Xing Zhao

Osteoarthritis (OA) is a whole-joint disorder that interferes with the quality of life in older individuals. Here we report that ZDHHC11 is highly expressed in articular chondrocytes but is downregulated in the degenerated cartilage of aged mice and patients with OA. ZDHHC11 prevents chondrocyte senescence and promotes cartilage anabolism, culminating in an improved OA phenotype. The deletion of Zdhhc11 in mice (Zdhhc11^fl/fl) exacerbates OA progression in a destabilized medial meniscus model. Specifically, we identify ZDHHC11 as a key palmitoyltransferase whose depletion leads to a GNB2-dependent E3 ubiquitin ligase-mediated proteasomal degradation of APOD. Mechanistically, ZDHHC11-mediated palmitoylation alleviates OA progression by deactivating the GATA4–P65 signaling pathway. We also propose an original lipid nanoparticle-based platform for Zdhhc11 mRNA delivery to rejuvenate impaired cartilage by specifically targeting chondrocytes in vivo. Collectively, ZDHHC11-dependent palmitoylation is essential for ameliorating OA, and the targeted delivery of ZDHHC11 may serve as a promising strategy for future OA treatment.

Thoracolumbar fractures involving severe collapse of the anterior and middle columns are difficult to reduce via posterior surgery. Therefore, we evaluated the effectiveness of balloon-assisted endplate reduction (BAER), transpedicular bone grafting, and pedicle screw fixation for this type of thoracolumbar fracture. This retrospective study included 87 patients with thoracolumbar fractures involving severe collapse of the anterior and middle columns treated from January 2020 to January 2022. Among them, 37 patients were treated via BAER, transpedicular bone grafting and pedicle screw fixation (Group A). Another 50 patients were treated via preoperative postural reduction combined with posterior pedicle screw fixation (Group B). Routine patient follow-ups were conducted to record the degree of vertebral height maintenance via X-ray and computed tomography (CT) images. The visual analog scale (VAS) score for low back pain and the Oswestry Disability Index (ODI) score were recorded. The operative time, blood loss and hospitalization cost were greater in Group A. Significant clinical improvements in the ODI, VAS score, AVBH, MVBH and VWA were achieved in the two groups after surgery. However, the improvements in the AVBH, MVBH and VWA were significantly greater in Group A. During the final follow-up, the VAS and ODI scores in Group A were lower. The spinopelvic parameters at the sagittal position did not significantly differ between the two groups at any time. The technique comprising BAER, transpedicular bone grafting, and pedicle screw fixation to treat thoracolumbar fractures with severe collapse of the anterior and middle columns is feasible and provides advantages.

Postmenopausal osteoporosis (PMOP) is a chronic systemic bone metabolism disorder. Promotion in the patterns of human bone marrow mesenchymal stem cells (hBMSCs) differentiation towards osteoblasts contributes to alleviating osteoporosis. Aucubin, a natural compound isolated from the well‐known herbal medicine Eucommia, was previously shown to possess various pharmacological effects. However, its effects on hBMSCs of PMOP patients are unknown. The aim of this present research was to investigate the impact and underlying process of aucubin on cell proliferation and osteogenic differentiation in hBMSCs isolated from PMOP patients. The ability of aucubin to inhibit the ferroptosis induced by erastin in hBMSCs was detected; ROS production, ferrous ion levels, SOD, MDA, and GPX activities were tested by using commercial kits. Next, ALP staining, ARS staining, RT‐qPCR, RNA‐sequencing, and Western blot were applied for determining the mRNA and protein expression levels associated with the osteogenesis of hBMSCs. The study also explored the involvement of BMP2/Smads signalling in aucubin promoting the osteogenesis of hBMSCs and evaluated the effects of aucubin intervention on osteoporosis using an ovariectomised rat model. The results indicated that aucubin significantly inhibited ROS generation and oxidative stress induced by erastin and protected against ferroptosis in hBMSCs. Additionally, aucubin facilitated osteogenic differentiation of hBMSCs by activating the BMP2/SMADs pathway and attenuated the progression of osteoporosis in OVX rats, suggesting a potential therapeutic benefit for postmenopausal osteoporosis (PMOP).

