Long-chain acyl-CoA synthetase 1 (ACSL1) plays an important role in fatty acid metabolism and fat deposition. The transcription of the
gene is regulated specifically among cells and physiological ...processes, and transcriptional regulation of
in adipogenesis remains elusive. Here, we characterize transcription factors (TFs) associated with adipogenesis in the porcine
gene. CCAAT-enhancer binding protein (C/EBP)α, a well-known adipogenic marker, was found to enhance the expression of the
gene via binding two tandem motifs in the promoter. Further, we demonstrate that ACSL1 mediates C/EBPα effects on adipogenesis in preadipocytes cultured from subcutaneous fat tissue of pigs via gain- and loss-of-function analyses. The cAMP-response element binding protein, another TF involved in adipogenesis, was also identified in the regulation of
gene expression. Additionally, single nucleotide polymorphisms (SNPs) were screened in the promoter of
among four breeds including the Chinese indigenous Min, and Duroc, Berkshire, and Yorkshire pigs through sequencing of PCR products. Two tightly linked SNPs, -517G>T and -311T>G, were found exclusively in Min pigs. The haplotype mutation decreases promoter activity in PK-15 and ST cells, and in vivo the expression of
, illustrating a possible role in adipogenesis regulated by C/EBPα/ACSL1 axis. Additionally, a total of 24 alternative splicing transcripts were identified, indicating the complexity of alternative splicing in the
gene. The results will contribute to further revealing the regulatory mechanisms of
during adipogenesis and to the characterization of molecular markers for selection of fat deposition in pigs.
The task of fast magnetic resonance (MR) image reconstruction is to reconstruct high-quality MR images from undersampled images. Most of the existing methods are based on U-Net, and these methods ...mainly adopt several simple connections within the network, which we call microscopic design ideas. However, these considerations cannot make full use of the feature information inside the network, which leads to low reconstruction quality. To solve this problem, we rethought the feature utilization method of the encoder and decoder network from a macroscopic point of view and propose a densely macroscopic feature fusion network for fast magnetic resonance image reconstruction. Our network uses three stages to reconstruct high-quality MR images from undersampled images from coarse to fine. We propose an inter-stage feature compensation structure (IFCS) which makes full use of the feature information of different stages and fuses the features of different encoders and decoders. This structure uses a connection method between sub-networks similar to dense form to fuse encoding and decoding features, which is called densely macroscopic feature fusion. A cross network attention block (CNAB) is also proposed to further improve the reconstruction performance. Experiments show that the quality of undersampled MR images is greatly improved, and the detailed information of MR images is enriched to a large extent. Our reconstruction network is lighter than many previous methods, but it achieves better performance. The performance of our method is about 10% higher than that of the original method, and about 3% higher than that of most existing methods. Compared with the nearest optimal algorithms, the performance of our method is improved by about 0.01–0.45%, and our computational complexity is only 1/14 of these algorithms.
The aim of this study was to determine the expression of B7-H3, B7-H4, Foxp3 and IL-2 in cervical cancer tissues, and evaluate the corresponding clinical significance. The expression of B7-H3, B7-H4, ...Foxp3 and IL-2 in 108 cervical cancer specimens was detected using immunohistochemistry, and their relationship with clinicopathologic parameters was determined. B7-H3, B7-H4 and Foxp3 had high levels of expression in cervical cancer cells (72.22, 80.56, and 91.56%, respectively). B7-H3 levels were only significantly associated with tumor size (P=0.013), while B7-H4, Foxp3 and IL-2 levels were significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.023, 0.014 and 0.036, respectively) and tumor size (P=0.045, 0.010 and 0.021, respectively). Their expression levels were not correlated with age, histologic type, differentiation and lymph node metastasis (all P>0.05). Cox regression multivariate analysis confirmed that B7-H3 or B7-H4 overexpression was an independent prognostic factor. In addition, there were significant positive relationships between the expression of B7-H3 and B7-H4 with Foxp3 (P<0.001). In contrast, the expression of B7-H3 and B7-H4 was negatively correlated with IL-2 (P<0.05). B7-H3, B7-H4 and Foxp3 may be useful biomarkers in patients with cervical cancer for predicting treatment.
Although human core body temperature is known to decrease with age, the age dependency of facial temperature and its potential to indicate aging rate or aging-related diseases remains uncertain. ...Here, we collected thermal facial images of 2,811 Han Chinese individuals 20–90 years old, developed the ThermoFace method to automatically process and analyze images, and then generated thermal age and disease prediction models. The ThermoFace deep learning model for thermal facial age has a mean absolute deviation of about 5 years in cross-validation and 5.18 years in an independent cohort. The difference between predicted and chronological age is highly associated with metabolic parameters, sleep time, and gene expression pathways like DNA repair, lipolysis, and ATPase in the blood transcriptome, and it is modifiable by exercise. Consistently, ThermoFace disease predictors forecast metabolic diseases like fatty liver with high accuracy (AUC > 0.80), with predicted disease probability correlated with metabolic parameters.
