Development of a novel rabbit model for femoroacetabular impingement through surgically induced acetabular overcoverage.

There is a lack of validated small animal models for femoroacetabular impingement (FAI) that induce intra-articular lesions and cause osteoarthritis (OA) progression. The gene expression profile of articular cartilage in patients with FAI has not been characterized in animal studies. The purpose of this study is to describe a novel rabbit model for FAI with validated induction of intra-articular lesions and OA progression and to characterize the gene expression pattern in impinged cartilage using this model. Thirty 6-month-old New Zealand White rabbits underwent unilateral endobutton implant placement at the acetabular rim to surgically create overcoverage. Radiological assessment confirmed secure placement of endobutton at the acetabular rim for all operated hips with a mean alteration in lateral center-edge angle (ΔLCEA) of 16.2 ± 6.6°. Gross inspection revealed secondary cartilage injuries in the anterosuperior region of the femoral head for the operated hips. Cartilage injuries were shown to exacerbate with increased impingement duration, as demonstrated by the modified Outerbridge scores and Mankin scores. Immunostaining and quantitative real-time polymerase chain reaction revealed elevated expression of inflammatory, anabolic and catabolic genes in impinged cartilage. RNA sequencing analysis of cartilage tissue revealed a distinct transcriptome profile and identified C-KIT, CD86, and CD68 as central markers. Our study confirmed that the novel rabbit FAI model created acetabular overcoverage and produced articular cartilage injury at the impingement zone. Cartilage from the impingement zone demonstrated a heightened metabolic state, corroborating with the gene expression pattern observed in patients with FAI.

Salinity increases under sea level rise strengthens the chemical protection of SOC in subtropical tidal marshes.

The rise in sea levels due to global warming could significantly impact the soil organic carbon (SOC) pool in coastal tidal marshes by altering soil salinity and flooding conditions. However, the effects of these factors on SOC protection in coastal tidal marshes are not fully understood. In this study, we employed a space-for-time approach to investigate the variations in soil active carbon components and mineral-associated organic carbon under different salinity gradients (freshwater and brackish) and flooding frequencies (high and low tidal flats). The soil organic carbon (SOC) and easily oxidizable organic carbon (EOC) contents at the low-flooding frequency sites were higher than those at the high-flooding frequency sites. The dissolved organic carbon (DOC) content was higher at the high-salinity sites compared to the low-salinity sites, while the soil microbial biomass carbon (MBC) content was higher at the low-salinity sites than at the high-salinity sites. The EOC/SOC and DOC/SOC ratios were greater at the high-salinity sites than at the low-salinity sites, whereas the MBC/SOC ratios were higher at the low-salinity sites than at the high-salinity sites. Iron (Fe) and aluminum (Al) mineral-associated organic carbon [Fe(Al)-OC] and calcium-associated organic carbon (Ca-OC) contents were higher at the high-salinity sites compared to the low-salinity sites, and at the low-flooding frequency sites compared to the high-flooding frequency sites. Meanwhile, Fe(Al)-OC was the dominant fraction among mineral-associated organic carbon at all sites. The dominant phyla of bacterial community included Proteobacteria (49.31 %-66.36 %), Firmicutes (2.67 %-28.44 %), Chloroflexi (3.81 %-9.54 %), and Acidobacteria (4.28 %-7.02 %). In addition, Desulfobacca, a sulfate-reducing bacterium, promoted the formation of mineral-associated organic carbon. Random forest analysis showed that SOC and DOC were key factors in promoting mineral-associated organic carbon formation. Partial least squares path modeling (PLS-PM) indicated that sea level rise affects DOC content by altering soil physicochemical properties, promoting the formation of mineral-associated organic carbon. In summary, while soil organic carbon activity increases, the chemical association of minerals with organic carbon is becoming increasingly crucial for the protection of organic carbon under rising salinity conditions driven by sea level rise.

Positional Isomerism of Aromatic Heterocyclic Spacer Cations in Two-Dimensional Dion-Jacobson Hybrid Perovskites.

