Predicting the evolution of clinical skin aging in a multi-ethnic population: Developing causal Bayesian networks using dermatological expertise.

INTRODUCTION: Software to predict the impact of aging on physical appearance is increasingly popular. But it does not consider the complex interplay of factors that contribute to skin aging. OBJECTIVES: To predict the +15-year progression of clinical signs of skin aging by developing Causal Bayesian Belief Networks (CBBNs) using expert knowledge from dermatologists. MATERIAL AND METHODS: Structures and conditional probability distributions were elicited worldwide from dermatologists with experience of at least 15 years in aesthetics. CBBN models were built for all phototypes and for ages ranging from 18 to 65 years, focusing on wrinkles, pigmentary heterogeneity and facial ptosis. Models were also evaluated by a group of independent dermatologists ensuring the quality of prediction of the cumulative effects of extrinsic and intrinsic skin aging factors, especially the distribution of scores for clinical signs 15 years after the initial assessment. RESULTS: For easiness, only models on African skins are presented in this paper. The forehead wrinkle evolution model has been detailed. Specific atlas and extrinsic factors of facial aging were used for this skin type. But the prediction method has been validated for all phototypes, and for all clinical signs of facial aging. CONCLUSION: This method proposes a skin aging model that predicts the aging process for each clinical sign, considering endogenous and exogenous factors. It simulates aging curves according to lifestyle. It can be used as a preventive tool and could be coupled with a generative AI algorithm to visualize aging and, potentially, other skin conditions, using appropriate images.

Effect of DHCR7 on adipocyte differentiation in goats.

Cholesterol is regarded as a signaling molecule in regulating the metabolism and function of fat cells, in which 7-Dehydrocholesterol reductase (DHCR7) is a key enzyme that catalyzes the conversion of 7-dehydrocholesterol to cholesterol, however, the exact function of DHCR7 in goat adipocytes remains unknown. Here, the effect of DHCR7 on the formation of subcutaneous and intramuscular fat in goats was investigated in vitro, and the result indicated that the mRNA level of DHCR7 showed a gradual downward trend in subcutaneous adipogenesis, but an opposite trend in intramuscular adipogenesis. In the process of subcutaneous preadipocytes differentiation, overexpression of DHCR7 inhibited the expression of adipocytes differentiation marker genes (CEBP/α, CEBP/ß, SREBP1 and AP2), lipid metabolism-related genes (AGPAT6, FASN, SCD1 and LPL), and the lipid accumulation. However, in intramuscular preadipocyte differentiation, DHCR7 overexpression showed a promoting effect on adipocyte differentiation marker genes (CEBP/α, CEBP/ß, PPARγ and SREBP1) and lipid metabolism-related genes (GPAM, AGPAT6, DGAT1 and SCD1) expression, and on lipid accumulation. In summary, our work demonstrated that DHCR7 played an important role in regulating adipogenic differentiation and lipid metabolism in preadipocytes in goats, which is of great significance for uncovering the underlying molecular mechanism of adipocyte differentiation and improving goat meat quality.

[miR-23b-3p regulates the differentiation of goat intramuscular preadipocytes by targeting the PDE4B gene].

This study aimed to explore the effect of miR-23b-3p on the differentiation of goat intramuscular preadipocytes, and to confirm whether miR-23b-3p plays its roles via targeting the PDE4B gene. Based on the pre-transcriptome sequencing data obtained previously, the miR-23b-3p, which was differentially expressed in goat intramuscular adipocytes before and after differentiation, was used as an entry point. real-time quantitative-polymerase chain reaction (qPCR) was used to detect the expression pattern of miR-23b-3p during the differentiation of goat intramuscular preadipocytes. The effects of miR-23b-3p on adipose differentiation and adipose differentiation marker genes were determined at the morphological and molecular levels. The downstream target genes of miR-23b-3p were determined using bioinformatics prediction as well as dual luciferase reporter assay to clarify the targeting relationship between miR-23b-3p and the predicted target genes. The results indicated that overexpression of miR-23b-3p reduced lipid droplet accumulation in goat intramuscular adipocytes, significantly down-regulated the expression levels of adipogenic marker genes AP2, C/EBPα, FASN, and LPL (P < 0.01). In addition, the expressions of C/EBPß, DGAT2, GLUT4 and PPARγ were significantly downregulated (P < 0.05). After interfering with the expression of miR-23b-3p, lipid droplet accumulation was increased in goat intramuscular adipocytes. The expression levels of ACC, ATGL, AP2, DGAT2, GLUT4, FASN and SREBP1 were extremely significantly up-regulated (P < 0.01), and the expression levels of C/EBPß, LPL and PPARγ were significantly up-regulated (P < 0.05). It was predicted that PDE4B might be a target gene of miR-23b-3p. The mRNA expression level of PDE4B was significantly decreased after overexpression of miR-23b-3p (P < 0.01), and the interference with miR-23b-3p significantly increased the mRNA level of PDE4B (P < 0.05). The dual luciferase reporter assay indicated that miR-23b-3p had a targeting relationship with PDE4B gene. MiR-23b-3p regulates the differentiation of goat intramuscular preadipocytes by targeting the PDE4B gene.

