 × 0.8 mm 3 ). To improve the input impedance ...matching and increase the isolation for the frequencies ≥ 4.0 GHz, the two antenna elements with compact size of 5.5 × 11 mm 2 are connected to the two protruded ground parts, respectively. A 1/3 λ rectangular metal strip producing a 1.0 λ loop path with the corresponding antenna element is used to obtain the notched frequency from 5.15 to 5.85 GHz. For the rejected band of 3.30-3.70 GHz, a 1/4 λ open slot is etched into the radiator. Moreover, the two protruded ground parts are connected by a compact metal strip to reduce the mutual coupling for the band of 3.0-4.0 GHz. The simulated and measured results show a bandwidth with |S 11 | ≤ -10 dB, |S 21 | ≤ -20 dB and frequency ranged from 3.0 to 11.0 GHz excluding the two rejected bands, is achieved, and all the measured and calculated results show the proposed UWB MIMO antenna is a good candidate for UWB MIMO systems.
Here, we present a platelet‐facilitated photothermal tumor therapy (PLT‐PTT) strategy, in which PLTs act as carriers for targeted delivery of photothermal agents to tumor tissues and enhance the PTT ...effect. Gold nanorods (AuNRs) were first loaded into PLTs by electroporation and the resulting AuNR‐loaded PLTs (PLT‐AuNRs) inherited long blood circulation and cancer targeting characteristics from PLTs and good photothermal property from AuNRs. Using a gene‐knockout mouse model, we demonstrate that the administration of PLT‐AuNRs and localizing laser irradiation could effectively inhibit the growth of head and neck squamous cell carcinoma (HNSCC). In addition, we found that the PTT treatment augmented PLT‐AuNRs targeting to the tumor sites and in turn, improved the PTT effects in a feedback manner, demonstrating the unique self‐reinforcing characteristic of PLT‐PTT in cancer therapy.
Platelets (PLTs) are circulating sentinels that can accumulate in injured tissues to trigger the repair processes. Photothermal therapy (PTT) uses heat generated from light to ablate tumor tissues. Inspired by both observations, gold nanorods were loaded into PLTs for enhanced PTT of head and neck squamous cell carcinoma.
The bearing capacity and failure mechanism of encased stone columns are affected by many factors such as encasement length, relative density, strength and stiffness of the encasement material. In ...soft soils where surrounding soil pressure is low, especially in the top section, the stone columns may be close to a uniaxial compression state, where the uniaxial compression strength controls the bearing capacity of the stone columns. A series of large-scale triaxial tests on ordinary stone columns and uniaxial tests on geotextile encased stone columns have been performed. The stone columns were 300 mm in diameter and 600 mm in height. Samples of four different relative densities, and five types of geotextiles were used in the tests to study the effect of initial void ratio and encasing materials on the uniaxial compression behavior of the stone columns. The results show the uniaxial compressive strength of the encased stone columns is not affected by the initial void ratio but mainly by the tensile strength of the encasing geotextiles. The stress strain curves of the encased stone columns under uniaxial loading condition are nearly liner before failure, which is similar to the tensile behavior of the geotextiles.
Summary
Brown coloration and a rough appearance as russet and semi‐russet (partial russet) are features unique to the popular Asian sand pear (Pyrus pyrifolia Nakai). The degree of russeting is ...different between different genotypes. Russeting is sensitive to water fluctuations, where excessive rainwater can trigger/stimulate its development. However, the molecular mechanism of russeting is currently unclear. Here, we employed multi‐omics, i.e., metabolomics, transcriptomics, and proteomics, and analyzed the effect of different sand pear genotypes and artificial rainfall on russeting of pear fruits. This led to the identification of 79, 64, and 29 differentially produced/expressed metabolites, transcripts, and proteins that are involved in the biosynthesis of suberin, phenylpropane, cutin, and waxes. Further analysis of these differentially expressed genes and their encoded proteins revealed that four of them exhibited high expression at both transcript and protein levels. Transient expression of one such gene, PbHHT1 (accession number 103966555), which encodes ω‐hydroxypalmitate‐O‐feruloyl transferase, in young green non‐russet fruits triggered premature suberization in the russeting pear genotypes. This coincided with increased production of 16‐feruloyloxypalmitic acid, a conjugated compound between phenols and esters during the polymerization for suberin formation. Collectively, our data from the combined three omics demonstrate that russeting in sand pear is a complex process involving the biosynthesis and transport of suberin and many other secondary metabolites.
Significance Statement
Metabolomics, transcriptomics, and proteomics analysis demonstrates that russeting in sand pear fruit is a complex process involving the biosynthesis and transport of suberin and many other secondary metabolites. Transient expression of one of the identified genes, which encodes ω‐hydroxypalmitate‐O‐feruloyl transferase (HHT), triggered premature suberization in young green non‐russet sand pear fruit, which coincided with increased production of 16‐feruloyloxypalmitic acid, a conjugated compound between phenols and esters during the polymerization for suberin formation, indicating the important role of HHT in sand pear fruit russeting.
