CCR7 Mediated Mimetic Dendritic Cell Vaccine Homing in Lymph Node for Head and Neck Squamous Cell Carcinoma Therapy

Immunotherapy has been recognized as one of the most promising treatment strategies for head and neck squamous cell carcinoma (HNSCC). As a pioneering trend of immunotherapy, dendritic cell (DC) vaccines have displayed the ability to prime an immune response, while the insufficient immunogenicity and low lymph node (LN) targeting efficiency, resulted in an unsubstantiated therapeutic efficacy in clinical trials. Herein, a hybrid nanovaccine (Hy-M-Exo) is developed via fusing tumor-derived exosome (TEX) and dendritic cell membrane vesicle (DCMV). The hybrid nanovaccine inherited the key protein for lymphatic homing, CCR7, from DCMV and demonstrated an enhanced efficiency of LN targeting. Meanwhile, the reserved tumor antigens and endogenous danger signals in the hybrid nanovaccine activated antigen presenting cells (APCs) elicited a robust T-cell response. Moreover, the nanovaccine Hy-M-Exo displayed good therapeutic efficacy in a mouse model of HNSCC. These results indicated that Hy-M-Exo is of high clinical value to serve as a feasible strategy for antitumor immunotherapy

REPORT Whole-Exome Sequencing Links a Variant in DHDDS to Retinitis Pigmentosa

Increasingly, mutations in genes causing Mendelian disease will be supported by individual and small families only; however, exome sequencing studies have thus far focused on syndromic phenotypes characterized by low locus heterogeneity. In contrast, retinitis pigmentosa (RP) is caused by >50 known genes, which still explain only half of the clinical cases. In a single, one-generation, nonsyndromic RP family, we have identified a gene, dehydrodolichol diphosphate synthase (DHDDS), demonstrating the power of combining whole-exome sequencing with rapid in vivo studies. DHDDS is a highly conserved essential enzyme for dolichol synthesis, permitting global N-linked glycosylation. Zebrafish studies showed virtually identical photoreceptor defects as observed with N-linked glycosylation-interfering mutations in the light-sensing protein rhodopsin. The identified Lys42Glu variant likely arose from an ancestral founder, because eight of the nine identified alleles in 27,174 control chromosomes were of confirmed Ashkenazi Jewish ethnicity. These findings demonstrate the power of exome sequencing linked to functional studies when faced with challenging study designs and, importantly, link RP to the pathways of N-linked glycosylation, which promise new avenues for therapeutic interventions. Retinitis pigmentosa (RP) refers to a large group of genetically heterogeneous retinal degenerative disorders characterized by early rod photoreceptor dysfunction followed by progressive rod and cone photoreceptor dysfunction and photoreceptor death (MIM 268000). Impaired night vision followed by impaired peripheral vision generally starts in adolescence to young adulthood, with subsequent impaired central vision in later life. We studied a family of Ashkenazi Jewish (AJ) origin in which three out of four siblings (two females and one male) were diagnosed with RP in their teenage years ( To identify the genetic cause of this likely recessive subtype of RP, we screened all genes known to harbor RP mutations and found that they were negative for mutations. Classic linkage approaches were not applicable because of the size of the nonconsanguineous family, so we performed whole-exome sequencing in the three affected siblings and one unaffected sibling (Whole Human Exome Capture kit, Roche). We produced approximately 10 gigabases (Gb) of paired-end 75 bp sequence reads per individual on the Illumina GAII platform. To test the overall quality of the sequence data, we compared the genotypes of variants found in the sequence data to variants derived from genotyping via a genome-wide SN

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Characterization and sorption ability of wool powder

This work focused on the characterisation of wool powders and their sorption capacity for dyes and metal ions. It provides new information to the field of wool and the potential use of wool to sorb contaminants from wastewater. It also suggests a new use for inferior and waste wool

Study on the microstructure and wear resistance of AlCrCuFeNiTix high entropy alloys for surfacing welding

