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Objective: To understand and analyze the situation of contraceptive use among women seeking abortions in Shanghai. Methods: The computer-assisted anonymous questionnaire was used to collect data among 1 261 women seeking abortions in 4 hospitals in Shanghai from August to October in 2013. Results: Nearly 60% of the respondents were under the age of 29 and 32.6% were unmarried. Over 50% of the respondents reported having abortion experiences before. Compared with those married women, the unmarried women had a higher proportion of unprotected intercourse (48.0% vs. 33.9%) and a lower proportion of contraceptive use failure (38.6% vs. 47.8%). Logistic regression analysis indicated that younger or sexually inactive women tended not to take contraceptive measures among those married respondents, and that those women who were young, unmarried, with a higher income or a history of abortion were more likely to use emergency contraception. Conclusions: Young women with high proportion of repeated abortion constituted the majority of respondents in Shanghai. Two main factors of unwanted pregnancy are the low proportion of contraceptive use and the high proportion of failure use of contraceptives. It is important to strengthen the post-abortion care services and the contraceptive education, especially to teach them how to use contraceptives, because those induced abortion women were lack of contraceptive precaution or knowledge. [ABSTRACT FROM AUTHOR]

Objective: To explore heterosexual and homosexual behaviors, and influencing factors, in those unmarried out-of-school young people aged 15 to 24 years, so as to provide the basis on the education and service of sexual and reproductive health for those young people. Methods: The questionnaire survey form was anonymously filled out by 1 113 unmarried out-of-school young people on six target spots in urban and rural areas of six provinces by the computer assisted self-interview (CASI) system. Results: The incidences of hetero-or homo- sexual behaviors in the 15 to 18 years male group and the 19 to 24 years male group were significantly higher than those in female groups (P < 0.05). 7.14% of the first heterosexual behaviors in the 15 to 18 years female group were forced. Sexual safety precautions were used in 66.67% of males and 40.00% of females in the 15 to 18 years group, and in 58.82% of males and 49.11% of females in the 19 to 24 years group. About 30.00% of males reported that they had partners' pregnancies, and 30% of females reported that they had pregnancies. The incidence of multiple sexual partners in the 19 to 24 years male group was significantly higher than that in the age-matched female group (P < 0.01). On homosexual behaviors, the average age of the first homosexual behaviors in the 15 to 18 years group was about 14 years, 15.79% of males in the 19 to 24 years group were forced to have, and 46.15% of males and 33.33% females reported that they had more than two sexual partners. Multivariate analyses showed that watching pornographic materials and being older were common risk factors of heterosexual behaviors for males (OR, 3.51 and 3.81 respectively) and females (OR, 6.41 and 3.85 respectively). Compared with those factors approving premarital sexual behaviors, the attitudes rejecting premarital sexual behaviors from respondents themselves (OR = 0.18) and their parents (OR = 0.37), and the neutral attitude from friends (OR =0.47), were protective factors in males, while the options that the female respondents thought it being not good but acceptable (OR =0.14) or opposed (OR = 0.06), and that friends thought it being unacceptable (OR = 0.16) or unknown (OR = 0.21), were protective factors and the neutral attitude from parents was risk factor (OR = 12.56) in females. Conclusions: The incidences of heterosexual and homosexual behaviors, and unsafe sexual behaviors, in those unmarried out-of-school young people were high, which were positively related to the pornographic material and the open attitudes from respondents themselves, parents and friends. [ABSTRACT FROM AUTHOR]

