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Background Untreated acute ankle sprains often result in chronic ankle instability (CAI) and can ultimately lead to the development of post-traumatic osteoarthritis (PTOA). At present, a typical animal model of ankle instability in mice is established by transecting the ligaments around the ankle joint. This study aimed to establish a grade I acute ankle sprain animal model by rapid stretching of peri-ankle joint ligaments. Furthermore, we tried to explore the pathophysiological mechanism of ankle osteoarthritis. Methods In all, 18 male C57BL/6 J mice (7 weeks) were randomly divided into three groups: calcaneofibular ligament (CFL) laxity group, deltoid ligament (DL) laxity group, and SHAM group. One week after the surgical procedure, all mice were trained to run in the mouse rotation fatigue machine daily. The mice were tested on the balance beam before surgery and three days, 4 weeks, 8 weeks, and 12 weeks after surgery. Footprint analyses were performed on each mouse before surgery and 12 weeks after surgery. Micro-CT scanning was then performed to evaluate the degeneration of ankle joints and histological staining was performed to analyze and evaluate PTOA caused by ankle joint instability. Results After surgery, the mice in the CFL and DL laxity groups took longer to cross the balance beam and slipped more often than those in the SHAM group ( p  < 0.05). The step length and width in the CFL and DL laxity groups were significantly shorter and smaller than those in the SHAM group 12 weeks after surgery ( p  < 0.05). There was a significant increase in the bone volume fraction (BV/TV) in the CFL and DL laxity groups compared with the SHAM group ( p  < 0.05). Histological staining results suggested obvious signs of PTOA in the CFL and DL laxity groups. Conclusions Based on CFL and DL laxity in a mouse ankle instability model, this study suggests that grade I ankle sprain can contribute to chronic ankle instability, impair motor coordination and balance, and eventually lead to PTOA of ankle with significant degeneration of its adjacent joints.

Nucleus pulposus (NP) tissue engineering brings new hope in the repair of intervertebral disc degeneration (IVDD). IVDD is often accompanied by multiscale changes in the mechanical microenvironment, including the changes of mechanical property of collagen fibril, NP tissue, and mechanical instability of spine. In this study, a multiscale mechanically-adapted strategy is proposed to promote NP repair. To achieve this goal, a viscoelastic-adapted dual-network hydrogel (PVA-DN) is constructed. The hydrogel with multiscale tunable viscoelasticity and dynamic compression condition is used to meet the multiscale mechanical requirements of NP regeneration. The results show that the viscoelastic hydrogel promotes the proliferation, migration and adhesion of nucleus pulposus cell (NPC) as well as the secretion of NP-specific extracellular matrix. RNA-seq results show that it attenuates the inflammatory microenvironment by inhibiting the IL-17 signaling pathway. Appropriate dynamic compression applied to the viscoelastic scaffold further promotes the physiological function of NPC, and the viscoelasticity of hydrogel protects against NPC damage induced by excessive compression. Animal experiments demonstrate that the viscoelastic hydrogel effectively restores disc mechanical function and delays disc degeneration in rats. Findings from this study highlight that the multiscale mechanically-adapted strategy is effective in the repair of IVDD. [Display omitted] •A multiscale mechanically-adapted hydrogel is constructed for the repair of IVDD.•Viscoelastic hydrogel with fast stress relaxation times at multiscale can attenuate the inflammatory microenvironment by blocking the IL-17 signaling pathway.•Viscoelastic hydrogel with fast stress relaxation times at multiscale promotes the formation of stress fibers, earlier adhesion and ECM secretion of NPCs.

Estimating the elasticity of hydrogel phantoms in a cell culture plane is important for understanding the cell behavior in response to various types of mechanical stimuli. Hence, a noncontact tool for measuring the elastic properties of hydrogel phantoms in such three-dimensional cell cultures is required. A well-known method to determine the mechanical properties of hydrogels is the transient wave method. However, due to the multiple reflections of waves from the boundaries, a bigger cell culture plane or multiple directional filters may be required. In this study, we utilized reverberant shear wave elastography, which is based on the autocorrelation principle, to evaluate the shear wave speed in hydrogel samples within a culture dish. Numerical simulations were performed first to confirm the validity of the reverberant elastography method. Subsequently, we used this method to measure the wave speeds in hydrogel phantoms with different concentrations. Shear rheology tests were also performed, and their results were found to be in good agreement with the measured shear wave speeds. The proposed method could be useful for measuring the elasticity of tissues in tissue engineering applications in an inexpensive and noncontact manner.

