Chitosan modified with PAP as a promising delivery system for melatonin in the treatment of osteoporosis: targeting the divalent metal transporter 1.

The demands for novel and efficient therapies have gradually increased with the rising concerns of osteoporosis (OP). The most popular method in promoting bone regeneration during osteoporotic conditions consists of loading bioactive materials with different drugs to treat osteoporotic bones by either promoting the process of osteogenesis, or by inhibiting the activity of osteoclasts. By analyzing single cell sequencing results, we found that divalent metal transporter 1 (DMT1) played a role in OP. Based on our previous results, we found that melatonin (MT) suppressed expression of DMT1 induced by high glucose during OP, so we determined the efficacy of MT for the treatment of OP. However, the clinical effects of MT on OP were unsatisfactory. To enhance its biological efficacy, we combined MT with porous gelatin chitosan (chitosan) and the conductive material, PLA-b-AP-b-PLA (PAP), then determined how MT incorporation in chitosan@PAP nanoparticles affected the ability to promote MC3T3-E1 osteogenesis and mineralization, both in vitro and in vivo. The results confirmed the effect of MT on DMT1. We then prepared and characterized composites prepared as nanofibers, and determined the efficacy of MT combined with chitosan-PAP modified hydrogels as a slow-release system in a femur model of osteoporosis mice, with associated properties suitable for bone tissue engineering. The results indicated that MT-loaded chitosan@PAP nanospheres showed favorable osteogenic functions, both in vivo and in vitro, providing a practical solution for bone regeneration for OP patients.

Study on the Inhibition Mechanism of Hydration Expansion of Yunnan Gas Shale using Modified Asphalt.

Drilling fluids play an essential role in shale gas development. It is not possible to scale up the use of water-based drilling fluid in shale gas drilling in Yunnan, China, because conventional inhibitors cannot effectively inhibit the hydration of the illite-rich shale formed. In this study, the inhibition performance of modified asphalt was evaluated using the plugging test, expansion test, shale recovery experiment, and rock compressive strength test. The experimental results show that in a 3% modified asphalt solution, the expansion of shale is reduced by 56.3%, the recovery is as high as 97.8%, water absorption is reduced by 24.3%, and the compression resistance is doubled compared with those in water. Moreover, the modified asphalt can effectively reduce the fluid loss of the drilling fluid. Modified asphalt can form a hydrophobic membrane through a large amount of adsorption on the shale surface, consequently inhibiting shale hydration. Simultaneously, modified asphalt can reduce the entrance of water into the shale through blocking pores, micro-cracks, and cracks and further inhibit the hydration expansion of shale. This demonstrates that modified asphalt will be an ideal choice for drilling shale gas formations in Yunnan through water-based drilling fluids.

Preparation and Performance Evaluation of Ionic Liquid Copolymer Shale Inhibitor for Drilling Fluid Gel System.

An inhibitor that can effectively inhibit shale hydration is necessary for the safe and efficient development of shale gas. In this study, a novel ionic liquid copolymer shale inhibitor (PIL) was prepared by polymerizing the ionic liquid monomers 1-vinyl-3-aminopropylimidazolium bromide, acrylamide, and methacryloyloxyethyl trimethyl ammonium chloride. The chemical structure was characterized using fourier transform infrared spectroscopy (FT-IR) and hydrogen-nuclear magnetic resonance (H-NMR), and the inhibition performance was evaluated using the inhibition of slurrying test, bentonite flocculation test, linear expansion test, and rolling recovery test. The experimental results showed that bentonite had a linear expansion of 27.9% in 1 wt% PIL solution, 18% lower than that in the polyether amine inhibitor. The recovery rate of shale in 1 wt% PIL was 87.4%. The ionic liquid copolymer could work synergistically with the filtrate reducer, reducing filtration loss to 7.2 mL with the addition of 1%. Mechanism analysis showed that PIL adsorbed negatively charged clay particles through cationic groups, which reduced the electrostatic repulsion between particles. Thus, the stability of the bentonite gel systems was destroyed, and the hydration dispersion and expansion of bentonite were inhibited. PIL formed a hydrophobic film on the surface of clay and prevented water from entering into the interlayer of clay. In addition, PIL lowered the surface tension of water, which prevented the water from intruding into the rock under the action of capillary force. These are also the reasons for the superior suppression performance of PIL.

Poly-3-hydroxybutyrate-co-3-hydroxyvalerate(PHBV)-Polyethylene glycol 20k(PEG20k) as a promising delivery system for PT2399 in the treatment of disc degeneration.

Disc degeneration often leads to a highly prevalent symptom known as low back pain. Healthy nucleus pulposus tissue exhibited a hypoxic environment devoid of blood vessels, while degenerated nucleus pulposus experienced hypoxic deterioration and the formation of new blood vessels. In this study, the expression of important genes like HIF-2α was found to vary between normal and degenerated nucleus pulposus cells when compared to the hypoxic surroundings. The aim of this study was to examine how HIF-2α is controlled in nucleus pulposus cells under hypoxic conditions and its role in angiogenic mechanisms. To assess the impact of gradual inhibition of HIF-2α on disc degeneration, we utilized PHBV-based synthetic materials loaded with inhibitors of HIF-2α. Specifically, we employed LPS and PT2399 loaded PHBV-PEG20k (PP20) to intervene with human nucleus pulposus cells. Additionally, we treated APD rat models with PT2399 loaded PP20 to evaluate its effects. The expression levels of target markers in nucleus pulposus cells were detected using PCR, WB, and immunofluorescence. Additionally, the effect of drugs on disc degeneration was identified through HE staining. The findings indicated that HIF-2α, CAIX, PPP1R15A, VEGFA, and EGLN3 could potentially serve as new indicators of disc degeneration. Additionally, HIF-2α might contribute to the progression of disc degeneration through involvement in angiogenesis and the regulation of hypoxia. Furthermore, the utilization of PT2399 loaded PHBV-PEG20k (PP20) could potentially offer a fresh alternative for treating disc degeneration.