FOS Inhibits the Differentiation of Intramuscular Adipocytes in Goats.

Goat intramuscular fat (IMF) deposition is precisely regulated by many key genes as well as transcription factors. Nevertheless, the potential of the regulators of goat IMF deposition remains undefined. In this work, we reported that the transcription factor FOS is expressed at a low level at the early differentiation stage and at a high level in late differentiation. The overexpression of FOS inhibited intramuscular adipocyte lipid accumulation and significantly downregulated the expressions of PPARγ, C/EBPß, C/EBPα, AP2, SREBP1, FASN, ACC, HSL, and ATGL. Consistently, the knockdown of FOS, facilitated by two distinct siRNAs, significantly promoted intramuscular adipocyte lipid accumulation. Moreover, our analysis revealed multiple potential binding sites for FOS on the promoters of PPARγ, C/EBPß, and C/EBPα. The expression changes in PPARγ, C/EBPß, and C/EBPα during intramuscular adipogenesis were opposite to that of FOS. In summary, FOS inhibits intramuscular lipogenesis in goats and potentially negatively regulates the expressions of PPARγ, C/EBPß, and C/EBPα genes. Our research will provide valuable data for the underlying molecular mechanism of the FOS regulation network of intramuscular lipogenesis.

Prognostic model of hepatocellular carcinoma based on cancer grade.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. With highly invasive biological characteristics and a lack of obvious clinical manifestations, HCC usually has a poor prognosis and ranks fourth in cancer mortality. The aetiology and exact molecular mechanism of primary HCC are still unclear. AIM: To select the characteristic genes that are significantly associated with the prognosis of HCC patients and construct a prognosis model of this malignancy. METHODS: By comparing the gene expression levels of patients with different cancer grades of HCC, we screened out differentially expressed genes associated with tumour grade. By protein-protein interaction (PPI) network analysis, we obtained the top 2 PPI networks and hub genes from these differentially expressed genes. By using least absolute shrinkage and selection operator Cox regression, 13 prognostic genes were selected for feature extraction, and a prognostic risk model of HCC was established. RESULTS: The model had significant prognostic ability in HCC. We also analysed the biological functions of these prognostic genes. CONCLUSION: By comparing the gene profiles of patients with different stages of HCC, We have constructed a prognosis model consisting of 13 genes that have important prognostic value. This model has good application value and can be explained clinically.

Effect of CXCL17 on Subcutaneous Preadipocytes Proliferation in Goats.

The presence or absence of subcutaneous adipose accumulation will affect the energy storage, insulation resistance and metabolism of animals. Proliferation and differentiation of preadipocytes play a significant role in lipid deposition. The objective of this study was to clone the goat CXCL17 gene and investigate its potential functions on goat subcutaneous preadipocytes' proliferation by gaining or losing function in vitro. The goat CXCL17 gene was cloned by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and bioinformatics analysis was performed. The expression of the CXCL17 gene in the different goat tissues and adipocytes at different differentiation stages was detected by real-time fluorescence quantitative PCR (qPCR). The results showed that the cloned sequence of goat CXCL17 gene is 728 bp and the CDS region is 357 bp, encoding 118 amino acids. CXCL17 protein is located in nucleus, cytoplasm, mitochondria and extracellular matrix. Tissue-expression profiles revealed that CXCL17 expressed in all of the examined tissues. In visceral tissues, the highest expression level was found in lung (p < 0.01); in muscle tissues, the highest CXCL17 expression level was found in the longissimus dorsi (p < 0.01) and in adipose tissues, the highest expression level was found in subcutaneous adipose (p <0.01). Compared with those cells before differentiation, CXCL17 expression levels upregulated at 48 h (p < 0.01), 72 h (p < 0.01), 120 h (p < 0.01) and downregulated at 96 h (p < 0.01). Furthermore, the results of crystal violet staining and semi-quantitative assay showed that transfection with 1 µg CXCL17 expression plasmid reduced the cell numbers in vitro. Meanwhile, the expression of CCND1 was significantly decreased. A similar consequence happened after interfering with CXCL17 expression. However, plasmid transfected with 2 µg pEGFPN1-CXCL17 increased the number of cells in vitro. These results suggest that CXCL17 is involved in the proliferation of goat subcutaneous preadipocytes.