Ligand engineering of aromatic heterocyclic cations in two-dimensional (2D) Dion-Jacobson (DJ) perovskites has been widely explored in recent years. In this study, how the positional isomers of aromatic heterocyclic cations tune the lattice of 2D perovskites, thereby influencing the transport and recombination dynamics of charge carriers, has been investigated through nonadiabatic molecular dynamics simulations. We demonstrate that the meta-substituted 3-(aminomethyl)pyridinium (3AMPY) cations greatly reduce the strength of electron-vibration coupling since the strong hydrogen-bonding network introduced by the changes in the arrangement of spacer cations significantly suppresses the structural thermal fluctuations. Compared to the para-substituted 4-(aminomethyl)pyridinium (4AMPY) cation, using the asymmetric 3AMPY as a spacer cation can achieve improved in-plane transport performance, enhanced thermal stability, and suppressed charge carrier recombination through weakening electron-vibration interactions. Our results explain the observed lifetime difference between the two types of DJ-phase perovskites in experiments and provide new guidance for optimizing the performance of perovskite devices.

Comparison of the efficacy and safety of unilateral and bilateral approach kyphoplasty in the treatment of osteoporotic vertebral compression fractures: A meta-analysis.

OBJECTIVES: The study aimed to compare the efficacy and safety of unilateral versus bilateral percutaneous kyphoplasty (PKP) in treating osteoporotic vertebral compression fractures. MATERIALS AND METHODS: Adhering to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, three English-language databases were systematically reviewed: PubMed, Web of Science, and the National Library of Medicine. The search was conducted between their inception and January 1, 2023. Studies that were replications or that used regression analysis were excluded. Randomized controlled trials and cohort studies that met the criteria were included, and a meta-analysis was performed. RESULTS: The mean follow-up duration was 17.9±9.7 months for the unilateral group and 18.4±8.3 months for the bilateral group. Eight randomized controlled trials and four cohort studies were included, comprising a total of 1,391 patients (499 males, 697 females; 195 cases did not report sex; mean age: 70.9 years; range, 45 to 82 years). Of these patients, 710 underwent the unilateral surgical approach and 681 the bilateral approach. The meta-analysis revealed that the long-term VAS was marginally higher in the unilateral PKP group (mean difference [MD]=0.09; 95% confidence interval [CI]: 0.06-0.13; p<0.001). The unilateral group also demonstrated a greater recovery rate in the postoperative kyphosis angle (MD=2.27; 95% CI: 0.67-3.87; p=0.006), shorter operation duration (MD=18.56 min; 95% CI: 8.96-28.17; p<0.001), and a lower bone cement dosage (MD=1.20 mL; 95% CI: 0.39-2.01; p=0.004). CONCLUSION: Unilateral PKP appears equally effective as bilateral PKP for treating osteoporotic vertebral compression fractures but with advantages in terms of procedure time, cement use, and pain reduction.

Personalized composite scaffolds for accelerated cell- and growth factor-free craniofacial bone regeneration.

Approaches to regenerating bone often rely on integrating biomaterials and biological signals in the form of cells or cytokines. However, from a translational point of view, these approaches are challenging due to the sourcing and quality of the biologic, unpredictable immune responses, complex regulatory paths, and high costs. We describe a simple manufacturing process and a material-centric 3D-printed composite scaffold system (CSS) that offers distinct advantages for clinical translation. The CSS comprises a 3D-printed porous polydiolcitrate-hydroxyapatite composite elastomer infused with a polydiolcitrate-graphene oxide hydrogel composite. Using a micro-continuous liquid interface production 3D printer, we fabricate a precise porous ceramic scaffold with 60 wt% hydroxyapatite resembling natural bone. The resulting scaffold integrates with a thermoresponsive hydrogel composite in situ to fit the defect, which is expected to enhance surface contact with surrounding tissue and facilitate biointegration. The antioxidative properties of citrate polymers prevent long-term inflammatory responses. The CSS stimulates osteogenesis in vitro and in vivo. Within 4 weeks in a calvarial critical-sized bone defect model, the CSS accelerated ECM deposition (8-fold) and mineralized osteoid (69-fold) compared to the untreated. Through spatial transcriptomics, we demonstrated the comprehensive biological processes of CSS for prompt osseointegration. Our material-centric approach delivers impressive osteogenic properties and streamlined manufacturing advantages, potentially expediting clinical application for bone reconstruction surgeries.

