Association between Serum Ferritin Levels and Metabolic-associated Fatty Liver Disease in Adults: a Cross-sectional Study Based on the NHANES.

OBJECTIVE: Ferritin, initially acting as an iron-storage protein, was found to be associated with metabolic diseases. Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease (MAFLD) using data from the National Health and Nutrition Examination Survey (NHANES) of the United State of America. METHODS: A cross-sectional study was conducted, enrolling a total of 2145 participants from the NHANES in the 2017-2018 cycles. Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes. Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis. RESULTS: The analysis revealed that participants with higher serum ferritin levels (Q3 and Q4 groups) had a higher prevalence of MAFLD than those with the lowest serum ferritin levels [Q3 vs. Q1: OR=2.17 (1.33, 3.53), P<0.05 in fatty liver index (FLI); Q4 vs. Q1: OR=3.13 (1.91, 5.13), P<0.05 in FLI]. Additionally, participants with the highest serum ferritin levels (Q4 group) displayed a higher prevalence of liver fibrosis [Q4 vs. Q1: OR=2.59 (1.19, 5.62), P<0.05 in liver stiffness measurement; OR=5.06 (1.12, 22.94), P<0.05 in fibrosis-4 index], with significantly increased risk observed in participants with concomitant diabetes [OR=7.45 (1.55, 35.72), P=0.012]. CONCLUSION: Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients. Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.

ARTC1-mediated VAPB ADP-ribosylation regulates calcium homeostasis.

Mono-ADP-ribosylation (MARylation) is a post-translational modification that regulates a variety of biological processes, including DNA damage repair, cell proliferation, metabolism, and stress and immune responses. In mammals, MARylation is mainly catalyzed by ADP-ribosyltransferases (ARTs), which consist of two groups: ART cholera toxin-like (ARTCs) and ART diphtheria toxin-like (ARTDs, also known as PARPs). The human ARTC (hARTC) family is composed of four members: two active mono-ADP-ARTs (hARTC1 and hARTC5) and two enzymatically inactive enzymes (hARTC3 and hARTC4). In this study, we systematically examined the homology, expression, and localization pattern of the hARTC family, with a particular focus on hARTC1. Our results showed that hARTC3 interacted with hARTC1 and promoted the enzymatic activity of hARTC1 by stabilizing hARTC1. We also identified vesicle-associated membrane protein-associated protein B (VAPB) as a new target of hARTC1 and pinpointed Arg50 of VAPB as the ADP-ribosylation site. Furthermore, we demonstrated that knockdown of hARTC1 impaired intracellular calcium homeostasis, highlighting the functional importance of hARTC1-mediated VAPB Arg50 ADP-ribosylation in regulating calcium homeostasis. In summary, our study identified a new target of hARTC1 in the endoplasmic reticulum and suggested that ARTC1 plays a role in regulating calcium signaling.

CLCA2 overexpression suppresses epithelial-to-mesenchymal transition in cervical cancer cells through inactivation of ERK/JNK/p38-MAPK signaling pathways.

Cervical cancer is an important malignant tumor threatening the physical and mental health of women in the world. As a new calcium activated chloride channel protein, calcium activated chloride channel (CLCA2) plays an important role in tumorigenesis and development. But its role and exact regulatory mechanism in cervical cancer are still unclear. In our study, we found CLCA2 was significantly decreased in cervical cancer cells, and overexpression of CLCA2 inhibited the proliferation, migration and invasion, and promotes apoptosis of cervical cancer cells, and CLCA2 inhibited EMT (Epithelial-mesenchymal transition) through an p38 / JNK / ERK pathway. The results in vivo were consistent with those in vitro. In conclusion, overexpression of CLCA2 inhibited the progression of cervical cancer in vivo and in vitro. This may provide a theoretical basis for CLCA2 as a new indicator of clinical diagnosis and prognosis of cervical cancer or as a potential target of drug therapy.

The Psychological and Behavioral Patterns of Online Psychological Help-Seekers before and during COVID-19 Pandemic: A Text Mining-Based Longitudinal Ecological Study.