In order to investigate the effect of Ti element content on the microstructure and wear resistance of AlCrCuFeNiTi _x (x = 0, 0.3, 0.6, 0.9) high entropy surfacing alloy, a melting electrode gas shielded welding technology was used to prepare AlCrCuFeNiTi _x high entropy surfacing alloy on the surface of carbon steel plates. The microstructure, phase composition, and wear resistance of the alloy were analyzed. The results show that the phase composition of the surfacing alloy becomes a BCC+FCC solid solution phase, with a much higher content of BCC phase than FCC phase. The microstructure consists of disordered BCC phase rich in Fe and Cr, ordered BCC phase rich in Al and Ni, and FCC phase rich in Cu. The microstructure exhibits typical dendritic (DR) and interdendritic (ID) structures. With the increase of Ti element, hard Fe _2 Ti phase precipitates in the interdendritic zone, and the micro hardness of the alloy shows an increasing trend. The maximum hardness can reach 636 HV, which is 2.4 times that of the base material. With the increase of Ti element, the friction coefficient of the alloy shows a trend of first decreasing and then increasing, and the wear amount first decreases and then increases. When Ti is 0.6, the wear resistance of the high entropy surfacing alloy reaches its best

Effect of Boric Acid on the Ionization Equilibrium of α-Hydroxy Carboxylic Acids and the Study of Its Applications

To investigate the synergistic catalytic effects of boric acid and α-hydroxycarboxylic acids (HCAs), we analyzed and measured the effects of the complexation reactions between boric acid and HCAs on the ionization equilibrium of the HCAs. Eight HCAs, glycolic acid, D-(−)-lactic acid, (R)-(−)-mandelic acid, D-gluconic acid, L-(−)-malic acid, L-(+)-tartaric acid, D-(−)-tartaric acid, and citric acid, were selected to measure the pH changes in aqueous HCA solutions after adding boric acid. The results showed that the pH values of the aqueous HCA solutions gradually decreased with an increase in the boric acid molar ratio, and the acidity coefficients when boric acid formed double-ligand complexes with HCAs were smaller than those of the single-ligand complexes. The more hydroxyl groups the HCA contained, the more types of complexes could be formed, and the greater the rate of change in the pH. The total rates of change in the pH of the HCA solutions were in the following order: citric acid > L-(−)-tartaric acid = D-(−)-tartaric acid > D-gluconic acid > (R)-(−)-mandelic acid > L-(−)-malic acid > D-(−)-lactic acid > glycolic acid. The composite catalyst of boric acid and tartaric acid had a high catalytic activity—the yield of methyl palmitate was 98%. After the reaction, the catalyst and methanol could be separated by standing stratification

A Simple and Selective Nanocatalytic Resonance Rayleigh Scattering Spectral Method for the Determination of Trace Re

In the HCl medium, rhenium (VII) or Re nanoparticles exhibited strong catalytic effect on the slow Te particle reaction between Te(VI) and Sn(II) at 70°C. The product of formed Te particles shows two strong resonance Rayleigh scattering peaks at 778 nm and 540 nm. The RS intensity at 778 nm enhanced linearly with Re concentration. The enhanced RS intensity was linear Re concentration in the range of 0.01–2.0 nmol·L−1, with a detection limit of 0.005 nmol·L−1 Re. This method was applied to the analysis of Re in ore sample, and the results were in agreement with that of the spectrophotometry

Resonance Rayleigh Scattering and SERS Spectral Detection of Trace Hg(II) Based on the Gold Nanocatalysis

Mercury (Hg) is a heavy metal pollutant, there is an urgent need to develop simple and sensitive methods for Hg(II) in water. In this article, a simple and sensitive resonance Rayleigh scattering (RRS) method was developed for determination of 0.008–1.33 µmol/L Hg, with a detection limit of 0.003 μmol/L, based on the Hg(II) regulation of gold nanoenzyme catalysis on the HAuCl4-H2O2 to form gold nanoparticles (AuNPs) with an RRS peak at 370 nm. Upon addition of molecular probes of Victoria blue B (VBB), the surface-enhanced Raman scattering (SERS) peak linearly decreased at 1612 cm−1 with the Hg(II) concentration increasing in the range of 0.013–0.5 μmol/L. With its good selectivity and good accuracy, the RRS method is expected to be a promising candidate for determining mercury ions in water samples