Postoperative adding-on phenomenon in Lenke 1A/B and 2A/B adolescent idiopathic scoliosis: risk factors and predictive index.

PURPOSE: The aim of this study was to identify associated risk factors of distal adding-on phenomenon in Lenke 1A/B and 2A/B adolescent idiopathic scoliosis (AIS) patients and establish the corresponding prediction model. METHODS: The clinical data of 119 Lenke 1A/B and 2A/B AIS patients were retrospectively analyzed. Preoperative, first erect (FE) radiographic parameters and radiographic parameters at the last follow-up were measured. Patients were divided into the adding-on group and the no adding-on group according to whether the adding-on phenomenon was observed at the last follow-up. Univariate analysis and multivariate logistic regression analysis were used to establish the corresponding prediction model. RESULTS: Adding-on affected 39 (32.8%) patients at the last follow-up. Risser sign and 19 radiographic parameters showed significant differences between the two groups by univariate analysis. Stepwise logistic regression analysis found that the Risser sign and so on five predictor variable, and the nomogram was drawn. The calibration curve showed that the model fitted well. The area under the receiver operating characteristic (ROC) curve is 0.949. And the decision curve analysis curve model within the threshold range for interventions to improve clinical outcomes. There was no significant difference in SRS-22 scores between the two groups. CONCLUSIONS: This study established a prediction model with adding-on in Lenke 1A/B and 2A/B AIS patients. The nomogram contains five predictive variables, which can effectively predict the probability of adding-on phenomenon during follow-up, and may have greater clinical value for the treatment and prevention of adding-on phenomenon.

Precise Lubrication and Protection of Cartilage Damage by Targeting Hydrogel Microsphere.

Osteoarthritis (OA) is a degenerative bone and joint disease characterized by decreased cartilage lubrication, leading to continuous wear and ultimately irreversible damage. This situation is particularly challenging for early-stage OA, as current bio-lubricants lack precise targeting for small inflammatory lesions. In this work, an antibody-mediated targeting hydrogel microspheres (HMS) is developed to precisely lubricate the local injury site of cartilage and prevent the progression of early OA. Anti-Collagen type I (Anti-Col1) is an antibody that targets cartilage injury sites in early OA stages. It is anchored on a HMS matrix made of Gelatin methacrylate (GelMA) and poly (sulfobetaine methacrylate) (PSBMA) to create targeted HMS (T-G/S HMS). The T-G/S HMS's high hydrophilicity, along with the dynamic interaction between its surficial Anti-Col1 and the Col1 on cartilage injury site, ensures its precise and effective lubrication of early OA lesions. Consequently, injecting T-G/S HMS into rats with early OA significantly slows disease progression and reduces symptoms. In conclusion, the developed injectable targeted lubricating HMS and the precisely targeted lubrication strategy represent a promising, convenient technique for treating OA, particularly for slowing the early-stage OA progression.

Cobalt nanoparticles attenuate microplastic-induced vascular endothelial injury via Nrf2 pathway activation.

The widespread utilization of plastic and cobalt alloy products in industries and medicine has led to the increased presence of their degradation byproducts, microplastics (MPs), and cobalt nanoparticles (Co NPs), in the environment and organisms. While these particles can circulate throughout the body via the circulatory system, their specific adverse effects and mechanisms on the vascular system remain unclear. Employing scanning electron microscope (SEM) analysis and other methodologies, we demonstrate the potential adsorption and aggregation phenomena between MPs and Co NPs. In vitro experiments illustrate that ingestion of either MPs or Co NPs compromises vascular endothelial cell function and induces the generation of reactive oxygen species (ROS). Notably, this effect is markedly attenuated when a combination of MPs and Co NPs is administered compared to MPs alone. Additionally, zebrafish experiments validate our in vitro findings. Mechanistic studies have demonstrated that both MPs and Co NPs induce aberrant Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Intriguingly, a weaker activation level is observed when these agents are administered in combination compared to when they are administered individually. Our study provides novel insights into the interaction between MPs and Co NPs and their detrimental effects on vascular endothelial cells.

Titanium nanoparticles released from orthopedic implants induce muscle fibrosis via activation of SNAI2.

