Study on the Preparation and Process Parameter-Mechanical Property Relationships of Carbon Fiber Fabric Reinforced Poly(Ether Ether Ketone) Thermoplastic Composites.

Carbon fiber fabric-reinforced poly(ether ether ketone) (CFF-PEEK) composites exhibit exceptional mechanical properties, and their flexibility and conformability make them a promising alternative to traditional prepregs. However, the formation of the CFF-PEEK composite is trapped in the high viscosity of PEEK, the smooth surface, and tightly interwoven bundles of CFF. It is more difficult for the resin to flow through the fibers of complex textile structures. Here, a simple film stacking method using the hot-pressing process of plain-woven CFF-PEEK thermoplastic composites is discussed. The uniform distribution of PEEK resin between each layer of CFF reduces the flow distance during the molding process, preventing defects in the composite material effectively. Four process parameters, including molding temperature (370, 385, 400, and 415 °C), molding pressure (1, 2, 4, 8, and 10 MPa), molding time (10, 20, 30, 40, 60, and 90 min), and pre-compaction process, are considered. Interlaminar shear strength (ILSS), tensile strength, and flexural strength of CFF/PEEK composites are evaluated to optimize the process parameters. Moreover, ultrasonic scanning microscopy and scanning electron microscopy are employed to observe the formation quality and microscopic failure modes of CFF/PEEK composites, respectively. The ultimate process parameters are a molding temperature of 410 °C, molding pressure of 10 MPa, molding time of 60 min, and the need for the pre-compaction process. Under the best process parameters, the ILSS is 62.5 MPa, the flexural strength is 754.4 MPa, and the tensile strength is 796.1 MPa. This work provides valuable insight for studying the process parameters of fiber fabric-reinforced thermoplastic polymer composites and revealing their impact on mechanical properties.

Discovery and validation of molecular patterns and immune characteristics in the peripheral blood of ischemic stroke patients.

Background: Stroke is a disease with high morbidity, disability, and mortality. Immune factors play a crucial role in the occurrence of ischemic stroke (IS), but their exact mechanism is not clear. This study aims to identify possible immunological mechanisms by recognizing immune-related biomarkers and evaluating the infiltration pattern of immune cells. Methods: We downloaded datasets of IS patients from GEO, applied R language to discover differentially expressed genes, and elucidated their biological functions using GO, KEGG analysis, and GSEA analysis. The hub genes were then obtained using two machine learning algorithms (least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE)) and the immune cell infiltration pattern was revealed by CIBERSORT. Gene-drug target networks and mRNA-miRNA-lncRNA regulatory networks were constructed using Cytoscape. Finally, we used RT-qPCR to validate the hub genes and applied logistic regression methods to build diagnostic models validated with ROC curves. Results: We screened 188 differentially expressed genes whose functional analysis was enriched to multiple immune-related pathways. Six hub genes (ANTXR2, BAZ2B, C5AR1, PDK4, PPIH, and STK3) were identified using LASSO and SVM-RFE. ANTXR2, BAZ2B, C5AR1, PDK4, and STK3 were positively correlated with neutrophils and gamma delta T cells, and negatively correlated with T follicular helper cells and CD8, while PPIH showed the exact opposite trend. Immune infiltration indicated increased activity of monocytes, macrophages M0, neutrophils, and mast cells, and decreased infiltration of T follicular helper cells and CD8 in the IS group. The ceRNA network consisted of 306 miRNA-mRNA interacting pairs and 285 miRNA-lncRNA interacting pairs. RT-qPCR results indicated that the expression levels of BAZ2B, C5AR1, PDK4, and STK3 were significantly increased in patients with IS. Finally, we developed a diagnostic model based on these four genes. The AUC value of the model was verified to be 0.999 in the training set and 0.940 in the validation set. Conclusion: Our research explored the immune-related gene expression modules and provided a specific basis for further study of immunomodulatory therapy of IS.

Silencing circATXN1 in Aging Nucleus Pulposus Cell Alleviates Intervertebral Disc Degeneration via Correcting Progerin Mislocalization.

Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications in intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that a novel circATXN1 highly accumulates in aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, and inhibits mitochondrial respiration. Mechanistically, circATXN1, regulated by heterogeneous nuclear ribonucleoprotein A2B1-mediated splicing circularization, promotes progerin translocation from the cell nucleus to the cytoplasm and inhibits the expression of insulin-like growth factor 1 receptor (IGF-1R). To demonstrate the therapeutic potential of circATXN1, siRNA targeting the backsplice junction of circATNX1 was screened and delivered by tetrahedral framework nucleic acids (tFNAs) due to their unique compositional and tetrahedral structural features. Our siRNA delivery system demonstrates superior abilities to transfect aging cells, clear intracellular ROS, and enhanced biological safety. Using siRNA-tFNAs to silence circATXN1, aging NPCs exhibit reduced mislocalization of progerin in the cytoplasm and up-regulation of IGF-1R, thereby demonstrating a rejuvenated cellular phenotype and improved mitochondrial function. In vivo, administering an aging cell-adapted siRNA nucleic acid framework delivery system to progerin pathologically expressed premature aging mice (zmpste24-/-) can ameliorate the cellular matrix in the nucleus pulposus tissue, effectively delaying IVDD. This study not only identified circATXN1 functioning as a cell senescence promoter in IVDD for the first time, but also successfully demonstrated its therapeutic potential via a tFNA-based siRNA delivery strategy.

