Reduced APPL1 impairs osteogenic differentiation of mesenchymal stem cells by facilitating MGP expression to disrupt the BMP2 pathway in osteoporosis.

An imbalance of human mesenchymal stem cells (MSCs) adipogenic and osteogenic differentiation plays an important role in the pathogenesis of osteoporosis. Our previous study verified that Adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1)/myoferlin deficiency promotes adipogenic differentiation of MSCs by blocking autophagic flux in osteoporosis. However, the function of APPL1 in the osteogenic differentiation of MSCs remains unclear. This study aimed to investigate the role of APPL1 in the osteogenic differentiation of MSCs in osteoporosis and the underlying regulatory mechanism. In this study, we demonstrated the downregulation of APPL1 expression in patients with osteoporosis and osteoporosis mice. The severity of clinical osteoporosis was negatively correlated with the expression of APPL1 in bone marrow MSCs. We found that APPL1 positively regulates the osteogenic differentiation of MSCs in vitro and in vivo. Moreover, RNA sequencing showed that the expression of MGP, an osteocalcin/matrix Gla family member, was significantly upregulated after APPL1 knockdown. Mechanistically, our study showed that reduced APPL1 impaired the osteogenic differentiation of mesenchymal stem cells by facilitating Matrix Gla protein expression to disrupt the BMP2 pathway in osteoporosis. We also evaluated the significance of APPL1 in promoting osteogenesis in a mouse model of osteoporosis. These results suggest that APPL1 may be an important target for the diagnosis and treatment of osteoporosis.

Advancing Adsorption and Separation with Modified SBA-15: A Comprehensive Review and Future Perspectives.

Mesoporous silica SBA-15 has emerged as a promising adsorbent and separation material due to its unique structural and physicochemical properties. To further enhance its performance, various surface modification strategies, including metal oxide and noble metal incorporation for improved catalytic activity and stability, organic functionalization with amino and thiol groups for enhanced adsorption capacity and selectivity, and inorganic-organic composite modification for synergistic effects, have been extensively explored. This review provides a comprehensive overview of the recent advances in the surface modification of SBA-15 for adsorption and separation applications. The synthesis methods, structural properties, and advantages of SBA-15 are discussed, followed by a detailed analysis of the different modification strategies and their structure-performance relationships. The adsorption and separation performance of functionalized SBA-15 materials in the removal of organic pollutants, heavy metal ions, gases, and biomolecules, as well as in chromatographic and solid-liquid separation, is critically evaluated. Despite the significant progress, challenges and opportunities for future research are identified, including the development of low-cost and sustainable synthesis routes, rational design of SBA-15-based materials with tailored properties, and integration into practical applications. This review aims to guide future research efforts in developing advanced SBA-15-based materials for sustainable environmental and industrial applications, with an emphasis on green and scalable modification strategies.

Water Leaching Kinetics of Boron from the Alkali-Activated Ludwigite Ore.

The primary aim of this study was to investigate the boron leaching process from alkali-activated ludwigite ore. Initially, the ore underwent activation through roasting at 1050 °C for 60 min with 20% sodium carbonate. Subsequently, the study examined the influence of leaching parameters, including temperature, time, liquid-to-solid ratio, and particle size, using the activated ore as the raw material. Additionally, water leaching characteristics of the residues and boron kinetics were analyzed. The results demonstrated that boron leaching efficiency reached 93.71% from the reduced ludwigite ore under specific conditions: leaching temperature of 180 °C, leaching time of 6 h, liquid-to-solid ratio of 8:1, and feed particle size of 52.31 µm (average particle size). Leach residue characteristics indicated the dissolution of minerals during the process. The boron behavior during water leaching followed the Avrami Equation, and the kinetics equation was derived by fitting the leaching data. Moreover, the activation energy (Ea) value for boron leaching was determined to be 8.812 kJ·mol-1 using the Arrhenius Equation, indicating that the leaching process is controlled by diffusion.

Impairment of APPL1/Myoferlin facilitates adipogenic differentiation of mesenchymal stem cells by blocking autophagy flux in osteoporosis.

