Preparation of hepatocellular carcinoma mRNA vaccines based on potential tumor targets and immunophenotypes.

Background: With the development of messenger RNA (mRNA)-based therapeutics for malignant tumor, mRNA vaccines have shown considerable promise for tumor immunotherapy. Immunophenotypes can reflect the tumor microenvironment, which might have a significant influence on the effect of immunotherapy. This study seeks to discover and validate effective antigens that can be employed to develop mRNA vaccines for hepatocellular carcinoma (HCC) and to construct immunophenotypes and immune landscapes to identify potential beneficiaries. Methods: RNA sequencing (RNASeq) data, mutation information, and clinical information were obtained from HCC patients and control cases from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium - Liver Cancer (ICGC-LIRI) and Gene Expression Omnibus (GEO) cohorts. Gene Expression Profiling Interactive Analysis (GEPIA2.0), cBioPortal for Cancer Genomics (cBioPortal), Tumor IMmune Estimation Resource (TIMER2.0), and immunohistochemistry (IHC) were employed to discover tumor antigens. ConsensusClusterPlus was employed to perform consistency matrix building and immunophenotypic clustering. Single sample gene set enrichment analysis (ssGSEA), ESTIMATE and monocle2 were employed to map immune cell distribution. Weighted correlation network analysis (WGCNA) was employed to identify potential gene modules that influence the efficacy of mRNA vaccines. Results: Six antigen targets were discovered in the TCGA cohort, including AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1, which were associated with antigen-presenting cell infiltration and poor prognosis. IHC scores of AURKA, CDC25C and MCM3 were higher in tumor tissues, and high scores of AURKA and CDC25C indicated poor prognosis in the validation cohort. Five immunophenotypes derived from TCGA-LIHC and ICGC-LIRI cohorts were consistent. Furthermore, increased expression of blue and black modules may reduce vaccine responsiveness. Conclusions: AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 may be potential targets for mRNA vaccine development for HCC, especially AURKA and CDC25C. HCC patients with IS1 and IS5 subtypes perhaps present an autoimmunosuppressed state, then IS2 and IS3 subtypes perhaps the potential beneficiaries.

Exploration of the causal effects of leukocyte telomere length and four gastrointestinal diseases: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: To explore the underlying causality between leukocyte telomere length (LTL) and four gastrointestinal diseases, we designed a two-sample bidirectional Mendelian randomization study. METHODS: Two-sample Mendelian randomization (MR) was used to explore genetic causality between LTL and four gastrointestinal diseases, including irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), gastrointestinal ulcers disease (GUD), and nonalcoholic fatty liver disease (NAFLD). We utilized inverse-variance weighted (IVW) as the primary method for MR analysis. Supplementary analyses were conducted using methods such as MR-Egger regression, weighted-median, Maximum Likelihood (MaxLik), Robust adjusted profile score (MR-RAPS), Contamination mixture (ConMix), and MR-mix. Cochran's Q was calculated to check for heterogeneity. The MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) were detected for pleiotropy. RESULTS: The IVW analysis suggests that there may be a potential causal relationship between LTL and two diseases (odds ratio (OR): 1.062; 95% confidence interval (CI): 1.003, 1.124; p = 0.038 for IBS and OR: 0.889; 95% CI: 0.798, 0.990; p = 0.032 for GERD). However, other methods do not entirely align with the results of the IVW analysis. In the reverse MR analysis, we did not find statistically significant associations between LTL and these four diseases. CONCLUSION: The current evidence does not definitively rule out a causal relationship between LTL and these four gastrointestinal diseases but suggests a potential association between LTL and IBS, or LTL and GERD. Exploring the relationship between gastrointestinal diseases and LTL may offer new insights into the onset, progression, and treatment of these diseases.

The characteristic of the key aroma-active components in white tea using GC-TOF-MS and GC-olfactometry combined with sensory-directed flavor analysis.

BACKGROUND: White tea has become more and more popular with consumers due to its health benefits and unique flavor. However, the key aroma-active compounds of white tea during the aging process are still unclear. Thus, the key aroma-active compounds of white tea during the aging process were investigated using gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS) and gas chromatography-olfactometry (GC-O) combined with sensory-directed flavor analysis. RESULTS: A total of 127 volatile compounds were identified from white tea samples with different aging years by GC-TOF-MS. Fifty-eight aroma-active compounds were then determined by GC-O, and 19 of them were further selected as the key aroma-active compounds based on modified frequency (MF) and odor activity value (OAV). CONCLUSION: Aroma recombination and omission testing confirmed that 1-octen-3-ol, linalool, phenethyl alcohol, geraniol, (E)-ß-ionone, α-ionone, hexanal, phenylacetaldehyde, nonanal, (E, Z)-(2,6)-nonadienal, safranal, γ-nonalactone and 2-amylfuran were the common key aroma-active compounds to all samples. Cedrol, linalool oxide II and methyl salicylate were confirmed peculiar in new white tea, while ß-damascenone and jasmone were peculiar in aged white tea. This work will offer support for further studies on the material basis of flavor formation of white tea. © 2023 Society of Chemical Industry.

