Sex dimorphism of IL-17-secreting peripheral blood mononuclear cells in ankylosing spondylitis based on bioinformatics analysis and machine learning.

BACKGROUND: Ankylosing spondylitis (AS) with radiographic damage is more prevalent in men than in women. IL-17, which is mainly secreted from peripheral blood mononuclear cells (PBMCs), plays an important role in the development of AS. Its expression is different between male and female. However, it is still unclear whether sex dimorphism of IL-17 contribute to sex differences in AS. METHODS: GSE221786, GSE73754, GSE25101, GSE181364 and GSE205812 datasets were collected from the Gene Expression Omnibus (GEO) database. Differential expressed genes (DEGs) were analyzed with the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods. CIBERSORTx and EcoTyper algorithms were used for immune infiltration analyses. Machine learning based on the XGBoost algorithm model was used to identify the impact of DEGs. The Connectivity Map (CMAP) database was used as a drug discovery tool for exploring potential drugs based on the DEGs. RESULTS: According to immune infiltration analyses, T cells accounted for the largest proportion of IL-17-secreting PBMCs, and KEGG analyses suggested an enhanced activation of mast cells among male AS patients, whereas the expression of TNF was higher in female AS patients. Other signaling pathways, including those involving metastasis-associated 1 family member 3 (MAT3) or proteasome, were found to be more activated in male AS patients. Regarding metabolic patterns, oxidative phosphorylation pathways and lipid oxidation were significantly upregulated in male AS patients. In XGBoost algorithm model, DEGs including METRN and TMC4 played important roles in the disease process. we integrated the CMAP database for systematic analyses of polypharmacology and drug repurposing, which indicated that atorvastatin, famciclocir, ATN-161 and taselisib may be applicable to the treatment of AS. CONCLUSIONS: We analyzed the sex dimorphism of IL-17-secreting PBMCs in AS. The results showed that mast cell activation was stronger in males, while the expression of TNF was higher in females. In addition, through machine learning and the CMAP database, we found that genes such as METRN and TMC4 may promote the development of AS, and drugs such as atorvastatin potentially could be used for AS treatment.

Tenascin-C promotes endochondral ossification and fracture healing through Hedgehog and Hippo signaling.

Fractures are frequent and severe musculoskeletal injuries. This study aimed to investigate the function of tenascin-C (TNC) in regulating chondrogenic during fracture healing and elucidate the underlying molecular mechanisms. A well-established femur fracture model in male C57BL/6J mice was used to transect the middle diaphysis of the femur. To identify the essential role of TNC, shTNC lentiviruses or TNC protein were administered in the animal model. Micro-CT analysis, histologic analysis, immunostaining assays, and gene expression analysis were employed to investigate the effect of TNC during fracture healing. An in vitro mesenchymal stem cell culture system was developed to investigate the role and molecular mechanism of TNC in regulating chondrogenesis. TNC expression was induced at the inflammatory phase and peaked at the cartilaginous callus phase during fracture healing. Knockdown of TNC expression in callus results in decreased callus formation and impaired fracture healing. Conversely, administration of exogenous TNC promoted chondrogenic differentiation, cartilage template formation and ultimately improved fracture healing. Both the Hedgehog and Hippo signaling pathways were found to be involved in the pro-chondrogenic function of TNC. Our observations demonstrate that TNC is a crucial factor responsible for endochondral ossification in fracture healing and provide a potential therapeutic strategy for promoting fracture healing.

A double-layered gastric floating tablet for zero-order controlled release of dihydromyricetin: Design, development, and in vitro/in vivo evaluation.

