In the past 50 years there have been considerable efforts to identify the cellular receptor of hepatitis B virus (HBV). Recently, in vitro evidence from several groups has shown that the sodium-taurocholate cotransporting polypeptide (NTCP, which is encoded by SLC10A1 and transports bile acids into hepatic cells in enterohepatic recirculation) is a strong candidate. In particular, in vitro the p.Ser267Phe variation of SLC10A1 results in loss of HBV receptor function. We tested the role of NTCP as a receptor for HBV in chronic hepatitis B patients using a genetic association study. We selected SLC10A1 variants from 189 exomes. We used Sanger sequencing to follow up the association of the various SLC10A1 variants in a Han Chinese cohort of 1899 chronic hepatitis B patients and 1828 healthy controls. We further investigated the potential impact of the p.Ser267-Phe variant on NTCP function using structural analysis. The p.Ser267Phe variant was associated with healthy status (P 5 5.7 3 10 223 , odds ratio 5 0.36) irrespective of hepatitis B virus surface antibody status (P 5 6.2 3 10 221 and 1.5 3 10 210 , respectively, when the cases were compared with hepatitis B virus surface antibody-positive and -negative controls). The variation was also associated with a lower incidence of acute-on-chronic liver failure (P 5 0.007). The estimated heritability explained by this single variation was 3.2%. The population prevented fraction was around 13.0% among the southern Chinese. Our structural modeling showed that the p.Ser267Phe variant might interfere with ligand binding, thereby preventing HBV from cellular entry. Conclusion: The p.Ser267Phe NTCP variant is significantly associated with resistance to chronic hepatitis B and a lower incidence of acute-on-chronic liver failure. Our results support that NTCP is a cellular receptor for HBV in human infection. (HEPATOLOGY 2015;61:1251-1260 C hronic hepatitis B (CHB) affects approximately 240 million people worldwide and is responsible for about 780,000 deaths annually (http://www.who.int/mediacentre/factsheets/fs204/en/).Clinically, CHB holds the most significant medical consequences among hepatitis B virus (HBV)-infected individuals. Acute-on-chronic liver failure (ACLF) is the most urgent and lethal condition related to CHB.Abbreviations: ACLF, acute-on-chronic liver failure; AIM, ancestry-informative marker; ASBT, apical sodium-dependent bile acid transporter; CHB, chronic hepatitis B; HBV, hepatitis B virus; HBsAb, hepatitis B virus surface antibody; HBsAg, hepatitis B virus surface antigen; HDV, hepatitis D virus; NTCP, sodiumtaurocholate cotransporting polypeptide..From the

BackgroundRadiation caries is a complication of radiotherapy characterized by enamel erosion and dentin exposure. The mechanisms of characteristic radiation caries formation are not well-understood. The aim of this study was to evaluate the direct radiation-induced effects on dental hard tissue and investigate their role in the formation of radiation caries.MethodsSixty non-carious third molars were divided into three groups (n = 20), which would be exposed to 0 Gy, 30 Gy, and 60 Gy radiation, respectively. After radiation, microhardness and elastic modulus were measured at four depths by means of a Vickers microhardness tester and atomic force microscopy (AFM). The microstructure was observed by scanning electron microscopy (SEM). X-ray diffraction and Raman microspectroscopy were used to determine crystal properties and protein/mineral (2931/960 cm− 1) ratios.ResultsA statistically significant decrease in microhardness and elastic modulus values 50 μm from the dentino-enamel junction (DEJ) in enamel was revealed in the 30-Gy and 60-Gy groups. With the increasing dose, destruction of interprismatic substance and fissures at the DEJ-adjacent region were found. A greater reduction of crystallinity was revealed in enamel compared with dentin. Raman spectroscopic analysis showed a slight increase of the protein/mineral ratio for enamel following accumulated radiation, while the protein/mineral ratio for dentin was decreased.ConclusionsRadiation could directly alter the mechanical properties, micro-morphology, crystal properties, and chemical composition of dental hard tissue. The early destruction of DEJ-adjacent enamel, combined with decreased crystallinity of enamel under radiation exposure, may be related to the formation of characteristic radiation caries.

Pristine GO nanosheets at a concentration of 0.1 μg/mL provide benefits to promote BMSCs proliferation and osteogenesis under a sequential-seeding method, contributing to the use of GO for dental implantation.