Accurate estimation of hydrogel phantom elasticity in 3D cell culture systems provides valuable insights into cellular responses to various mechanical stimuli. Although reverberant wave elastography has been applied to measure hydrogel elasticity in 3D cell cultures using multi-point loading, achieving a high-quality reverberant displacement field remains critical for accurate reverberant wave elastography. We develop an innovative approach using 3D-printed randomly distributed scatterers to improve displacement field quality in reverberant wave elastography, inspired by scattering-coded architectured boundaries in object localization. Numerical simulations were performed to analyze the reverberant displacement fields under various loading conditions. The results were compared to determine the optimal loading configuration to enhance the reverberation level of the displacement field. Subsequently, both numerical and experimental reverberant wave elastography were carried out to validate the elasticity measurement with 3D-printed randomly distributed scatterers. The comparison of reverberant displacement patterns under various loading conditions revealed that the displacement pattern under circular loading with 64 scatterers most closely approximated a diffuse wave field, exhibiting both spatial uniformity and directional isotropy. Numerical reverberant wave elastography was subsequently performed, successfully demonstrating its capability for elasticity measurements. Furthermore, the shear wave speeds obtained through optical coherence elastography showed good agreement with shear rheometry measurements. The developed 3D-printed randomly distributed scatterers successfully enhanced the quality of the reverberant displacement field for reverberant wave elastography. Our approach presents a novel and promising tool for quantifying tissue elasticity in reverberant wave elastography applications.

Let \\(g=gl_M|N(k)\\) be the general linear Lie superalgebra over an algebraically closed field \\(k\\) of characteristic zero. Fix an arbitrary even nilpotent element \\(e\\) in \\(g\\) and let \\(U(g,e)\\) be the finite \\(W\\)-superalgebra associated to the pair \\((g,e)\\). In this paper we will give a complete classification of one-dimensional representations for \\(U(g,e)\\). To achieve this, we use the tool of shifted super Yangians to determine the commutative quotients of the finite \\(W\\)-superalgebras.

Suppose \\(\\mathfrak{g}=\\mathfrak{g}_{\\bar 0}+\\mathfrak{g}_{\\bar 1} is a Lie superalgebra of queer type or periplectic type over an algebraically closed field \\)\\textbf{k}\\( of characteristic \\)p>2\\(. In this article, we initiate preliminarily to investigate modular representations of periplectic Lie superalgebras and then verify the first super Kac-Weisfeiler conjecture on the maximal dimensions of irreducible modules for \\)\\mathfrak{g}\\( proposed by the second-named author in [Shu] where the conjecture is targeted at all finite-dimensional restricted Lie superalgebras over \\)\\bk$, and already proved to be true for basic classical Lie superalgebras and completely solvable restricted Lie superalgebras.

Early diagnosis is critical to improve outcomes in rheumatoid arthritis (RA), but current diagnostic tools have limited sensitivity. Here we report a large-scale multicenter study involving training and validation cohorts of 3,262 participants. We show that serum levels of soluble scavenger receptor-A (sSR-A) are increased in patients with RA and correlate positively with clinical and immunological features of the disease. This discriminatory capacity of sSR-A is clinically valuable and complements the diagnosis for early stage and seronegative RA. sSR-A also has 15.97% prevalence in undifferentiated arthritis patients. Furthermore, administration of SR-A accelerates the onset of experimental arthritis in mice, whereas inhibition of SR-A ameliorates the disease pathogenesis. Together, these data identify sSR-A as a potential biomarker in diagnosis of RA, and targeting SR-A might be a therapeutic strategy. Scavenger receptor-A (SR-A) is mostly expressed by myeloid cells and has been attributed a variety of biological functions. Here the authors assess SR-A as a biomarker for diagnosis of rheumatoid arthritis (RA) using large-scale training and validation cohorts and show that modulating SR-A levels can alter progression of collagen-induced arthritis in mice.

Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) that cannot be fully explained by traditional cardiometabolic risk factors. The observed ‘lipid paradox’, where RA patients with lower total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels exhibit higher CVD risk, may be attributed to post-translational modifications (PTMs). These lipoprotein PTMs likely arise from inflammatory pathways. While PTMs like citrullination and carbamylation are well recognized in RA joint pathology, their occurrence in other protein compartments and their role in CVD have been less well explored. This scoping review summarizes the current literature on PTMs of lipoproteins, including oxidation, nitration, carbamylation, and citrullination, and their impacts on CVD in RA. We also discuss immune responses to these PTMs, their interactions with scavenger receptors, and the effects of disease-modifying antirheumatic drugs. Further research on PTMs may uncover new pathways linking autoimmunity, inflammation, and vascular damage, offering novel diagnostic and therapeutic opportunities for RA-associated CVD.

PrPc is expressed in various tumors and is associated with cancer progression, but previous studies have shown conflicting results regarding its relationship with patient prognosis—potentially due to differences in the antibodies used. This study aimed to clarify the relationship between PrPc expression and primary esophageal squamous cell carcinoma (ESCC) and primary hepatocellular carcinoma (HCC) using a novel anti-PrPc antibody, 4AA-m, noted for its high specificity and sensitivity. We used flow cytometry to detect PrPc expression in ESCC and HCC cell lines. Immunohistochemistry with 4AA-m was then performed on tissue microarrays from 179 patients with primary ESCC and 92 patients with primary HCC. PrPc expression was semi-quantitatively assessed using the Tumor-DAB-H-Score, and its association with tumor prognosis was analyzed. In ESCC, PrPc expression was negatively correlated with lymph node metastasis, and patients with high PrPc expression had better overall survival compared to those with low expression. PrPc expression was identified as an independent prognostic factor for overall survival in ESCC. In HCC, patients with positive PrPc expression had shorter recurrence-free survival (RFS) than those without PrPc expression. PrPc expression was also found to be an independent prognostic factor for RFS in HCC.

Background Adult-onset Still’s disease (AOSD) is a systemic autoinflammatory disorder of unknown etiology. B cells are critical participants in different rheumatic diseases, and their roles in AOSD are rarely investigated. This study aimed to unveil the B cell subset features in AOSD and provide evidence for B cell-based diagnosis and targeted therapies of AOSD. Methods B cell subsets in the peripheral blood of AOSD patients and healthy controls (HCs) were detected by flow cytometry. Firstly, the frequencies of B cell subsets were compared. Then, the correlation analysis was performed to explore the correlation between B cell subsets and clinical manifestations in AOSD. Finally, unbiased hierarchical clustering was performed to divide AOSD patients into three groups with different B cell subset features, and the clinical characteristics of the three groups were compared. Results The frequencies of B cell subsets were altered in AOSD patients. Disease-promoting subsets (such as naïve B cells, double negative B cells (DN B cells), and plasmablasts) increased, and potential regulatory subsets (such as unswitched memory B cells (UM B cells) and CD24 hi CD27 + B cells (B10 cells)) decreased in the peripheral blood of AOSD patients. In addition, the altered B cell subsets in AOSD correlated with the clinical and immunological features, such as immune cells, coagulation features, and liver enzymes. Intriguingly, AOSD patients could be divided into three groups with distinct B cell immunophenotyping: group 1 (naïve B cells-dominant), group 2 (CD27 + memory B cells-dominant), and group 3 (precursors of autoantibody-producing plasma cells-dominant). Moreover, these three group patients demonstrated differential manifestations, including immune cells, liver or myocardial enzymes, coagulation features, and systemic score. Conclusions B cell subsets are significantly altered in AOSD patients, potentially contributing to the disease pathogenesis. These findings would inspire B cell-based diagnosis and targeted therapies for this refractory disease.