Impact of Dietary Supplementation of Cysteamine on Egg Taurine Deposition, Egg Quality, Production Performance and Ovary Development in Laying Hens.

This study aimed to examine the effect of dietary cysteamine on yolk taurine content in hens during different egg production periods. In Exp. 1, China Agricultural University-3 (CAU-3) hens at the peak stage of egg production (aged 31 wks) were used to explore the effect of diets supplemented with 0.1% cysteamine on yolk taurine content, egg quality and production performance. In Exp.2, two breeds of hens (half Hy-Line Brown and half CAU-3 hens) at the late stage of egg production (68 wks) were used to investigate the influence of diets supplemented with 0, 0.02%, 0.04%, 0.08% or 0.10% cysteamine on yolk taurine content, egg quality, production performance and ovary development. In Exp.1, diets supplemented with 0.1% cysteamine significantly increased yolk taurine content (p < 0.05) without negative influence on production performance or egg quality. In Exp.2, the highest yolk taurine content was observed when cysteamine was supplemented at 0.08% (p < 0.001). However, supplemental cysteamine linearly or quadratically decreased production performance over the first few weeks of feeding, and the effects disappeared with continued feeding (p < 0.05). In conclusion, this study indicated that cysteamine supplementation benefits yolk taurine deposition in hens at both peak and late stage of egg production, but hens at the late stage of egg production show depressed production performance and egg quality.

PSTPIP2 is associated with disease severity in patients with pressure ulcer sepsis and has anti-inflammatory effects.

BACKGROUND: One of the common adverse reactions in patients with pressure ulcers (PU) is sepsis, which is mainly related to microbial infections caused by pathogenic organisms. The activation of nuclear factor kappa-B (NF-κB) frequently occurs in conjunction with pathogenic microbial infections. Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) is closely related to inflammatory disorders. The role and mechanism of PSTPIP2 in sepsis because of pressure ulcers is unclear. In this study, we discovered that PSTPIP2 was lowly expressed in peripheral blood of patients with sepsis induced by pressure ulcers. METHODS: Peripheral blood was collected from 20 patients with sepsis due to pressure ulcers and 10 healthy controls, and the expression of PSTPIP2 in peripheral blood was discovered by polymerase chain reaction and Western blot analysis. Information on the clinical characteristics of patients was summarized, and the expression data of PSTPIP2 were correlated with the patients' acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and C-reactive protein (CRP) and procalcitonin (PCT) scores by Spearman's correlation analysis. One of the main mediators of Gram-negative sepsis is lipopolysaccharide (LPS). In order to establish an in vitro sepsis model, THP-1 cells were treated with LPS, and the cells were transfected with PSTPIP2. Contents of interleukin 6 (IL-6), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in each group of cells were detected by enzyme-linked--immunosorbent serologic assay, and NF-κB-related proteins were detected by Western blot analysis. RESULTS: When compared to healthy controls, the peripheral blood of patients with pressure sepsis had lower PSTPIP2 expression, which had a negative correlation with the APACHE II, SOFA, CRP, and PCT scores. LPS-induced THP-1 cells expressed less PSTPIP2 than the untreated control cells, and PSTPIP2 transfection decreased IL-6, IL-1ß, and TNF-α levels and inhibited the activation of NF-κB pathway. CONCLUSION: PSTPIP2 is associated with disease severity in patients with pressure ulcer sepsis and has anti-inflammatory effects.

Experiment-based computational model predicts that IL-6 classic and trans-signaling exhibit similar potency in inducing downstream signaling in endothelial cells.