Future orientation and moral judgment in chinese youths: the mediating role of moral disengagement and the moderating role of self-control.

Based on the self-regulation theory, this study aims to examine the relationship between youths' future orientation and judgment of their own immoral behaviors. A moderated mediation model was constructed to investigate the mediating role of moral disengagement and moderating role of self-control. Six hundred and twenty-eight Chinese youths, with an age range from 16 to 34 years (M = 23.08, SD = 2.65), were recruited to take part in an anonymous survey about future orientation, moral disengagement, self-control, and moral judgment. Results revealed that youths with high future orientation judged their own moral transgressions more harshly and that moral disengagement partially mediated the relationship between the two. Moderated mediation analysis further demonstrated that self-control moderated the relationship between future orientation and moral disengagement and the indirect effect between future orientation and youths' judgment of their own immoral behaviors. To be specific, the indirect effect was much stronger for youths with high levels of self-control. These findings not only enrich the research about how future orientation affects youths' judgment of their own immoral behaviors, but also reveal the underlying mechanisms between future orientation and moral judgment, which can provide practical guidance for implementing measures that effectively enhance youths' moral character and cultivate their ability to think positively about the future.

Changes in Chinese adolescent college students' psychological security during 2004-2020: A cross-temporal meta-analysis.

INTRODUCTION: Psychological security is the outcome of interaction between individuals and society, and it is an important indicator reflecting adolescent mental health and self-growth. Previous studies have paid more attention to external security, but less attention to individual's internal psychological security. In addition, few previous studies have examined the changes of psychological security over time and the influence of socio-cultural environmental factors on psychological security. METHODS: A cross-temporal meta-analysis was performed using papers that measured the psychological security level of Chinese adolescent college students between 2004 and 2020. Moreover, a time-lag analysis was conducted to define whether the macro-social indicators can explain the changes in Chinese adolescent college students' psychological security. RESULTS: (1) A total of 85 papers was included in the final sample (included 48,817 Chinese adolescent college students); (2) the scores of psychological security and its two sub-dimensions were significantly negatively correlated with the year, indicating that Chinese college students' psychological security declined significantly over time; (3) seven macro social indicators from the socioeconomic environmental, social connectedness and overall social threats can predict the changes in college students' psychological security; (4) the psychological security of male and female college students decreased over time, but the gender difference was insignificant. CONCLUSIONS: Evidently, social changes play an important role in predicting changes in Chinese college students' psychological security. The results can provide a research basis for the mental health education of adolescent college students, and also provide an explanation perspective for the increasingly serious "involution" phenomenon among Chinese college students.

Improving radish phosphorus utilization efficiency and inhibiting Cd and Pb uptake by using heavy metal-immobilizing and phosphate-solubilizing bacteria.

Phosphate-solubilizing bacteria play a key role in increasing plant growth as potential suppliers of soluble phosphorus and have great potential for the remediation of heavy metal-polluted soils. However, the soil and microbiological mechanisms by which phosphate-solubilizing bacteria prevent heavy metal absorption in radish have not been adequately studied. Here, the mechanisms of phosphorus solubilization, Cd and Pb immobilization, and the inhibition of heavy metal absorption by phosphate-solubilizing bacteria were studied in radish through solution adsorption and pot experiments. Two phosphate-solubilizing bacteria with high Cd and Pb removal rates (46.9-97.12 %), Klebsiella sp. M2 and Kluyvera sp. M8, were isolated. The soluble phosphorus content released by strains M2 and M8 was 265-277 mg L-1, achieved by secreting oxalic acid, ascorbic acid, citric acid, and succinic acid in an inorganic phosphorus medium containing 3 mg L-1 Cd and 5 mg L-1 Pb. Furthermore, these two functional strains induced the formation of Pb2(PO4)2, Cd(PO3)2, Fe2Pb3(PO4)2, CdS, and PbS precipitates that immobilized Cd and Pb in the solution. In general, strains M2 and M8 inhibited the absorption of Cd and Pb by radish by the following mechanisms: i) bacterial cell wall adsorption, ii) induction of Pb2(PO4)2, Cd(PO3)2, Fe2Pb3(PO4)2, CdS, and PbS precipitation in the solution/soil, iii) increases in the Ca2P and FeP contents in the radish rhizosphere, and iv) the promotion of bacterial community enrichment toward phosphorus-solubilizing and plant growth-promoting properties (Ramlibacter, Enterobacter, Bacillus, Gemmatimonas, and Lysinibacillusin) in the radish rhizosphere. These results provide bacterial resources and technical approaches to heavy metal pollution amelioration and efficient phosphorus fertilizer use in farmland.

