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Modifiable risk factors related to lifestyle choices contribute to the disproportionate impact of poor physical health among individuals with serious mental illness (SMI). This mixed methods study sought to elucidate factors that promote and challenge healthy lifestyle engagement. Focus groups were conducted to assess the lived perspectives of twelve individuals with SMI living independently in the community or utilizing group housing about their dietary and exercise habits. A survey was administered pre-focus group to explore participant views on and motivations for healthier living. Three major themes emerged based on focus group discussion: Meaning of Healthy Living, Obstacles to Maintaining Good Health, and Importance of Community. Overall, participants demonstrated positive attitudes and readiness for healthy lifestyle changes. Healthy lifestyle interventions with careful consideration of determinants related to health disparities and existing community resources to support such activities are recommended to improve physical health in people with SMI., Author(s): Amy Cheung [sup.1] , Zilin Cui [sup.1] , Kareem Hamada [sup.1] , Jennifer Selland [sup.1] , Mathew Chiang [sup.1] , Xiaoduo Fan [sup.1] Author Affiliations: (1) grid.168645.8, 0000 0001 [...]

Adenosine-to-inosine (A-to-I) RNA editing is an important post-transcriptional modification mediated by the adenosine deaminases acting on RNA (ADAR) family of enzymes, expanding the transcriptome by altering selected nucleotides A to I in RNA molecules. Recently, A-to-I editing has been explored for correcting disease-causing mutations in RNA using therapeutic guide oligonucleotides to direct ADAR editing at specific sites. Humans have two active ADARs whose preferences and specificities are not well understood. To investigate their substrate specificity, we introduced hADAR1 and hADAR2, respectively, into Schizosaccharomyces pombe (S. pombe), which lacks endogenous ADARs, and evaluated their editing activities in vivo. Using transcriptome sequencing of S. pombe cultured at optimal growth temperature (30 °C), we identified 483 A-to-I high-confident editing sites for hADAR1 and 404 for hADAR2, compared with the non-editing wild-type control strain. However, these sites were mostly divergent between hADAR1 and hADAR2-expressing strains, sharing 33 common sites that are less than 9% for each strain. Their differential specificity for substrates was attributed to their differential preference for neighboring sequences of editing sites. We found that at the -3-position relative to the editing site, hADAR1 exhibits a tendency toward T, whereas hADAR2 leans toward A. Additionally, when varying the growth temperature for hADAR1- and hADAR2-expressing strains, we observed increased editing sites for them at both 20 and 35 °C, compared with them growing at 30 °C. However, we did not observe a significant shift in hADAR1 and hADAR2's preference for neighboring sequences across three temperatures. The vast changes in RNA editing sites at lower and higher temperatures were also observed for hADAR2 previously in budding yeast, which was likely due to the influence of RNA folding at these different temperatures, among many other factors. We noticed examples of longer lengths of dsRNA around the editing sites that induced editing at 20 or 35 °C but were absent at the other two temperature conditions. We found genes' functions can be greatly affected by editing of their transcripts, for which over 50% of RNA editing sites for both hADAR1 and hADAR2 in S. pombe were in coding sequences (CDS), with more than 60% of them resulting in amino acid changes in protein products. This study revealed the extensive differences in substrate selectivity between the two active human ADARS, i.e., ADAR1 and ADAR2, and provided novel insight when utilizing the two different enzymes for in vivo treatment of human genetic diseases using the RNA editing approach. [ABSTRACT FROM AUTHOR]

T helper 17 (Th17) cells play important role in the defense against pathogens and autoimmune diseases. Many cytokines can induce Th17 cell differentiation. However, the mechanism of Th17 cell differentiation is not well clarified. RankL, a member of the TNF superfamily, binds with Rank and then participates in the proliferation and differentiation of many kinds of cells. Recent studies showed that RankL-Rank signaling is closely related to Th17 differentiation and function. The detail of the Rank-RankL pathway in Th17 cell differentiation is still unclear. To illustrate the role of Rank-RankL in Th17 differentiation, naive CD4 + T cells were differentiated into Th17 cells with or without RankL stimulation. During Th17 differentiation, the expression of Rank obviously increased. The RankL stimulation significantly increased Th17 cell differentiation indicated by increased IL-17-positive cell number, highly expressed IL-17 and IL-22 and elevated IL-17 secretion. These effects were canceled by Rank-Fc addition. In further study, RankL treatment during Th17 differentiation up-regulated Fas expression. Fas knockdown inhibited the Th17 differentiation promoted by RankL. In this study, it was confirmed that Rank-RankL signaling could promote Th17 cell differentiation through Fas induction. [ABSTRACT FROM AUTHOR]

