Contribution of FOS in neutrophils to venous thromboembolism via miR-144 based on bioinformatic prediction and validation.

The Finkel-Biskis-Jinkins Osteosarcoma (c-Fos; encoded by FOS) plays an important role in several cardiovascular diseases, including atherosclerosis and stroke. However, the relationship between FOS and venous thromboembolism (VTE) remains unknown. We identified differentially expressed genes in Gene Expression Omnibus dataset, GSE48000, comprising VTE patients and healthy individuals, and analysed them using CIBERSORT and weighted co-expression network analysis (WGCNA). FOS and CD46 expressions were significantly downregulated (FOS p = 2.26E-05, CD64 p = 8.83E-05) and strongly linked to neutrophil activity in VTE. We used GSE19151 and performed PCR to confirm that FOS and CD46 had diagnostic potential for VTE; however, only FOS showed differential expression by PCR and ELISA in whole blood samples. Moreover, we found that hsa-miR-144 which regulates FOS expression was significantly upregulated in VTE. Furthermore, FOS expression was significantly downregulated in neutrophils of VTE patients (p = 0.03). RNA sequencing performed on whole blood samples of VTE patients showed that FOS exerted its effects in VTE via the leptin-mediated adipokine signalling pathway. Our results suggest that FOS and related genes or proteins can outperform traditional clinical markers and may be used as diagnostic biomarkers for VTE.

Modulation of HOXA9 after skeletal muscle denervation and reinnervation.

Homeobox A9 (HOXA9), the expression of which is promoted by mixed lineage leukemia 1 (MLL1) and WD-40 repeat protein 5 (WDR5), is a homeodomain-containing transcription factor that plays an essential role in regulating stem cell activity. HOXA9 has been found to inhibit skeletal muscle regeneration and delay recovery after muscle wounding in aged mice, but little is known about its role in denervated/reinnervated muscles. We performed detailed time-dependent expression analyses of HOXA9 and its promoters, MLL1 and WDR5, in rat gastrocnemius muscles after the following three types of sciatic nerve surgeries: nerve transection (denervation), end-to-end repair (repair), and sham operation (sham). Then, the specific mechanisms of HOXA9 were detected in vitro by transfecting primary satellite cells with empty pIRES2-DsRed2, pIRES2-DsRed2-HOXA9, empty pPLK/GFP-Puro, and pPLK/GFP-Puro-HOXA9 small hairpin RNA (shRNA) plasmids. We found, for the first time, that HOXA9 protein expression simultaneously increased with increasing denervated muscle atrophy severity and that upregulated MLL1 and WDR5 expression was partly associated with denervation. Indeed, in vitro experiments revealed that HOXA9 inhibited myogenic differentiation, affected the best known atrophic signaling pathways, and promoted apoptosis but did not eliminate the differentiation potential of primary satellite cells. HOXA9 may promote denervated muscle atrophy by regulating the activity of satellite cells.

Genetic evidence for a causal link between gut microbiota and arterial embolism and thrombosis: a two-sample Mendelian randomization study.

Background: Previous research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study. Methods: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Results: We identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08-2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42-0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25-3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P<0.05). Conclusion: Our systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.

Enhanced Piezoelectricity of PVDF-TrFE Nanofibers by Intercalating with Electrosprayed BaTiO3.

Over the past few decades, flexible piezoelectric devices have gained increasing interest due to their wide applications as wearable sensors and energy harvesters. Poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE), as one of piezoelectric polymers, has caught considerable attention because of its high flexibility, high thermal stability, and biocompatibility. However, its relatively lower piezoelectricity limits its broader applications. Herein, we present a new approach to improving the piezoelectricity of PVDF-TrFE nanofibers by integrating barium titanate (BTO) nanoparticles. Instead of being directly dispersed into PVDF-TrFE nanofibers, the BTO nanoparticles were electrosprayed between the nanofiber layers to create a sandwich structure. The results showed that the sample with BTO sandwiched between PVDF-TrFE nanofibers showed a much higher piezoelectric output compared to the sample with BTO uniformly dispersed in the nanofibers, with a maximum of ∼ 457% enhancement. Simulation results suggested that the enhanced piezoelectricity is due to the larger strain induced in the BTO nanoparticles in the sandwich structure. Additionally, BTO might be better poled during electrospraying with higher field strength, which is also believed to contribute to enhanced piezoelectricity. The potential of the piezoelectric nanofiber mats as a sensor for measuring biting force and as a sensor array for pressure mapping was demonstrated.

Surface Functionalization of Electrodes and Synthesis of Dual-Phase Solid Electrolytes for Structural Supercapacitors.

