Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) Promotes the Adipogenesis of Intramuscular Preadipocytes through PI3K/AKT Pathway in Goats.

As a transcription factor, Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) binds to downstream target genes to participate in cell proliferation and cell differentiation. We found that the NR4A1 reached the highest expression at 60 h after the differentiation of goat intramuscular preadipocytes. Overexpression of goat NR4A1 increased the number of intracellular lipid droplets and up-regulated the expression of adipocyte-differentiation-related marker genes including AP2, SREBP1, ACC, GPAM, and DGAT2, while the relative expression levels of Pref-1 and HSL were significantly decreased. On the contrary, after NR4A1 was knocked down by siRNA, the number of intracellular lipid droplets and the relative expression levels of LPL, CEBPα, CEBPß, ACC, and DGAT2 were significantly decreased, and the relative expression levels of Pref-1 and HSL were significantly up-regulated. These results suggest that NR4A1 promotes the differentiation of goat intramuscular preadipocytes. Transcriptome sequencing was carried out after overexpression of goat NR4A1, and the KEGG enrichment analysis result showed that the most differentially expressed genes were related to adipocyte differentiation and were enriched in the PI3K-Akt signaling pathway. LY249002, an inhibitor of the PI3K-Akt signaling pathway, was introduced and decreased the number of intracellular lipid droplets, and the relative expression levels of C/EBPα, SREBP1, AP2, C/EBPß, GPAM, ACC, DGAT1, DGAT2, and ATGL were decreased accordingly. The above results indicate that overexpression of goat NR4A1 may promote the differentiation of intramuscular preadipocytes through the PI3K-Akt signaling pathway.

Targeting SEZ6L2 in Colon Cancer: Efficacy of Bexarotene and Implications for Survival.

BACKGROUND: Bexarotene, also recognized as Targretin, is categorized as a retinoid, a type of cancer drug. Nevertheless, the precise mechanisms of bexarotene in relation to colon cancer remain unclear. In colon cancer, SEZ6L2 was suggested as one of the biomarkers and targets. This study presents a comprehensive exploration of the role of SEZ6L2 in colon cancer. METHODS: We utilized both TCGA data and a cohort of Chinese patients. In a meticulous analysis of 478 colon cancer cases, SEZ6L2 expression levels were examined in relation to clinical characteristics, staging parameters, and treatment outcomes. Additionally, we investigated the pharmacological impact of bexarotene on SEZ6L2, demonstrating a significant downregulation of SEZ6L2 at both mRNA and protein levels in colon cancer patients following bexarotene treatment. RESULTS: SEZ6L2 consistently overexpresses in colon cancer, serving as a potential universal biomarker with prognostic significance, validated in a diverse Chinese cohort. In vitro, SEZ6L2 promotes cell viability without affecting migration. Bexarotene treatment inhibits SEZ6L2 expression, correlating with reduced viability both in vitro and in vivo. SEZ6L2 overexpression accelerates declining survival rates in an in vivo context. Bexarotene's efficacy is context-dependent, effective in parental cells but not with SEZ6L2 overexpression. Computational predictions suggest a direct SEZ6L2-bexarotene interaction, warranting further experimental exploration. CONCLUSION: The study provides valuable insights into SEZ6L2 as a prognostic biomarker in colon cancer, revealing its intricate relationship with clinical parameters, treatment outcomes, and bexarotene effects. Context-dependent therapeutic responses emphasize the nuanced understanding required for SEZ6L2's role in colon cancer, paving the way for targeted therapeutic strategies.

GT-LSTM: A spatio-temporal ensemble network for traffic flow prediction.

Traffic flow prediction plays an instrumental role in modern intelligent transportation systems. Numerous existing studies utilize inter-embedded fusion routes to extract the intrinsic patterns of traffic flow with a single temporal learning approach, which relies heavily on constructing graphs and has low training efficiency. Different from existing studies, this paper proposes a spatio-temporal ensemble network that aims to leverage the strengths of different sequential capturing approaches to obtain the intrinsic dependencies of traffic flow. Specifically, we propose a novel model named graph temporal convolutional long short-term memory network (GT-LSTM), which mainly consists of features splicing and patterns capturing. In features splicing, the spatial dependencies of traffic flow are captured by employing self-adaptive graph convolutional network (GCN), and a non-inter-embedded approach is designed to integrate the spatial and temporal states. Further, the aggregated spatio-temporal states are fed into patterns capturing, which can effectively exploit the advantages of temporal convolutional network (TCN) and bidirectional long short-term memory network (Bi-LSTM) to extract the intrinsic patterns of traffic flow. Extensive experiments conducted on four real-world datasets demonstrate that the proposed network obtains excellent performance in both forecasting accuracy and training efficiency.