Inflammatory cytokine mediated responses are important in the development of many diseases that are associated with angiogenesis. Targeting angiogenesis as a prominent strategy has shown limited effects in many contexts such as cardiovascular diseases and cancer. One potential reason for the unsuccessful outcome is the mutual dependent role between inflammation and angiogenesis. Inflammation-based therapies primarily target inflammatory cytokines such as interleukin-6 (IL-6) in T cells, macrophages, cancer cells, and muscle cells, and there is a limited understanding of how these cytokines act on endothelial cells. Thus, we focus on one of the major inflammatory cytokines, IL-6, mediated intracellular signaling in endothelial cells by developing a detailed computational model. Our model quantitatively characterized the effects of IL-6 classic and trans-signaling in activating the signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and mitogen-activated protein kinase (MAPK) signaling to phosphorylate STAT3, extracellular regulated kinase (ERK) and Akt, respectively. We applied the trained and validated experiment-based computational model to characterize the dynamics of phosphorylated STAT3 (pSTAT3), Akt (pAkt), and ERK (pERK) in response to IL-6 classic and/or trans-signaling. The model predicts that IL-6 classic and trans-signaling induced responses are IL-6 and soluble IL-6 receptor (sIL-6R) dose-dependent. Also, IL-6 classic and trans-signaling showed similar potency in inducing downstream signaling; however, trans-signaling induces stronger downstream responses and plays a dominant role in the overall effects from IL-6 due to the in vitro experimental setting of abundant sIL-6R. In addition, both IL-6 and sIL-6R levels regulate signaling strength. Moreover, our model identifies the influential species and kinetic parameters that specifically modulate the downstream inflammatory and/or angiogenic signals, pSTAT3, pAkt, and pERK responses. Overall, the model predicts the effects of IL-6 classic and/or trans-signaling stimulation quantitatively and provides a framework for analyzing and integrating experimental data. More broadly, this model can be utilized to identify potential targets that influence IL-6 mediated signaling in endothelial cells and to study their effects quantitatively in modulating STAT3, Akt, and ERK activation.

PSTPIP2 is associated with disease severity in patients with pressure ulcer sepsis and has anti-inflammatory effects

Background: One of the common adverse reactions in patients with pressure ulcers (PU) is sepsis, which is mainly related to microbial infections caused by pathogenic organisms. The activation of nuclear factor kappa-B (NF-κB) frequently occurs in conjunction with pathogenic microbial infections. Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) is closely related to inflammatory disorders. The role and mechanism of PSTPIP2 in sepsis because of pressure ulcers is unclear. In this study, we discovered that PSTPIP2 was lowly expressed in peripheral blood of patients with sepsis induced by pressure ulcers. Methods: Peripheral blood was collected from 20 patients with sepsis due to pressure ulcers and 10 healthy controls, and the expression of PSTPIP2 in peripheral blood was discovered by polymerase chain reaction and Western blot analysis. Information on the clinical characteristics of patients was summarized, and the expression data of PSTPIP2 were correlated with the patients’ acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and C-reactive protein (CRP) and procalcitonin (PCT) scores by Spearman’s correlation analysis. One of the main mediators of Gram-negative sepsis is lipopolysaccharide (LPS). In order to establish an in vitro sepsis model, THP-1 cells were treated with LPS, and the cells were transfected with PSTPIP2. Contents of interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor-α (TNF-α) in each group of cells were detected by enzyme-linked--immunosorbent serologic assay, and NF-κB-related proteins were detected by Western blot analysis (AU)

Clinical significance of serum S100 calcium-binding protein A12 concentrations in patients with community-acquired pneumonia.

OBJECTIVE: This study aimed to investigate the clinical significance of serum S100 calcium-binding protein A12 (S100A12) concentrations in patients with community-acquired pneumonia (CAP). METHODS: This was a case-control study. We selected 120 patients with CAP treated in Xichang People's Hospital from January to June 2022 as the case group. Sixty healthy adults without a history of basic diseases were selected as the control group. The patients in the case group were divided into the low S100A12 and high S100A12 subgroups. Serum S100A12, C-reactive protein (CRP), and procalcitonin (PCT) concentrations, the leukocyte count, and other study parameters were compared. RESULTS: Serum S100A12, CRP, and PCT concentrations and the leukocyte count were higher in the case group than in the control group. The baseline confusion, urea, respiratory rate, blood pressure, and age ≥ 65 score, baseline pneumonia severity index score, and 30-day mortality rate were higher in the high S100A12 subgroup than in the low S100A12 subgroup. Serum CRP and PCT concentrations and the leukocyte count were higher in the high S100A12 subgroup than in the low S100A12 subgroup. CONCLUSION: Patients with high serum S100A12 concentrations have more severe CAP, a more serious inflammatory reaction, and higher 30-day mortality.

