Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

Visible-Light-Catalyzed N-Radical-Enabled Cyclization of Alkenes for the Synthesis of Five-Membered N-Heterocycles.

Five-membered N-heterocycles play an important role in organic synthesis and material chemistry, as they are widespread through pharmaceutical molecules and natural products. Chemists have developed many synthetic strategies for constructing five-membered N-heterocycles from N-centered radicals, but the availability of mild and green methods for these transformations is still limited. The cyclization of visible-light-generated N-centered radicals with alkenes has emerged as a powerful tool to enable these chemical transformations in recent years. Through chosen representative examples, the significant developments in this promising field were outlined, including the selection of catalysts, substrate scope, mechanistic understanding (especially density functional theory calculations), and applications. The contents of this Minireview are categorized by intramolecular cyclization and intermolecular N-centered radical addition/cyclization reactions.

In Vitro Analysis of Wearing of Hip Joint Prostheses Composed of Different Contact Materials.

Cobalt-chromium-molybdenum alloy (CoCrMo) and ceramic are the two most common materials for the femoral head in hip joint prostheses, and the acetabular liner is typically made from ultra-high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (XLPE), or highly cross-linked polyethylene blended with Vitamin E (VEXLPE). The selection of suitable materials should consider both wear performance and cost-effectiveness. This study compared the wear rate between different friction pairs using a hip joint simulator and then recommended a suitable prosthesis based on the corresponding processing technology and cost. All wear simulations were performed in accordance with ISO 14242, using the same hip joint simulator and same test conditions. This study found that when using the same material for the femoral head, the XLPE and VEXLPE liners had a lower wear rate than the UHMWPE liners, and the wear rate of the XLPE liners increased after blending with Vitamin E (VEXLPE). There was no significant difference in the wear rate of XLPE when using a CoCrMo or ceramic head. Considering the wear rate and cost-effectiveness, a CoCrMo femoral head with an accompanying XLPE liner is recommended as the more suitable combination for hip prostheses.

Association Between the Morphology of Proximal Tibiofibular Joint and the Presence of Knee OA.

Objective: The aim of this study was to evaluate the association between the morphology of the proximal tibiofibular joint (PTFJ) and the presence of knee osteoarthritis (OA). Methods: Twenty-eight OA subjects and 30 healthy subjects were enrolled in this study. A 3D model of the lower limb of each subject was constructed from CT scans and used to measure the characteristics of the PTFJ, including the shape of the articular facets, articular surface area, joint inclination, relative articular height, and joint declination. The association between the characteristics of the PTFJ and presence of knee OA was assessed using binomial logistic regression analysis. Results: There was a significant difference between the OA and healthy groups in terms of the inclination (p = 0.028) and declination (p = 0.020) of the PTFJ and relative articular height (p = 0.011). A greater inclination angle (OR: 1.463, 95% CI: 1.124-1.582, p = 0.021), greater declination angle (OR: 1.832, 95% CI: 1.691-2.187, p = 0.009), and lower relative articular height (OR: 0.951, 95% CI: 0.826-0.992, p = 0.008) were found to be associated with an increased likelihood of knee OA being present. Conclusion: The results of this study suggest that abnormal PTFJ morphology is associated with the presence of knee OA.

Biomechanical Comparison of Three Internal Fixation Techniques for Stabilizing Posterior Pelvic Ring Disruption: A 3D Finite Element Analysis.

OBJECTIVE: To compare the biomechanical stability and compatibility of two iliosacral screws (ISS), a tension band plate (TBP), and a minimally invasive adjustable plate (MIAP) for treating Tile C pelvic fractures. METHODS: Three groups of finite element models of the intact pelvis, including the main ligament and the proximal one-third of both femurs, were developed to simulate vertical sacral fractures and treated with the three abovementioned internal fixation techniques. A 500 N vertical load, a 500 N vertical load plus a 10 Nm moment of forward sagittal direction, and 500 N vertical load plus a 10 Nm moment of right lateral direction were applied to the sacrum to simulate standing status, bending status, and flexion status, respectively. The maximum displacement value, the stress value, and the stress value of the fracture interface were compared among the three internal fixation techniques. RESULTS: The results showed that all three internal fixation techniques effectively restored the biomechanical transmission of the injured pelvis. The stress on the implants in the TBP model was 167.47% and 53.41% higher than that in the ISS model and the MIAP model, respectively, and the stress shielding phenomenon of the TBP model was more obvious than in the other two models. Meanwhile, the stress between the fracture interfaces in the TBP fixation models was apparently higher than that in the other two models. However, the vertical displacement of the MIAP model was not significantly different from that in the ISS and TBP model; therefore, strong fixation could be obtained in all three models. CONCLUSION: Based on our results, we believe that the stability of Tile C pelvic fracture fixed with MIAP was similar to that of fractures fixed with ISS and TBP, but the stress shielding phenomenon and safety of implants in the TBP models were inferior to those in the MIAP and ISS fixation models. Meanwhile, MIAP and ISS fixation were more helpful to the healing processing than was TBP fixation, especially at the fracture interface of the second and third vertebral body levels.

Influence of Different Boundary Conditions in Finite Element Analysis on Pelvic Biomechanical Load Transmission.

OBJECTIVE: To observe the effects of boundary conditions and connect conditions on biomechanics predictions in finite element (FE) pelvic models. METHODS: Three FE pelvic models were constructed to analyze the effect of boundary conditions and connect conditions in the hip joint: an intact pelvic model assumed contact of the hip joint on both sides (Model I); and a pelvic model assumed the hip joint connecting surfaces fused together with (Model II) or without proximal femurs (Model III). The model was validated by bone surface strains obtained from strain gauges in an in vitro pelvic experiment. Vertical load was applied to the pelvic specimen, and the same load was simulated in the FE model. RESULTS: There was a strong correlation between the FE analysis results of Model I and the experimental results (R 2 = 0.979); meanwhile, the correlation coefficient and the linear regression function increased slightly with increasing load force. Comparing the three models, the stress values in the point near the pubic symphysis in Model III were 48.52 and 39.1% lower, respectively, in comparison with Models I and II. Furthermore, the stress values on the dome region of the acetabulum in Models II and III were 103.61 and 390.53% less than those of Model I. Besides, the posterior acetabular wall stress values of Model II were 197.15 and 305.17% higher than those of Models I and III, respectively. CONCLUSIONS: These findings suggest that the effect of the connect condition in the hip joint should not be neglected, especially in studies related to clinical applications.

Detection of tumor marker CA125 in ovarian carcinoma using quantum dots.

Semiconductor quantum dots (QDs) offer several advantages over organic dyes in fluorescence-imaging applications, such as higher quantum yield, exceptional photostability, and a narrow, tunable, and symmetric emission spectrum. To explore whether QDs could specifically and effectively label tumor markers and be used in immunohistochemistry as a novel type of fluorescent probe, we used quantum dots with maximum emission wavelength 605 nm (QD605) to detect the ovarian carcinoma marker CA125 in specimens of different types (fixed cells, tissue sections, and xenograft piece). Additionally, we compared the photostability of QD signals with that of a conventional organic dye, FITC. All labeling signals of QDs were found to be more specific and brighter than those of FITC. Moreover, the QDs exhibited exceptional photostability during continuous illumination for 1 h by a high-intensity laser (Ar laser power 100 mW) at 488 nm, while the FITC signals faded very quickly and became undetectable after 24 min of illumination. These results indicate that QD-based probes can offer substantial advantages over existing fluorophores in many applications, and can be used effectively in immunohistochemistry as a novel class of fluorescent probes.