How Is Virtuous Personality Trait Related to Online Deviant Behavior among Adolescent College Students in the Internet Environment? A Moderated Moderated-Mediation Analysis.

Online deviant behavior is a series of maladaptive behaviors that may have adverse effects on the physical and mental health of others and adolescents in the Internet environment. Previous studies have paid more attention to the risk factors of adolescent online deviant behavior. However, its protective factors and psychological mechanisms remain unclear. Thus, this study explored the protective effect of virtuous personality trait on adolescents' online deviant behavior and its psychological mechanism. A total of 851 Chinese college students anonymously completed a series of questionnaires about virtuous personality trait, moral disengagement, perspective taking, and online deviant behavior. The findings showed the following: (1) Virtuous personality trait was negatively correlated with online deviant behavior. (2) Moral disengagement mediated the relationship between virtuous personality trait and online deviant behavior. (3) Perspective taking moderated the first half stage of the mediation model in which college students' virtuous personality trait influences online deviant behavior via moral disengagement. (4) A moderated moderated-mediation analysis found that gender moderated the moderating effect of perspective taking on the relationship between virtuous personality trait and moral disengagement. This study is helpful to demonstrate the protective effect and psychological mechanism of virtuous personality trait on online deviant behavior. Some theoretical and practical significance and limitations were also analyzed and discussed.

Why dispositional awe promotes psychosocial flourishing? An investigation of intrapersonal and interpersonal pathways among Chinese emerging adults.

Promoting the psychosocial flourishing of emerging adults is crucially important. The tendency to feel awe, as captured by dispositional awe, may be a protective factor that promotes psychosocial flourishing. Inspired by the broaden-and-build theory, the present study sought to investigate the underexplored relationship between dispositional awe and psychosocial flourishing among emerging adults by establishing a dual-mediated model, which focuses on an intrapersonal mechanism of meaning in life and an interpersonal mechanism of social connectedness. Data were collected from a cross-sectional sample of 1213 Chinese emerging adults who completed a series of anonymous questionnaires regarding dispositional awe, psychosocial flourishing, meaning in life, and social connectedness. Results of the correlation analysis revealed positive and significant associations among dispositional awe, meaning in life, social connectedness, and psychosocial flourishing. Structural equation modeling demonstrated that meaning in life and social connectedness fully mediated the association between dispositional awe and psychosocial flourishing. The mediation effect of meaning in life was stronger than that of social connectedness. These findings contributes to the science of flourishing by identifying the internal mechanisms of why dispositional awe promotes the psychosocial flourishing of emerging adults.

How personal relative deprivation influences moral disengagement: The role of malicious envy and Honesty-Humility.

Scant research has investigated the potential influence of personal relative deprivation on moral disengagement, and little is known regarding the mechanisms underlying this relationship. Inspired by relative deprivation theory, this study proposed a moderated mediation model to explore the relationship between personal relative deprivation and moral disengagement by examining the mediating role of malicious envy and the moderating role of Honesty-Humility. Five hundred and eighty-nine Chinese adults completed anonymous measures of personal relative deprivation, malicious envy, Honesty-Humility, and moral disengagement. Results revealed that personal relative deprivation was positively correlated with moral disengagement and that malicious envy fully mediated this relationship. Moderated mediation analysis indicated that Honesty-Humility moderated the relationship between personal relative deprivation and malicious envy and that between malicious envy and moral disengagement. Specifically, both relationships became weaker for adults with higher levels of Honesty-Humility. These findings not only highlight the importance of identifying the underlying mechanisms between personal relative deprivation and moral disengagement, but also provide valuable implications for the effective prevention and mitigation of moral disengagement.

[Clinical efficacy of Longjintonglin Capsules on chronic prostatitis with damp-heat stasis syndrome Re-evaluation based on multicenter real-world study].

