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Objectives The prevalence of multi‐level cervical spinal stenosis complicated with traumatic cervical instability and spinal cord injury (MCSS‐TCISCI) is low, and the optimal surgical approach remains unclear. Open‐door laminoplasty combined with bilateral lateral mass screw fixation (ODL‐BLMSF) is a relatively new surgical technique; however, its clinical effectiveness in managing MCSS‐TCISCI has not been well‐established. This study aims to assess the clinical value of ODL‐BLMSF against MCSS‐TCISCI. Methods We retrospectively analyzed 20 cases of MCSS‐TCISCI treated with ODL‐BLMSF from July 2016 to June 2020. Radiographic alterations of all included patients were measured using plain radiographs, CT scans, and MRI scans. Cervical lordosis was evaluated using C2‐C7 Cobb angle and cervical curvature index (CCI) on lateral radiographs, and Pavlov ratio at the C5 level. Neurological functional recovery was assessed using Japanese Orthopaedic Association (JOA) scores and Nurick grade, while neck and axial symptoms were assessed using the neck disability index (NDI) and the visual analog scale (VAS). The paired t‐test was utilized for statistical analysis. Results All included patients were followed up for an average period of 26.5 months (range: 24–30 months) after ODL‐BLMSF. The average Pavlov ratio at the C5 level significantly improved from 0.57 ± 0.1 preoperatively to 1.13 ± 0.1 and 1.12 ± 0.04 at 6 months postoperatively and at the last follow‐up (t = 16.347, 16.536, p

Abstract Semiconductor excitations can hybridize with cavity photons to form exciton-polaritons (EPs) with remarkable properties, including light-like energy flow combined with matter-like interactions. To fully harness these properties, EPs must retain ballistic, coherent transport despite matter-mediated interactions with lattice phonons. Here we develop a nonlinear momentum-resolved optical approach that directly images EPs in real space on femtosecond scales in a range of polaritonic architectures. We focus our analysis on EP propagation in layered halide perovskite microcavities. We reveal that EP–phonon interactions lead to a large renormalization of EP velocities at high excitonic fractions at room temperature. Despite these strong EP–phonon interactions, ballistic transport is maintained for up to half-exciton EPs, in agreement with quantum simulations of dynamic disorder shielding through light-matter hybridization. Above 50% excitonic character, rapid decoherence leads to diffusive transport. Our work provides a general framework to precisely balance EP coherence, velocity, and nonlinear interactions.

Abstract Background Dermatophyte caused by Trichophyton mentagrophytes is a global disease with a growing prevalence that is difficult to cure. Perilla frutescens (L.) Britt. is an edible and medicinal plant. Ancient books of Traditional Chinese Medicine and modern pharmacological studies have shown that it has potential anti-fungi activity. This is the first study to explore the inhibitory effects of compounds from P. frutescens on Trichophyton mentagrophytes and its mechanism of action coupled with the antifungal activity in vitro from network pharmacology, transcriptomics and proteomics. Methods Five most potential inhibitory compounds against fungi in P. frutescens was screened with network pharmacology. The antifungal activity of the candidates was detected by a broth microdilution method. Through in vitro antifungal assays screening the compound with efficacy, transcriptomics and proteomics were performed to investigate the pharmacological mechanisms of the effective compound against Trichophyton mentagrophytes. Furthermore, the real-time polymerase chain reaction (PCR) was applied to verify the expression of genes. Results The top five potential antifungal compounds in P. frutescens screened by network pharmacology are: progesterone, luteolin, apigenin, ursolic acid and rosmarinic acid. In vitro antifungal assays showed that rosmarinic acid had a favorable inhibitory effect on fungi. The transcriptomic findings exhibited that the differentially expressed genes of fungus after rosmarinic acid intervention were mainly enriched in the carbon metabolism pathway, while the proteomic findings suggested that rosmarinic acid could inhibit the average growth of Trichophyton mentagrophytes by interfering with the expression of enolase in the glycolysis pathway. Comparison of real-time PCR and transcriptomics results showed that the trends of gene expression in glycolytic, carbon metabolism and glutathione metabolic pathways were identical. The binding modes and interactions between rosmarinic acid and enolase were preliminary explored by molecular docking analysis. Conclusion The key findings of the present study manifested that rosmarinic acid, a medicinal compound extracted from P. frutescens, had pharmacological activity in inhibiting the growth of Trichophyton mentagrophytes by affecting its enolase expression to reduce metabolism. Rosmarinic acid is expected to be an efficacious product for prevention and treatment of dermatophytes.