Rice straw hydrolysate produced in rice straw pretreatment, comprising a lot of fermentable sugars, is generally released into the environment. This not only causes environment pollution but also wastes fermentable sugars from rice straw. To alleviate environment impact, maximize ethanol production from rice straw, and reduce the cost of ethanol production, rice straw hydrolysate and NaOH-pretreated rice straw were converted to ethanol using ethanol-type fermentation and simultaneous saccharification and fermentation (SSF) by sludge. Meanwhile, microbial community in sludge was analyzed to find the relationship between ethanol production and microbial community succession during ethanol-type fermentation and SSF. Under the optimal condition of the COD, pH and oxidation–reduction potential (ORP) value of rice straw hydrolysate with 6280.56 mg/L, 6.7, and − 42 mV, ethanol-type fermentation with the sludge of 15 g obtained the highest ethanol concentration (8.34 g/L) and the highest COD removal rate (54.83%). For SSF, the maximum ethanol concentration (3.75 g/L) produced by pretreated rice straw and sludge from ethanol-type fermentation with the sludge of 15 g was higher than that (2.61 g/L) generated by pretreated rice straw and sludge from ethanol-type fermentation with the sludge of 22.5 g. This indicated that sludge from ethanol-type fermentation with the sludge of 15 g more efficiently converted rice straw to ethanol than sludge from ethanol-type fermentation with the sludge of 22.5 g. Microbial community analysis suggested that ethanol production had a negative correlation with the relative abundance changes of Bacteroidetes, when the relative abundance of Firmicutes constantly rose in ethanol-type fermentation and SSF. This study provides a scientific basis for maximizing ethanol production from rice straw by microbial regulation in sludge, which could further reduce the cost of ethanol production. [ABSTRACT FROM AUTHOR]

Background: Osteonecrosis of the femoral head caused by glucocorticoids (GIONFH) is a significant issue resulting from prolonged or excessive clinical glucocorticoid use. Astaxanthin, an orange-red carotenoid present in marine organisms, has been the focus of this study to explore its impact and mechanism on osteoblast apoptosis induced by dexamethasone (Dex) and GIONFH. Methods: In this experiment, bioinformatic prediction, molecular docking and dynamics simulation, cytotoxicity assay, osteogenic differentiation, qRT-PCR analysis, terminal uridine nickend labeling (TUNEL) assay, determination of intracellular ROS, mitochondrial function assay, immunofluorescence, GIONFH rat model construction, micro-computed tomography (micro-CT) scans were performed. Results: Our research demonstrated that a low dose of astaxanthin was non-toxic to healthy osteoblasts and restored the osteogenic function of Dex-treated osteoblasts by reducing oxidative stress, mitochondrial dysfunction, and apoptosis. Furthermore, astaxanthin rescued the dysfunction in poor bone quality, bone metabolism and angiogenesis of GIONFH rats. The mechanism behind this involves astaxanthin counteracting Dex-induced osteogenic damage by activating the Nrf2 pathway. Conclusion: Astaxanthin shields osteoblasts from glucocorticoid-induced oxidative stress and mitochondrial dysfunction via Nrf2 pathway activation, making it a potential therapeutic agent for GIONFH treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Asiatic Acid (AA) has therapeutic potential for glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). • AA prevents GIONFH may related to anti-apoptosis and alleviation of oxidative stress. • AA can inhibit GIONFH by modulating the PI3K/AKT signaling pathway. Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) represents a predominant etiology of non-traumatic osteonecrosis, imposing substantial pain, restricting hip mobility, and diminishing overall quality of life for affected individuals. Centella asiatica (L.) Urb. (CA), an herbal remedy deeply rooted in traditional oriental medicine, has exhibited noteworthy therapeutic efficacy in addressing inflammation and facilitating wound healing. Drawing from CA's historical applications, its anti-inflammatory, anti-apoptotic, and antioxidant attributes may hold promise for managing GIONFH. Asiatic acid (AA), a primary constituent of CA, has been substantiated as a key contributor to its anti-apoptotic, antioxidant, and anti-inflammatory capabilities, showcasing a close association with orthopedic conditions. For the investigation of whether AA could alleviate GIONFH through suppressing oxidative stress, apoptosis, and to delve into its potential cellular and molecular mechanisms, the connection between AA and disease was analyzed through network pharmacology. DEX-induced apoptosis in rat osteoblasts and GIONFH in rat models, got utilized for the verification in vitro/vivo, on underlying mechanism of AA in GIONFH. Network pharmacology analysis reveals a robust correlation between AA and GIONFH in multiple target genes. AA has demonstrated the inhibition of DEX-induced osteoblast apoptosis by modulating apoptotic factors like BAX, BCL-2, Cleaved-caspase3, and cleaved-caspase9. Furthermore, it effectively diminishes the ROS overexpression and regulates oxidative stress through mitochondrial pathway. Mechanistic insights suggest that AA's therapeutic effects involve phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) pathway activation. Additionally, AA has exhibited its potential to ameliorate GIONFH progression in rat models. Our findings revealed that AA mitigated DEX-induced osteoblast apoptosis and oxidative stress through triggering PI3K/AKT pathway. Also, AA can effectively thwart GIONFH occurrence and development in rats. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. Result: This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. Conclusion: This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming. [ABSTRACT FROM AUTHOR]

