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Summary: Insomnia displays heterogeneous trajectories across adolescence, which may induce addictive behaviours, including internet gaming disorder and substance use. This study aimed to investigate the latent trajectory classes of insomnia symptoms over 2 years and to examine the associations between insomnia trajectories and these addictive behaviours. Participants were 910 adolescents from six middle schools in Shanghai, China (52.7% males; mean age = 13.17 years). The three‐wave survey measured insomnia symptoms, internet gaming disorder, substance use, depressive symptoms, and sociodemographic characteristics from 7th to 9th grade. Latent class growth modelling was performed to identify the latent trajectory classes of insomnia symptoms. Then multivariable logistic regressions were conducted within the best‐fitting latent class growth model to examine the associations of insomnia trajectories with internet gaming disorder and substance use. Two latent trajectory classes of insomnia symptoms were recognised: the non‐insomnia group (71.8%) and the insomnia group (28.2%). In the multivariable analysis controlling for baseline demographic variables and depressive symptoms, the insomnia group had a higher risk of developing internet gaming disorder (OR = 2.203 [95% CI: 1.258–3.858]) and substance use (OR = 2.215 [95% CI: 1.324–3.705]) compared with the non‐insomnia group. These findings add to a growing body of research on heterogeneous trajectories of insomnia symptoms during adolescence, suggesting that intervention strategies are needed to target the characteristics or developmental patterns of different insomnia subgroups. The ultimate goal is to mitigate the impact of insomnia symptoms on adolescent addictive behaviours. [ABSTRACT FROM AUTHOR]

Laboratorial and epidemiological research has established a relationship between paraquat (PQ) exposure and a risk for Parkinson's disease. Previously, we have investigated the effects of nuclear factor erythroid 2 related factor 2 (Nrf2) and microRNAs in PQ-induced neurotoxicity, addressing the function of miR-380-3p, a microRNA dysregulated by PQ, as well as Nrf2 deficiency. Nrf2 is known to mediate the expression of a variety of genes, including noncoding genes. By chromatin immunoprecipitation, we identified the relationship between Nrf2 and miR-380-3p in transcriptional regulation. qRT-PCR, Western blots, and dual-luciferase reporter gene assay showed that miR-380-3p blocked the translation of the transcription factor specificity protein-3 (Sp3) in the absence of degradation of Sp3 mRNA. Results based on cell counting analysis, annexin v-fluorescein isothiocyanate/propidium iodide double-staining assay, and propidium iodide staining showed that overexpression of miR-380-3p inhibited cell proliferation, increased the apoptotic rate, induced cell cycle arrest, and intensified the toxicity of PQ in mouse neuroblastoma (N2a [Neuro2a]) cells. Knockdown of Sp3 inhibited cell proliferation and eclipsed the alterations induced by miR-380-3p in cell proliferation. Two mediators of apoptosis and cell cycle identified in previous studies as Sp3-regulated, namely cyclin-dependent kinase inhibitor 1 (p21) and calmodulin (CaM), were dysregulated by PQ, but not Sp3 deficiency. In conclusion, Nrf2-regulated miR-380-3p inhibited cell proliferation and enhanced the PQ-induced toxicity in N2a cells potentially by blocking the translation Sp3 mRNA. We conclude that CaM and p21 were involved in PQ-induced toxicity. [ABSTRACT FROM AUTHOR]

Increasing amounts of evidence have indicated that non-coding RNAs (ncRNAs) have important regulatory potential in various biological processes. However, the contribution of ncRNAs, especially long non-coding RNAs (lncRNAs) to drug induced steatosis remain largely unknown. The aim of this study is to investigate miRNA, lncRNA and mRNA expression profiles and their potential roles in the process of drug induced steatosis. Microarray expression profiles of miRNAs, lncRNAs and mRNAs were determined in dexamethasone treated HepG2 cell as well as control cell. Differential expression, pathway and gene network analyses were developed to identify possible functional RNA molecules in dexamethasone induced steatosis. Compared with control HepG2 cell, 652 lncRNAs (528 up-regulated and 124 down-regulated), 655 mRNAs (527 upregulated and 128 down-regulated) and 114 miRNAs (55 miRNAs up-regulated and 59 down-regulated) were differentially expressed in dexamethasone treated HepG2 cell. Pathway analysis showed that the fatty acid biosynthesis, insulin resistance, PPAR signaling pathway, regulation of lipolysis in adipocytes, carbohydrate digestion and absorption, steroid hormone biosynthesis signaling pathways had a close relationship with dexamethasone induced steatosis. 10 highly dysregulated mRNAs and 20 miRNAs, which are closely related to lipid metabolism, were identified and validated by PCR, which followed by ceRNA analysis. CeRNA network analysis identified 5 lipid metabolism related genes, including CYP7A1, CYP11A1, PDK4, ABHD5, ACSL1. It also identified 12 miRNAs (miR-23a-3p, miR-519d-3p, miR-4328, miR-15b-5p etc.) and 177 lncRNAs (ENST00000508884, ENST00000608794, ENST00000568457 etc.). Our results provide a foundation and an expansive view of the roles and mechanisms of ncRNAs in dexamethasone induced steatosis. [ABSTRACT FROM AUTHOR]