Abstract Background The purpose of this study was to analyze the efficacy of U-shaped internal fixation for calcaneal tubercle fracture after nearly 3 years of case follow-up and data collection. Method We retrospectively analyzed the collected data from 16 patients with avulsion fracture of calcaneal tubercle between December 2018 and February 2021 at our institute. All patients were required to conform to regular follow up postoperatively. X-ray film was applied to all cases. The American Orthopaedic Foot and Ankle Association (AOFAS) score, Cedell score and the visual analog scale (VAS) were used to evaluate functional results. Results All patients achieved bone union. The preoperative AOFAS score was 26.34 ± 3.34, which was significantly different from 91.38 ± 6.15 half a year after operation (p = 0.003). The preoperative Cedell score was 31.05 ± 4.18 and the score half a year after operation was 92.17 ± 5.39(p = 0.011). The VAS score was 8.91 ± 1.51 before operation and decreased to 0.58 ± 1.31 half a year after operation (p = 0.014). Conclusions In the treatments of calcaneal tubercle fracture, U-shaped internal fixation is a new attempt. Through the short-term follow-up study, we found that its therapeutic effect is excellent, which is a recommended treatment in clinic.

Mitochondrial dysfunction is one of the key features of acute kidney injury (AKI) and associated fibrosis. Leucine-rich repeat kinase 2 (LRRK2) is highly expressed in kidneys and regulates mitochondrial homeostasis. How it functions in AKI is unclear. Herein we reported that LRRK2 was dramatically downregulated in AKI kidneys. Lrrk2−/− mice exhibited less severity of AKI when compared to wild-type counterparts with less mitochondrial fragmentation and decreased reactive oxygen species (ROS) production in proximal renal tubular cells (PTCs) due to mitofusin 2 (MFN2) accumulation. Overexpression of LRRK2 in human PTC cell lines promoted LRRK2-MKK4/JNK-dependent phosphorylation of MFN2Ser27 and subsequently ubiquitination-mediated MFN2 degradation, which in turn exaggerated mitochondrial damage upon ischemia/reperfusion (I/R) mimicry treatment. Lrrk2 deficiency also alleviated AKI-to-chronic kidney disease (CKD) transition with less fibrosis. In vivo pretreatment of LRRK2 inhibitors attenuated the severity of AKI as well as CKD, potentiating LRRK2 as a novel target to alleviate AKI and fibrosis.

Abstract Reprogramming Müller glia (MG) into functional cells is considered a promising therapeutic strategy to treat ocular diseases and vision loss. However, current AAV-based system for MG-tracing was reported to have high leakage in recent studies. Here, we focused on reducing the leakage of AAV-based labeling systems and found that different AAV serotypes showed a range of efficiency and specificity in labeling MG, leading us to optimize a human GFAP-Cre reporter system packaged in the AAV9 serotype with the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) removed. The leakage ratio of the AAV9-hGFAP-Cre-ΔWPRE decreased by an approximate 40-fold compared with the AAV9-hGFAP-Cre-WPRE labeling system. In addition, we validated the specificity of the AAV-ΔWPRE system for tracing MG reprogramming under Ptbp1-suppression and observed strict non-MG-conversion, similar to previous studies using genetic lineage tracking mouse models. Thus, the AAV9-hGFAP-Cre-ΔWPRE system showed high efficiency and specificity for MG labeling, providing a promising tool for tracing cell fate in vivo.

Abstract Recently, a human mutation of OPG was identified to be associated with familial forms of osteoarthritis. This missense mutation (c.1205A = > T; p.Stop402Leu) occurs on the stop codon of OPG, which results in a 19-residue appendage to the C-terminus (OPG+19). The biochemical consequence of this unusual sequence alteration remains unknown. Here we expressed OPG+19 in 293 cells and the mutant OPG was purified to homogeneity by heparin affinity chromatography and size exclusion chromatography. We found that in sharp contrast to wildtype OPG, which mainly exists in dimeric form, OPG+19 had a strong tendency to form higher-order oligomers. To our surprise, the hyper-oligomerization of OPG+19 had no impact on how it binds cell surface heparan sulfate, how it inhibits RANKL-induced osteoclastogenesis and TRAIL-induced chondrocytes apoptosis. Our data suggest that in biological contexts where OPG is known to play a role, OPG+19 functions equivalently as wildtype OPG. The disease-causing mechanism of OPG+19 likely involves an unknown function of OPG in cartilage homeostasis and mineralization. By demonstrating the biochemical nature of this disease-causing OPG mutant, our study will likely help elucidating the biological roles of OPG in cartilage biology.