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•Collected >2,800 thermal facial images and developed ThermoFace aging clock models•ThermoFace is related to metabolic indicators, DNA repair, ATPase, and lipolysis•ThermoFace aging rate increases with metabolic diseases and decreases with adequate sleep•ThermoFace can rapidly assess aging and metabolic diseases and intervention
By collecting and analyzing thermal facial images, Yu et al. find that human facial temperature distribution contains information on aging and metabolic states and has potential for rapid screening of aging and metabolic disorders and for revealing intervention strategies.
Aim
Ankylosing spondylitis (AS) is a chronic, progressive, and inflammatory autoimmune disease of unknown origin that affects the axial skeleton and sacroiliac joints, resulting in pain and loss of ...function. AS is characterized by the overdifferentiation of T helper 17 (Th17) cells, which contribute to the development of the disease. The Hippo signaling pathway is an important regulator of Th17 differentiation, but its role in patients with AS is unclear. We aimed to investigate the role of key molecules of the Hippo signaling pathway in inflammatory Th17 differentiation in patients with AS and to examine their correlation with disease stages.
Methods
We examined the activity of the Hippo pathway in patients with AS and the regulation of Th17 differentiation during AS‐mediated inflammation. Blood samples were collected from 60 patients with AS at various stages and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood by density gradient centrifugation. The Serum Interleukin‐17 (IL‐17) levels in patients with AS and healthy controls were quantified by ELISA. The key molecules of Hippo pathway were assessed by real‐time PCR for their mRNA expression, and protein levels were determined by Western blot analysis.
Results
Elevated serum interleukin‐17 (IL‐17) levels were observed in patients with AS compared with healthy controls. The protein and mRNA levels of retinoic acid receptor‐related orphan receptor γt (RORγt), transcriptional coactivator with a PDZ‐binding motif (TAZ), and key upstream transcription factors in the Hippo signaling pathway were measured. The expression of RORγt and TAZ was increased in the blood of patients with AS, whereas the expression of other Hippo pathway proteins, such as MST1/2 and NDR1/2, was significantly decreased. Increased levels of IL‐17 and TAZ were significantly associated with disease activity. In addition, MST1, MST2, and NDR1 levels were negatively correlated with TAZ, RORγt, and IL‐17 levels.
Conclusion
Our findings suggest that the Hippo pathway plays a significant role in the regulation of Th17 differentiation and disease activity in patients with AS. The upregulation of TAZ and downregulation of key Hippo pathway proteins, such as MST1/2 and NDR1/2, may contribute to AS pathogenesis. These proteins may serve as biomarkers and may lead to the development of novel therapeutic strategies for AS.
Key molecules of the Hippo pathway were measured at both the mRNA and protein levels, using peripheral blood samples from 60 patients with AS at various stages and 30 healthy controls. The expression levels of these key molecules were associated with AS stages, indicating that the Hippo pathway plays a significant role in AS.
Interprofessional education (IPE) facilitates interprofessional collaborative practice (IPCP) to encourage teamwork among dental care professionals and is increasingly becoming a part of training ...programs for dental and dental technology students. However, the focus of previous IPE and IPCP studies has largely been on subjective student and instructor perceptions without including objective assessments of collaborative practice as an outcome measure.
The purposes of this study were to develop the framework for a novel virtual and interprofessional objective structured clinical examination (viOSCE) applicable to dental and dental technology students, to assess the effectiveness of the framework as a tool for measuring the outcomes of IPE, and to promote IPCP among dental and dental technology students.
The framework of the proposed novel viOSCE was developed using the modified Delphi method and then piloted. The lead researcher and a group of experts determined the content and scoring system. Subjective data were collected using the Readiness for Interprofessional Learning Scale and a self-made scale, and objective data were collected using examiner ratings. Data were analyzed using nonparametric tests.
We successfully developed a viOSCE framework applicable to dental and dental technology students. Of 50 students, 32 (64%) participated in the pilot study and completed the questionnaires. On the basis of the Readiness for Interprofessional Learning Scale, the subjective evaluation indicated that teamwork skills were improved, and the only statistically significant difference in participant motivation between the 2 professional groups was in the mutual evaluation scale (P=.004). For the viOSCE evaluation scale, the difference between the professional groups in removable prosthodontics was statistically significant, and a trend for negative correlation between subjective and objective scores was noted, but it was not statistically significant.
The results confirm that viOSCE can be used as an objective evaluation tool to assess the outcomes of IPE and IPCP. This study also revealed an interesting relationship between mutual evaluation and IPCP results, further demonstrating that the IPE and IPCP results urgently need to be supplemented with objective evaluation tools. Therefore, the implementation of viOSCE as part of a large and more complete objective structured clinical examination to test the ability of students to meet undergraduate graduation requirements will be the focus of our future studies.
