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Background: Osteoarthritis (OA) is the most common degenerative joint disease, with articular cartilage degeneration as primary manifestation. Intra-articular injection of exogenous liposomal adenosine in mice knee has been shown to alleviate OA progression. However, the role of CD73, the rate-limiting enzyme of extracellular adenosine synthesis, in OA is still unknown. Methods: In this work, we explored the expression changes of adenosine-related molecules via bioinformatic analysis. In addition, the expression level of these molecules was detected in OA cartilage. We also conducted a case–control study to investigate the genetic variants of selected SNPs on genes encoded adenosine-related molecules. To further explore the function of CD73 in chondrocytes, we knocked down the expression of CD73 with small interfering RNA and overexpressed CD73 with the use of lentivirus, and detected the expression of markers for anabolism and catabolism in mouse primary chondrocytes with or without IL-1β treatment. We also conducted in vivo experiments to explore the role of CD73 in OA. Results: We found that the expression of CD73 was upregulated in OA, and the variants of SNP rs2229523 (base A to G) on NT5E (the encoding gene of CD73) were significantly higher in OA population, which might cause the amino acid encoded by this SNP change from threonine to alanine. The original helix structure in the adjacent region of amino acid encoded by SNP rs2229523 would be deconstructed after its mutation. Furthermore, we found that CD73 promoting the expression of Col2a1 but suppressing the expression of Mmp13 expression in mouse primary chondrocytes under inflammatory environment. The overexpression of CD73 attenuated bone remodeling and alleviated cartilage degeneration in DMM mice. Moreover, the physical activities were also improved in DMM mice overexpressed CD73 with the use of adeno-associated virus. Conclusions: The variants of SNP rs2229523 (base A to G) on NT5E were significantly higher in OA population, and CD73 could alleviate OA by maintaining anabolism and suppressing catabolism of chondrocytes extracellular matrix. The Translational Potential of this Article: This work showed that CD73 might be one of the biological therapeutic targets of OA, which would provide a reference for future novel treatment strategy of OA.

Osteoarthritis (OA) is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis. The cartilage matrix is mainly composed of collagen, a matrix protein with a hallmark triple-helix structure, which unfolds with collagen degradation on the cartilage surface. A collagen hybridizing peptide (CHP) is a synthetic peptide that binds the denatured collagen triple helix, conferring a potential disease-targeting possibility for early-stage OA. Here, we constructed an albumin nanoparticle (An) conjugated with CHP, loaded with a chondrogenesis-promoting small molecule drug, kartogenin (KGN). The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA. Compared to treatment with KGN alone, CHP-KGN-An robustly attenuated cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation. Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for early-stage OA therapeutics.

In the 21st century, China’s electric vehicle (EV) industry has demonstrated remarkable growth, rapidly catching up with and surpassing other nations in scale and development. Understanding the policy mechanisms behind this rapid ascent is crucial for analyzing the evolution of China’s EV sector and making informed decisions for its future development. This study provides a comprehensive analysis of the evolution of China’s EV policies from 2009 to 2023, with projections through 2027, using a mixed-method approach that incorporates text mining, co-word network analysis, and BERT-based trajectory models to explore the operational logic of various policy frameworks and predict future policy directions. The study findings reveal distinct phases in the evolution of China’s EV policies. Initially, the focus was on building industrial capacity through supply-side measures, laying the foundation for growth. As the industry matured, policies expanded to include demand-side incentives and environmental regulations, reflecting a shift towards a balanced and sustainable approach. Our research shows that early policy decisions significantly influenced later adjustments, highlighting the role of path dependence. By mapping the trajectory of China’s EV policies, this study offers a framework for predicting future trends, providing guidance for Chinese policymakers and offering strategies that would allow other countries to effectively compete with China. Ultimately, this research underscores the importance of adaptive and coordinated policy strategies for fostering sustainable growth in strategic industries, providing valuable lessons for China and beyond.

Abstract In-sensor processing has the potential to reduce the energy consumption and hardware complexity of motion detection and recognition. However, the state-of-the-art all-in-one array integration technologies with simultaneous broadband spectrum image capture (sensory), image memory (storage) and image processing (computation) functions are still insufficient. Here, macroscale (2 × 2 mm2) integration of a rippled-assisted optoelectronic array (18 × 18 pixels) for all-day motion detection and recognition. The rippled-assisted optoelectronic array exhibits remarkable uniformity in the memory window, optically stimulated non-volatile positive and negative photoconductance. Importantly, the array achieves an extensive optical storage dynamic range exceeding 106, and exceptionally high room-temperature mobility up to 406.7 cm2 V−1 s−1, four times higher than the International Roadmap for Device and Systems 2028 target. Additionally, the spectral range of each rippled-assisted optoelectronic processor covers visible to near-infrared (405 nm–940 nm), achieving function of motion detection and recognition.