Osteoporosis, which manifests as reduced bone mass and deteriorated bone quality, is common in the elderly population. It is characterized by persistent elevation of macrophage-associated inflammation and active osteoclast bone resorption. Currently, the roles of intracellular metabolism in regulating these processes remain unclear. In this study, we initially performed bioinformatics analysis and observed a significant increase in the proportion of M1 macrophages in bone marrow with aging. Further metabolomics analysis demonstrated a notable reduction in the expression of carnitine metabolites in aged macrophages, while carnitine was not detected in osteoclasts. During the differentiation process, osteoclasts took up carnitine synthesized by macrophages to regulate their own activity. Mechanistically, carnitine enhanced the function of Nrf2 by inhibiting the Keap1-Nrf2 interaction, reducing the proteasome-dependent ubiquitination and degradation of Nrf2. In silico molecular ligand docking analysis of the interaction between carnitine and Keap1 showed that carnitine binds to Keap1 to stabilize Nrf2 and enhance its function. In this study, we found that the decrease in carnitine levels in aging macrophages causes overactivation of osteoclasts, ultimately leading to osteoporosis. A decrease in serum carnitine levels in patients with osteoporosis was found to have good diagnostic and predictive value. Moreover, supplementation with carnitine was shown to be effective in the treatment of osteoporosis. Carnitine activates Nrf2 in macrophage by inhibiting Keap1-Nrf2 protein-protein interaction (PPI), which further exerts anti-osteoporosis effects. In addition, carnitine serves a diagnostic indicator for osteoporosis. [Display omitted] [ABSTRACT FROM AUTHOR]

A pre-rolling (PR) process with a small pre-strain was applied along the transverse direction (TD) and the extrusion direction (ED) of non-basal and basal textured AZ61 Mg alloys at room temperature to investigate the induced twinning behavior. The microstructural evolution of the alloys was used to evaluate the grain-boundary effect in terms of the texture variation. The results demonstrated that {10 1 ¯ 2} extension twinning was introduced by the PR process and that the volume fraction of twins increased with increasing thickness reduction. The subdivision of grains via twinning induced grain reorientation that generated a prominent basal texture with the c -axis parallel to the normal direction (ND) after PR. The textured Mg alloy with this c -axis//TD feature can promote twinning activity. The twinning performance was critical to initiate plastic deformation, therefore to determine deformation behavior at room temperature. The deformation mechanism was also addressed related to the extension twin lamellae. Image 1 • Pre-rolling was processed to investigate the induced twinning behavior. • The texture with this c -axis//TD feature can promote twinning activity. • Basal texture with the c-axis oriented to the ND processed by PR. • Twins can control basal texture based on volume fraction of twinned region. [ABSTRACT FROM AUTHOR]

In order to study the axial tensile properties of polypropylene fiber reinforced concrete, an axial tensile test device for concrete is developed in this paper. The device is composed of three parts: rigid frame, spherical hinge and puller, and specimen fabrication part. The test device can accurately measure the tensile strength and peak tensile strain of concrete, and perfectly solves the eccentricity problem of concrete specimens under tension. It can measure the post peak segment tensile strain, such that the whole process tensile stress–strain curve can be obtained. The axial tensile test of polypropylene fiber concrete was carried out using the above test device, and the results show that the tensile strength of concrete can be clearly improved by adding polypropylene fiber, which makes the tensile failure of concrete show certain plastic characteristics. The test results show that with the increase in fiber content, the tensile strength of concrete increases first and then decreases. The effects of polypropylene fiber content and curing age on the tensile properties of concrete were studied and the optimum polypropylene fiber content was determined. When the fiber content is 0.9 kg/m3, the tensile strength of concrete reaches the maximum value. The splitting tensile test of concrete under the same condition was carried out simultaneously. The damage phenomenon and test results of the axial tensile test and splitting tensile test of concrete were compared and analyzed, and the applicability of the new developed device in the concrete axial tensile test was verified. [ABSTRACT FROM AUTHOR]