Highly disordered and resorbable lithiated nanoparticles with osteogenic and angiogenic properties.

In this study, we have developed unique bioresorbable lithiated nanoparticles (LiCP, d50 = 20 nm), demonstrating a versatile material for bone repair and regeneration applications. The LiCPs are biocompatible even at the highest concentration tested (1000 µg mL-1) where bone marrow derived mesenchymal stem cells (BM-MSCs) maintained over 90% viability compared to the control. Notably, LiCP significantly enhanced the expression of osteogenic and angiogenic markers in vitro; collagen I, Runx2, angiogenin, and EGF increased by 8-fold, 8-fold, 9-fold, and 7.5-fold, respectively. Additionally, LiCP facilitated a marked improvement in tubulogenesis in endothelial cells across all tested concentrations. Remarkably, in an ectopic mouse model, LiCP induced mature bone formation, outperforming both the control group and non-lithiated nanoparticles. These findings establish lithiated nanoparticles as a highly promising material for advancing bone repair and regeneration therapies, offering dual benefits in osteogenesis and angiogenesis. The results lay the groundwork for future studies and potential clinical applications, where precise modulation of lithium release could tailor therapeutic outcomes to meet specific patient needs in bone and vascular tissue engineering.

GAPDH suppresses adenovirus-induced oxidative stress and enables a superfast production of recombinant adenovirus.

Recombinant adenovirus (rAdV) is a commonly used vector system for gene transfer. Efficient initial packaging and subsequent production of rAdV remains time-consuming and labor-intensive, possibly attributable to rAdV infection-associated oxidative stress and reactive oxygen species (ROS) production. Here, we show that exogenous GAPDH expression mitigates adenovirus-induced ROS-associated apoptosis in HEK293 cells, and expedites adenovirus production. By stably overexpressing GAPDH in HEK293 (293G) and 293pTP (293GP) cells, respectively, we demonstrated that rAdV-induced ROS production and cell apoptosis were significantly suppressed in 293G and 293GP cells. Transfection of 293G cells with adenoviral plasmid pAd-G2Luc yielded much higher titers of Ad-G2Luc at day 7 than that in HEK293 cells. Similarly, Ad-G2Luc was amplified more efficiently in 293G than in HEK293 cells. We further showed that transfection of 293GP cells with pAd-G2Luc produced much higher titers of Ad-G2Luc at day 5 than that of 293pTP cells. 293GP cells amplified the Ad-G2Luc much more efficiently than 293pTP cells, indicating that exogenous GAPDH can further augment pTP-enhanced adenovirus production. These results demonstrate that exogenous GAPDH can effectively suppress adenovirus-induced ROS and thus accelerate adenovirus production. Therefore, the engineered 293GP cells represent a superfast rAdV production system for adenovirus-based gene transfer and gene therapy.

Establishment and characterization of a rat model of scalp-cranial composite defect for multilayered tissue engineering.

Composite cranial defects have individual functional and aesthetic ramifications, as well as societal burden, while posing significant challenges for reconstructive surgeons. Single-stage composite reconstruction of these deformities entail complex surgeries that bear many short- and long-term risks and complications. Current research on composite scalp-cranial defects is sparse and one-dimensional, often focusing solely on bone or skin. Thus, there is an unmet need for a simple, clinically relevant composite defect model in rodents, where there is a challenge in averting healing of the skin component via secondary intention. By utilizing a customizable (3D-printed) wound obturator, the scalp wound can be rendered non-healing for a long period (more than 6 weeks), with the cranial defect patent. The wound obturator shows minimal biotoxicity and will not cause severe endocranium-granulation adhesion. This composite defect model effectively slowed the scalp healing process and preserved the cranial defect, embodying the characteristics of a "chronic composite defect". In parallel, an autologous reconstruction model was established as the positive control. This positive control exhibited reproducible healing of the skin within 3 weeks with variable degrees of osseointegration, consistent with clinical practice. Both models provide a stable platform for subsequent research not only for composite tissue engineering and scaffold design but also for mechanistic studies of composite tissue healing.