Background: Osteoarthritis (OA) is the most common age-related musculoskeletal disease. However, there is still a lack of therapy that can modify OA progression due to the complex pathogenic mechanisms. The aim of the study was to explore the role and mechanism of XJB-5-131 inhibiting chondrocytes ferroptosis to alleviate OA progression. Methods: We treated tert-butyl hydroperoxide (TBHP)-induced ferroptosis of mouse primary chondrocytes with XJB-5-131 in vitro. The intracellular ferroptotic hallmarks, cartilage anabolic and catabolic markers, ferroptosis regulatory genes and proteins were detected. Then we established a mouse OA model via destabilization of the medial meniscus (DMM) surgery. The OA mice were treated with intra-articular injection of XJB-5-131 regularly (2 μM, 3 times per week). After 4 and 8 weeks, we performed micro-CT and histological examination to evaluate the protection role of XJB-5-131 in mouse OA subjects. RNA sequencing analysis was performed to unveil the key downstream gene of XJB-5-131 exerting the anti-ferroptotic effect in OA. Results: XJB-5-131 significantly suppressed TBHP-induced increases of ferroptotic hallmarks (ROS, lipid peroxidation, and Fe2+ accumulation), ferroptotic drivers (Ptgs2, Pgd, Tfrc, Atf3, Cdo1), while restored the expression of ferroptotic suppressors (Gpx4, Fth1). XJB-5-131 evidently promoted the expression of cartilage anabolic and decreased the expression of cartilage catabolic markers. Moreover, intra-articular injection of XJB-5-131 significantly inhibited the expression of Cox2 and Mmp13, while promoted the expression of Col2a1, Gpx4 and Fth1 in DMM-induced mouse articular cartilage. Further, we identified Pebp1 as a potential target of XJB-5-131 by RNA sequencing analysis. The anti-ferroptosis and chondroprotective effects of XJB-5-131 were significantly diminished by Locostatin, a specific antagonist of Pebp1. Conclusion: XJB-5-131 significantly protects chondrocytes from ferroptosis in TBHP-induced mouse primary chondrocytes and DMM surgery-induced OA mice model via restoring the expression of Pebp1. XJB-5-131 is a potential therapeutic drug in the management of OA progression.

Since the 21st century, the electric vehicle (EV) industry has become a key driver of global transformation, with increasing emphasis on the study and evaluation of industrial policies across nations. However, traditional frameworks struggle to capture the dynamic interactions between policies at different government levels or effectively analyze large volumes of policy texts. This study adopted a central–local policy interaction perspective, employing the BERT deep semantic learning model and a threshold regression model to investigate the impact of policy differences on industrial development. The findings reveal an inverted U-shaped relationship between central–local policy thematic similarity and EV market penetration, with the optimal similarity shifting as policy volume increases. This suggests the necessity of dynamically allocating central and local policies to balance national consistency with regional flexibility and promote synergy among regions. Recommendations include optimizing multi-level coordination, maintaining a balance between uniformity and specialization, strengthening policy error tolerance mechanisms, and fostering innovation. By integrating text analysis with econometric modeling, this study offers a novel framework aligned with China’s political system, providing insights into central–local policy interactions and serving as a reference for other countries seeking to refine their industrial strategies.

Abstract Background Cartilage defects are common sports injuries without significant treatment. Articular cartilage with inferior regenerative potential resulted in the poor formation of hyaline cartilage in defects. Acellular matrix scaffolds provide a microenvironment and biochemical properties similar to those of native tissues and are widely used for tissue regeneration. Therefore, we aimed to design a novel acellular cartilage matrix scaffold (ACS) for cartilage regeneration and hyaline-like cartilage formation. Methods Four types of cartilage injury models, including full-thickness cartilage defects (6.5 and 8.5 mm in diameter and 2.5 mm in depth) and osteochondral defects (6.5 and 8.5 mm in diameter and 5 mm in depth), were constructed in the trochlear groove of the right femurs of pigs (n = 32, female, 25–40 kg). The pigs were divided into 8 groups (4 in each group) based on post-surgery treatment differences. was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (micro-CT), and histologic and immunohistochemistry tests. Results At 6 months, the ACS-implanted group exhibited better defect filling and a greater number of chondrocyte-like cells in the defect area than the blank groups. MRI and micro-CT imaging evaluations revealed that ACS implantation was an effective treatment for cartilage regeneration. The immunohistochemistry results suggested that more hyaline-like cartilage was generated in the defects of the ACS-implanted group. Conclusions ACS implantation promoted cartilage repair in full-thickness cartilage defects and osteochondral defects with increased hyaline-like cartilage formation at the 6-month follow-up.