Clarifying interfacial electronic effects on molecular adsorption is significant in many chemical and biochemical processes. Here, we used STM breaking junction and shell‐isolated ...nanoparticle‐enhanced Raman spectroscopy to probe electron transport and adsorption geometries of 4,4′‐bipyridine (4,4′‐BPY) at Au(111). Modifying the surface with 1‐butyl‐3‐methylimidazolium cation‐containing ionic liquids (ILs) decreases surface electron density and stabilizes a vertical orientation of pyridine through nitrogen atom σ‐bond interactions, resulting in uniform adsorption configurations for forming molecular junctions. Modulation from vertical, tilted, to flat, is achieved on adding water to ILs, leading to a new peak ascribed to CC stretching of adsorbed pyridyl ring and 316 % modulation of single‐molecule conductance. The dihedral angle between adsorbed pyridyl ring and surface decreases with increasing surface electronic density, enhancing electron donation from surface to pyridyl ring.
STM breaking junction and shell‐isolated nanoparticle‐enhanced Raman spectroscopy techniques have been successfully applied to probe a solvent modification induced interfacial electronic effect on tuning contact geometries and electron transport of pyridyl molecules at atomically flat Au (111). Modulation of binding geometry from vertical to tilted and flat is observed and a 316 % modulation of single‐molecule conductance is achieved.
We describe the identification and characterization of circular intronic long noncoding RNAs in human cells, which accumulate owing to a failure in debranching. The formation of such circular ...intronic RNAs (ciRNAs) can be recapitulated using expression vectors, and their processing depends on a consensus motif containing a 7 nt GU-rich element near the 5′ splice site and an 11 nt C-rich element close to the branchpoint site. In addition, we show that ciRNAs are abundant in the nucleus and have little enrichment for microRNA target sites. Importantly, knockdown of ciRNAs led to the reduced expression of their parent genes. One abundant such RNA, ci-ankrd52, largely accumulates to its sites of transcription, associates with elongation Pol II machinery, and acts as a positive regulator of Pol II transcription. This study thus suggests a cis-regulatory role of noncoding intronic transcripts on their parent coding genes.
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•Circular intronic RNAs accumulate in human cells owing to escape from debranching•Their processing depends on RNA motifs near 5′ splice site and branchpoint•ciRNAs regulate parent gene expression by modulating elongation Pol II activity
Mindin is important in broad spectrum of immune responses. On the other hand, we previously reported that mindin attenuated human colon cancer development by blocking angiogenesis through ...Egr‐1–mediated regulation. However, the mice original mindin directly suppressed the syngenic colorectal cancer (CRC) growth in our recent study and we aimed to further define the role of mindin during CRC development in mice. We established the mouse syngeneic CRC CMT93 and CT26 WT cell lines with stable mindin knock‐down or overexpression. These cells were also subcutaneously injected into C57BL/6 and BALB/c mice as well as established a colitis‐associated colorectal cancer (CAC) mouse model treated with lentiviral‐based overexpression and knocked‐down of mindin. Furthermore, we generated mindin knockout mice using a CRISPR‐Cas9 system with CAC model. Our data showed that overexpression of mindin suppressed cell proliferation in both of CMT93 and CT26 WT colon cancer cell lines, while the silencing of mindin promoted in vitro cell proliferation via the ERK and c‐Fos pathways and cell cycle control. Moreover, the overexpression of mindin significantly suppressed in vivo tumour growth in both the subcutaneous transplantation and the AOM/DSS‐induced CAC models. Consistently, the silencing of mindin reversed these in vivo observations. Expectedly, the tumour growth was promoted in the CAC model on mindin‐deficient mice. Thus, mindin plays a direct tumour suppressive function during colon cancer progression and suggesting that mindin might be exploited as a therapeutic target for CRC.
Sepsis, a hyperinflammatory response that can result in multiple organ dysfunctions, is a leading cause of mortality from infection. Here, we show that orphan nuclear receptor Nur77 (also known as ...TR3) can enhance resistance to lipopolysaccharide (LPS)-induced sepsis in mice by inhibiting NF-κB activity and suppressing aberrant cytokine production. Nur77 directly associates with p65 to block its binding to the κB element. However, this function of Nur77 is countered by the LPS-activated p38α phosphorylation of Nur77. Dampening the interaction between Nur77 and p38α would favor Nur77 suppression of the hyperinflammatory response. A compound, n-pentyl 2-3,5-dihydroxy-2-(1-nonanoyl) phenylacetate, screened from a Nur77-biased library, blocked the Nur77-p38α interaction by targeting the ligand-binding domain of Nur77 and restored the suppression of the hyperinflammatory response through Nur77 inhibition of NF-κB. This study associates the nuclear receptor with immune homeostasis and implicates a new therapeutic strategy to treat hyperinflammatory responses by targeting a p38α substrate to modulate p38α-regulated functions.
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