OBJECTIVE: To re-evaluate the clinical efficacy of Longjintonglin Capsules (LJTL) in the treatment of chronic prostatitis with damp-heat stasis syndrome. METHODS: This multicenter real-world study included 1 352 cases of chronic prostatitis with damp-heat and stagnation syndrome treated with LJTL (3 capsules once, tid, 30 minutes after meals, for 2 four-week courses) in addition to routine treatment. Before and after treatment, we analyzed the NIH-CPSI scores, the scores of Chinese medicine symptom quantitative classification and changes in individual symptom scores, and observed adverse reactions to medication. RESULTS: The total effectiveness rate of LJTL was 93.64%. Compared with the baseline, the NIH-CPSI scores were significantly decreased after treatment (ï¼»24.27 ± 6.04ï¼½ vs ï¼»8.17 ± 4.21ï¼½, P < 0.05), and so were the scores on the pain symptoms (ï¼»9.63 ± 3.65ï¼½ vs ï¼»3.02 ± 2.23ï¼½, P < 0.05), voiding symptoms (ï¼»5.65 ± 2.15ï¼½ vs ï¼»1.62 ± 1.36) and quality of life (ï¼»8.96 ± 2.32ï¼½ vs ï¼»3.16 ± 1.89ï¼½, P < 0.05). The effectiveness rate of LJTL was 95.9% on the Chinese medicine symptom frequent urination, 90.4% on painful urination, and 91.4% scanty dark urine, with a total effectiveness rate of 82.4% － 95.9%, all with statistically significant difference in comparison with the baseline (P < 0.05). CONCLUSION: Longjintonglin Capsules combined with routine treatment can significantly improve the clinical symptoms of chronic prostatitis with damp-heat stasis syndrome, especially effective on the symptoms of frequent urination, painful urination and scanty dark urine. Besides, it recommendable for its antidepressant and antianxiety effects, and the effect of improving the quality of life of the chronic prostatitis patients with damp-heat stasis.

SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. SET and MYND domain-containing protein 3 (SMYD3) has been shown to promote the progression of various types of human cancers, including liver cancer; however, the detailed molecular mechanism is still largely unknown. Here, we report that SMYD3 expression in HCC is an independent prognostic factor for survival and promotes the proliferation and migration of HCC cells. We observed that SMYD3 upregulated sphingosine-1-phosphate receptor 1 (S1PR1) promoter activity by methylating histone 3 (H3K4me3). S1PR1 was expressed at high levels in HCC samples, and high S1PR1 expression was associated with shorter survival. S1PR1 expression was also positively correlated with SMYD3 expression in HCC samples. We confirmed that SMYD3 promotes HCC cell growth and migration in vitro and in vivo by upregulating S1PR1 expression. Further investigations revealed that SMYD3 affects critical signaling pathways associated with the progression of HCC through S1PR1. These findings strongly suggest that SMYD3 has a crucial function in HCC progression that is partially mediated by histone methylation at the downstream gene S1PR1, which affects key signaling pathways associated with carcinogenesis and the progression of HCC.

Development and validation of the good and evil character traits (GECT) scale.

The present study describes the development and validation of the good and evil character traits (GECT) scale. A set of 3,614 good and evil moral character descriptors (i.e., moral and immoral character traits) was selected from a dictionary of contemporary Chinese language and daily life expressions and ultimately condensed into 55 items. Then, exploratory factor analysis (EFA) and parallel analysis (PA) were conducted to explore the structure and final items of the GECT with sample 1 (n = 350), resulting in 21 good items and 32 evil items. After that, in confirmatory factor analysis (CFA) with sample 2 (n = 350), the resulting factor structure was confirmed for the 53-item scale (Study 1). Additionally, evidence of validity based on correlations with Honesty-Humility and Dirty Dozen was demonstrated (Study 2). The implications of our findings for the assessment of good and evil characters and further theoretical exploration are discussed.

Influence of urban residents' life satisfaction on prosocial behavioral intentions in the community: A multiple mediation model.

Prosocial behavior is a category of acts that benefits other people and society. However, previous researchers have paid little attention to the study of community prosocial behavior. Accordingly, the present study adopts multiple mediation analysis to investigate how urban residents' life satisfaction influences their prosocial behavioral intentions in the community. This study collects data from an online survey of Chinese urban residents (N = 765) using self-administered questionnaires. Results show the following: (1) a positive association exists between urban residents' life satisfaction and their community prosocial behavioral intentions; (2) multiple mediation analysis reveals that orientation to meaning life, perception of virtuous humanity, and cognitive reappraisal mediated the relationship between urban residents' life satisfaction and prosocial behavioral intentions. These findings suggest that urban residents' life satisfaction may facilitate their community prosocial behavioral intentions via high levels of orientation to meaning life, perception of virtuous humanity, and cognitive reappraisal. This study also discusses certain contributions and limitations.

Dark personality traits and cyber aggression in adolescents: A moderated mediation analysis of belief in virtuous humanity and self-control.