Effects of Artificial Aging on Rice Lysophospholipids.

Lysophospholipids (LPLs) represent a major class of polar lipids crucial for rice's nutritional and functional properties. This study investigates the impact of varying storage temperatures (20, 30, and 40 °C) and humidity (50 and 95%) on the nonstarch and starch LPLs of paddy and milled rice. The findings revealed that the average nonstarch LPL content in paddy rice aged at 20 °C (82.6 µg/g) and 40 °C (83.6 µg/g) was significantly lower than that at 30 °C (95.0 µg/g). The nonstarch LPL content of milled rice aged at 20 °C (78.0 µg/g) was significantly higher than that at 30 and 40 °C. High storage temperature (40 °C) and humidity (95%) resulted in a significant reduction in rice total starch LPC and LPE content when compared to low humidity (50%). The ratio of rice starch/nonstarch LPL components such as LPC16:0 and LPC18:2 remarkably increased with increased storage temperature and humidity.

Recent advances in injectable hydrogel therapies for periodontitis.

Periodontitis is an immune-inflammatory disease caused by dental plaque, and deteriorates the periodontal ligament, causes alveolar bone loss, and may lead to tooth loss. To treat periodontitis, antibacterial and anti-inflammation approaches are required to reduce bone loss. Thus, appropriate drug administration methods are significant. Due to their "syringeability", biocompatibility, and convenience, injectable hydrogels and associated methods have been extensively studied and used for periodontitis therapy. Such hydrogels are made from natural and synthetic polymer materials using physical and/or chemical cross-linking approaches. Interestingly, some injectable hydrogels are stimuli-responsive hydrogels, which respond to the local microenvironment and form hydrogels that release drugs. Therefore, as injectable hydrogels are different and highly varied, we systematically reviewed the periodontal treatment field from three perspectives: raw material sources, cross-linking methods, and stimuli-responsive methods. We then discussed current challenges and opportunities for the translation of hydrogels to clinic, which may guide further injectable hydrogel designs for periodontitis.

Coastal conversion alters topsoil carbon, nitrogen and phosphorus stocks and stoichiometric balances in subtropical coastal wetlands.

The extensive conversion of coastal wetlands into agricultural and aquaculture areas has significant repercussions on soil nutrient balance. However, how coastal conversion specifically influences the dynamics and stoichiometry of topsoil carbon (C), nitrogen (N), and phosphorus (P) remains limited due to the considerable spatial variability and a lack of comprehensive field data. Here, we investigated the concentration and distribution of total C (TC), N (TN) and P (TP), along with their stoichiometric balance in four distinct coastal landscapes, including natural marshes and tidal flats, as well as converted agricultural croplands and ponds. The results revealed that converted croplands and ponds exhibited significantly higher concentrations of soil C, N and P, particularly in comparison to tidal flats. Furthermore, croplands and ponds have higher topsoil C stocks than tidal flats, but little difference or even lose stored C compared to marshes. Cropland soils showed considerably higher levels of available N (NH4+-N and NO3--N) and available P compared to those in natural marshes and tidal flats. The distribution of soil TC, TN, and TP demonstrated greater spatial heterogeneity in natural marshes and tidal flats, while the converted areas were more uniform and became hotspots for N and P accumulation. Coastal conversion altered soil C:N:P stoichiometry, with cropland soils exhibiting a lower N:P ratio (2.9 ± 1.1), indicating that long-term application of N and P fertilizers could decrease the N:P ratio, as P is more retained in the soil than N. Furthermore, it was observed that the dynamics of C, N and P, as well as their stoichiometry, are closely linked to soil physicochemical properties, especially soil organic matter and texture. These findings highlight that coastal conversion and associated management practices markedly affected soil C, N and P dynamics in a representative wetland area of the subtropical regions, leading to a reshaping of their stoichiometric balances, particularly in the topsoil layer.