An imbalance of human mesenchymal stem cells (hMSCs) adipogenic and osteogenic differentiation is crucial in the pathogenesis of osteoporosis, and elucidation of the underlying mechanism is urgently needed. APPL1, an adaptor protein of the adiponectin receptor, was recently shown to be closely related to bone mass. However, the role of APPL1 in the imbalance of hMSC differentiation in osteoporosis is unclear. Therefore, we aimed to explore the mechanisms by which APPL1 alters hMSCs adipogenic differentiation in osteoporosis. Here, we found that APPL1 expression was downregulated in elderly patients with osteoporosis and in mouse osteoporosis model. APPL1 negatively regulated hMSC adipogenic differentiation in vivo and in vitro. Mechanistically, by enhancing ubiquitination-mediated Myoferlin degradation, downregulated APPL1 expression increased the risk of lysosome dysfunction during hMSCs adipogenic differentiation. Lysosomal dysfunction inhibited autophagy flux by suppressing autophagosome degradation and promoted hMSC differentiation towards the adipocyte lineage. Our findings suggest that APPL1/Myoferlin downregulation promoted hMSCs adipogenic differentiation by inhibiting autophagy flux, further impairing the balance of hMSCs adipogenic and osteogenic differentiation in osteoporosis; the APPL1/ Myoferlin axis may be a promising diagnostic and therapeutic target for osteoporosis.

Preparation of chitosan mesoporous membrane/halloysite composite for efficiently selective adsorption of Al(III) from rare earth ions solution through constructing pore structure on substrate.

The removal of impurity Al(III) from rare earth ion solution by selective adsorption method was one of the challenging tasks. Herein, calcination and acid dissolution treatment were used to construct the pore structure for the halloysite substrate (Hal-650-H) and provide conditions for the formation of the chitosan mesoporous membrane to prepare composite (Hal-H-2CS). The selective adsorption properties and mechanism of the Hal-H-2CS for Al(III) in the rare earth ion solution were studied. The results showed that the formation of mesoporous structures for chitosan provided abundant sites for the adsorption of Al(III). Hal-H-2CS showed remarkable selective adsorption properties for Al(III) in a wide pH range and the binary mixtures with high content of Al(III) or La(III). The maximum adsorption capacity of Al(III) was 106 mg/g, while the adsorption capacity of La(III) was only 1.41 mg/g at pH 4.0. In addition, the Hal-H-2CS exhibited excellent regeneration and structural stability. The remarkable selective properties of Hal-H-2CS was achieved by the synergistic effect between chitosan mesoporous membrane and Hal-650-H, the main adsorption sites were the OH, NH2, CONH2 of chitosan and the oxygen sites of the Hal-650-H. This work provides a new strategy for the design and preparation of outstanding selective adsorbent for Al(III).

Ion-imprinted chitosan prepared without cross-linking agent for efficient selective adsorption of Al(III) from rare earth solution.

In the aqueous phase, ion-imprinted materials exhibit excellent selective adsorption properties for specific ions, but their complicated preparation process and large amount of crosslinker consumption limit their application. In this study, ion-imprinted chitosan (IIP-CS) was prepared by a simple one-step hydrothermal method without a cross-linking agent for the efficient adsorption of trace amounts of Al(III) from a rare earth solution. The structures and morphology of IIP-CS were analyzed by FT-IR, SEM, and XRD. The Al(III) adsorption characteristics of IIP-CS were investigated under various preparation processes and adsorption conditions. It was found that the optimum mass ratio of IIP-CS is 3 : 1 and pH is 3 and the adsorption capacity reaches up to 40.36 mg g-1. In addition, three different isothermal models-Temkin, Freundlich, and Langmuir-were used to analyze the equilibrium adsorption of IIP-CS in aqueous solution. The results obtained are consistent with the Langmuir model. The adsorption process of Al(III) on IIP-CS follows a pseudo-secondary kinetic model, suggesting that electron sharing or exchange between IIP-CS and Al(III) is a key factor affecting its adsorption rate. IIP-CS shows high selectivity coefficients for Al(III) in mixtures of La(III), Y(III), and Gd(III), which are 792.50, 163.26, and 55.16, respectively. The mechanism of action is the formation of a complex via amidation between Al(III) and IIP-CS. IIP-CS is an adsorbent with excellent regeneration and selective adsorption performance in aqueous solution.

Value of different preoperative bone evaluation methods in predicting intraoperative screw insertion torque-a prospective clinical comparative trial.