Since China's launch of the COVID-19 vaccination, the situation of the public, especially the mobile population, has not been optimistic. We investigated 782 factory workers for whether they would get a COVID-19 vaccine within the next 6 months. The participants were divided into a training set and a testing set for external validation conformed to a ratio of 3:1 with R software. The variables were screened by the Lead Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Then, the prediction model, including important variables, used a multivariate logistic regression analysis and presented as a nomogram. The Receiver Operating Characteristic (ROC) curve, Kolmogorov–Smirnov (K-S) test, Lift test and Population Stability Index (PSI) were performed to test the validity and stability of the model and summarize the validation results. Only 45.54% of the participants had vaccination intentions, while 339 (43.35%) were unsure. Four of the 16 screened variables—self-efficacy, risk perception, perceived support and capability—were included in the prediction model. The results indicated that the model has a high predictive power and is highly stable. The government should be in the leading position, and the whole society should be mobilized and also make full use of peer education during vaccination initiatives. [ABSTRACT FROM AUTHOR]

The contribution of ncRNAs, especially long non-coding RNAs (lncRNAs) to drug induced steatosis remains largely unknown. The aim of this study was to investigate the role of lncRNA ENST00000608794 in dexamethasone induced steatosis. We found that ENST00000608794 is expressed at higher levels in dexamethasone treated HepG2 cell, and ENST00000608794 can bind and be regulated by miR-15b-5p. Ectopic expression of ENST00000608794 enhanced steatosis and the protein expression of PDK4 which is a critical gene in lipid metabolism and also is a target of miR-15b-5p. However, the differentiated PDK4 expression between control and ectopic expression of ENST00000608794 was absence in the presence of miR-15b-5p inhibitor. Moreover, in dexamethasone treated HepG2 cell lines, ENST00000608794 increased whether with miR-15b-5p inhibitor treatment or not, while increase of PDK4 expression by dexamethasone was greatly compromised in the presence of miR-15b-5p mimic. Meanwhile, dexamethasone induced steatosis could be ameliorated by silencing ENST00000608794 or expressing miR-15b-5p. Taken together, the results suggested that ENST00000608794 plays an important role in dexamethasone induced steatosis, which was partly mediated by derepressing of PDK4 through competitively binding to miR-15b-5p. • PDK4 could be regulated by a ceRNA mechanism which mediated by ENST00000608794 and miR-15b-5p. • ENST00000608794 derepressed expression of PDK4 through competitively binding to miR-15b-5p. • ENST00000608794 plays an important role in dexamethasone induced steatosis by regulating PDK4. [ABSTRACT FROM AUTHOR]

Elderly individuals face a high risk of hospitalization and death related to influenza, thus prioritizing them for influenza vaccination. Due to variations in the influenza virus and waning protective antibodies, annual influenza vaccination is recommended. However, research on repeated influenza vaccination among elderly individuals in China is limited. From 2020 to 2022, the average influenza vaccination coverage among registered elderly individuals in Shanghai was 4.1%, showing a declining trend over time. In 2020, the rate of repeated influenza vaccination among elderly individuals was 28.35%, which rose to almost two-thirds both in 2021 and 2022. No increased risk of adverse events following immunization was observed after repeated influenza vaccination during this period. Our study also found that elderly individuals with Shanghai household registration, managed by community clinics, and older age tended to receive more doses of repeated influenza vaccination throughout the period from 2020 to 2022. Increasing influenza vaccine coverage among elderly individuals in Shanghai is both urgent and challenging. Health authorities should intensify educational and promotional campaigns to encourage uptake of annual repeated influenza vaccination among elderly individuals.