Online mental health service (OMHS) platforms have contributed significantly to the public's mental health during the COVID-19 pandemic in China. However, it remains unclear why the public used OMHS platforms for psychological help-seeking (PHS) behavior and how PHS behavior varied across different stages of the COVID-19 pandemic. Based on the ecological PHS behavior data from two OMHS platforms, we extracted population, psychological problems, and influential factors of PHS behavior by text mining and time series analysis methods. Seven top-ranked psychological problems (i.e., depression and anxiety, lack of interest, suicidal tendencies, social phobia, feelings of being worried and afraid, suffering, anger) and seven influential factors (i.e., interpersonal relationships, love, family, work, psychotherapy, personal characteristics, marriage) were found. The online PHS behaviors related to different psychological problems and influential factors remained a growing trend before 2020 and have been increasing significantly due to the COVID-19 outbreak. Four main stages were found during the pandemic according to the changes in the online PHS population: sharp growth, significant decline, slight rebound, and slow decline. This study identified large-scale, spontaneous PHS behaviors among the online public during the COVID-19 pandemic and the various psychological problems and influential factors that varied across different stages of the pandemic, suggesting that the government and health practitioners should adopt effective policies and strategies to prevent and intervene in mental health problems for the online public.

Childhood Trauma and Psychological Distress: A Serial Mediation Model among Chinese Adolescents.

The consequence of childhood trauma may last for a long time. The purpose of the present study was to examine the effect of childhood trauma on general distress among Chinese adolescents and explore the potential mediating roles of social support and family functioning in the childhood trauma-general distress linkage. A total of 2139 valid questionnaires were collected from two high schools in southeast China. Participants were asked to complete the questionnaires measuring childhood trauma, social support, family functioning, and general distress. Pathway analysis was conducted by using SPSS AMOS 24.0 and PROCESS Macro for SPSS 3.5. Results showed that childhood trauma was positively associated with general distress among Chinese adolescents. Social support and family functioning independently and serially mediated the linkage of childhood trauma and general distress. These findings confirmed and complemented the ecological system theory of human development and the multisystem developmental framework for resilience. Furthermore, these findings indicated that the mental and emotional problems of adolescents who had childhood trauma were not merely issues of adolescents themselves, but concerns of the whole system and environment.

Physical Health and Quality of Life among Older People in the Context of Chinese Culture.

Population aging has become a crucial problem in China. Recently, the Chinese government has adopted many strategies and policies to solve this problem and improve the quality of life of older individuals. The present study aimed to examine the effect of physical health on quality of life among older individuals in the context of Chinese culture and explore the potential mediating roles of positive cognition and negative emotions in the association between physical health and quality of life. Data were from the wave of 2017-2018 of the Chinese Longitudinal Healthy Longevity Survey. Data on physical health, quality of life, positive cognition, and negative emotions of 15,874 older people were included in the present study. Pathway analysis was conducted by using IBM SPSS AMOS 21.0, and double verified using PROCESS Macro for SPSS 3.5.3. Results showed that physical health was positively associated with quality of life among older individuals in the context of Chinese culture. The effect size was small to moderate. Positive cognition and negative emotions independently and serially mediated the linkage of physical health and quality of life. These findings provided empirical evidence for the activating event-belief-consequence theory of emotion and hierarchy of needs theory and indicated that Chinese older people focused more on physical health rather than mental health. Practitioners could teach older individuals strategies of emotion regulation and cognitive appraisal to improve the quality of life of older individuals.

Comparative efficacy and acceptability of psychosocial treatments for disruptive behaviour disorders in children and adolescents: study protocol for a systematic review and network meta-analysis.

INTRODUCTION: Disruptive behaviour disorders are common among children and adolescents, with negative impacts on the youths, their families and society. Although multiple psychosocial treatments are effective in decreasing the symptoms of disruptive behaviour disorders, comprehensive evidence regarding the comparative efficacy and acceptability between these treatments is still lacking. Therefore, we propose a systematic review and network meta-analysis, integrating both direct and indirect comparisons to obtain a hierarchy of treatment efficacy and acceptability. METHODS AND ANALYSIS: The present protocol will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Ten databases, including Web of Science, PubMed, PsycINFO, MEDLINE, APA PsycArticles, Psychology and Behavioral Sciences Collection, OpenDissertations, The Cochrane Library, Embase and CINAHL, will be searched from inception for randomised controlled trials of psychosocial treatments for children and adolescents with disruptive behaviour disorders, without restrictions on language, publication year and status. The primary outcomes will be efficacy at post-treatment (severity of disruptive behaviour disorders at post-treatment) and acceptability (dropout rate for any reason) of psychosocial treatments. The secondary outcomes will involve efficacy at follow-up, severity of internalising problems and improvement of social functioning. Two authors will independently conduct the study selection and data extraction, assess the risk of bias using the revised Cochrane Collaboration's Risk of Bias tool and evaluate the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework to network meta-analysis. We will perform Bayesian network meta-analyses with a random effects model. Subgroup and sensitivity analyses will be performed to evaluate the robustness of the findings. ETHICS AND DISSEMINATION: The research does not require ethical approval. Results are planned to be published in journals or presented at conferences. The network meta-analysis will provide information on a hierarchy of treatment efficacy and acceptability and help make a clinical treatment choice. PROSPERO REGISTRATION NUMBER: CRD42020197448.

