Molecular Etiology of Hearing Impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis

<p>Abstract</p> <p>Background</p> <p>The molecular etiology of hearing impairment in Chinese has not been thoroughly investigated. Study of <it>GJB2 </it>gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried <it>GJB2 </it>mutations. The <it>SLC26A4 </it>gene mutations and relevant phenotype are analyzed in this study.</p> <p>Methods</p> <p>One hundred and thirty-five deaf patients were included. The coding exons of <it>SLC26A4 </it>gene were sequence analyzed in 111 patients, not including 22 patients carrying bi-allelic <it>GJB2 </it>mutations or one patient carrying a known <it>GJB2 </it>dominant mutation as well as one patient with <it>mtDNA </it>1555A>G mutation. All patients with <it>SLC26A4 </it>mutations or variants were subjected to high resolution temporal bone CT scan and those with confirmed enlarged vestibular aqueduct and/or other inner ear malformation were then given further ultrasound scan of thyroid and thyroid hormone assays.</p> <p>Results</p> <p>Twenty-six patients (19.26%, 26/135) were found carrying <it>SLC26A4 </it>mutation. Among them, 17 patients with bi-allelic <it>SLC26A4 </it>mutations were all confirmed to have EVA or other inner ear malformation by CT scan. Nine patients were heterozygous for one <it>SLC26A4 </it>mutation, including 3 confirmed to be EVA or EVA and Mondini dysplasia by CT scan. The most common mutation, IVS7-2A>G, accounted for 58.14% (25/43) of all <it>SLC26A4 </it>mutant alleles. The shape and function of thyroid were confirmed to be normal by thyroid ultrasound scan and thyroid hormone assays in 19 of the 20 patients with EVA or other inner ear malformation except one who had cystoid change in the right side of thyroid. No Pendred syndrome was diagnosed.</p> <p>Conclusion</p> <p>In Inner Mongolia, China, mutations in <it>SLC26A4 </it>gene account for about 12.6% (17/135) of the patients with hearing loss. Together with <it>GJB2 </it>(23/135), <it>SLC26A4 </it>are the two most commonly mutated genes causing deafness in this region. Pendred syndrome is not detected in this deaf population. We established a new strategy that detects <it>SLC26A4 </it>mutations prior to the temporal bone CT scan to find EVA and inner ear malformation patients. This model has a unique advantage in epidemiologic study of large deaf population.</p

Anomalous thermo-osmotic conversion performance of ionic covalent-organic-framework membranes in response to charge variations

Authors of the article systematically investigated how the membrane charge populations affect permselectivity by decoupling their effects from the impact of the pore structure using a multivariate strategy for constructing covalent-organic-framework membranes. The complex interplay between pore-pore interactions in response to charge variations for ion transport across the upscaled nanoporous membranes helps explain the obtained results. This study has far-reaching implications for the rational design of ionic membranes to augment energy extraction rather than intuitively focusing on achieving high densities

Improving the Efficacy of Conventional Therapy by Adding Andrographolide Sulfonate in the Treatment of Severe Hand, Foot, and Mouth Disease: A Randomized Controlled Trial

Background. Herb-derived compound andrographolide sulfonate (called Xiyanping injection) recommended control measure for severe hand, foot, and mouth disease (HFMD) by the Ministry of Health (China) during the 2010 epidemic. However, there is a lack of good quality evidence directly comparing the efficacy of Andrographolide Sulfonate combination therapy with conventional therapy. Methods. 230 patients were randomly assigned to 7–10 days of Andrographolide Sulfonate 5–10 mg/Kg/day and conventional therapy, or conventional therapy alone. Results. The major complications occurred less often after Andrographolide Sulfonate (2.6% versus 12.1%; risk difference [RD], 0.94; 95% CI, 0.28–1.61; P=0.006). Median fever clearance times were 96 hours (CI, 80 to 126) for conventional therapy recipients and 48 hours (CI, 36 to 54) for Andrographolide Sulfonate combination-treated patients (χ2=16.57, P<0.001). The two groups did not differ in terms of HFMD-cause mortality (P=1.00) and duration of hospitalization (P=0.70). There was one death in conventional therapy group. No important adverse event was found in Andrographolide Sulfonate combination therapy group. Conclusions. The addition of Andrographolide Sulfonate to conventional therapy reduced the occurrence of major complications, fever clearance time, and the healing time of typical skin or oral mucosa lesions in children with severe HFMD