Background: Steroid-induced avascular necrosis of the femoral head (SANFH) is characterized by osteoblast apoptosis, leading to a loss of bone structure and impaired hip joint function. It has been demonstrated that erythropoietin (EPO) performs a number of biological roles. Objective: We examined the effects of EPO on SANFH and its regulation of the STAT1-caspase 3 signaling pathway. Method: In vitro, osteoblasts were treated with dexamethasone (Dex) or EPO. We identified the cytotoxicity of EPO by CCK-8, the protein expression of P-STAT1, cleaved-caspase9, cleaved-caspase3, Bcl-2, BAX, and cytochrome c by Western blotting, and evaluated the apoptosis of osteoblasts by flow cytometry. In vivo, we analyzed the protective effect of EPO against SANFH by hematoxylin and eosin (H&E), Immunohistochemical staining, and Micro-computed tomography (CT). Results: In vitro, EPO had no apparent toxic effect on osteoblasts. In Dex-stimulated cells, EPO therapy lowered the protein expression of BAX, cytochrome c, p-STAT1, cleaved-caspase9, and cleaved-caspase3 while increasing the expression of Bcl-2. EPO can alleviate the apoptosis induced by Dex. In vivo, EPO can lower the percentage of empty bone lacunae in SANFH rats. Conclusion: The present study shows that EPO conferred beneficial effects in rats with SANFH by inhibiting STAT1-caspase 3 signaling, suggesting that EPO may be developed as a treatment for SANFH. [ABSTRACT FROM AUTHOR]

Efficient steam pipe insulation is critical for minimizing heat loss during transportation, ensuring the economic viability of thermal processes or end-user applications. Unlike water-based systems, steam heat loss mechanisms are intricate, predominantly influenced by the transition of steam to condensate which introduces latent heat, thus significantly impacting overall heat loss. This study employs a life-cycle cost approach, integrating a comprehensive steam transport model to evaluate the optimal insulation thickness under varying temperature, flow rates and composite insulation schemes. The steam transport model incorporates a drainage energy loss term, providing a detailed depiction of the energy balance along the steam pipe. Results from the steam transportation simulation conducted on a single long pipe demonstrate a ∼4.6 % deviation between simulated and measured heat loss values. Furthermore, Life cycle cost analysis highlights the economically advantageous insulation configuration, comprising an aerogel blanket as the inner layer and glass wool as the outer layer. With increasing temperature, augmenting the proportion of aerogel blanket yields economic benefit, with the optimum thickness exhibiting a linear growth trend. Conversely, as the flow rate increases, the optimum insulation thickness remains constant. • Utilize the steam transport model to evaluate the heat loss of steam pipes. • The most thermal and economical effective composite insulation scheme of steam pipe. • Illustrate the optimal percentage of aerogel at varying steam temperature. • Present the optimum insulation thickness, energy saving and payback period of differ temperature and flow reate scenarios. [ABSTRACT FROM AUTHOR]

Barium titanate (BaTiO 3 ) powders were synthesized through hydrothermal process with Ba(OH) 2 ·8H 2 O and TiO 2 . By increasing the feedstock concentration (FC) from 0.25 to 1.50 M, BaTiO 3 powders maintain a stable average particle size (~180 nm and ~6.4441 m 2 /g) with an increasing tetragonality ( c/a : 1.0065–1.0075). Johnson-Mehl-Avrami and standard reaction rate equations were adopted to analyze the kinetic process of BaTiO 3 formation. The reaction is governed by first-order and phase-boundary-controlled mechanism for 0.25 M and 1.50 M, respectively. Lower extent of reaction is believed to lead to the better tetragonality for BaTiO 3 powders fabricated with higher FC. On the other hand, the relative stable particle size is correlated with the unvaried nucleation frequency and grain growth rate with various FC. This work can provide a guideline to manipulate the properties of BaTiO 3 powders used in electronic industry. [ABSTRACT FROM AUTHOR]