Abstract Osteoarthritis (OA) is the most common degenerative joint disease worldwide, with the main pathological manifestation of articular cartilage degeneration. It have been investigated that pharmacological activation of transient receptor potential vanilloid 1 (TRPV1) significantly alleviated cartilage degeneration by abolishing chondrocyte ferroptosis. In this work, in view of the thermal activated feature of TRPV1, Citrate‐stabilized gold nanorods (Cit‐AuNRs) is conjugated to TRPV1 monoclonal antibody (Cit‐AuNRs@Anti‐TRPV1) as a photothermal switch for TRPV1 activation in chondrocytes under near infrared (NIR) irradiation. The conjugation of TRPV1 monoclonal antibody barely affect the morphology and physicochemical properties of Cit‐AuNRs. Under NIR irradiation, Cit‐AuNRs@Anti‐TRPV1 exhibited good biocompatibility and flexible photothermal responsiveness. Intra‐articular injection of Cit‐AuNRs@Anti‐TRPV1 followed by NIR irradiation significantly activated TRPV1 and attenuated cartilage degradation by suppressing chondrocytes ferroptosis. The osteophyte formation and subchondral bone sclerosis are remarkably alleviated by NIR‐inspired Cit‐AuNRs@Anti‐TRPV1. Furthermore, the activation of TRPV1 by Cit‐AuNRs@Anti‐TRPV1 evidently improved physical activities and alleviated pain of destabilization of the medial meniscus (DMM)‐induced OA mice. The study reveals Cit‐AuNRs@Anti‐TRPV1 under NIR irradiation protects chondrocytes from ferroptosis and attenuates OA progression, providing a potential therapeutic strategy for the treatment of OA.

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K–AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.

In this paper, MoS2 nanosheets with an ultrathin structure were fabricated using a solvothermal method and further added into PAO oil, which was further combined with W-DLC coating to constitute a solid–liquid lubricating state. The influences of MoS2 concentration, applied load and counter surfaces on the lubricating of the solid–liquid hybrid lubricating system were explored through a ball-on-disk tribometer. The friction results indicated that the steel/W-DLC and W-DLC/W-DLC tribopairs lubricated with ultrathin MoS2 possessed better friction reduction and wear resistance behaviors in comparison to pure PAO oil. However, compared to the steel/steel couple case, the prepared MoS2 nanosheets exhibited a more efficient lubricating effect for the W-DLC/W-DLC couple. The beneficial boundary lubricating impact of MoS2 nanosheets on self-mated W-DLC coated rubbing surfaces could be attributed to the tribochemical reaction between MoS2 and doping W element in DLC, resulting in a formation of a thin tribofilm at both counterparts. Meanwhile, the extent of graphitization of W-DLC film induced by friction was alleviated because of the lubrication and protection from the formation of MoS2-based tribofilm at both counterparts.