Titanium alloys represent the prevailing material employed in orthopedic implants, which are present in millions of patients worldwide. The prolonged presence of these implants in the human body has raised concerns about possible health effects. This study presents a comprehensive analysis of titanium implants and surrounding tissue samples obtained from patients who underwent revision surgery for therapeutic reasons. The surface of the implants exhibited nano-scale corrosion defects, and nanoparticles were deposited in adjacent samples. In addition, muscle in close proximity to the implant showed clear evidence of fibrotic proliferation, with titanium content in the muscle tissue increasing the closer it was to the implant. Transcriptomics analysis revealed SNAI2 upregulation and activation of PI3K/AKT signaling. In vivo rodent and zebrafish models validated that titanium implant or nanoparticles exposure provoked collagen deposition and disorganized muscle structure. Snai2 knockdown significantly reduced implant-associated fibrosis in both rodent and zebrafish models. Cellular experiments demonstrated that titanium dioxide nanoparticles (TiO2 NPs) induced fibrotic gene expression at sub-cytotoxic doses, whereas Snai2 knockdown significantly reduced TiO2 NPs-induced fibrotic gene expression. The in vivo and in vitro experiments collectively demonstrated that Snai2 plays a pivotal role in mediating titanium-induced fibrosis. Overall, these findings indicate a significant release of titanium nanoparticles from the implants into the surrounding tissues, resulting in muscular fibrosis, partially through Snai2-dependent signaling.

Fibroblast Growth Factor 23 is a Potential Prognostic Biomarker in Uterine Sarcoma.

BACKGROUND: Uterine sarcoma (US) is a highly malignant cancer with poor prognosis and high mortality in women. In this study, we evaluated the expression of human fibroblast growth factor 23 (FGF23) in different US subtypes and the relationship between survival and clinicopathological characteristics. METHODS: We conducted a comparative analysis of FGF23 gene expression in different pathological types of US. Utilizing a cohort from The Cancer Genome Atlas of 57 patients, a 50-patient microarray dataset (GSE119043) from the Gene Expression Omnibus and a Suining cohort of 44 patients, we analyzed gene expression profiles and corresponding clinicopathological information. Immunohistochemistry was used to examine the expression level of FGF23 in four US subtypes. Survival analysis was used to assess the relationship between FGF23 expression and prognosis in US patients. RESULTS: Compared with uterine normal smooth muscle and uterine leiomyoma, FGF23 expression was significantly upregulated in US and was differentially expressed in four US subtypes. Uterine carcinosarcoma exhibited the highest expression of FGF23 among the subtypes. Survival analysis revealed no correlation between FGF23 expression and either overall survival or progression-free survival in US (P > 0.05). Similar results were obtained from the validation cohorts. Univariate and multivariate analyses showed no significant correlation between FGF23 expression and the US prognosis. Tumor stage, CA125, and tumor recurrence were independent prognostic factors for survival of US patients. CONCLUSION: FGF23 was highly expressed in US and was promising as a novel potential biomarker for the diagnosis and prognosis of US.

A Mechanistic Study of the Osteogenic Effect of Arecoline in an Osteoporosis Model: Inhibition of Iron Overload-Induced Osteogenesis by Promoting Heme Oxygenase-1 Expression.

Iron overload-associated osteoporosis presents a significant challenge to bone health. This study examines the effects of arecoline (ACL), an alkaloid found in areca nut, on bone metabolism under iron overload conditions induced by ferric ammonium citrate (FAC) treatment. The results indicate that ACL mitigates the FAC-induced inhibition of osteogenesis in zebrafish larvae, as demonstrated by increased skeletal mineralization and upregulation of osteogenic genes. ACL attenuates FAC-mediated suppression of osteoblast differentiation and mineralization in MC3T3-E1 cells. RNA sequencing analysis suggests that the protective effects of ACL are related to the regulation of ferroptosis. We demonstrate that ACL inhibits ferroptosis, including oxidative stress, lipid peroxidation, mitochondrial damage, and cell death under FAC exposure. In this study, we have identified heme oxygenase-1 (HO-1) as a critical mediator of ACL inhibiting ferroptosis and promoting osteogenesis, which was validated by HO-1 knockdown and knockout experiments. The study links ACL to HO-1 activation and ferroptosis regulation in the context of bone metabolism. These findings provide new insights into the mechanisms underlying the modulation of osteogenesis by ACL. Targeting the HO-1/ferroptosis axis is a promising therapeutic approach for treating iron overload-induced bone diseases.

Ultra-Wideband Ranging Error Mitigation with Novel Channel Impulse Response Feature Parameters and Two-Step Non-Line-of-Sight Identification.

The effective identification and mitigation of non-line-of-sight (NLOS) ranging errors are essential for achieving high-precision positioning and navigation with ultra-wideband (UWB) technology in harsh indoor environments. In this paper, an efficient UWB ranging-error mitigation strategy that uses novel channel impulse response parameters based on the results of a two-step NLOS identification, composed of a decision tree and feedforward neural network, is proposed to realize indoor locations. NLOS ranging errors are classified into three types, and corresponding mitigation strategies and recall mechanisms are developed, which are also extended to partial line-of-sight (LOS) errors. Extensive experiments involving three obstacles (humans, walls, and glass) and two sites show an average NLOS identification accuracy of 95.05%, with LOS/NLOS recall rates of 95.72%/94.15%. The mitigated LOS errors are reduced by 50.4%, while the average improvement in the accuracy of the three types of NLOS ranging errors is 61.8%, reaching up to 76.84%. Overall, this method achieves a reduction in LOS and NLOS ranging errors of 25.19% and 69.85%, respectively, resulting in a 54.46% enhancement in positioning accuracy. This performance surpasses that of state-of-the-art techniques, such as the convolutional neural network (CNN), long short-term memory-extended Kalman filter (LSTM-EKF), least-squares-support vector machine (LS-SVM), and k-nearest neighbor (K-NN) algorithms.