Introduction: The prevalence of suicidal ideation among medical students is high. Evidence indicates that feelings of entrapment are a predictor of suicidal ideation. In this study, we aimed to (1) investigate the prevalence of first-onset suicidal ideation among Chinese medical students and (2) explore the predictive effects of perceived entrapment on first-onset suicidal ideation., Methods: This longitudinal study was conducted between 2018 and 2019 among 211 newly enrolled medical students in Shanghai. Using an anonymous questionnaire, we collected information on sociodemographic (sex, major, parents' income, and academic performance) and psychological (entrapment, depression, loneliness, defeat, social support, and interpersonal needs) variables as well as suicidal ideation. Participants were divided into four subgroups based on their exposure to entrapment (control, new-onset, reduced, and persistent). The primary outcome, first-onset suicidal ideation, was defined as suicidal ideation absent at baseline but present at follow-up., Results: In total, 54.98% of participants (116/211) were women, and 76.78% (162/211) majored in clinical medicine. In the follow-up survey, 6.16% of participants (16/211) reported first-onset suicidal ideation, 17.54% (37/211) reported new-onset entrapment, and 12.80% (27/211) reported persistent entrapment during follow-up. Compared with the control group who reported no perceived entrapment at baseline and follow-up, participants who reported new-onset entrapment had the highest risk of new-onset suicidal ideation [odds ratio (OR) = 14.700, 95% confidence interval (CI) = 2.906-74.364; adjusted OR = 8.798; 95% CI = 1.588-48.757; multivariate OR = 8.238, 95% CI = 1.394-48.693)., Conclusion: New-onset entrapment can significantly predict suicidal ideation. Therefore, greater attention is needed for new-onset entrapment, such as intervention for suicidal ideation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wei, Zhu, Li, Liu, Cai and Gong.)

Nuclear located hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) remains the key obstacle to cure chronic hepatitis B (CHB). In our previous investigation, it was found that FoxO4 could inhibit HBV core promoter activity through downregulating the expression of HNF4α. However, the exact mechanisms whereby FoxO4 inhibits HBV replication, especially its effect on cccDNA, remain unclear. Here, our data further revealed that FoxO4 could effectively inhibit cccDNA mediated transcription and HBV replication without affecting cccDNA level. Mechanistic study showed that FoxO4 could cause epigenetic suppression of cccDNA. Although FoxO4-mediated downregulation of HNF4α contributed to inhibiting HBV core promoter activity, it had little effect on cccDNA epigenetic regulation. Further, it was found that FoxO4 could colocalize within promyelocytic leukemia protein (PML) nuclear bodies and interact with PML. Of note, PML was revealed to be critical for FoxO4-mediated inhibition of cccDNA epigenetic modification and of the following cccDNA transcription and HBV replication. Furthermore, FoxO4 was found to be downregulated in HBV-infected hepatocytes and human liver tissues, and it was negatively correlated with cccDNA transcriptional activity in CHB patients. Together, these findings highlight the role of FoxO4 in suppressing cccDNA transcription and HBV replication via genetic downregulation of HNF4α and epigenetic suppression of cccDNA through interacting with PML. Targeting FoxO4 may present as a new therapeutic strategy against chronic HBV infection. IMPORTANCE HBV cccDNA is a determining factor for viral persistence and the main obstacle for a cure of chronic hepatitis B. Strategies that target cccDNA directly are therefore of great importance in controlling persistent HBV infection. In present investigation, we found that FoxO4 could efficiently suppress cccDNA transcription and HBV replication without affecting the level of cccDNA itself. Further, our data revealed that FoxO4 might inhibit cccDNA function via a two-part mechanism: one is to epigenetically suppress cccDNA transcription via interacting with PML, and the other is to inhibit HBV core promoter activity via the genetic downregulation of HNF4α. Of note, HBV might dampen the expression of FoxO4 for its own persistent infection. We propose that manipulation of FoxO4 may present as a potential therapeutic strategy against chronic HBV infection.

Chronic hepatitis B (CHB) remains a global health problem, carrying a high risk for progression into cirrhosis and liver failure. Molecular chaperones are involved in diverse pathophysiological processes including viral infection. However, the role of molecular chaperones in hepatitis B virus (HBV) infection and its underlying mechanisms remain unclear. Here, we identified GRP78 as one of the molecular chaperones most strongly induced by HBV in human hepatocytes. Gain- and loss-of-function analyses demonstrated that GRP78 exerted an inhibitory effect on HBV transcription and replication. Further study showed that GRP78 was involved in the activation of AKT/mTOR signaling in hepatocytes, which contributed to GRP78-mediated inhibition of HBV. Of note, HBV-upregulated GRP78 was found to play a crucial role in maintaining the survival of hepatocytes via facilitating a mild endoplasmic reticulum (ER) stress. Together, our findings suggest that HBV may sacrifice part of its replication for establishing a persistent infection through induction of GRP78, a master ER stress regulator. Targeting GRP78 may help develop to design novel therapeutic strategies against chronic HBV infection and the associated hepatocellular carcinoma., (Copyright © 2020 American Society for Microbiology.)