S100A16 Regulates HeLa Cell through the Phosphatidylinositol 3 Kinase (PI3K)/AKT Signaling Pathway.

BACKGROUND S100 calcium-binding protein A16 (S100A16) is closely related to the onset and progression of tumors. MATERIAL AND METHODS In the research, the mainly purpose was to investigate the effect of S100A16 on the proliferation ability, invasion, and angiogenesis of HeLa cells. An adenoviral vector overexpressing S100A16 (Ad-S100A16) was constructed and transfected into HeLa cells, forming a stable cells line of overexpression. The effect of S100A16 on the proliferative capacity of HeLa cells was evaluated by a Cell Counting Kit-8 (CCK-8) assay. Cell migration capacity was determined by a Transwell migration assay. Changes in matrix metalloproteinase-2 (MMP-2), MMP-9, E-cadherin, and vimentin expression were evaluated by a cell-based immunofluorescence assay. The effect of S100A16 on angiogenesis was verified by knockout experiment. RESULTS Overexpression of S100A16 significantly enhanced the proliferative and migratory capacities of HeLa cells (P<0.05), upregulated expression of matrix MMP-2, MMP-9, vimentin, phosphatidylinositol 3 kinase, and phosphorylated protein kinase B, and downregulated expression of E-cadherin. Vascular endothelial growth factor expression increased, phosphatase and tensin homolog expression decreased, and angiogenesis was positively correlated with S100A16 expression. These effects were largely mediated by the activation of the phosphatidylinositol 3 kinase/protein kinase B pathways. CONCLUSIONS S100A16 could promote the proliferation, migration, and tumor angiogenesis of HeLa cells by regulating the phosphatidylinositol 3 kinase/protein kinase B signaling pathways.

MicroRNA-224 impairs adipogenic differentiation of bovine preadipocytes by targeting LPL.

In this study, the potential functions of miR-224 in regulating adipogenic differentiation were explored in bovine preadipocytes. Comparative transcriptome analysis between castrated male cattle with increased intramuscular fat (IMF) and intact male cattle revealed that miR-224 and LPL were abnormally expressed, correlating negatively, and LPL was a predicted target of miR-224. A dual luciferase reporter assay confirmed the negative targeting regulatory relationship between miR-224 and LPL. When miR-224 was either overexpressed or silenced, qRT-PCR showed a negative regulatory effect on LPL. mRNA expression levels of the fat-formation-related biomarkers C/EBPα, C/EBPß, PPARγ, FASN and PLIN1 decreased when miR-224 was overexpressed, while the opposite effect occurred and adipogenic differentiation followed when miR-224 was inhibited. Oil Red O staining. Triglyceride (TG) levels and immunostaining revealed that the accumulation of lipid droplets decreased or increased accordingly. Taken together, our data demonstrated that miR-224 regulated the adipogenic differentiation of bovine preadipocytes by targeting LPL. This provides insight into the molecular basis of IMF deposition in beef cattle.

Identification of Potential Key Genes Associated with Adipogenesis through Integrated Analysis of Five Mouse Transcriptome Datasets.