The Morphological Evaluation of the Cervical Muscle in Patients With Basilar Invagination: A Magnetic Resonance Imaging-Based Study.

OBJECTIVE: To investigate the characteristics of functional muscle and muscle size in patients with basilar invagination (BI) and explore the effects of atlantoaxial dislocation. METHODS: Eighty BI patients (BI group) and 80 age- and sex-matched asymptomatic people (control group) were included. Axial T2 magnetic resonance imaging image was used to measure the cross-sectional area (CSA) and functional CSA (FCSA). The sternocleidomastoid (SCM), longus capitis and longus colli (LCap & LC), trapezius (Trap), splenius capitis (SpCap), splenius cervicis (SpC), semispinalis capitis (SSCap), semispinalis cervicis (SSC), multifidus (MS), levator scapulae (LS) and posterior deep layer muscles (PDLM) were evaluated. Correlations between age, atlantodental interval (ADI), Chamberlain distance and muscles were observed. RESULTS: BI group (39.4 ± 18.4 years; 33 males/47 females) exhibited significantly lower FCSA/CSA ratios than the control group in all extensor and flexor muscles, and presented smaller CSAs on the right and left Trap, SSC, LS, SCM, and left LCap & LC. FCSA/CSA ratios were significantly lower in BI patients with dislocation on the right Trap, SpCap, SpC, SSCap, MS, LS, LCap & LC, and PDLM, and the left SSCap, MS, and LCap & LC than in patients without deformity. Additionally, functional muscles of all parameters decreased with age in BI patients. Excluding children, the Trap, SpC, MS, and LS muscle sizes of BI patients tended to increase with age. ADI and Chamberlain distance tended to correlate negatively with FCSA/CSA ratio. CONCLUSION: The BI patients, especially those with atlantoaxial dislocation, had less functional muscles compared with the control group. Moreover, their functional muscles decreased with age more obviously.

Feasibility of C2 Pedicle Screw Fixation with the "in-out-in" Technique for Patients with Basilar Invagination.

STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate the feasibility of C2 pedicle screw (C2PS) fixation with the "in-out-in" technique in patients with basilar invagination (BI). SUMMARY OF BACKGROUND DATA: The "in-out-in" technique is a fixation technique in which the screw enters the vertebrae through the parapedicle. The technique has been used in upper cervical spine fixation. However, anatomic parameters associated with the application of this technique in patients with BI are unclear. METHODS: We measured the C2 pedicle width (PW), the distance between vertebral artery (VA) and the transverse foramen (VATF), the safe zone and the limit zone. The lateral safe zone is the distance from the medial/lateral cortex of the C2 pedicle to the VA (LPVA/MPVA), and the medial safe zone is the distance from the medial/lateral cortex of the C2 pedicle to the dura (MPD/LPD). The lateral limit zone is the sum of LPVA/MPVA and VATF (LPTF/MPTF), and the medial limit zone is the distance from the medial/lateral cortex of the C2 pedicle to the spinal cord (MPSC/LPSC). PW, LPVA, MPVA and VATF were measured on the reconstructed CT angiography. PW, MPD, LPD, MPSC and LPSC were measured on MRI. We define a width greater than 4 mm as safe for screw. The t-test was used to compare the parameters between male and female, left and right sides in all patients, and PW in CTA and MRI data in the same patient. For intrarater reliabilities, interclass correlation coefficients were calculated. RESULTS: A total of 154 patients (49 CTA, 143 MRI) were included. The average PW, LPVA, MPVA, LPTF, MPTF, MPD, LPD, MPSC and LPSC were 5.30 mm, 1.28 mm, 6.60 mm, 2.45 mm, 8.94 mm, 2.09 mm, 7.07 mm, 5.51 mm and 10.48 mm, respectively. Furthermore, in patients with PW ˂4 mm, 53.6% of MPVA, 86.2% of LPTF, and all limit zones were larger than 4 mm. CONCLUSIONS: In patients with basilar invagination, there is sufficient space medially and laterally to the C2 pedicle for partial screw encroachment to achieve "in-out-in" fixation, even if the pedicle is small. LEVEL OF EVIDENCE: 4.