[Gene cloning and sequence analysis of the RPL29 gene and its effect on lipogenesis in goat intramuscular adipocytes].

The aim of this study was to clone the goat RPL29 gene and analyze its effect on lipogenesis in intramuscular adipocytes. Using Jianzhou big-eared goats as the object, the goat RPL29 gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR), the gene structure and expressed protein sequence were analyzed by bioinformatics, and the mRNA expression levels of RPL29 in various tissues and different differentiation stages of intramuscular adipocytes of goats were detected by quantitative real-time PCR (qRT-PCR). The RPL29 overexpression vector pEGFP-N1-RPL29 constructed by gene recombination was used to transfect into goat intramuscular preadipocytes and induce differentiation. Subsequently, the effect of overexpression of RPL29 on fat droplet accumulation was revealed morphologically by oil red O and Bodipy staining, and changes in the expression levels of genes related to lipid metabolism were detected by qRT-PCR. The results showed that the length of the goat RPL29 was 507 bp, including a coding sequence (CDS) region of 471 bp which encodes 156 amino acid residues. It is a positively charged and stable hydrophilic protein mainly distributed in the nucleus of cells. Tissue expression profiling showed that the expression level of this gene was much higher in subcutaneous adipose tissue and inter-abdominal adipose tissue of goats than in other tissues (P < 0.05). The temporal expression profile showed that the gene was expressed at the highest level at 84 h of differentiation in goat intramuscular adipocytes, which was highly significantly higher than that in the undifferentiated period (P < 0.01). Overexpression of RPL29 promoted lipid accumulation in intramuscular adipocytes, and the optical density values of oil red O staining were significantly increased (P < 0.05). In addition, overexpression of RPL29 was followed by a highly significant increase in ATGL and ACC gene expression (P < 0.01) and a significant increase in FASN gene expression (P < 0.05). In conclusion, the goat RPL29 may promote intra-muscular adipocyte deposition in goats by up-regulating FASN, ACC and ATGL.

miR-130b duplex (miR-130b-3p/miR-130b-5p) negatively regulates goat intramuscular preadipocyte lipid droplets accumulation by inhibiting Krüppel-like factor 3 expression.

Intramuscular lipid deposition is important for meat quality improvement. microRNAs and their target mRNAs provide a new approach for studying the mechanism of fat deposition. The present study aimed to investigate the effect of miR-130b duplex (miR-130b-5p, miR-130b-3p) and its target gene KLF3 in regulating goat intramuscular adipocyte differentiation. Goat intramuscular preadipocytes were isolated from 7-d-old male Jianzhou big-ear goats and identified by Oil red O staining after differentiation induction. miR-130b-5p and miR-130b-3p mimics or inhibitors and their corresponding controls were transfected into goat intramuscular preadipocytes, respectively, and differentiation was induced by 50µM oleic acid for 48 h. Oil red O and Bodipy staining indicated that both miR-130b-5p and miR-130b-3p can reduce lipid droplets accumulation and triglyceride (TG) content (P < 0.01). Differentiation markers C/EBPα, C/EBPß, PPARγ, pref1, fatty acids synthesis markers ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, AP2, SREBP1, and TG markers LPL, ATGL, HSL were assessed by qPCR. All the markers measured were downregulated by miR-130b-5p and miR-130b-3p analog (P < 0.01), suggesting that miR-130b inhibits goat intramuscular adipocyte adipogenic differentiation, fatty acids synthesis, and lipid lipolysis. To examine the mechanism of miR-130b duplex inhibition of lipid deposition, TargetScan, miRDB, and starBase were used to predict the potential targets, KLF3 was found to be the only one intersection. Furthermore, the 3'UTR of KLF3 was cloned, qPCR analysis and dual luciferase activity assay showed that both miR-130b-5p and miR-130b-3p could directly regulate KLF3 expression (P < 0.01). In addition, overexpression and interference of KLF3 were conducted, it was found that KLF3 positively regulated lipid droplets accumulation by Oil red O, Bodipy staining, and TG content detection (P < 0.01). Quantitative PCR result indicated that KLF3 overexpression promoted lipid droplets accumulation relative genes C/EBPß, PPARγ, pref1, ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, SREBP1, LPL, and ATGL expression (P < 0.01). Downregulation of KLF3 inhibited the expression of genes such as C/EBPα, C/EBPß, PPARγ, pref1, TIP47, GPAM, ADRP, AP2, LPL, and ATGL expression (P < 0.01). Taken together, these results indicate that miR-130b duplex could directly inhibit KLF3 expression, then attenuated adipogenic and TG synthesis genes expression, thus leading to its anti-adipogenic effect.