Adipose tissue is the most important energy metabolism and secretion organ, and these functions are conferred during the adipogenesis process. However, the cause and the molecular events underlying adipogenesis are still unclear. In this study, we performed integrated bioinformatics analyses to identify vital genes involved in adipogenesis and reveal potential molecular mechanisms. Five mouse high-throughput expression profile datasets were downloaded from the Gene Expression Omnibus (GEO) database; these datasets contained 24 samples of 3T3-L1 cells during adipogenesis, including 12 undifferentiated samples and 12 differentiated samples. The five datasets were reanalyzed and integrated to select differentially expressed genes (DEGs) during adipogenesis via the robust rank aggregation (RRA) method. Functional annotation of these DEGs and mining of key genes were then performed. We also verified the expression levels of some potential key genes during adipogenesis. A total of 386 consistent DEGs were identified, with 230 upregulated genes and 156 downregulated genes. Gene Ontology (GO) analysis showed that the biological functions of the DEGs primarily included fat cell differentiation, lipid metabolic processes, and cell adhesion. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were mainly associated with metabolic pathways, the peroxisome proliferator-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, the tumor necrosis factor (TNF) signaling pathway, and the FoxO signaling pathway. The 30 most closely related genes among the DEGs were identified from the protein⁻protein interaction (PPI) network and verified by real-time quantification during 3T3-L1 preadipocyte differentiation. In conclusion, we obtained a list of consistent DEGs during adipogenesis through integrated analysis, which may offer potential targets for the regulation of adipogenesis and treatment of adipose dysfunction.

Bta-miR-130a/b regulates preadipocyte differentiation by targeting PPARG and CYP2U1 in beef cattle.

Deposition of intramuscular fat (IMF) is one of the most important traits for the evaluation of beef carcass quality grade. MicroRNA (miRNA) is an endogenous non-coding RNA that can play a role in the post-transcriptional regulation of mammalian preadipocyte differentiation. Previously, we identified that bta-miR-130a regulates milk fat biosynthesis by targeting PPARG mRNA. However, the role of miR-130 in the regulation of bovine adipocyte differentiation remains unknown. In this study, we found that overexpression of bta-miR-130a/b led to significantly decreased cellular triacylglycerol (TAG) levels during adipogenesis process as well as reduced lipid droplet formation. In contrast, the inhibition of bta-miR-130a/b resulted in larger lipid droplets and TAG accumulation. In addition, overexpression of bta-miR-130a/b inhibited the expression of adipocyte differentiation-related genes, including PPARG, C/EBPα, C/EBPß, FABP4, LPIN1, and LPL. Western blot analysis verified qPCR results on the expression of PPARG and CYP2U1. A luciferase reporter assay further verified bta-miR-130a/b significantly affects PPARG and CYP2U1 expression by directly binding to their 3'-untranslated regions (UTR). We conducted in vitro rescue assay to confirm that bta-miR-130a/b affect bovine adipocyte differentiation by targeting PPARG and CYP2U1. This study shows that bta-miR-130a and bta-miR-130b play similar roles in the regulation of adipocyte differentiation in beef muscles by targeting the 3'UTR of PPARG and CYP2U1. Our result provides a reference for illustrating how noncoding RNAs affects beef quality traits in cattle.

Characterization of the promoter region of bovine SIX4: Roles of E-box and MyoD in the regulation of basal transcription.

The sine oculis homeobox 4 (SIX4) gene belongs to the Six gene family and encodes an evolutionarily conserved transcription factor. Previous studies have demonstrated that SIX4 plays an essential role in proper muscle regeneration. However, the mechanisms regulating SIX4 transcription remain elusive. In the present study, we determined that bovine SIX4 was highly expressed in the longissimus thoracis and in undifferentiated Qinchuan cattle muscle cells (QCMCs) and that its protein localizes to both the cytoplasm and the nucleus. To elucidate the bovine the molecular mechanisms of SIX4 regulation, 1.3 kb of the 5'-regulatory region was obtained. MyoD and Ebox recognition sites were identified in the core promoter region at -522/-193 of the bovine SIX4 using a series of 5' deletion promoter plasmids in luciferase reporter assays. An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay in combination with site-directed mutation and siRNA interference demonstrated that MyoD binding occurs at MyoD and Ebox recognition sites through direct and indirect mechanisms and play important roles in the transcriptional regulation of the bovine SIX4 promoter. Taken together, these interactions provide insight into the regulatory mechanisms of SIX4 transcription in mediating skeletal muscle growth in cattle.

Association between FASN gene polymorphisms ultrasound carcass traits and intramuscular fat in Qinchuan cattle.