• Stevioside can suppress IL-1β-induced cartilage metabolic imbalance, inflammation and apoptosis. • Stevioside can delay disease progression in a mice osteoarthritis model. • Stevioside mediates its cellular effect by inhibiting the activation of MAPK and NF-κB signaling pathways. Osteoarthritis (OA) is a joint disease that is characterized by articular cartilage degeneration and destruction. Stevioside (SVS) is a diterpenoid glycoside extracted from Stevia rebaudiana Bertoni with some specific effects against inflammatory and apoptotic, whereas it is still unclear what function SVS has in osteoarthritis. This study focuses on the anti-inflammatory and anti-apoptosis functions of SVS on chondrocytes induced by interleukin (IL)-1beta, and the role of SVS in an osteoarthritis model for mice. We can detect the production of inflammatory factors such as nitric oxide (NO) and prostaglandin E2 (PGE2) using real-time quantitative polymerase chain reaction (RT-qPCR), the Griess reaction, and enzyme linked immunosorbent assay (ELISA). On the basis of Western blot, we have observed the protein expressions of cartilage matrix metabolism, inflammatory factors, and apoptosis of chondrocytes. Simultaneously, the pharmacological effects of SVS in mice were evaluated by hematoxylin and eosin (HE), toluidine blue, Safranin O, and immunohistochemical staining. The results show that SVS slows extracellular matrix degradation and chondrocyte apoptosis. In addition, SVS mediates its cellular effect by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Meanwhile, molecular docking studies revealed that SVS has excellent binding capabilities to p65, extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). The study suggests that SVS can be developed as a potential osteoarthritis treatment. [ABSTRACT FROM AUTHOR]

• This is the first report on the potential therapeutic effect of plantamajoside on osteoarthritis. • In vitro analyses, plantamajoside inhibits NF-κB (nuclear factor kappa-B) and MAPK (mitogen-activated protein kinase) signaling pathways, promoting chondrocyte repair. • In-vivo study demonstrated that plantamajoside could ameliorate progression in the mouse osteoarthritis model. Osteoarthritis (OA) is a common degenerative bone and joint disorder characterized by progressive cartilage degeneration and secondary synovial inflammation. It is a common chronic joint disorder that affects people of all ages (especially the old). Plantamajoside is a phenylpropanoside derived from plantain. It has a variety of biological properties, including antioxidant, anti-malignant cell proliferation, and anti-inflammatory properties. In this study, the latent mechanism of plantamajoside was explored by slowing the in-vivo and in-vitro progression of osteoarthritis. The results revealed that plantamajoside pre-conditioning inhibited IL-1β induced pro-inflammatory factors like COX-2, iNOS, IL-6, and TNF-α. Moreover, plantamajoside also reversed the IL-1 β mediated type II collagen and aggrecan degradation within the extracellular matrix (ECM). The protective effects of plantamajoside have been attributed to the inhibition of both MAPK and NF-κB pathways. Furthermore, our in-vivo research found that plantamajoside could slow the progression of OA in mice. Finally, all findings point to plantamajoside as a potential anti-OA therapeutic candidate. [ABSTRACT FROM AUTHOR]