BACKGROUND CONTEXT: Establishing good screw-bone structural stability is conducive to reducing the risk of postoperative screw loosening. Screw insertion torque is an objective index for evaluating screw-bone structural stability. Therefore, accurate prediction of screw insertion torque can improve the preoperative evaluation of patients, optimize the surgical plan, and improve the surgical effect. At present, the correlation between different bone assessment methods and screw insertion torque is unclear. PURPOSE: The aim of this study was to evaluate the correlation between different bone assessment methods and screw insertion torque and to optimize the predictive performance of screw insertion torque through mathematical modeling combined with different radiology methods. DESIGN: Prospective cross-sectional study. PATIENT SAMPLES: 77 patients with preoperatively available DXA, CT and MRI data who underwent spinal fixation surgeries between October 2022 and September 2023 and 357 sets of screw data were included in this analysis. OUTCOME MEASURES: Spinal, vertebrae-specific and screw trajectory's BMD were measured preoperatively by different imaging modalities. Intraoperative screw insertion torque was measured using an electronic torque wrench. METHODS: Pearson linear correlation, scatter plots and univariate linear regression were used to evaluate the correlation between different bone evaluation methods and screw insertion torque. Different bone evaluation methods were fitted into the prediction model of screw torque and the related equations were obtained. RESULTS: Screw insertion torque had the strongest positive correlation with the volumetric bone mineral density (vBMD) of the screw trajectory (Pedicle screw insertion torque (PSIT): R = 0.618, p<.001; Terminal screw insertion torque (TSIT): R = 0.735, p<.001). A weak negative correlation was found between the screw insertion torque and level specific vertebral bone quality (VBQ) (PSIT: R = -0.178, p=.001; TSIT: R = -0.147, p=.006). We also found that the PSIT was strongly correlated with the TSIT (R = 0.812, p<.001). CONCLUSIONS: Compared to other bone quality assessment methods, screw trajectory vBMD may be better predict the magnitude of screw insertion torque. In addition, we further optimized preoperative assessments by constructing a mathematical model to better predict screw insertion torque. In conclusion, clinicians should select appropriate preoperative bone quality assessment methods, identify potential low-torque patients, optimize surgical plans, and ultimately improve screw insertion accuracy and reduce postoperative screw loosening rate.

USP7 promotes the osteoclast differentiation of CD14+ human peripheral blood monocytes in osteoporosis via HMGB1 deubiquitination.

Background: Abnormal osteoclast and osteoblast differentiation is an essential pathological process in osteoporosis. As an important deubiquitinase enzyme, ubiquitin-specific peptidase 7 (USP7) participates in various disease processes through posttranslational modification. However, the mechanism by which USP7 regulates osteoporosis remains unknown. Herein, we aimed to investigate whether USP7 regulates abnormal osteoclast differentiation in osteoporosis. Methods: The gene expression profiles of blood monocytes were preprocessed to analyze the differential expression of USP genes. CD14+ peripheral blood mononuclear cells (PBMCs) were isolated from whole blood collected from osteoporosis patients (OPs) and healthy donors (HDs), and the expression pattern of USP7 during the differentiation of CD14+ PBMCs into osteoclasts was detected by western blotting. The role of USP7 in the osteoclast differentiation of PBMCs treated with USP7 siRNA or exogenous rUSP7 was further investigated by the F-actin assay, TRAP staining and western blotting. Moreover, the interaction between high-mobility group protein 1 (HMGB1) and USP7 was investigated by coimmunoprecipitation, and the regulation of the USP7-HMGB1 axis in osteoclast differentiation was further verified. Osteoporosis in ovariectomized (OVX) mice was then studied using the USP7-specific inhibitor P5091 to identify the role of USP7 in osteoporosis. Results: The bioinformatic analyses and CD14+ PBMCs from osteoporosis patients confirmed that the upregulation of USP7 was associated with osteoporosis. USP7 positively regulates the osteoclast differentiation of CD14+ PBMCs in vitro. Mechanistically, USP7 promoted osteoclast formation by binding to and deubiquitination of HMGB1. In vivo, P5091 effectively attenuates bone loss in OVX mice. Conclusion: We demonstrate that USP7 promotes the differentiation of CD14+ PBMCs into osteoclasts via HMGB1 deubiquitination and that inhibition of USP7 effectively attenuates bone loss in osteoporosis in vivo.The translational potential of this article:The study reveals novel insights into the role of USP7 in the progression of osteoporosis and provides a new therapeutic target for the treatment of osteoporosis.

Cyclosporin-A reduced the cytotoxicity of propranolol in HUVECs via p38 MAPK signaling.