SLC10A1 codes for the sodium-taurocholate cotransporting polypeptide (NTCP), which is a hepatocellular transporter for bile acids (BAs) and the receptor for hepatitis B and D viruses. NTCP is also a target of multiple drugs. We aimed to evaluate the medical consequences of the loss of function mutation p.Ser267Phe in SLC10A1. We identified eight individuals with homozygous p.Ser267Phe mutation in SLC10A1 and followed up for 8–90 months. We compared their total serum BAs and 6 species of BAs with 170 wild-type and 107 heterozygous healthy individuals. We performed in-depth medical examinations and exome sequencing in the homozygous individuals. All homozygous individuals had persistent hypercholanemia (P = 5.8 × 10–29). Exome sequencing excluded the involvement of other BA metabolism-associated genes in the hypercholanemia. Although asymptomatic, all individuals had low vitamin D levels. Of six adults that were subjected to bone mineral density analysis, three presented with osteoporosis/osteopenia. Sex hormones and blood lipids were deviated in all subjects. Homozygosity of p.Ser267Phe in SLC10A1 is associated with asymptomatic hypercholanemia. Individuals with homozygous p.Ser267Phe in SLC10A1 are prone to vitamin D deficiency, deviated sex hormones and blood lipids. Surveillance of these parameters may also be needed in patients treated with drugs targeting NTCP.

Accumulating evidence has demonstrated that circular RNAs (circRNAs) play important roles in regulating gene expression involved in tumor development. However, the role of circRNAs in modulating the radiosensitivity of oral squamous cell carcinoma (OSCC) and its potential mechanisms have not been documented. We performed high-throughput RNA sequencing (RNA-seq) to investigate the circRNA expression profile in OSCC patients and discovered that the circATRNL1 expression was significantly downregulated and closely related to tumor progression. The circATRNL1 was structurally validated via Sanger sequencing, RNase R treatment, and specific convergent and divergent primer amplification. Importantly, the expression levels of circATRNL1 decreased after irradiation treatment, and upregulation of circATRNL1 enhanced the radiosensitivity of OSCC through suppressing proliferation and the colony survival fraction, inducing apoptosis and cell-cycle arrest. Moreover, we observed that circATRNL1 could directly bind to microRNA-23a-3p (miR-23a-3p) and relieve inhibition for the target gene PTEN. In addition, the tumor radiosensitivity-promoting effect of circATRNL1 overexpression was blocked by miR-23a-3p in OSCC. Further experiments also showed that PTEN can reverse the inhibitory effect of OSCC radiosensitivity triggered by miR-23a-3p. We concluded that circANTRL1 may function as the sponge of miR-23a-3p to promote PTEN expression and eventually contributes to OSCC radiosensitivity enhancement. This study indicates that cir-cANTRL1 may be a novel therapeutic target to improve the efficiency of radiotherapy in OSCC.

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This study extended the mutation spectrum of XLHED and revealed the relationship between genotype and the number of missing permanent teeth.

Many open access transcriptomic data of coronavirus disease 2019 (COVID-19) were generated, they have great heterogeneity and are difficult to analyze. To utilize these invaluable data for better understanding of COVID-19, additional software should be developed. Especially for researchers without bioinformatic skills, a user-friendly platform is mandatory. We developed the COVID19db platform (http://hpcc.siat.ac.cn/covid19db & http://www.biomedical-web.com/covid19db) that provides 39 930 drug–target–pathway interactions and 95 COVID-19 related datasets, which include transcriptomes of 4127 human samples across 13 body sites associated with the exposure of 33 microbes and 33 drugs/agents. To facilitate data application, each dataset was standardized and annotated with rich clinical information. The platform further provides 14 different analytical applications to analyze various mechanisms underlying COVID-19. Moreover, the 14 applications enable researchers to customize grouping and setting for different analyses and allow them to perform analyses using their own data. Furthermore, a Drug Discovery tool is designed to identify potential drugs and targets at whole transcriptomic scale. For proof of concept, we used COVID19db and identified multiple potential drugs and targets for COVID-19. In summary, COVID19db provides user-friendly web interfaces to freely analyze, download data, and submit new data for further integration, it can accelerate the identification of effective strategies against COVID-19.