[Display omitted] Osteoporosis is a metabolic disorder of reduced bone mass, accompanied by the deterioration of the bone microstructure, resulting in increased brittleness and easy fracture. Its pathogenesis can be explained by mainly excessive osteoclast formation or bone resorption hyperfunction. Oxidative stress is intricately linked with bone metabolism, and the maturation and bone resorption of osteoclasts respond to intracellular ROS levels. SIS3 is a small-molecule compound that selectively suppresses Smad3 phosphorylation in the TGF-β/Smad signaling pathway and attenuates the ability to bind to target DNA. Several studies have reported that Smad3 plays a significant role in bone metabolism. However, whether SIS3 can modulate bone metabolism by affecting osteoclastogenesis and the specific molecular mechanisms involved remain unknown. Here, we demonstrated that SIS3 could suppress osteoclastogenesis and ameliorate bone loss in ovariectomized mice. Mechanistically, SIS3 inhibited Smad3 phosphorylation in BMMs, and the deficiency of phosphorylated Smad3 downregulated ROS production and Nox4-dependent expression during osteoclast formation, thereby blocking MAPK phosphorylation and the synthesis of downstream osteoclast marker proteins. Similarly, Nox4 plasmid transfection significantly alleviated osteoclast formation inhibited by SIS3. In addition, we identified the interaction region between Smad3 and Nox4 by ChIP and dual luciferase reporter assays. Collectively, we found that SIS3 could inhibit Smad3 phosphorylation, reduce Nox4-dependent ROS generation induced by RANKL, and prevent osteoclast differentiation and maturation, making it a promising alternative therapy for osteoporosis. [ABSTRACT FROM AUTHOR]

[Display omitted] Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory mediator involved in various pathophysiological and inflammatory states. Accumulating line of evidence suggests a role for MIF in regulating bone metabolism and therefore a prime candidate for therapeutic targeting. In this study, we showed that Chicago sky blue 6B (CSB6B) suppresses RANKL-induced osteoclast and bone resorption in vitro via the inhibition of NF-κB signaling activation and promoting proteasome-mediated degradation of MIF. Consequently, the induction of NFATc1 was impaired resulting in downregulation of NFATc1-responsive osteoclast genes. We also demonstrated that CSB6B treatment enhanced primary calvarial osteoblast differentiation and bone mineralization in vitro via the suppression of NF-κB activation and upregulation of Runx expression. Using two murine models of osteolytic bone disorders, we further showed that administration of CSB6B protected mice against pathological inflammatoryc calvarial bone destruction induced by titanium particles mice as well as estrogen-deficiency induced bone loss as a result of ovariectomy. Together, as an MIF inhibitor, CSB6B can inhibit osteoclast differentiation and bone resorption function and enhance the mineralization of osteoblasts through the inhibition of NF-κB pathway. MIF is a prime target for therapeutic targeting for the treatment of osteolytic bone disorders and the MIF inhibitor CSB6B could be potential anti-osteoporosis drug. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have demonstrated considerable potential in the treatment of ischemic bone diseases, such as glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). However, the clinical application of EVs faces challenges such as low yield, poor bioactivity, and lack of targeting. Herein, we have developed a platform of multiengineered extracellular vesicle mimetics (EVMs) to address these challenges. By stimulating mesenchymal stem cells (MSCs) with multibioactive ions from TS (Trisilicate, a mixture of calcium silicate, magnesium silicate, and strontium silicate), we obtained endogenously modified TS-MSCs. From these, we further prepared a large quantity of bioactive EVM TS-MSCs through a straightforward extrusion method. Moreover, by integrating metabolic glycoengineering with click chemistry strategies, alendronate (ALN) was surface-modified on EVM TS-MSCs to further prepare ALN-EVM TS-MSCs . The engineered ALN-EVM TS-MSCs demonstrated bone-targeting effects, promoting osteogenesis and angiogenesis. This promoting effect is attributed to the rich presence of miR-21 in the TS-modified EVM, which further silences PTEN to activate the PI3K/AKT signaling pathway, thereby enhancing osteogenesis and angiogenesis. Our treatment strategy for ischemic bone diseases is based on a multiengineered, biomaterial-inspired, metabolic glycoengineering, and click chemistry-based platform of EVM. This study also provides an enhanced understanding of the development and application of engineered vesicles in disease treatment.