Dihydromyricetin (DHM) is an important natural flavonoid. However, most of DHM preparations have shown shortcomings such as low drug loading, poor drug stability, and/or large fluctuations in blood concentration. This study aimed to develop a gastric floating tablet with a double-layered structure for zero-order controlled release of DHM (DHM@GF-DLT). The final product DHM@GF-DLT showed a high average cumulative drug release at 24 h that best fit the zero-order model, and had a good floating ability in the stomach of the rabbit with a gastric retention time of over 24 h. The FTIR, DSC, and XRPD analyses indicated the good compatibility among the drug and the excipients in DHM@GF-DLT. The pharmacokinetic study revealed that DHM@GF-DLT could prolong the retention time of DHM, reduce the fluctuation of blood drug concentration, and enhance the bioavailability of DHM. The pharmacodynamic studies demonstrated that DHM@GF-DLT had a potent and long-term therapeutic effect on systemic inflammation in rabbits. Therefore, DHM@GF-DLT had the potential to serve as a promising anti-inflammatory agent and may develop into a once-a-day preparation, which was favorable to maintain a steady blood drug concentration and a long-term drug efficacy. Our research provided a promising development strategy for DHM and other natural products with a similar structure to DHM for improving their bioavailability and therapeutic effect.

Graphene Oxide-Crospolyvinylpyrrolidone Hybrid Microspheres for the Efficient Adsorption of 2,4,6-Trichlorophenol.

Microspheres of the graphene oxide and crospolyvinylpyrrolidone composite (GO-PVPP) were prepared via suspension polymerization and investigated for the adsorption of 2,4,6-trichlorophenol (2,4,6-TCP) from wastewater. The microspheres were thoroughly characterized using scanning electron microscopy, infrared spectroscopy, N2 physisorption, elemental analysis, X-ray diffraction, and thermogravimetric analysis. The GO-PVPP microspheres comprised GO sheets on the surface and demonstrated good thermal stability, good swelling rate, and excellent adsorption capacity of 2,4,6-TCP (up to 466.77 mg/g). The adsorptions were determined as a function of pH, temperature, adsorbent loading, adsorption time, and initial content of 2,4,6-TCP in the solutions. The sorption kinetics was satisfactorily modeled using the pseudo-second-order rate equation, and the sorption equilibrium can be described using the Freundlich model. The 2,4,6-TCP adsorption by GO-PVPP was shown to be endothermic and spontaneous. The reusability of GO-PVPP was also demonstrated by the adsorption and desorption cycles.

Ultrasound aided photochemical synthesis of Ag loaded TiO2 nanotube arrays to enhance photocatalytic activity.

This work presents a novel approach for preparing TiO(2) nanotube array photocatalyst loaded with highly dispersed Ag nanoparticles through an ultrasound aided photochemical route. The Ag content loaded on the array was controlled by changing the concentration of AgNO(3) solution. The Ag-TiO(2) nanotube arrays were characterized by SEM, XRD, XPS and UV-vis absorption. The effects of Ag content on the photoelectrochemical (PEC) property and photocatalytic activity of TiO(2) nanotube array electrode were studied. The results showed that Ag loading significantly enhanced the photocurrent and photocatalytic degradation rate of TiO(2) nanotube array under UV-light irradiation. The photocurrent and photocatalytic degradation rate of Ag-TiO(2) nanotube array prepared in 0.006 M AgNO(3) solution were about 1.2 and 3.7 times as that of pure TiO(2) nanotube array, respectively.

Toward the light field display: autostereoscopic rendering via a cluster of projectors.

Ultimately, a display device should be capable of reproducing the visual effects observed in reality. In this paper we introduce an autostereoscopic display that uses a scalable array of digital light projectors and a projection screen augmented with microlenses to simulate a light field for a given three-dimensional scene. Physical objects emit or reflect light in all directions to create a light field that can be approximated by the light field display. The display can simultaneously provide many viewers from different viewpoints a stereoscopic effect without head tracking or special viewing glasses. This work focuses on two important technical problems related to the light field display; calibration and rendering. We present a solution to automatically calibrate the light field display using a camera and introduce two efficient algorithms to render the special multi-view images by exploiting their spatial coherence. The effectiveness of our approach is demonstrated with a four-projector prototype that can display dynamic imagery with full parallax.