Basivertebral foramen (BF) is a natural orifice in the posterior wall of the vertebral body existing in humans and mammals, through which the basal vertebral vein, branch of lumbar artery and recurrent branch of spinal nerve enter and exit the vertebral body. BF changes the local microstructure of the vertebral body, resulting in cortical defect and sparse trabecular bone in the central region of the vertebral body, thus affecting its biomechanical characteristics and making its central region a “weak” area of the vertebra. Some characteristic injuries of the vertebra are related to BF, such as vertebral compression fracture and intervertebral cleft, vertebral burst fracture and posterior upper vertebral fracture fragment, and cement leakage during treatment. In this article, the anatomical and developmental biological characteristics of BF, the impact of BF on biomechanical characteristics, and the treatment of BF related vertebral diseases are reviewed, in order to provide references for the clinical diagnosis and treatment of vertebral injuries.

Ossification of the sacrotuberous ligament is a rare occurrence in soft tissue, with only 15 cases reported in the past few decades. We reported two cases of bilateral ossification in sacrotuberous ligaments and provided a concise review of the literature on this pathology. Clinical data, radiographic outcomes, and diagnostic and treatment details were obtained. This study aimed to summarize this disease's characteristics and investigate its pathogenesis through a review of literature from the last thirty years. This condition is often incidentally confirmed in elderly males via imagiological examination or gross anatomy and presents a low morbidity rate. Its pathogenesis may be related to stress concentration, excessive intake of element ions, injury repair, and improper operative technique. The majority of patients may not exhibit any clinical symptoms or signs and typically do not require medical interventions. It may be complicated with pudendal nerve entrapment syndrome. The long‐term effects of surgical resection and the most effective treatment approach remain areas for further research.

Background: Osteoarthritis (OA) is the most prevalent age-related disease in the world. Chondrocytes undergo an age-dependent decline in their proliferation and synthetic capacity, which is the main cause of OA development. However, the intrinsic mechanism of chondrocyte senescence is still unclear. This study aimed to investigate the role of a novel long non-coding RNA (lncRNA), AC006064.4–201 in the regulation of chondrocyte senescence and OA progression and to elucidate the underlying molecular mechanisms. Methods: The function of AC006064.4–201 in chondrocytes was assessed using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF) and β-galactosidase staining. The interaction between AC006064.4–201 and polypyrimidine tract-binding protein 1 (PTBP1), as well as cyclin-dependent kinase inhibitor 1B (CDKN1B), was evaluated using RPD-MS, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down assays. Mice models were used to investigate the role of AC006064.4–201 in post-traumatic and age-related OA in vivo. Results: Our research revealed that AC006064.4–201 was downregulated in senescent and degenerated human cartilage, which could alleviate senescence and regulate metabolism in chondrocytes. Mechanically, AC006064.4–201 directly interacts with PTBP1 and blocks the binding between PTBP1 and CDKN1B mRNA, thereby destabilizing CDKN1B mRNA and decreasing the translation of CDKN1B. The in vivo experiments were consistent with the results of the in vitro experiments. Conclusions: The AC006064.4–201/PTBP1/CDKN1B axis plays an important role in OA development and provides new molecular markers for the early diagnosis and treatment of OA in the future. Graphical Schematic diagram of AC006064.4–201 mechanism. A schematic diagram of the mechanism underlying the effect of AC006064.4–201

A wide-band divide-by-2 injection-locked frequency divider (ILFD) based on a dual-resonance high-order tank is presented. The ILFD employs a distributed LC network as the dual resonance tank, and achieves an ultra-wide locking range. Fabricated in 1P7M 65 nm LP-CMOS process, the divide-by-2 ILFD consumes 7 mW from a 0.7V power supply, and realized a locking range of 87.0%, from 13 GHz to 33 GHz. The core circuit occupies an area of 0.22 mm×0.5 mm.