Meat quality is one of the most important traits in pig production. Long non-coding RNAs (lncRNAs) have been involved in diverse biological processes such as muscle development through regulating ...gene expression. However, studies on lncRNAs lag behind and a comparatively small number of lncRNAs have been identified in pigs. Also, the effects of lncRNAs on meat quality remain to be characterized. Here, we analyzed lncRNAs in longissimus thoracis (LT) and semitendinosus (ST) muscles, being different in meat quality, with RNA-sequencing technology. A total of 500 differentially expressed lncRNAs (DELs) and 2,094 protein-coding genes (DEGs) were identified. Through KEGG analysis on DELs, we first made clear that fat deposition might be the main reason resulting in the differential phenotype of LT and ST, for which cGMP–PKG and VEGF signaling pathways were the most important ones. In total, forty-one key DELs and 50 DEGs involved in the differential fat deposition were then characterized. One of the key genes, cAMP-response element binding protein 1, was selected to confirm its role in porcine adipogenesis with molecular biology methods and found that it promotes the differentiation of porcine preadipocytes, consistent with its higher expression level and intramuscular fat contents in LT than that in ST muscle. Furthermore, through integrated analysis of DELs and DEGs, transcription factors important for differential fat deposition were characterized among which BCL6 has the most target DEGs while MEF2A was targeted by the most DELs. The results provide candidate genes crucial for meat quality, which will contribute to improving meat quality with molecular-breeding strategies.
Accurately and rapidly distinguishing long noncoding RNAs (lncRNAs) from transcripts is prerequisite for exploring their biological functions. In recent years, many computational methods have been ...developed to predict lncRNAs from transcripts, but there is no systematic review on these computational methods. In this review, we introduce databases and features involved in the development of computational prediction models, and subsequently summarize existing state-of-the-art computational methods, including methods based on binary classifiers, deep learning and ensemble learning. However, a user-friendly way of employing existing state-of-the-art computational methods is in demand. Therefore, we develop a Python package ezLncPred, which provides a pragmatic command line implementation to utilize nine state-of-the-art lncRNA prediction methods. Finally, we discuss challenges of lncRNA prediction and future directions.
Summary
Post‐Golgi vesicle trafficking is indispensable for precise movement of proteins to the pellicle, the sub‐pellicle network and apical secretory organelles in Apicomplexa. However, only a ...small number of molecular complexes involved in trafficking, tethering and fusion of vesicles have been identified in Toxoplasma gondii. Consequently, it is unclear how complicated vesicle trafficking is accomplished in this parasite. Sec1/Munc18‐like (SM) proteins are essential components of protein complexes involved in vesicle fusion. Here, we found that depletion of the SM protein TgSec1 using an auxin‐inducible degron‐based conditional knockout strategy led to mislocalization of plasma membrane proteins. By contrast, conditional depletion of the SM protein TgVps45 led to morphological changes, asymmetrical loss of the inner membrane complex and defects in nucleation of sub‐pellicular microtubules, polarization and symmetrical assembly of daughter parasites during repeated endodyogeny. TgVps45 interacts with the SNARE protein TgStx16 and TgVAMP4‐1. Conditional ablation of TgStx16 causes the similar growth defect like TgVps45 deficiency suggested they work together for the vesicle fusion at TGN. These findings indicate that these two SM proteins are crucial for assembly of pellicle and sub‐pellicle network in T. gondii respectively.
TgSec1, a Sec1/Munc18‐like protein, is essential for the plasma membrane protein trafficking in T. gondii.
TgVps45 is required for the vesicle transport of inner membrane proteins and nucleation of sub‐pellicular microtubules during assembly of daughter parasites.
TgStx16 (Qa), a TgSNARE protein, interacted with TgVps45 (SM) and TgVAMP4‐1 (R) and participated in vesicle transport from TGN in T. gondii.
Background: H19 is the first long noncoding RNA (lncRNA) found to be associated with gene imprinting. It is highly expressed in the embryonic stage and may have important regulatory effects on human ...embryonicdevelopment. We investigated the differences between the levels of H19 promoter DNA methylation in the chorionic villi of patients who experienced spontaneous abortion (SA) following in vitro fertilization embryo transfer (IVF-ET) and those of patients with a normal early pregnancy (NEP). We also analyzed the associated DNA methyltransferase (DNMT) activity.Methods: Chorionic villus tissue from patients with SA and NEP were collected. The DNA methylation levels of two CpG islands in the promoter region of the H19 gene in the two groups were detected by bisulfite sequencing, and the mRNA expression of DNMTs was analyzed by real-time polymerase chain reaction.Results: The sample size of each group was 32, and there were no significant differences in baseline data, including age, parity, and body mass index, between the two groups. Among the 7 CpG islands measured, the methylation rates of 3 CpG islands (CpG 1, 6, and 7) were significantly lower in the SA group than in the NEPgroup (P < 0.01). The methylation levels of the other 4 CpG islands were not significantly different between the two groups. There were no differences in the expression of DNMT1 between the two groups (P > 0.05), but DNMT3a and DNMT3b RNA levels were significantly lower in SA group than in the NEP group (P < 0.01).Conclusions: The lower H19 promoter DNA methylation levels found in the chorionic villi of patients with SA patients following IVF-ET may be explained by decreased expression of DNMT3a and DNMT3b.
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