Fatty acid synthase (FASN) is an enzyme involved with fat deposition and fatty acid composition in cattle. This study was conducted to detect single nucleotide polymorphisms (SNPs) of the FASN gene and explore their relationships with ultrasound carcass traits in order to assess the potential use of the FASN gene for the breeding selection of Qinchuan cattle for desirable carcass traits. The frequencies of SNP g.12740C>T, g.13192T>C and g.13232C>T were identified in 525 individual Qinchuan cattle which were also assessed for backfat depth, eye muscle area and intramuscular fat by ultrasound. According to the PIC values, g.13192T>C possessed an intermediate polymorphism (0.25T, g.12740C>T possessed low polymorphism (PIC<0.25). Chi-square tests showed that g.13192T>C were in Hardy-Weinberg disequilibrium (c2C was associated with a greater eye muscle area and the TT genotype at g.13232C>T was associated with greater intramuscular fat. When these genotypes were combined there was no difference in eye muscle area and intramuscular fat between the diplotypes. The H2H2 diplotype was associated with carcass traits that are likely to provide economic advantage in Qinchuan cattle. Variations in the FASN genes and their corresponding genotypes may be considered as molecular markers for economic traits in cattle breeding.

Characterization of the promoter region of the bovine SIX1 gene: Roles of MyoD, PAX7, CREB and MyoG.

The SIX1 gene belongs to the family of six homeodomain transcription factors (TFs), that regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway and mediate skeletal muscle growth and regeneration. Previous studies have demonstrated that SIX1 is positively correlated with body measurement traits (BMTs). However, the transcriptional regulation of SIX1 remains unclear. In the present study, we determined that bovine SIX1 was highly expressed in the longissimus thoracis. To elucidate the molecular mechanisms involved in bovine SIX1 regulation, 2-kb of the 5' regulatory region were obtained. Sequence analysis identified neither a consensus TATA box nor a CCAAT box in the 5' flanking region of bovine SIX1. However, a CpG island was predicted in the region -235 to +658 relative to the transcriptional start site (TSS). An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay in combination with serial deletion constructs of the 5' flanking region, site-directed mutation and siRNA interference demonstrated that MyoD, PAX7 and CREB binding occur in region -689/-40 and play important roles in bovine SIX1 transcription. In addition, MyoG drives SIX1 transcription indirectly via the MEF3 motif. Taken together these interactions suggest a key functional role for SIX1 in mediating skeletal muscle growth in cattle.

National survey of therapeutic orientation and associated factors of counselors and psychotherapists in China.

The aim of the present study was to determine the most commonly used and primary psychotherapeutic orientations adopted by Chinese practitioners and to examine the factors associated with the choice of orientation. A nationwide survey using multi-stage convenience sampling without replacement was conducted. A total of 1,232 respondents out of the 1,325 participants selected completed the survey, which corresponds to an overall response rate of 93.0%. The respondents were practitioners who were providing consultations and psychotherapy in China at the time. The main outcome measures were the most commonly used and primary psychotherapeutic orientations. A Chi-square test was used to examine the factors associated with therapeutic orientation. The most commonly used psychotherapies were cognitive therapy (59.2%), behavioral therapy (38.1%) and the psychoanalytic/psychodynamic model (29.4%). The primary orientations were cognitive therapy (41.6%), the psychoanalytic/psychodynamic model (15.7%) and cognitive-behavioral therapy (10.3%). Gender had no effect on the orientation choice. Cognitive therapy was used significantly more by respondents who were ≤30 years old (50.5%), who had been in practice ≤3 years (45.9%), received continuing education ≤64 h (47.2%) and accepted no clinical supervision (53.1%). Those who were ≥31 years old (18.4%), had been in practice ≥7 years (21.0%), received continuing education ≥65 h (23.6%), worked full-time (20.2%) and accepted clinical supervision (20.6%) used the psychoanalytic/psychodynamic model significantly more. The respondents who used cognitive-behavioral therapy had graduated from the medical profession (14.1%) and were not licensed (15.8%). Cognitive therapy and the psychoanalytic/psychodynamic model were the two most popular orientations adopted by Chinese counselors and psychotherapists. Age, years of practice, graduate profession, continuing education, working hours (full/part-time), licensure and supervision are significant factors that affect the choice of orientation.