MicroRNAs play an important role in the modulation of the immune system. T helper 17 (Th17) cells are involved in the modulation of the tumour microenvironment. However, the function of miRNA in Th17 cells in the tumour microenvironment is unclear. In this study, we analysed miR‐132 expression in Th17 cells and assessed the function of miR‐132 on Th17 cell differentiation. In addition, the effect of miR‐132 on Th17 cells in the tumour microenvironment, especially hepatic stellate cells (HSCs), was confirmed. CD4+ IL‐17 ∓ cells were isolated from hepatocellular carcinoma (HCC) tumour tissues. The expression of miR‐132 was higher in CD4+ IL‐17 + cells than in CD4+ IL‐17‐ cells. Human primary CD4+ T cells were used for Th17 cell differentiation. Compared with primary CD4+ T cells, Th17 cells expressed high levels of miR‐132. During Th17 cell differentiation, a miR‐132 mimic and inhibition were applied. After treatment with the miR‐132 mimic, the differentiation of Th17 cells accelerated, showing a a higher percentage of Th17 cells and the expression and secretion of IL‐17 and IL‐22. Smad nuclear interacting protein 1 (SNIP1), as one of the targets of miR‐132, decreased during Th17 cell differentiation–related Th17 differentiation and IL‐17 expression. The conditioned medium of miR‐132–overexpressing Th17 cells could increase the activation of the HSCs, which strongly promoted HCC cell migration and epithelial‐mesenchymal transition (EMT). In summary, miR‐132 positively regulates Th17 cell differentiation and improves the function of Th17 on HSCs for their tumour‐promoting effects. [ABSTRACT FROM AUTHOR]

In view of the wide use of tungsten in fusion experimental devices and the importance of hydrogen isotopes permeation, here we studied the adsorption, dissociation, diffusion and invasion behavior of hydrogen on W doped α-Al 2 O 3 (0001) surface. Based on the first-principle approaches, we found the W substitution for a top surface Al atom is the most energetically favorable. H 2 molecule prefers to be adsorbed on the surface W and spontaneously dissociates into two H anions. Near the W defects, H atoms favor to be adsorbed at the W and Al sites rather than O sites on the surface, and within the subsurface layer H can only bond to W stably. As a result, H migration to subsurface should occur around W with an energy barrier as large as 4.22 eV which is much larger than the 1.91 eV around the O atom on undoped α-Al 2 O 3 (0001) surface. These findings suggest that W surface doping is beneficial to α-Al 2 O 3 as tritium permeation barrier. • Tungsten doping promotes spontaneous dissociation of H 2 on α-Al 2 O 3 surface. • H atoms prefer to be adsorbed at W site and hardly to diffuse to surface O or to Al sites. • H migration to subsurface should occur around W. • Energy barrier of H invasion on W doped surface is much higher than the undoped α-Al 2 O 3 (0001) surface. [ABSTRACT FROM AUTHOR]

Background: The RESORCE-III trial demonstrated that advanced hepatocellular carcinoma (HCC) patients who progressed on sorafenib and had second-line therapy with regorafenib improved overall survival compared with placebo. Later, immunotherapy with immune checkpoint inhibitors (ICIs) combined with antiangiogenetic antibodies has evolved as the preferred first-line treatment for fit patients. We aimed to explore the efficacy and safety of regorafenib as a first-line agent alone or in combination with ICIs in patients with advanced HCC., Methods: We identified 50 patients with advanced HCC treated with regorafenib as a first-line agent. Two patients were lost to follow-up and excluded. Baseline factors, dosing, concomitant use of ICIs, toxicity and outcome of treatment were recorded from electronic medical records., Results: Twenty-six patients received regorafenib as monotherapy and twenty-two received regorafenib + ICI in combination. In the total cohort, the median progression-free survival (mPFS) was 7.7 months and the median overall survival (mOS) was 16.7 months (P=0.02). Objective response rate (ORR) and disease control rate (DCR) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were 21% and 73%. In the regorafenib monotherapy group, mPFS was 5.9 months, and mOS was 13.9 months; in the combination group, mPFS was 7.8 months, and mOS was 23.6 months. ORR and DCR were 15% and 65% in the monotherapy group, and 27% and 82% in the combined treatment group, respectively., Conclusions: Regorafenib used in combination with ICIs had a mild safety profile and resulted in improved response and an almost doubling of mOS compared to monotherapy, warranting further prospective evaluation in a randomized study., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-315/coif). M.L. reports research funding by Scandion Oncology A/S, Denmark. The other authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)