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.

Goat miR-92a-3p Targets APOL6 Gene to Regulate the Differentiation of Intramuscular Precursor Adipocytes.

The quality of lamb meat is positively correlated with intramuscular fat content. In recent years, a large number of studies have shown that miRNAs play an important role in the proliferation and differentiation of adipocytes. In this study, we aimed to explore the effect of miR-92a-3p on the differentiation of goat intramuscular preadipocytes. The results showed that the expression level of miR-92a-3p was low in the early stage of differentiation, reached the highest level on the third day of differentiation, and then decreased. And miR-92a-3p can inhibit the accumulation of lipid droplets and down-regulate the determinants of adipogenic differentiation. Mechanistically, by predicting target genes, we found that miR-92a-3p affects the differentiation of goat intramuscular preadipocytes and the accumulation of lipid droplets by regulating the expression of goat gene APOL6. This study provides important new information to better understand the relationship between miRNAs and the differentiation of goat intramuscular preadipocytes, thus providing a new reference for goat intramuscular adipogenesis.

Successfully treated recalcitrant atopic eczema with acupoint autohemotherapy: A case report and hypothesized mechanism of the therapy.

Acupoint autohemotherapy at bilateral Zusanli (ST36) and Xuehai (SP10) was used to treat a 26-year-old female patient who had suffered from recalcitrant atopic eczema (AE) for five years. The treatment was applied at a frequency of once per week for the first month, followed by a three-month period of once every other week. At the end of treatment, the patient's AE symptoms were entirely resolved, and by the end of a six-month follow-up her immunoglobulin E level had returned to the normal range. Further, there was no relapse of AE symptoms during the six-month follow-up. Therefore, we hypothesized that after the repeated treatments the local inflammatory reaction induced by autologous blood injection triggered a local immune response, followed by a systemic immune response after the repeated treatment, finally leading to the anti-inflammation and immunomodulation effects. This case suggests that acupoint autohemotherapy could be used as an effective complementary treatment for recalcitrant AE, especially in cases where other treatments have failed. Further comparative studies are needed to corroborate the value and mechanisms of this therapy.

The Caprini thrombosis risk model predicts the risk of peripherally inserted central catheter-related upper extremity venous thrombosis in patients with cancer.

BACKGROUND: A peripherally inserted central catheter (PICC) is often necessary for patients receiving chemotherapy, but there is a risk of PICC-related venous thrombosis (VT). We sought to use the Caprini thrombosis risk model and color Doppler flow imaging for the dynamic monitoring of an eventual thrombosis in patients receiving chemotherapy. METHODS: This prospective study was carried out from January 2018 to May 2019 in patients who underwent PICC implantation and maintenance at the First Affiliated Hospital of Fujian Medical University. The outcome event was the occurrence of PICC-related upper extremity venous thrombosis confirmed by color Doppler flow imaging. RESULTS: A total of 201 participants were enrolled, of whom 108 (53.7%) developed VT. Three participants (1.5%) developed symptomatic VT. Univariable logistic regression analysis suggested that the Caprini score (odds ratio [OR], 1.243; 95% confidence interval [CI], 1.074-1.438; P = .003), the PICC model (OR, 0.448; 95% CI, 0.223-0.901; P = .024), and a previous history of PICC-related deep vein thrombosis (OR, 9.388; 95% CI, 1.178-74.786; P = .034) were associated with PICC-related upper extremity VT. Multivariable logistic regression analysis showed that only the Caprini score (OR, 1.188; 95% CI, 1.018-1.386; P = .029) was an independent risk factor for PICC-related venous thrombus. A receiver operating characteristic curve analysis showed the Caprini risk assessment model had a predictive value for upper extremity VT, with an area under the curve of 0.615 (95% CI, 0.538-0.693), 74.1% sensitivity, and 44.1% specificity. CONCLUSIONS: The Caprini score is an independent predictor of the development of PICC-related VT in patients with cancer. However, the moderate sensitivity and low specificity of the Caprini risk assessment model may limit its predictive value in the clinical setting.

Poly(Dopamine) Coating on 3D-Printed Poly-Lactic-Co-Glycolic Acid/ß-Tricalcium Phosphate Scaffolds for Bone Tissue Engineering.