Cyber aggressive behavior among adolescents is a widespread concern. However, little is known about the influencing factors and psychological mechanism of cyber aggressive behavior in adolescents. This study examined whether dark personality traits would be associated with cyber aggression in adolescents, whether belief in virtuous humanity would mediate the relationship between dark personality traits and cyber aggression, and whether self-control would play a moderating role in the links. A total of 675 Chinese college students completed a series of anonymous questionnaires regarding dark personality traits, belief in virtuous humanity, self-control, and cyber aggression. Results showed the following: (1) dark personality was positively related to cyber aggression in adolescents; (2) belief in virtuous humanity mediated the relationship between dark personality traits (i.e., Machiavellianism and psychopathy) and cyber aggression; (3) self-control play a moderating role in the relationship between dark personality traits (i.e., Machiavellianism and psychopathy) and cyber aggression, and the relationship between belief in virtuous humanity and cyber aggression. This study could help demonstrate the risk and protective factors and psychological mechanism of cyber aggressive behavior in adolescents. Some theoretical and practical implications and limitations were also discussed.

Floralozone Ameliorated Atherosclerosis in Experimental Atherosclerotic Rats Involved with Sphingosine 1-Phosphate 1 Enhancement.

Atherosclerosis (AS) is a chronical pathological process of the arterial narrows due to the AS plaque formation. The aim of this study was to explore the therapeutic effect and the underlying mechanism of Floralozone on experimental atherosclerotic model rats. Experimental atherosclerotic model rats were induced by the right carotid artery balloon injury and intraperitoneal injection of vitamin D3 in rats after 4 weeks high-fat diet. The results exhibited that Floralozone could ameliorate vascular injury and vasorelaxation of descending aortas and increase the superoxide dismutase activity and the expression of sphingosine 1-phosphate (S1P) 1 and reduce the intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, interleukin (IL)-1, IL-6 level, and the malondialdehyde activity in experimental atherosclerotic rats. However, Fingolimod, an S1P1 inhibitor, could reverse these Floralozone effects in experimental atherosclerotic rats. Our results indicated that Floralozone could inhibit the atherosclerotic plaque formation and improves arterial stenosis and reduces endothelial dysfunction in experimental atherosclerotic rats, which might be involved with S1P1 enhancement.

HBx/ERα complex-mediated LINC01352 downregulation promotes HBV-related hepatocellular carcinoma via the miR-135b-APC axis.

Hepatitis B virus (HBV) infection plays an important role in hepatocarcinogenesis, especially in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers. Novel lncRNAs involved in the initiation and progression of HBV-related hepatocellular carcinoma (HCC) need to be investigated. Here, we report that the long non-coding RNA LINC01352 is markedly downregulated by HBV/HBx (HBV X protein) in HCC cells and clinical samples. The LINC01352 expression level in HCC is an independent prognostic factor for survival. We found that HBx suppresses LINC01352 promoter activity by forming a complex with the estrogen receptor (ERα). Furthermore, using a combination of in vitro and in vivo studies, we confirmed that HBx promotes HCC cell growth and metastasis by inhibiting LINC01352 expression. Further investigation revealed that the downregulation of LINC01352, which acts as an endogenous sponge, increases the expression of miR-135b, leading to the reduced production of adenomatous polyposis coli (APC), consequently activating Wnt/ß-catenin signalling to facilitate tumour progression. These findings strongly suggest that the LINC01352-miR-135b-APC axis regulated by the HBx/ERα complex acts as an important pathogenic factor for tumour progression, which may help provide a theoretical basis for the identification of new therapeutic targets for HBV-related HCC.

Why Are People High in Dispositional Awe Happier? The Roles of Meaning in Life and Materialism.

Awe is an intense emotional response to perceptually vast stimuli that dramatically transcend one's ordinary reference frame and provoke a need to adjust the current mental structures. Dispositional awe reflects individual differences in the tendency to experience awe. The current study aims to examine the effect of dispositional awe on subjective well-being, with a focus on confirming the mediating role of meaning in life and materialism. A sample of 563 Chinese adults completed measures of dispositional awe, meaning in life, materialism, and subjective well-being. Correlation analysis revealed that dispositional awe, meaning in life, and materialism were all significantly correlated with subjective well-being. Structural equation modeling showed significant paths from dispositional awe to subjective well-being through both meaning in life and materialism. Bootstrap analysis also indicated that meaning in life and materialism mediated the relationship between dispositional awe and subjective well-being. These findings not only corroborate the critical role of dispositional awe in promoting subjective well-being, but also shed some light on why people high in dispositional awe are happier than those low in dispositional awe. Limitations and directions for future research were also discussed.