ABSTRACT: Propranolol (PROP) is a nonselective ß-adrenergic receptor antagonist used to treat hypertension and cardiac arrhythmias. Oral administration of PROP has recently emerged as a new treatment modality for hemangiomas. However, the side effects of PROP at the cellular level have not been adequately described.The present study investigates and highlights the mechanisms of coupling of the drugs cyclosporin-A (CyA) and PROP on cell proliferation and the occurrence of apoptosis. It also relays the antioxidant effect of PROP on human umbilical vein endothelial cells (HUVECs).HUVECs were treated with CyA and PROP. At 24 hours after treatment, the levels of reactive oxygen species (ROS), cell proliferation, and apoptosis were determined using the ROS kit, MTT assay, and Annexin V staining. In addition, the related proteins of phospho-p38 mitogen-activated protein kinase were determined by western blotting. Subsequently, HUVECs pretreated with CyA or PROP were treated with the p38 inhibitor (SB203580). Finally, the ROS level, cell proliferation, and apoptosis were measured again in both active HUVECs and HUVECs, in which the p38 proteins were inhibited.The combination of CyA and PROP reversed the effect of CyA on cell viability, reduced the ROS level and the cell apoptosis induced by PROP. Moreover, inhibition of p38 protein catalase activity immediately stopped the effect of CyA-propranolol in HUVECs.The effect of the CyA-propranolol combination on HUVECs is associated with the p38 pathway changes, which is proven to be a potential chemotherapeutic agent that minimizes the side effects of PROP in hemangioma therapy.

Facile preparation of MoS2@Kaolin composite by one-step hydrothermal method for efficient removal of Pb(II).

MoS2@Kaolin was prepared by facile one-step hydrothermal method for the efficient adsorption of Pb(II) from aqueous solution. XRD, TG, SEM, BET, XPS and FTIR were used to characterize the phase and structure of composite before and after the adsorption of Pb(II). The results showed that MoS2 nanosheets were successfully assembled on kaolinite surface to form MoS2@Kaolin, and the adsorption capacity of the MoS2@Kaolin is 1.74 and 16.95 times than that of single MoS2 and kaolinite, respectively. MoS2@Kaolin composite exhibited a fast adsorption rate for Pb(II) and an excellent adsorption efficiency for Pb(II) in a wide pH range (2-5.5). The adsorption process followed the Langmuir isotherm model and maximum adsorption capacity was 280.39 mg/g. The adsorption kinetics of MoS2@Kaolin composite to Pb(II) fitted well with the pseudo-second-order kinetics models, which showed that the adsorption process was controlled by chemical sorption. MoS2@Kaolin showed excellent regeneration and maintained high selectivity adsorption with co-existence metal ions. The adsorption mechanism was that the Pb(II) reacted with the S atoms on surface of MoS2@Kaolin under oxidation conditions provided by molybdenum disulfide to form the insoluble compound ß-Pb3O2SO4 in aqueous solution. MoS2@Kaolin was an adsorbent for Pb(II) in aqueous solution with excellent adsorption properties and application potential.

Effect of Teriparatide on pain relief, and quality of life in postmenopausal females with osteoporotic vertebral compression fractures, a retrospective cohort study.

BACKGROUND: Osteoporotic vertebral compression fracture (OVCF) is a common disease in elderly population, which could cause serious back pain and has a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to identify the effect of Teriparatide as a conservative treatment on reducing back pain, and improving quality of life for postmenopausal women with osteoporotic vertebral fractures. METHODS: In a 12-month, retrospective study, 112 postmenopausal women with OVCFs were assigned to Teriparatide group (20 µg Teriparatide, subcutaneous, once daily, n=38) or control group (500 mg calcium and 400-800 IU Vitamin D per day, oral administration, n=74) according to patients' choices between January 2016 and October 2018. Patient-reported outcomes scores including the visual analogue score (VAS), Oswestry disability index (ODI), and short form 36 questionnaire (SF-36) were assessed at baseline, the 3rd months, the 6th months and 1 year after treatment. RESULTS: Treatments with Teriparatide or calcium plus vitamin D supplements had significant effect on improvement of patients' back pain as well as HRQoL, with significantly reduced VAS and ODI and increased SF-36 physical component summary (PCS) and mental component summary (MCS) scores. At the endpoint, Teriparatide showed better therapeutic effect, with greater reductions in VAS and ODI and more increases in SF-36 PCS and MCS scores. However, more adverse events (AEs) were found in Teriparatide group, but symptoms were relatively mild and of short duration. CONCLUSIONS: In postmenopausal women with OVCFs, the consequent persistent back pain and impaired HRQoL, treatment with Teriparatide was associated with more profound therapeutic effects and more AEs compared with calcium plus vitamin D supplements.