Bone defects caused by osteoporosis, bone malignant tumors, and trauma are very common, but there are many limiting factors in the clinical treatment of them. Bone tissue engineering is the most promising treatment and is considered to be the main strategy for bone defect repair. We prepared polydopamine-coated poly-(lactic-co-glycolic acid)/ß-tricalcium phosphate composite scaffolds via 3D printing, and a series of characterization and biocompatibility tests were carried out. The results show that the mechanical properties and pore-related parameters of the composite scaffolds are not affected by the coatings, and the hydrophilicities of the surface are obviously improved. Scanning electron microscopy and micro-computed tomography display the nanoscale microporous structure of the bio-materials. Biological tests demonstrate that this modified surface can promote cell adhesion and proliferation and improve osteogenesis through the increase of polydopamine (PDA) concentrations. Mouse cranial defect experiments are conducted to further verify the conclusion that scaffolds with a higher content of PDA coatings have a better effect on the formation of new bones. In the study, the objective of repairing critical-sized defects is achieved by simply adding PDA as coatings to obtain positive results, which can suggest that this modification method with PDA has great potential.

siRNAs Derived from Cymbidium Mosaic Virus and Odontoglossum Ringspot Virus Down-modulated the Expression Levels of Endogenous Genes in Phalaenopsis equestris.

Interplay between Cymbidium mosaic virus (CymMV)/Odontoglossum ringspot virus (ORSV) and its host plant Phalaenopsis equestris remain largely unknown, which led to deficiency of effective measures to control disease of P. equestris caused by infecting viruses. In this study, for the first time, we characterized viral small interfering RNAs (vsiRNAs) profiles in P. equestris co-infected with CymMV and ORSV through small RNA sequencing technology. CymMV and ORSV small interfering RNAs (siRNAs) demonstrated several general and specific/new characteristics. vsiRNAs, with A/U bias at the first nucleotide, were predominantly 21-nt long and they were derived predominantly (90%) from viral positive-strand RNA. 21-nt siRNA duplexes with 0-nt overhangs were the most abundant 21-nt duplexes, followed by 2-nt overhangs and then 1-nt overhangs 21-nt duplexes in infected P. equestris. Continuous but heterogeneous distribution and secondary structures prediction implied that vsiRNAs originate predominantly by direct Dicer-like enzymes cleavage of imperfect duplexes in the most folded regions of the positive strand of both viruses RNA molecular. Furthermore, we totally predicted 54 target genes by vsiRNAs with psRNATarget server, including disease/stress response-related genes, RNA interference core components, cytoskeleton-related genes, photosynthesis or energy supply related genes. Gene Ontology classification showed that a majority of the predicted targets were related to cellular components and cellular processes and performed a certain function. All target genes were down-regulated with different degree by vsiRNAs as shown by real-time reverse transcription polymerase chain reaction. Taken together, CymMV and ORSV siRNAs played important roles in interplay with P. equestris by down modulating the expression levels of endogenous genes in host plant.

Peripheral Blood miR-181-5p Serves as a Marker for Screening Patients with Osteoarthritis by Targeting TNFα.

BACKGROUND: Increasing evidence has suggested the important role of miRNAs in the progression of osteoarthritis (OA). In the current study, we explored the role of miR-181-5p in the peripheral blood and bone tissues of OA patients for the first time. METHODS: The level of miR-181-5p was evaluated in the peripheral blood and cartilage of OA patients using real time PCR analysis. ROC analysis was performed to explore whether peripheral blood and cartilage miR-181-5p could screen OA patients from normal controls. Western blot assay and dual luciferase reporter assay were carried out to validate the possible target gene of miR-181-5p in SW1353 cells. RESULTS: For the first time, we confirmed that the expression of miR-181-5p was significantly reduced in the peripheral blood and cartilage of OA patients, suggesting that miR-181-5p may be involved in the process of cartilage injury in OA degradation. Furthermore, ROC analysis showed that both peripheral blood and cartilage miR181-5p could screen OA patients from healthy controls. Moreover, we found that overexpression of miR-181-5p significantly suppressed the expression of TNFα, while inhibition of miR-181-5p enhanced the level of TNFα. Bioinformatic predictions identified a conserved binding site in the 3'UTR of TNFα by miR-181-5p. In addition, dual luciferase reporter assay indicated that miR-181-5p markedly suppressed the relative luciferase activity of TNFα. These data indicated that TNFα was a target gene of miR-181-5p. CONCLUSIONS: In summary, reduced miR-181-5p expression in the peripheral blood and cartilage tissues may serve as a potential biomarker to screen OA patients from healthy controls mainly by targeting TNFα.