USP3 promotes osteosarcoma progression via deubiquitinating EPHA2 and activating the PI3K/AKT signaling pathway.

Ubiquitin-specific protease 3 (USP3) plays an important role in the progression of various tumors. However, the role of USP3 in osteosarcoma (OS) remains poorly understood. The aim of this study was to explore the biological function of USP3 in OS and the underlying molecular mechanism. We found that OS had higher USP3 expression compared with that of normal bone tissue, and high expression of USP3 was associated with poor prognosis in patients with OS. Overexpression of USP3 significantly increased OS cell proliferation, migration, and invasion. Mechanistically, USP3 led to the activation of the PI3K/AKT signaling pathway in OS by binding to EPHA2 and then reducing its protein degradation. Notably, the truncation mutant USP3-F2 (159-520) interacted with EPHA2, and amino acid 203 was found to play an important role in this process. And knockdown of EPHA2 expression reversed the pro-tumour effects of USP3-upregulating. Thus, our study indicates the USP3/EPHA2 axis may be a novel potential target for OS treatment.

Selective Autophagy Receptor NBR1 Retards Nucleus Pulposus Cell Senescence by Directing the Clearance of SRBD1.

Intervertebral disc degeneration (IDD) is a prevalent degenerative disorder that closely linked to aging. Numerous studies have indicated the crucial involvement of autophagy in the development of IDD. However, the non-selective nature of autophagy substrates poses great limitations on the application of autophagy-related medications. This study aims to enhance our comprehension of autophagy in the development of IDD and investigate a novel therapeutic approach from the perspective of selective autophagy receptor NBR1. Proteomics and immunoprecipitation and mass spectrometry analysis, combined with in vivo and in vitro experimental verification were performed. NBR1 is found to be reduced in IDD, and NBR1 retards cellular senescence and senescence-associated secretory phenotype (SASP) of nucleus pulposus cells (NPCs), primarily through its autophagy-dependent function. Mechanistically, NBR1 knockdown leads to the accumulation of S1 RNA-binding domain-containing protein 1 (SRBD1), which triggers cellular senescence via AKT1/p53 and RB/p16 pathways, and promotes SASP via NF-κß pathway in NPCs. Our findings reveal the function and mechanism of selective autophagy receptor NBR1 in regulating NPCs senescence and degeneration. Targeting NBR1 to facilitate the clearance of detrimental substances holds the potential to provide novel insights for IDD treatment.

Automated machine learning-based model for the prediction of delirium in patients after surgery for degenerative spinal disease.

OBJECTIVE: This study used machine learning algorithms to identify critical variables and predict postoperative delirium (POD) in patients with degenerative spinal disease. METHODS: We included 663 patients who underwent surgery for degenerative spinal disease and received general anesthesia. The LASSO method was used to screen essential features associated with POD. Clinical characteristics, preoperative laboratory parameters, and intraoperative variables were reviewed and were used to construct nine machine learning models including a training set and validation set (80% of participants), and were then evaluated in the rest of the study sample (20% of participants). The area under the receiver-operating characteristic curve (AUROC) and Brier scores were used to compare the prediction performances of different models. The eXtreme Gradient Boosting algorithms (XGBOOST) model was used to predict POD. The SHapley Additive exPlanations (SHAP) package was used to interpret the XGBOOST model. Data of 49 patients were prospectively collected for model validation. RESULTS: The XGBOOST model outperformed the other classifier models in the training set (area under the curve [AUC]: 92.8%, 95% confidence interval [CI]: 90.7%-95.0%), validation set (AUC: 87.0%, 95% CI: 80.7%-93.3%). This model also achieved the lowest Brier Score. Twelve vital variables, including age, serum albumin, the admission-to-surgery time interval, C-reactive protein level, hypertension, intraoperative blood loss, intraoperative minimum blood pressure, cardiovascular-cerebrovascular disease, smoking, alcohol consumption, pulmonary disease, and admission-intraoperative maximum blood pressure difference, were selected. The XGBOOST model performed well in the prospective cohort (accuracy: 85.71%). CONCLUSION: A machine learning model and a web predictor for delirium after surgery for the degenerative spinal disease were successfully developed to demonstrate the extent of POD risk during the perioperative period, which could guide appropriate preventive measures for high-risk patients.