The interface between structural electrodes and solid electrolytes plays a key role in the electrical-mechanical properties of energy storage structures. Herein, we present a surface functionalization method to improve the ion conduction efficiency at the interface between a structural electrode and a solid electrolyte that consists of a bi-continuous network of epoxy and ionic liquid (IL). Composite supercapacitors made with this electrolyte and carbon fiber (CF) electrodes coated with manganese dioxide (MnO2) demonstrate that treating the electrodes with the silane can increase the areal capacitance by 300% without degrading the tensile strength. The dual-phase electrolyte containing 40 wt % IL and 60 wt % epoxy exhibits the highest multifunctional performance, measured by the product of stiffness and ionic conductivity. The outstanding mechanical and energy storage properties demonstrate that the silane treatment of MnO2-coated CF fabric structural electrodes is a promising method for future high-performance structural composite supercapacitors.

Microwave-assisted solvothermal synthesis of hierarchical TiO2 microspheres for efficient electro-field-assisted-photocatalytic removal of tributyltin in tannery wastewater.

Organotin compounds have been widely used in recent decades, however, the residential tributyltin (TBT) in environment has potential harmful effects on human health due to the disruption of endocrine system even at trace level. Herein, this work reports on an effective electro-field-assisted-photocatalytic technique for removal of TBT by applying an electric field to photocatalysis of as-prepared hierarchical TiO2 microspheres. The synthesis of catalytic materials is based on a self-assembly process induced by microwave-assisted solvothermal reaction. Hierarchical TiO2 microspheres consisting of nanowires can be obtained in short time with this facile method and possess high surface area and superior optical properties. As the catalyst, it was found that the reaction rate constant of electro-field-assisted-photocatalytic removal (0.0488 min-1) of TBT exhibited almost a 9 fold improvement as compared to that of photocatalysis (0.0052 min-1). The proposed mechanism of electro-field-assisted-photocatalytic removal of TBT was verified by using 117Sn-enriched TBT spike solution as an isotopic tracer. In addition, varying impacts from some key reaction conditions, such as voltage of potential, pH value and the presence of Cr and formaldehyde were also discussed. The overall satisfactory TBT removal performance of the proposed electro-field-assisted-photocatalysis procedure with hierarchical TiO2 microspheres, which was validated using actual tannery wastewater samples from three different kinds of tanning procedures. These attributes suggest that this electro-field-assisted-photocatalysis may have broad applications for the treatment of tannery wastewater.

miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy.

Denervation often results in skeletal muscle atrophy. Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy. At the epigenetic level, miRNAs are thought to be highly involved in the pathophysiological progress of denervated muscles. We used miRNA microarrays to determine miRNA expression profiles from a typical slow muscle (soleus muscle) and a typical fast muscle (tibialis anterior muscle) at an early denervation stage in a rat model. Results showed that miR-206, miR-195, miR-23a, and miR-30e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles. Additionally, certain miRNA molecules (miR-214, miR-221, miR-222, miR-152, miR-320, and Let-7e) could be key regulatory factors in the denervated atrophy process involved in fast muscle. Analysis of signaling pathway networks revealed the miRNA molecules that were responsible for regulating certain signaling pathways, which were the final targets (e.g., p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/mTOR pathway regulates atrogin-1 and MuRF1 expression via FoxO phosphorylation). Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.

Biomimetic composite scaffolds based mineralization of hydroxyapatite on electrospun calcium-containing poly(vinyl alcohol) nanofibers.

Nanocomposite materials consisting of polymer matrix and inorganic salts in the form of nanocrystals of hydroxyapatite (HA) are regarded as superior candidates for bone treatment. A biomimetic nanocomposite scaffold with HA formation on the electrospun poly(vinyl alcohol) (PVA) nanofibrous structure by employing a Ca-P alternate soaking method was developed in this work. The calcium-containing PVA nanofibers were prepared by adding calcium nitrate to the starting solution prior to electrospinning, and then mineralized by Ca-P treatment in incubation solution. With this rapid and effective procedure, a continuous biomimetic crystalline HA layer could be formed successfully without the need of a prior chemical modification of the substrate surface under very mild reaction conditions. Moreover, the HA formed with a relatively accelerated growth had a carbonated and poor crystalline structure, resembling biological apatite in the bone mineral. The introduction of calcium ions in nanofibers by electrospinning was a favorable approach to induce the deposition of calcium phosphate and improve the distribution, nucleation, and growth of crystalline HA layer on nanofibrous scaffolds. Bioactivity tests revealed that these mineralized PVA/HA composite scaffolds improved the biocompatibility. The porous polymer/HA composite scaffolds produced in the present study might have potential applications in bone tissue engineering.