microRNAs (miRNAs) are small (19 to 24 nucleotides), single-stranded, noncoding RNAs that are evolutionarily conserved and can be complimentary bound to the 3ʹ-untranslated region (3ʹUTR) of their target mRNA for cleavage or translation inhibition to participate in almost all biological processes. We demonstrated miR-130b duplex (miR-130b-3p/miR-130b-5p) negatively regulates goat intramuscular preadipocyte lipid droplets accumulation by targeting Krüppel-like factor 3 (KLF3) expression. This research opens new visions to study and understand the functions and mechanisms of goat miRNAs in lipid deposition.

Association between atherogenic index of plasma and prehypertension or hypertension among normoglycemia subjects in a Japan population: a cross-sectional study.

OBJECTIVE: The atherogenic index of plasma (AIP), consisting of triglycerides and high-density lipoprotein cholesterol, is applied to estimate the cardiovascular disease risk. The evidence regarding the association between AIP and prehypertension or hypertension remains inconclusive. This study was conducted to investigate the association of AIP and prehypertension or hypertension in normoglycemic subjects in Japan. METHODS: In the present cross-sectional study, 15,453 normoglycemic participants aged 18 years or older in Gifu, Japan, were evaluated. The selected participants were separated into four groups in the light of AIP quartiles, ranging from the lowest quartile (Q1) to the highest quartile (Q4). And the association between AIP and prehypertension or hypertension was explored with multivariate logistic regression by gradually adjusting model. RESULTS: Among the 15,453 participants, aged of 43.7 ± 8.9 years, and of whom 45.5% were females, the prevalence rates of prehypertension or hypertension were 27.68% (4,278) and 6.23% (962) respectively. In multivariate logistic regression analyses, participants in the highest AIP quartile had an increase risk in prehypertension and hypertension, compared with participants the lowest one, the odds ratios (OR) were 1.15 (95%CI: 1.00-1.13, P = 0.045) for prehypertension and 1.54 (95%CI:1.16-2.04, P = 0.003) for hypertension after adjusting confounders. In subgroup analyses, the high risk of hypertension was also observed for female participants in the highest AIP quartile (Q4) (OR = 2.19, 95%CI: 1.37-3.49, P = 0.001), especially between the ages of 40 and 60 years (OR = 2.20, 95%CI: 1.24-3.88, P = 0.007). CONCLUSIONS: Higher AIP is significantly and positively associated with the risk of prehypertension or hypertension in normoglycemic subjects in Gifu, Japan, which was more pronounced in the female population, especially between the years of 40 and 60.

The relationship between preschool teacher trait mindfulness and teacher-child relationship quality: the chain mediating role of emotional intelligence and empathy.

The teacher-child relationship plays an important role in children's future development. However, the existing research mainly focuses on the influence of preschool teachers' external conditions on the teacher-student relationship, while the research on the influence of teachers' internal psychological characteristics on the teacher-student relationship is relatively lacking. In this study, three hundred and seventeen preschool teachers were tested were tested with Five Facet Mindfulness Questionnaire, Emotional Intelligence Scale, Chinese Interpersonal Response Index, and Teacher-student Relationship Scale. The results showed that trait mindfulness positively predicted the quality of parent-teacher relationship (ß = 0.173, p = 0.026). Emotional intelligence played a mediating role in trait mindfulness and teacher-child relationship quality (ß = 0.118, p = 0.004), and empathy played a mediating role in trait mindfulness and teacher-child relationship quality (ß = 0.112, p = 0.001). Meanwhile, emotional intelligence and empathy played a chain mediating role in trait mindfulness and parent-teacher relationship quality (ß = 0.044, p = 0.038). On the one hand, this study enriches attachment theory. The conclusions of this study verify the diversity of proximal factors in attachment theory, and confirm the influence of teachers' own characteristics and abilities on the teacher-child relationship quality. On the other hand, by exploring the factors affecting the teacher-child relationship quality, we can find ways to improve teacher-child relationship from a new perspective, and then provide some new methods and approaches for improving the quality of preschool teacher-child relationship.