GelMA Hydrogel as a Promising Delivery System for Osthole in the Treatment of Rheumatoid Arthritis: Targeting the miR-1224-3p/AGO1 Axis.

Rheumatoid arthritis (RA) is a multifaceted, chronic, progressive autoimmune disease. This study aims to explore the potential benefits of an enhanced drug delivery system utilizing optimized Gelatin Methacryloyl (GelMA) vectors in RA management. We evaluated the levels of miR-1124-3p and AGO1 in RA tissues and cell lines using qPCR, WB, and immunofluorescence. The effects of osthole on inflammatory response and joint morphology were determined by qPCR, H&E staining, and micro-CT. The data showed that miR-1224-3p was downregulated in RA tissues and HUM-iCell-s010RA cells, while the overexpression of miR-1224-3p in HUM-iCell-s010RA cells reduced the expression of IL-6 and IL-1ß. Luciferase assay demonstrated that AGO1 was a direct target gene of miR-1224-3p. Additionally, osthole treatment increased miR-1224-3p levels and decreased AGO1 expression. The release data showed that osthole loaded on GelMA was released at a slower rate than free osthole. Further studies in a mouse model of CIA confirmed that osthole-loaded GelMA was more effective in attenuating osteopenia in RA as well as alleviating autoimmune arthritis. These findings suggest that osthole can regulate the miR-1224-3p/AGO1 axis in RASFs cells and has the potential to be developed as a clinical anti-RA drug. GelMA could provide a new approach to long-term RA treatment.

A Novel Amphoteric Ion-Modified, Styrene-Based Nano-Microsphere and Its Application in Drilling Fluid.

With the gradual depletion of shallow oil and gas, deep oil and gas has become the focus of development. However, deep formations generally face the challenge of high-temperature and high-salinity, and drilling fluid agents are prone to failure, leading to drilling fluid intrusion into the formation that can cause serious drilling accidents such as well bore collapse. For this, a styrene-based nano-microsphere (SSD) modified with amphoteric ions was developed, with a particle size of 228 nm which could resist temperatures up to 200 °C and sodium chloride (NaCl) up to saturation. SSD has significant salt-responsive properties and its aqueous dispersion becomes transparent with increasing salinity. The SSD provided superior plugging performance in solutions containing NaCl, with a core plugging efficiency of 95.2%, and it was significantly better than the anion-modified microspheres. In addition, in drilling fluids under high temperature and high-salinity conditions, the SSD promotes particle gradation of drilling fluids and improves the zeta potential through its own plugging and synergistic effect with clay, which significantly improves the comprehensive performance of drilling fluids, such as stability, rheological performance, and filtration reduction performance. The development of SSD provides a new idea for research of high-temperature and high-salinity-resistant drilling fluid agents.

A novel poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)-PEG-melatonin composite scaffold enhances for inhibiting bone tumor recurrence and enhancing bone regeneration.

Introduction: Postoperative comprehensive treatment has become increasingly important in recent years. This study was to repair tissue defects resulting from the removal of diseased tissue and to eliminate or inhibit the recurrence and metastasis of residual tumors under the condition of reducing the systemic side effects of chemotherapeutic drugs. To address these challenges, multifunctional scaffolds based local drug delivery systems will be a promising solution. Methods: An optimal drug-loaded scaffold material PHBV-mPEG5k (PP5) was prepared, which is biocompatible, hydrophilic and biodegradable. Furthermore, this material showed to promote bone healing, and could be conveniently prepared into porous scaffold by freeze-drying the solution. By means of introducing melatonin (MT) into the porous surfaces, the MT loaded PP5 scaffold with desirable sustained release ability was successfully prepared. The effectiveness of the MT loaded PP5 scaffold in promoting bone repair and anti-tumor properties was evaluated through both in vivo and in vitro experiments. Results and Discussion: The MT loaded PP5 scaffold is able to achieve the desired outcome of bone tissue repair and anti-bone tumor properties. Furthermore, our study demonstrates that the PP5 scaffold was able to enhance the anti-tumor effect of melatonin by improving cellular autophagy, which provided a therapeutic strategy for the comprehensive postoperative treatment of osteosarcoma.

Spin Hall magnetoresistance in Co2FeSi/Pt thin films: dependence on Pt thickness and temperature.

We have investigated the temperature and the Pt layer thickness dependence of the magnetoresistances (MRs) in Co2FeSi/Pt thin films. Based on the field dependent measurements, it can be seen that the spin-current-induced spin Hall magnetoresistance (SMR) plays the dominant role in the MRs in the Co2FeSi/Pt bilayers in the whole temperature range. Meanwhile, a quite small part of anisotropic magnetoresistance (AMR) existed in the MRs. It proved to be originated from magnetic proximity effect (MPE) by measuring the Pt thickness and temperature dependence of the AMR. Moreover, the Co2FeSi layer thickness has much weaker effect on the SMR and AMR compared to the Pt layer thickness. These results indicate that the Co2FeSi/Pt interface is beneficial to be used in the spin-current-induced physical phenomena.