Epitranscriptomic cytidine methylation of the hepatitis B viral RNA is essential for viral reverse transcription and particle production.

Epitranscriptomic RNA modifications have emerged as important regulators of the fate and function of viral RNAs. One prominent modification, the cytidine methylation 5-methylcytidine (m5C), is found on the RNA of HIV-1, where m5C enhances the translation of HIV-1 RNA. However, whether m5C functionally enhances the RNA of other pathogenic viruses remains elusive. Here, we surveyed a panel of commonly found RNA modifications on the RNA of hepatitis B virus (HBV) and found that HBV RNA is enriched with m5C as well as ten other modifications, at stoichiometries much higher than host messenger RNA (mRNA). Intriguingly, m5C is mostly found on the epsilon hairpin, an RNA element required for viral RNA encapsidation and reverse transcription, with these m5C mainly deposited by the cellular methyltransferase NSUN2. Loss of m5C from HBV RNA due to NSUN2 depletion resulted in a partial decrease in viral core protein (HBc) production, accompanied by a near-complete loss of the reverse transcribed viral DNA. Similarly, mutations introduced to remove the methylated cytidines resulted in a loss of HBc production and reverse transcription. Furthermore, pharmacological disruption of m5C deposition led to a significant decrease in HBV replication. Thus, our data indicate m5C methylations as a critical mediator of the epsilon elements' function in HBV virion production and reverse transcription, suggesting the therapeutic potential of targeting the m5C methyltransfer process on HBV epsilon as an antiviral strategy.

Influencing factors of examiner: Examples from certificated orthodontists board examination.

BACKGROUND: The rating result reflects not only the performance of the candidate but some extent of the examiner's preference. Examiner bias could be objective, which means it can't be changed by the examiner like gender, age, race, educational level, or professional experience. No study about examiner bias was performed in the dental education realm, especially in the orthodontic field. Therefore, this study aimed to figure out possible influencing factors in examiners from examples of the Taiwan Board of Orthodontist examination. METHODS: The examiner groups comprised 29 males and 21 females selected from the certificated Taiwan Board of Orthodontists. Every examiner would receive a series of lectures about rating standards before the exam. The score data were collected from 2009 to 2019. RESULTS: As for the univariate regression model of the Taiwan Board of Orthodontist examination, the experienced examiner with a certification of more than 15 years tends to rate more leniently, but female examiners tend to rate harsher. The scores would increase with the examiner's age in both the univariate regression model of self-prepared and assigned cases. CONCLUSION: As for the multivariate model of self-prepared exams, the elder and the examiner who work in private practice clinics tend to rate more leniently. As for the multivariate model of the assigned case exam, the score would be only affected by age. However, further studies are necessary to determine the direct relation among these factors.

Higher parity and earlier age at first birth are associated with lower risk of death from colon cancer.

This study was undertaken to examine whether there is an association between parity and age at first birth and risk of colon cancer. The study cohort consisted of 1,292,462 women who had a first and singleton childbirth between 1978 and 1987. We tracked each woman from the time of their first childbirth to December 31, 2009, and their vital status was ascertained by linking records with the computerized mortality database. We used the Cox proportional hazards model with time-dependent covariates to estimate the hazard ratios (HR) of death from colon cancer associated with parity and age at first birth. We limited eligible colon cancer deaths to those who were 45 years old or more to exclude possible heredity colon cancer cases, which usually occur at an early age. There were 670 colon cancer deaths during 34,980,246 person-years of follow-up. The colon cancer death rate was 1.96 cases per 100,000 person-years. The adjusted HR was 2.76 (95% CI = 1.60-4.75) for women who gave birth between 20 and 24 years and 7.35 (95% CI = 4.28-12.62) for women who gave birth after 24 years of age when compared with women who gave birth at younger than 20 years. A rising risk of colon cancer was seen with increasing age at first birth. The adjusted HR were 0.81 (95% CI = 0.65-1.02) among women with two live births, 0.93 (95% CI = 0.74-1.18) among women with three live births and 0.72 (95% CI = 0.51-1.00) for women with four or more births when compared with women who had given birth to only one child. The present study provides evidence that reproductive factors (parity and early age at first birth) may confer a protective effect on the risk of colon cancer.

Hostility in the real world and online: the effect of internet addiction, depression, and online activity.

Hostility online has not been evaluated by an empirical investigation. This study aims to evaluate (a) the difference between hostility in the real world and that online and (b) whether the difference is associated with Internet addiction, depression, or online activities. A total of 2,348 college students (1,124 males and 1,224 females) were recruited and completed the Chen Internet Addiction Scale, the Center for Epidemiological Studies' Depression Scale, and the questionnaire for online activity. Further, the Buss-Durkee Hostility Inventory-Chinese version-short form was utilized to evaluate hostility in both real and virtual worlds. The results demonstrated that the levels of all four dimensions of hostility were lower when getting online than those in the real world. Subjects with Internet addiction had higher hostility both in the real world and online as do subjects with depression. Further, college students with Internet addiction had increased expressive hostility behavior and those with depression had decreased hostility cognition, hostility affection, and suppressive hostility behavior when getting online. Lastly, the buffering effect of the Internet on hostility was attenuated among subjects paying the most online time in chatting, and those using the Internet mainly for online gaming had higher expressive hostility behavior not only in the real world but also online. These results suggest that attention should be paid to interventions concerning aggressive behavior among subjects with Internet addiction or online gaming and chatting. On the other hand, depressed college students would be less hostile after entering the Internet. It is suggested that the Internet would be one possible interactive media to provide intervention for depression.