Influence of ABO blood group on susceptibility to different pathological types of lung cancer: a retrospective study.

PURPOSE: Current research has shown a link between ABO blood group and many diseases. The purpose of this study aimed to investigate the influence of the ABO blood group on the risk of developing different pathological types of lung cancer. MATERIALS AND METHODS: This retrospective study was composed of 7681 patients with lung cancer and 12, 671 non-lung cancer patients who were admitted to the First Affiliated Hospital of Nanchang University from January 2016 to January 2021. The subjects with lung cancer were grouped into small cell lung cancer group (n = 725), lung adenocarcinoma group (n = 4520), and lung squamous cell carcinoma group (n = 2286) according to pathological types. The ABO blood group distribution of each lung cancer type group was compared with that of the control group. Statistical analysis was determined with chi-square and logistic regression. RESULTS: Univariate analysis showed that the ABO blood group distribution of lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer was different from that of the control group (P < 0.01). After adjusting for age, sex, smoking history, and drinking history, logistic regression analysis showed that the risk of lung adenocarcinoma in blood type O was higher than that in blood type A (P < 0.01). There was no significant difference in ABO blood group composition between small cell lung cancer group, lung squamous cell carcinoma group, and control group (P > 0.05). In addition, gender and age have an influence on all three types of lung cancer (P < 0.01). Smoking was a risk factor in lung squamous cell carcinoma and small cell carcinoma (P < 0.01). Alcohol consumption was a risk factor in lung adenocarcinoma (P < 0.01). CONCLUSION: ABO blood group may be correlated with the occurrence of lung adenocarcinoma in Jiangxi province, but not with lung squamous cell carcinoma and small cell carcinoma.

Aucubin promoted neuron functional recovery by suppressing inflammation and neuronal apoptosis in a spinal cord injury model.

BACKGROUND: Spinal cord injury (SCI) can cause severe motor impairment. Post-SCI treatment has focused primarily on secondary injury, with neuroinflammation and neuronal apoptosis as the primary therapeutic targets. Aucubin (Au), a Chinese herbal medicine, exerts anti-inflammatory and neuroprotective effects. The therapeutic effects of Aucubin in SCI have not been reported. METHODS: In this study, we carried out an in vivo SCI model and a series of in vitro experiments to explore the therapeutic effect of Aucubin. Western Blotting and immunofluorescence were used to study the effect of Aucubin on microglial polarization and neuronal apoptosis and its underlying mechanism. RESULTS: We found that Aucubin can promote axonal regeneration by reducing neuroinflammation and neuronal apoptosis, which is beneficial to motor recovery after spinal cord injury in rats. Our further in vitro experiments showed that Aucubin can activate the toll-like receptor 4 (TLR4)/myeloid differentiation protein-88 (MyD88)/IκBα/nuclear factor kappa B (NF-κB) signaling pathway to reduce neuroinflammation and reverse mitochondrial dysfunction to reduce neuronal apoptosis. CONCLUSIONS: In summary, these results suggest that Aucubin may ameliorate secondary injury after SCI by reducing neuroinflammation and neuronal apoptosis. Therefore, Au may be a promising post-SCI therapeutic drug.

Development and biomechanical test of a new pedicle screw for thoracolumbar spinal surgery.

Rupture of the medial pedicle wall often occurs during pedicle screw insertion. This allows the pedicle screw to compress or cut the nerve root and/or spinal cord. In this paper, we designed a new double-threaded pedicle screw that has a cylindrical outer diameter and a conical core diameter, with a wide thread at the front, no thread in the middle, and a narrow thread at the rear, according to an analysis of the shortcomings of the conventional pedicle screw and anatomical parameters in 300 healthy adult volunteers. After the screw was placed, the non-threaded portion of the screw was located at the vertebral pedicle. No nerve root cutting occurred if the screw was misplaced and the medial wall of the vertebral pedicle was broken. We then performed biomechanical tests using a static universal testing machine and compared the new double-threaded screws with the conventional full-threaded pedicle screws, however, the differences were not obvious. In compression bending fatigue tests, the novel double-threaded pedicle screws were subjected to 5 million fatigue cycle loads without failure. The current study demonstrated that the new pedicle screw possesses similar biomechanical features as those of the conventional fully threaded pedicle screw. This provides a basis for further clinical applications.