Molecular epidemiology of measles viruses in China, 1995–2003

This report describes the genetic characterization of 297 wild-type measles viruses that were isolated in 24 provinces of China between 1995 and 2003. Phylogenetic analysis of the N gene sequences showed that all of the isolates belonged to genotype H1 except 3 isolates, which were genotype A. The nucleotide sequence and predicted amino acid homologies of the 294-genotype H1 strains were 94.7%–100% and 93.3%–100%, respectively. The genotype H1 isolates were divided into 2 clusters, which differed by approximately 2.9% at the nucleotide level. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Even though other measles genotypes have been detected in countries that border China, this report shows that genotype H1 is widely distributed throughout the country and that China has a single, endemic genotype. This important baseline data will help to monitor the progress of measles control in China

GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment

Background: Mutations in GJB2 are the most common molecular defects responsible for autosomal recessive nonsyndromic hearing impairment (NSHI). The mutation spectra of this gene vary among different ethnic groups. Methods: In order to understand the spectrum and frequency of GJB2 mutations in the Chinese population, the coding region of the GJB2 gene from 2063 unrelated patients with NSHI was PCR amplified and sequenced. Results: A total of 23 pathogenic mutations were identified. Among them, five (p.W3X, c.99delT, c.155_c.158delTCTG, c.512_c.513insAACG, and p.Y152X) are novel. Three hundred and seven patients carry two confirmed pathogenic mutations, including 178 homozygotes and 129 compound heterozygotes. One hundred twenty five patients carry only one mutant allele. Thus, GJB2 mutations account for 17.9% of the mutant alleles in 2063 NSHI patients. Overall, 92.6% (684/739) of the pathogenic mutations are frame-shift truncation or nonsense mutations. The four prevalent mutations; c.235delC, c.299_c.300delAT, c.176_c.191del16, and c.35delG, account for 88.0% of all mutantalleles identified. The frequency of GJB2 mutations (alleles) varies from 4% to 30.4% among different regions of China. It also varies among different sub-ethnic groups. Conclusion: In some regions of China, testing of the three most common mutations can identify at least one GJB2 mutant allele in all patients. In other regions such as Tibet, the three most common mutations account for only 16% the GJB2 mutant alleles. Thus, in this region, sequencing of GJB2 would be recommended. In addition, the etiology of more than 80% of the mutant alleles for NSHI in China remains to be identified. Analysis of other NSHI related genes will be necessary

Adaptive Graph Convolution Using Heat Kernel for Attributed Graph Clustering

Attributed graphs contain a lot of node features and structural relationships, and how to utilize their inherent information sufficiently to improve graph clustering performance has attracted much attention. Although existing advanced methods exploit graph convolution to capture the global structure of an attributed graph and achieve obvious improvements for clustering results, they cannot determine the optimal neighborhood that reflects the relevant information of connected nodes in a graph. To address this limitation, we propose a novel adaptive graph convolution using a heat kernel model for attributed graph clustering (AGCHK), which exploits the similarity among nodes under heat diffusion to flexibly restrict the neighborhood of the center node and enforce the graph smoothness. Additionally, we take the Davies&ndash;Bouldin index (DBI) instead of the intra-cluster distance individually as the selection criterion to adaptively determine the order of graph convolution. The clustering results of AGCHK on three benchmark datasets&mdash;Cora, Citeseer, and Pubmed&mdash;are all more than 1% higher than the current advanced model AGC, and 12% on the Wiki dataset especially, which obtains a state-of-the-art result in the task of attributed graph clustering

Multifunctional Carbon Dots-Based Fluorescence Detection for Sudan I, Sudan IV and Tetracycline Hydrochloride in Foods