Summary: Background: Osteoarthritis (OA) is the most common degenerative joint disease primarily characterized by cartilage destruction. The aim of this study was to investigate the role, molecular characteristics and potential therapeutic target of chondrocyte ferroptosis in the pathogenesis of OA. Methods: The expression of ferroptotic hallmarks (iron and lipid peroxidation accumulation, glutathione deletion) were analyzed in paired intact and damaged cartilages from OA patients. Single cell RNA sequencing (scRNA-seq) analysis was performed on 17,638 chondrocytes to verify the presence, investigate the molecular signatures and unveil the potential therapeutic target of ferroptotic chondrocyte cluster in human OA cartilages. Destabilization of medial meniscus (DMM)-induced OA model and tert-butyl hydroperoxide (TBHP)-treated primary mouse chondrocytes and human cartilage explants were used to evaluate the protective effect of pharmacologically activated transient receptor potential vanilloid 1 (TRPV1). The downstream molecular mechanisms of TRPV1 was further investigated in glutathione peroxidase 4 (Gpx4) heterozygous genetic deletion mice (Gpx4+/−). Findings: The concentrations of iron and lipid peroxidation and the expression of ferroptotic drivers in the damaged areas of human OA cartilages were significantly higher than those in the intact cartilage. scRNA-seq analysis revealed a chondrocyte cluster characterized by preferentially expressed ferroptotic hallmarks and genes, namely ferroptotic chondrocyte cluster. Comprehensive gene set variation analysis revealed TRPV1 as an anti-ferroptotic target in human OA cartilage. Pharmacological activation of TRPV1 significantly abrogated cartilage degeneration by protecting chondrocytes from ferroptosis. Mechanistically, TRPV1 promoted the expression of GPX4, and its anti-ferroptotic role was largely mitigated in the OA model of Gpx4+/− mice. Interpretation: TRPV1 activation protects chondrocytes from ferroptosis and ameliorates OA progression by upregulating GPX4. Funding: National Key R&D Program of China (2018YFC1105904), Key Program of NSFC (81730067), National Science Foundation of China (81772335, 81941009, 81802196), Natural Science Foundation of Jiangsu Province, China (BK20180127), Jiangsu Provincial Key Medical Talent Foundation, Six Talent Peaks Project of Jiangsu Province (WSW-079).

Mammalian hindlimb development involves a variety of cells and the regulation of spatiotemporal molecular events, but regulatory networks of transcription factors contributing to hindlimb morphogenesis are not well understood. Here, we identified transcription factor networks during mouse hindlimb morphology establishment through transcriptome analysis. We used four stages of embryonic hindlimb transcription profiles acquired from the Gene Expression Omnibus database (GSE30138), including E10.5, E11.5, E12.5 and E13.5, to construct a gene network using Weighted Gene Co-expression Network Analysis (WGCNA), and defined seven stage-associated modules. After filtering 7625 hub genes, we further prioritized 555 transcription factors with AnimalTFDB3.0. Gene ontology enrichment showed that transcription factors of different modules were enriched in muscle tissue development, connective tissue development, embryonic organ development, skeletal system morphogenesis, pattern specification process and urogenital system development separately. Six regulatory networks were constructed with key transcription factors, which contribute to the development of different tissues. Knockdown of four transcription factors from regulatory networks, including Sox9, Twist1, Snai2 and Klf4, showed that the expression of limb-development-related genes was also inhibited, which indicated the crucial role of transcription factor networks in hindlimb development.

Inorganic salts are important factors in the growth and secondary metabolites production of microorganisms. This study investigated the influences of divalent metal cations, Mn2+, Zn2+, and Mg2+ on the cell growth and Monacolin K production in Monascus M1. Then the concentration of the three kinds of divalent metal cations was optimized by response surface methodology, and the optimum conditions for the highest production of Monacolin K were determined. The optimum concentrations of the three divalent metal ions were selected as follow: Mn2+ 0.33%, Zn2+ 0.16%, and Mg2+ 1%. In this condition the concentration of Monacolin K reached 9.57mg/g which was close to the predicted values, indicating that the model was adequate for the Monacolin K production. The yield of Monacolin K in Monascus can be increased by adding metal ions during industrial production.

Osteoarthritis (OA) is a low-level inflammatory disease in which synovial macrophage M1 polarization exacerbates the progression of synovitis and OA. Notedly, the ROS (reactive oxygen species) level in macrophages is intimately implicated in macrophage M1 polarization. TRPV4 (transient receptor potential channel subfamily V member 4), as an ion channel, plays a pivotal role in oxidative stress and inflammation. In this study, we investigated the role of TRPV4 in OA progression and M1 macrophage polarization. Male adult Sprague–Dawley (SD) rats underwent a medial meniscus radial transection operation to create an OA model in vivo and RAW 264.7 cells were intervened with 100 ng/mL LPS (lipopolysaccharide) to induce M1-polarized macrophages in vitro. We demonstrated that the infiltration of M1 synovial macrophages and the expression of TRPV4 were increased significantly in OA synovium. In addition, intra-articular injection of HC067074 (a specific inhibitor of TRPV4) alleviated the progression of rat OA and significantly decreased synovial macrophage M1 polarization. Further mechanisms suggested that ROS production by M1 macrophages was decreased after TRPV4 inhibition. In addition, NLRP3 (pyrin domain containing protein 3) as a downstream effector of ROS in M1-polarized macrophage, was significantly suppressed following TRPV4 inhibition. In conclusion, this study discovered that inhibition of TRPV4 delays OA progression by inhibiting M1 synovial macrophage polarization through the ROS/NLRP3 pathway.