[Cloning and expression profile of ZFP36L1 gene in goat].

The purpose of this study was to clone and characterize the ZFP36L1 (zinc finger protein 36-like 1) gene, clarify its expression characteristics, and elucidate its expression patterns in different tissues of goats. Samples of 15 tissues from Jianzhou big-eared goats, including heart, liver, spleen, lung and kidney were collected. Goat ZFP36L1 gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR), then the gene and protein sequence were analyzed by online tools. Quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression level of ZFP36L1 in intramuscular preadipocytes in different tissues and adipocytes of goat at different differentiation stages. The results showed that the length of ZFR36L1 gene was 1 224 bp, and the coding sequence (CDS) region was 1 017 bp, encoding 338 amino acids, which was a non-secretory unstable protein mainly located in nucleus and cytoplasm. Tissue expression profile showed that ZFP36L1 gene was expressed in all selected tissues. In visceral tissues, the small intestine showed the highest expression level (P < 0.01). In muscle tissue, the highest expression level was presented in longissimus dorsi muscle (P < 0.01), whereas the expression level in subcutaneous adipose tissue was significantly higher than that in other tissues (P < 0.01). The results of induced differentiation showed that the expression of this gene was up-regulated during adipogenic differentiation of intramuscular precursor adipocytes (P < 0.01). These data may help to clarify the biological function of the ZFP36L1 gene in goat.

PDZK1-Interacting Protein 1(PDZKIP1) Inhibits Goat Subcutaneous Preadipocyte Differentiation through Promoting Autophagy.

PDZK1IP1 is highly expressed in tumor tissue and has been identified as a tumor biomarker. However, the role of PDZK1IP1 in goat subcutaneous preadipocyte differentiation remains largely unknown. The molecular mechanism of autophagy in regulating the differentiation of goat subcutaneous preadipocytes has not been clarified yet. In our study, PDZK1IP1 gain of function and loss of function were performed to reveal its functions in preadipocyte differentiation and autophagy. Our results showed that the overexpression of PDZK1IP1 inhibited the differentiation of goat subcutaneous preadipocytes, whereas it promoted autophagy. Consistently, the knockdown of PDZK1IP1 demonstrated the opposite tendency. Next, we investigated whether PDZK1IP1 inhibited the differentiation of goat preadipocytes by regulating autophagy. We found that inhibiting autophagy can rescue the PDZK1IP1-induced differentiation restraint in goat subcutaneous preadipocytes. In conclusion, PDZK1IP1 acts as a regulator of adipogenesis, and inhibits goat subcutaneous preadipocyte differentiation through promoting autophagy. Our results will contribute to further understanding the role and mechanism of PDZK1IP1 in controlling adipogenesis.

Effect of TEA domain transcription factor 1 (TEAD1) on the differentiation of intramuscular preadipocytes in goats.

TEA domain transcription factor 1 (TEAD1), also called TEF-1, acts as a transcriptional enhancer to regulate muscle-specific gene expression. However, the role of TEAD1 in regulating intramuscular preadipocyte differentiation in goats is unclear. The aim of this study was to obtain the sequence of TEAD1 gene and elucidate the effect of TEAD1 on goat intramuscular preadipocyte differentiation in vitro and its possible mechanism. The results showed that the goat TEAD1 gene CDS region sequence was 1311 bp. TEAD1 gene was widely expressed in goat tissues, with the highest expression in brachial triceps (p < 0.01). The expression of TEAD1 gene in goat intramuscular adipocytes at 72 h was extremely significantly higher than that at 0 h (p < 0.01). Overexpression of goat TEAD1 inhibited the accumulation of lipid droplets in goat intramuscular adipocyte. The relative expression of differentiation marker genes SREBP1, PPARγ, C/EBPß were significantly down-regulated (all p < 0.01), but PREF-1 was significantly up-regulated (p < 0.01). Binding analysis showed that there were multiple binding sites between the DNA binding domain of goat TEAD1 and the promoter binding region of SREBP1, PPARγ, C/EBPß and PREF-1. In conclusion, TEAD1 negatively regulates the differentiation of goat intramuscular preadipocytes.