Sudan dyes are strictly prohibited from being added to edible products as carcinogens and tetracycline hydrochloride (TC) remaining in animal-derived food may cause harm to the human body. Therefore, it is necessary to establish a high-sensitivity, simple and convenient method for the detection of Sudan dyes and TC in foods for safety purposes. In this work, multifunctional blue fluorescent carbon dots (B-CDs) were prepared by a one-step hydrothermal synthesis using glucose as the carbon source. The results show that the fluorescence intensity of B-CDs was significantly affected by the acidity of the solution and can be quenched by Sudan I, IV and TC through selective studies. Interestingly, the fluorescence quenching intensities of B-CDs have a good linear relationship with the concentration of Sudan I and IV at pH = 3&ndash;7. The wide range of pH is beneficial to broaden the application of B-CDs in a practical samples analysis. The method has been successfully applied to real food samples of tomato paste, palm oil and honey, and the detection limits are 26.3 nM, 54.2 nM and 31.1 nM for Sudan I, Sudan IV and TC, respectively. This method integrates Sudan dyes and TC into the same multifunctional B-CDs, which shows that the sensor has a great potential in food safety detection

Self-Matrix N-Doped Room Temperature Phosphorescent Carbon Dots Triggered by Visible and Ultraviolet Light Dual Modes

The synthesis of room temperature phosphorescent carbon dots (RTP-CDs) without any matrix is important in various applications. In particular, RTP-CDs with dual modes of excitation are more interesting. Here, we successfully synthesized matrix-free carbonized polymer dots (CPDs) that can generate green RTP under visible and ultraviolet light dual-mode excitation. Using acrylic acid (AA) and ammonium oxalate as precursors, a simple one-pot hydrothermal method was selected to prepare AA-CPDs. Here, acrylic acid is easy to polymerize under high temperature and high pressure, which makes AA-CPDs form a dense cross-linked internal structure. Ammonium oxalate as a nitrogen source can form amino groups during the reaction, which reacts with a large number of pendant carboxyl groups on the polymer chains to further form a cross-linked structure. The carboxyl and amino groups on the surface of AA-CPDs are connected by intermolecular hydrogen bonds. These hydrogen bonds can provide space protection (isolation of oxygen) around the AA-CPDs phosphor, which can stably excite the triplet state. This self-matrix structure effectively inhibits the non-radiative transition by blocking the intramolecular motion of CPDs. Under the excitation of WLED and 365 nm ultraviolet light, AA-CPDs exhibit the phosphorescence emission at 464 nm and 476 nm, respectively. The naked-eye observation exceeds 5 s and 10 s, respectively, and the average lifetime at 365 nm excitation wavelength is as long as 412.03 ms. In addition, it successfully proved the potential application of AA-CPDs in image anti-counterfeiting

Transcriptome and metabolomics analysis of adaptive mechanism of Chinese mitten crab (Eriocheir sinensis) to aflatoxin B1.

Aflatoxin B1 (AFB1), with the strong toxicity and carcinogenicity, has been reported to great toxicity to the liver and other organs of animals. It cause huge economic losses to breeding industry, including the aquaculture industry. Chinese mitten crabs (Eriocheir sinensis), as one of important species of freshwater aquaculture in China, are deeply disturbed by it. However, the molecular and metabolic mechanisms of hepatopancreas and ovary in crabs underlying coping ability are still unclear. Hence, we conducted targeted injection experiment with or without AFB1, and comprehensively analyzed transcriptome and metabolomics of hepatopancreas and ovary. As a result, 210 and 250 DEGs were identified in the L-C vs. L-30 m and L-C vs. L-60 m comparison, among which 14 common DEGs were related to six major functional categories, including antibacterial and detoxification, ATP energy reaction, redox reaction, nerve reaction, liver injury repair and immune reaction. A total of 228 and 401 DAMs in the ML-C vs. ML-30 m and ML-C vs. ML-60 m comparison both enriched 12 pathways, with clear functions of cutin, suberine and wax biosynthesis, tyrosine metabolism, purine metabolism, nucleotide metabolism, glycine, serine and threonine metabolism, ABC transporters and tryptophan metabolism. Integrated analysis of metabolomics and transcriptome in hepatopancreas discovered three Co-enriched pathways, including steroid biosynthesis, glycine, serine and threonine metabolism, and sphingolipid metabolism. In summary, the expression levels and functions of related genes and metabolites reveal the regulatory mechanism of Chinese mitten crab (Eriocheir sinensis) adaptability to the Aflatoxin B1, and the findings contribute to a new perspective for understanding Aflatoxin B1 and provide some ideas for dealing with it