Dedicator of Cytokinesis 2 (DOCK2) Silencing Protects Against Cerebral Ischemia/Reperfusion by Modulating Microglia Polarization via the Activation of the STAT6 Signaling Pathway.

Cerebral ischemia/reperfusion is the major pathophysiological process in stroke and could lead to severe and permanent disability. The current study aimed to investigate the effects of dedicator of cytokinesis 2 (DOCK2) on cerebral ischemia/reperfusion-induced cerebral injury. We established a mouse middle cerebral artery occlusion (MCAO) model with suture-occluded method in vivo. Then, BV-2 cells were conducted to oxygen-glucose deprivation and re-oxygenation (OGD/R) in vitro. The results showed that DOCK2 was highly expressed in ischemic brain following MCAO and in BV-2 cells induced by OGD/R. DOCK2 depletion protected against MCAO-induced brain infarcts and neuron degeneration. DOCK2 downregulation improved long-term neurological function, which was assessed by the Morris water-maze test. Moreover, silencing of DOCK2 promoted M2 polarization (anti-inflammation) and repressed M1 polarization (pro-inflammation) of microglia both in vivo and in vitro. Subsequently, we found that the loss of DOCK2 upregulated the expression of p-STAT6. DOCK2 knockdown-induced microglial cell polarization towards M2 phenotype was partly abrogated by the STAT6 inhibitor AS1517499. In conclusion, DOCK2 downregulation protected against cerebral ischemia/reperfusion by modulating microglia polarization via the activation of the STAT6 signaling pathway.

Association between exposure to air pollutants and the risk of inflammatory bowel diseases visits.

The topic of inflammatory bowel disease (IBD) has attracted more and more attention. Accumulating evidence suggests that exposure to air pollutants is associated with IBD, yet the results are inconsistent and study about daily exposure is few. This study evaluated the association between daily air pollution and IBD in Hefei, China. Daily IBD admission data were obtained from two hospitals in Hefei from January 1, 2019, to December 31, 2019. Daily concentrations of major air pollutants were provided by the Hefei Environmental Protection Bureau. Meteorological data were collected from China Meteorological Data Network. Distributed lag nonlinear model (DLNM) considering both the lag effects of exposure factors and nonlinear relationship of exposure-reaction was used to assess the effect of daily air pollutants exposure on IBD admission. During the study period, totally 886 cases of IBD were recruited, including 313 cases of ulcerative colitis (UC) and 573 cases of Crohn's disease (CD). The findings showed PM2.5, O3, and CO exposure significantly increased the risk of IBD. Mean concentrations of PM2.5, O3, and CO in Hefei were 43.85ug/m3, 100.78ug/m3, and 0.76 mg/m3, respectively. Each increase of 10 mg/m3 in PM2.5/O3 and 0.1 mg/m3 in CO increased the risk of IBD. The strongest effects of these three pollutants on IBD were observed in lag2-lag3 (RR = 1.037, 95% CI: 1.005-1.070%), lag3 (RR = 1.020, 95% CI: 1.002-1.038%), and lag2 (RR = 1.036, 95% CI: 1.003-1.071%), respectively. In warm seasons, PM2.5, O3, and CO had a stronger effect increased the risk of IBD, which were observed in lag2 (RR = 1.104, 95% CI: 1.032-1.181%), lag2 and lag5 (RR = 1.023, 95% CI: 1.002-1.044%; RR = 1.036, 95% CI: 1.004-1.069%), and lag2 (RR = 1.071, 95% CI: 1.012-1.133%), respectively. Air pollutant (PM2.5, O3, and CO) exposure could increase the risk of IBD, while the most susceptibility seasons for the exposure were mainly in warm seasons. The results of this study suggest that air pollutants increase the risk of IBD patients in Hefei, China, providing a basis for developing countries to improve effective prevention of IBD, and a potential opportunity to avoid part of the risk of the onset or recurrence of IBD. This study contributes to the knowledge of the association between air pollution and IBD, but the associations need to be verified by further studies.

Rational design of ultra-small photoluminescent copper nano-dots loaded PLGA micro-vessels for targeted co-delivery of natural piperine molecules for the treatment for epilepsy.

In recent days, reported researches demonstrated that encapsulation of natural hydrophobic drug molecules (Piperine) into the biodegradable polymer system with nanoformulations opens a novel prospect in bio-nanomedicine field. Generally, the nanostructured materials embedded with the drug molecules could render enhanced efficiency in therapies. Piperine is a chief alkaloid compound of natural black pepper exhibits excellent anti-convulsant efficiency in the anti-epileptic treatment. Nonetheless, the poor water solubility of the piperine molecules has some difficulties in drug delivery and clinical applications. Herein we report the synthesis of Copper oxide quantum dots coated Hyaluronic acid (HA)/ Poly(lactic-co-glycolic acid) (PLGA) with for the effective delivery of piperine in the targeted drug delivery for epilepsy treatment. The physicochemical characterization was performed using the as prepared material. The crystal structure, surface morphology and the elemental composition were investigated from XRD, SEM, TEM and EDX analyses respectively. The surface morphology clearly stated the loading of CuO QDs loaded HA/PLGA microspheres. The capping of the polymer matrix was also studied using FTIR analysis. A Photoluminescence spectrum is also recorded. This study was illustrating that Piperine loaded CuQDs@HA/PLGA nanostructures exhibit improved neuroprotection and encourage the activation of astrocytes in chemical kindling model of epilepsy. This proposed material could be a novel and effective therapeutic platform for the targeted drug delivery systems.