The Important Role of m6A-Modified circRNAs in the Differentiation of Intramuscular Adipocytes in Goats Based on MeRIP Sequencing Analysis.

Intramuscular fat contributes to the improvement of goat meat quality. N6-Methyladenosine (m6A)-modified circular RNAs play important roles in adipocyte differentiation and metabolism. However, the mechanisms by which m6A modifies circRNA before and after differentiation of goat intramuscular adipocytes remain poorly understood. Here, we performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) and circRNA sequencing (circRNA-seq) to determine the distinctions in m6A-methylated circRNAs during goat adipocyte differentiation. The profile of m6A-circRNA showed a total of 427 m6A peaks within 403 circRNAs in the intramuscular preadipocytes group, and 428 peaks within 401 circRNAs in the mature adipocytes group. Compared with the intramuscular preadipocytes group, 75 peaks within 75 circRNAs were significantly different in the mature adipocytes group. Furthermore, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of intramuscular preadipocytes and mature adipocytes showed that the differentially m6A-modified circRNAs were enriched in the PKG signaling pathway, endocrine and other factor-regulated calcium reabsorption, lysine degradation, etc. m6A-circRNA-miRNA-mRNA interaction networks predicted the potential m6A-circRNA regulation mechanism in different goat adipocytes. Our results indicate that there is a complicated regulatory relationship between the 12 upregulated and 7 downregulated m6A-circRNAs through 14 and 11 miRNA mediated pathways, respectively. In addition, co-analysis revealed a positive association between m6A abundance and levels of circRNA expression, such as expression levels of circRNA_0873 and circRNA_1161, which showed that m6A may play a vital role in modulating circRNA expression during goat adipocyte differentiation. These results would provide novel information for elucidating the biological functions and regulatory characteristics of m6A-circRNAs in intramuscular adipocyte differentiation and could be helpful for further molecular breeding to improve meat quality in goats.

Experiment-based Computational Model Predicts that IL-6 Trans-Signaling Plays a Dominant Role in IL-6 mediated signaling in Endothelial Cells.

Inflammatory cytokine mediated responses are important in the development of many diseases that are associated with angiogenesis. Targeting angiogenesis as a prominent strategy has shown limited effects in many contexts such as peripheral arterial disease (PAD) and cancer. One potential reason for the unsuccessful outcome is the mutual dependent role between inflammation and angiogenesis. Inflammation-based therapies primarily target inflammatory cytokines such as interleukin-6 (IL-6) in T cells, macrophages, cancer cells, muscle cells, and there is a limited understanding of how these cytokines act on endothelial cells. Thus, we focus on one of the major inflammatory cytokines, IL-6, mediated intracellular signaling in endothelial cells by developing a detailed computational model. Our model quantitatively characterized the effects of IL-6 classic and trans-signaling in activating the signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and mitogen-activated protein kinase (MAPK) signaling to phosphorylate STAT3, extracellular regulated kinase (ERK) and Akt, respectively. We applied the trained and validated experiment-based computational model to characterize the dynamics of phosphorylated STAT3 (pSTAT3), Akt (pAkt), and extracellular regulated kinase (pERK) in response to IL-6 classic and/or trans-signaling. The model predicts that IL-6 classic and trans-signaling induced responses are IL-6 and soluble IL-6 receptor (sIL-6R) dose-dependent. Also, IL-6 trans-signaling induces stronger downstream signaling and plays a dominant role in the overall effects from IL-6. In addition, both IL-6 and sIL-6R levels regulate signaling strength. Moreover, our model identifies the influential species and kinetic parameters that specifically modulate the pSTAT3, pAkt, and pERK responses, which represent potential targets for inflammatory cytokine mediated signaling and angiogenesis-based therapies. Overall, the model predicts the effects of IL-6 classic and/or trans-signaling stimulation quantitatively and provides a framework for analyzing and integrating experimental data. More broadly, this model can be utilized to identify targets that influence inflammatory cytokine mediated signaling in endothelial cells and to study the effects of angiogenesis- and inflammation-based therapies.