Background: Osteoarthritis (OA) is a progressive joint condition marked by the slow degradation of articular cartilage. Vinpocetine (Vin), a synthetic derivative of vincamine derived from the vinca plant, exhibits anti-inflammatory and antioxidant properties. Nevertheless, the specific role and mechanism of Vin in the treatment of OA remain largely unexplored., Objectives: The study is designed to uncover the impacts of Vin on tert‑butyl hydroperoxide (TBHP)-induced ferroptosis and to explore its potential role and underlying mechanisms in the treatment of OA. Concurrently, we established an OA mouse model through medial meniscal instability surgery to assess the therapeutic effects of Vin in vivo., Methods: Through network pharmacology analysis, we have identified the key targets and potential pathways of Vin. To simulate an oxidative stress-induced OA environment in vitro, we induced chondrocyte injury using TBHP. We tested how Vin affects chondrocytes under TBHP induction by DHE and DCFH-DA probes, BODIPY-C11 and FerroOrange staining, mitochondrial function assessment, Western blotting, co-immunoprecipitation, and immunofluorescence techniques. Simultaneously, we established an OA mouse model through medial meniscal instability surgery to assess the in vivo therapeutic effects of Vin. In this model, we used X-ray and micro-CT imaging, SO staining, TB staining, H&E staining, and immunohistochemistry to analyze the role of Vin in detail., Results: This study demonstrated that Vin effectively suppressed TBHP-induced ferroptosis and extracellular matrix (ECM) degradation and significantly lessened mitochondrial damage associated with ferroptosis. In the OA mouse model, Vin improved cartilage degeneration, subchondral remodeling, synovitis, and ECM degradation. Vin worked by activating the Nrf2/GPX4 pathway and inhibiting the Keap1-Nrf2 interaction. This study focused on the function of ferroptosis in OA and its influence on chondrocyte damage and disease progression, offering novel perspectives on potential treatments., Conclusion: Vin activated the Nrf2/GPX4 pathway, thereby slowing OA progression, inhibiting ferroptosis, and preventing ECM degradation., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

As a crucial regulator of oxidative homeostasis, seleno-protein glutathione peroxidase 4 (GPX4) represents the primary defense system against ferroptosis, making it a promising target with important clinical application prospects. From the discovery of covalent and allosteric sites in GPX4, substantial advancements in GPX4-targeted small molecules have been made through diverse discovery and design strategies in recent years. Moreover, as an emerging hotspot in drug development, seleno-organic compounds can functionally mimic GPX4 to reduce hydroperoxides. To facilitate the further development of selective ferroptosis mediators as potential pharmaceutical agents, this review comprehensively covers all GPX4-targeted small molecules, including inhibitors, degraders, and activators. In addition, seleno-organic compounds as GPX mimics are also included. We also provide perspectives regarding challenges and future research directions in this field., Competing Interests: Declaration of competing interest All authors declare that they have no competing financial interests or personal relationships that could affect the work reported in the paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Ischemic osteonecrosis, particularly glucocorticoid-induced osteonecrosis of the femoral head (GIONFH), is primarily due to the dysfunction of osteogenesis and angiogenesis. miRNA, as a therapeutic system with immense potential, plays a vital role in the treatment of various diseases. However, due to the unique microenvironmental structure of bone tissue, especially in the case of GIONFH, where there is a deficiency in the vascular system, it is challenging to effectively target and deliver to the ischemic osteonecrosis area. A drug delivery system assisted by genetically engineered cell membranes holds promise in addressing the challenge of targeted miRNA delivery. Herein, we leverage the potential of miR-21 in modulating osteogenesis and angiogenesis to design an innovative biomimetic nanoplatform system. First, we employed metal-organic frameworks (MOFs) as the core structure to load miR-21-m (miR-21-m@MOF). The nanoparticles were further coated with the membrane of bone marrow mesenchymal stem cells overexpressing CXCR4 (CM-miR-21-m@MOF), enhancing their ability to target ischemic bone areas via the CXCR4-SDF1 axis. These biomimetic nanocomposites possess both bone-targeting and ischemia-guiding capabilities, actively targeting GIONFH lesions to release miR-21-m into target cells, thereby silencing PTEN gene and activating the PI3K-AKT signaling pathway to regulate osteogenesis and angiogenesis. This innovative miRNA delivery system provides a promising therapeutic avenue for GIONFH and potentially other related ischemic bone diseases. STATEMENT OF SIGNIFICANCE., Competing Interests: Declaration competing of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)