An electromagnetically induced transparency (EIT) analog in hybrid metal–dielectric metamaterials is proposed and numerically demonstrated in the terahertz region. The EIT analog consists of a metal bar and a silicon disk (SD) to support localized surface plasmon resonance and anapole modes. A high transmission EIT-like optical response was achieved with a Q-factor of ∼250 as interpreted by the destructive interference between these two modes through the hybrid metamaterial. The influences of the background index and SD radius on the hybrid metamaterial are also demonstrated. In addition, the proposed metamaterial has the potential to be integrated into microfluidic chips for tumor, pesticide, and poison sensing, which gives a new way to realize EIT in a way that is different using all-metal and all-dielectric materials.

Inspired by the development of terahertz (THz) technology, the demand for THz sensors with high quality and high sensitivity is significantly increasing. In this study, one-dimensional metallic metamaterials based on cavity mode resonance are proposed for sensing applications in the THz regime. Owing to the strong energy concentration in the cavity, metamaterials with a high quality factor were obtained. Thus, the presented device not only achieved narrowband selective absorption but also exhibited excellent refractive index sensing with high sensitivity, figure of merit, and quality factor. The physical mechanism was verified by comparing the simulation results with that of the coupled mode theory. The polarization dependence of absorption and dual-band sensing, which can be actively tuned by the broken symmetry between two adjacent units, were also discussed. Consequently, this study may open up new avenues for the development of biosensing and imaging applications.

It is of interest to use UV-sulfite based processes to degrade pollutants in wastewater treatment process. In this work, arsenic (As(III)) has been selected as a target pollutant to verify the efficacy of such a hypothesized process. The results showed that As(III) was quickly oxidized by a UV-sulfite system at neutral or alkaline pH and especially at pH 9.5, which can be mainly attributed to the generated oxysulfur radicals. In laser flash photolysis (LFP) experiments (λex = 266 nm), the signals of SO3•− and eaq− generated by photolysis of sulfite at 266 nm were discerned. Quantum yields for photoionization of HSO3− (0.01) and SO32− (0.06) were also measured. It has been established that eaq− does not react with SO32−, but reacts with HSO3− with a rate constant 8 × 107 M−1s−1.

The photo-oxidation of organic pollutants as induced by ferric-carboxylate complexes was known to be a photo-Fenton-like process. The use of a carboxylate ligand with higher efficiency and lower toxicity at near neutral pH is of high interest to researchers. In this work, photo-oxidation of bisphenol A (BPA) induced by a ferric-oxalacetic acid complex in aqueous solutions was investigated under 395 nm LED lamps. The results showed that the rate of BPA degradation increased in the order pH 10.0 << 8.0 < 6.5 < 4.0 within the first 10 min. More than 90% of BPA was successfully oxidized with Fe(III)/oxalacetic acid with a ratio of 1:5 at pH 6.5, which was primarily attributed to the generated hydroxyl radical. Iron in the Fe(III)-oxalacetic acid system was reused by simple addition of oxalacetic acid to the reaction mixture. Compared to common carboxylate ligands (pyruvic acid, oxalic acid, and citric acid), oxalacetic acid is more efficient and environmentally friendly for the Fe(III)-carboxylate complex-based photo-Fenton-like process at near neutral pH.

Used as a kind of feed additive, p-arsanilic acid can pose a potential risk to organisms when abandoned in the environment. The photodegradation of p-ASA was investigated under UV-C irradiation in the presence of persulfate (PS) in this work. The addition of PS facilitated the decomposition of p-ASA and notably, the presence of 50 mmol PS brought about a nearly complete mineralization after 3 h, while an insignificant total organic carbon (TOC) removal was observed under UV irradiation (λ = 254 nm) only. Experimental results proved that sulfate radical (SO4•−) was responsible for the promotion effect. The cleavage of As-C bond released inorganic arsenic and caused the occurrence of various organic products, for example, hydroxybenzaldehyde, nitrobenzene, benzenediol sulfate, and biphenylarsinic acid. The application of PS with UV-C light may throw a light on thorough treatment for p-ASA containing wastewater.