Collagen type X expression and chondrocyte hypertrophic differentiation during OA and OS development.

Chondrocyte hypertrophy and the expression of its specific marker, the collagen type X gene (COL10A1), constitute key terminal differentiation stages during endochondral ossification in long bone development. Mutations in the COL10A1 gene are known to cause schmid type metaphyseal chondrodysplasia (SMCD) and spondyloepiphyseal dyschondrodysplasia (SMD). Moreover, abnormal COL10A1 expression and aberrant chondrocyte hypertrophy are strongly correlated with skeletal diseases, notably osteoarthritis (OA) and osteosarcoma (OS). Throughout the progression of OA, articular chondrocytes undergo substantial changes in gene expression and phenotype, including a transition to a hypertrophic-like state characterized by the expression of collagen type X, matrix metalloproteinase-13, and alkaline phosphatase. This state is similar to the process of endochondral ossification during cartilage development. OS, the most common pediatric bone cancer, exhibits characteristics of abnormal bone formation alongside the presence of tumor tissue containing cartilaginous components. This observation suggests a potential role for chondrogenesis in the development of OS. A deeper understanding of the shifts in collagen X expression and chondrocyte hypertrophy phenotypes in OA or OS may offer novel insights into their pathogenesis, thereby paving the way for potential therapeutic interventions. This review systematically summarizes the findings from multiple OA models (e.g., transgenic, surgically-induced, mechanically-loaded, and chemically-induced OA models), with a particular focus on their chondrogenic and/or hypertrophic phenotypes and possible signaling pathways. The OS phenotypes and pathogenesis in relation to chondrogenesis, collagen X expression, chondrocyte (hypertrophic) differentiation, and their regulatory mechanisms were also discussed. Together, this review provides novel insights into OA and OS therapeutics, possibly by intervening the process of abnormal endochondral-like pathway with altered collagen type X expression.

Ddx5 participates in regulation of Col10a1 expression and chondrocyte hypertrophic differentiation in vitro.

BACKGROUND AND AIMS: The type X collagen gene (Col10a1), is a specific molecular marker of hypertrophic chondrocytes during endochondral ossification. Col10a1 expression is known to be influenced by many regulators. In this study, we aim to investigate how DEAD-box helicase 5 (DDX5), a potential binding factor for Col10a1 enhancer, may play a role in Col10a1 expression and chondrocyte hypertrophic differentiation in vitro. METHODS: The potential binding factors of the 150-bp Col10a1 cis-enhancer were identified with the hTFtarget database. The expression of DDX5 and COL10A1 was detected by quantitative real-time PCR (qRT-PCR) and Western blot in chondrogenic ATDC5 and MCT cell models with or without Ddx5 knockdown or overexpression. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) were performed to determine the interaction between DDX5 and the Col10a1 enhancer. The effect and mechanism of DDX5 on chondrocyte differentiation and maturation was evaluated by alcian blue, alkaline phosphatase (ALP), and alizarin red staining in ATDC5 cell lines with stable knockdown of Ddx5. RESULTS: DDX5 was identified as a potential binding factor for the Col10a1 enhancer. The expression of DDX5 in hypertrophic chondrocytes was higher than that in proliferative chondrocytes. Knockdown of Ddx5 decreased, while overexpression of Ddx5 slightly increased COL10A1 expression. DDX5 promotes the enhancer activity of Col10a1 as demonstrated by dual-luciferase reporter assay, and the ChIP experiment suggests a direct interaction between DDX5 and the Col10a1 enhancer. Compared to the control (NC) group, we observed weaker alcian blue and ALP staining intensity in the Ddx5 knockdown group of ATDC5 cells cultured both for 7 and 14 days. Whereas weaker alizarin red staining intensity was only found in the Ddx5 knockdown group of cells cultured for 7 days. Meanwhile, knockdown of Ddx5 significantly reduced the level of runt-related transcription factor 2 (RUNX2) in related ATDC5 cells examined. CONCLUSIONS: Our results suggest that DDX5 acts as a positive regulator for Col10a1 expression and may cooperate with RUNX2 together to control Col10a1 expression and promote the proliferation and maturation of chondrocytes.

The impact of metabolic disorders on management of periodontal health in children.

Periodontitis is a chronic inflammatory disease caused by plaque biofilm which shares risk factors with systemic chronic diseases such as diabetes, cardiovascular disease, and osteoporosis. Many studies have found increased prevalence and rate of progression of periodontal disease in children with common metabolic disorders. Although the causal relationship and specific mechanism between them has not been determined yet. The aim of this paper is to progress on the impact of metabolic disorders on periodontal health in children and the underlying mechanisms, which provides new evidences for the prevention and intervention of metabolic disorders and periodontitis in children.

Interaction between the gut microbiota and colonic enteroendocrine cells regulates host metabolism.

Nutrient handling is an essential function of the gastrointestinal tract. Hormonal responses of small intestinal enteroendocrine cells (EECs) have been extensively studied but much less is known about the role of colonic EECs in metabolic regulation. To address this core question, we investigated a mouse model deficient in colonic EECs. Here we show that colonic EEC deficiency leads to hyperphagia and obesity. Furthermore, colonic EEC deficiency results in altered microbiota composition and metabolism, which we found through antibiotic treatment, germ-free rederivation and transfer to germ-free recipients, to be both necessary and sufficient for the development of obesity. Moreover, studying stool and blood metabolomes, we show that differential glutamate production by intestinal microbiota corresponds to increased appetite and that colonic glutamate administration can directly increase food intake. These observations shed light on an unanticipated host-microbiota axis in the colon, part of a larger gut-brain axis, that regulates host metabolism and body weight.

Polyaniline Induced Trivalent Ni in Laser-Fabricated Nickel Oxides for Efficient Oxygen Evolution Reaction.

Although it is generally acknowledged that transition metals at high oxidation states represent superior oxygen evolution reaction (OER) activity, the preparation and stability of such a high-valence state are still a challenge, which requires relatively harsh reaction conditions and is unstable under ambient conditions. Herein, we report the formation of trivalent nickel (Ni3+) in laser-fabricated nickel oxides induced by polyaniline (PANI) under electrochemical activation via a significant charge transfer between Ni and N, as confirmed by X-ray photoelectron spectroscopy and density functional theory calculations. Thereafter, the presence of Ni3+ and the improved conductivity by PANI effectively increase the electrochemical OER activity of the samples together with excellent long-term stability. This work provides new insights for the rational manufacture of high-valence metal for electrochemical reactions.

In vitro and in vivo anti-inflammatory properties of an active fucoidan fraction from Sargassum fusiforme and a fraction-based hydrogel.

In a previous study, we separated an active fucoidan (JHCF4) from acid-processed Sargassum fusiforme, then analyzed and confirmed its structure. In the present study, we investigated the potential anti-inflammatory properties of JHCF4 and a JHCF4-based hydrogel in vitro and in vivo. JHCF4 reliably inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages, with an IC50 of 22.35 µg/ml. Furthermore, JHCF4 attenuated the secretion of prostaglandin E2, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6, indicating that JHCF4 regulates inflammatory reactions. In addition, JHCF4 downregulated iNOS and COX-2 and inhibited the activation of the MAPK pathway. According to further in vivo analyses, JHCF4 significantly reduced the generation of reactive oxygen species (ROS), NO production, and cell death in an LPS-induced zebrafish model, suggesting that JHCF4 exhibits anti-inflammatory effects. Additionally, a JHCF4-based hydrogel was developed, and its properties were evaluated. The hydrogel significantly decreased inflammatory and nociceptive responses in carrageenan (carr)-induced mouse paws by reducing the increase in paw thickness and decreasing neutrophil infiltration in the basal and subcutaneous layers of the toe epidermis. These results indicate that JHCF4 exhibits potential anti-inflammatory activity in vitro and in vivo and that JHCF4-based hydrogels have application prospects in the cosmetic and pharmaceutical fields.