Selenium Nanoparticles Attenuate Cobalt Nanoparticle-Induced Skeletal Muscle Injury: A Study Based on Myoblasts and Zebrafish.

Cobalt alloys have numerous applications, especially as critical components in orthopedic biomedical implants. However, recent investigations have revealed potential hazards associated with the release of nanoparticles from cobalt-based implants during implantation. This can lead to their accumulation and migration within the body, resulting in adverse reactions such as organ toxicity. Despite being a primary interface for cobalt nanoparticle (CoNP) exposure, skeletal muscle lacks comprehensive long-term impact studies. This study evaluated whether selenium nanoparticles (SeNPs) could mitigate CoNP toxicity in muscle cells and zebrafish models. CoNPs dose-dependently reduced C2C12 viability while elevating reactive oxygen species (ROS) and apoptosis. However, low-dose SeNPs attenuated these adverse effects. CoNPs downregulated myogenic genes and α-smooth muscle actin (α-SMA) expression in C2C12 cells; this effect was attenuated by SeNP cotreatment. Zebrafish studies confirmed CoNP toxicity, as it decreased locomotor performance while inducing muscle injury, ROS generation, malformations, and mortality. However, SeNPs alleviated these detrimental effects. Overall, SeNPs mitigated CoNP-mediated cytotoxicity in muscle cells and tissue through antioxidative and antiapoptotic mechanisms. This suggests that SeNP-coated implants could be developed to eliminate cobalt nanoparticle toxicity and enhance the safety of metallic implants.

Ginsenoside Rg1 modulates PI3K/AKT pathway for enhanced osteogenesis via GPER.

BACKGROUND: Osteoporosis is a systemic skeletal disorder characterized by decreased bone density and the degradation of bone tissue microarchitecture. Ginsenoside Rg1, derived from Panax ginseng, has been a part of traditional Chinese medicine in China for centuries, particularly for treating osteoporosis. However, there remains limited research on the osteogenic potential of Rg1 within the glucocorticoid-induced osteoporosis (GIOP) model and its specific mechanisms. PURPOSE: The primary objective of this study is to investigate the osteogenic potential of Rg1 within the GIOP model and explore the signaling pathways associated with its in vivo and in vitro effects. METHODS: Cell proliferation, differentiation and mineralization were evaluated by the Cell counting kit 8(CCK8) assay, alkaline phosphatase (ALP) test and Alizarin Red S staining, respectively. The qPCR technique was used to determine the relative expression of mRNA and the western blot was used to determine the relative expression of protein. In vivo experiments, spinal vertebrae staining in zebrafish larvae was accomplished by alizarin red S staining. RESULTS: Zebrafish larvae's hatching, survival, malformation, and heart rate were unaffected by 50 µM of Rg1 in vivo, while the MEC3T3-E1 cell line's proliferation was unaffected by 50 µM of Rg1 in vitro. Meanwhile, Rg1 was shown to improve osteogenic differentiation or bone formation as well as the level of mRNA expression of osteogenic markers in vivo and in vitro. Treatment with Rg1 significantly increased the expression of G protein-coupled estrogen receptor (GPER) and pAKT. In addition, the GPER inhibitor G15 could significantly reduce the mRNA and protein expression levels of GPER and phosphorylated AKT, LY294002, a PI3K/AKT pathway inhibitor, markedly suppresses the expression of phosphorylated AKT, yet shows no significant impact on GPER expression. Both G15 and LY294002 can significantly blocked the Rg1-mediated enhancement of osteogenesis capacity in the GIOP model. In contrast, when both the agonists G1 of GPER and LY294002 were added, G1 increased the relative expression of mRNA and protein of GPER, but not the expression of osteogenic capacity and osteogenic markers. CONCLUSIONS: This study investigates the mineralization effects and mechanisms of Ginsenoside Rg1 both in vitro and in vivo. For the first time, we propose that Rg1 might regulate osteogenesis by modulating AKT phosphorylation through mediating GPER expression within the PI3K/AKT pathway in the GIOP model. This discovery introduces novel targets and avenues for osteoporosis treatment.

High-salt diet induces dyslipidemia through the SREBP2/PCSK9 pathway in dahl salt-sensitive rats.

A high-salt diet is known to increase serum cholesterol levels; however, the underlying mechanism of salt-induced dyslipidemia in patients with salt-sensitivity remains poorly understood. We aimed to investigate whether high-salt diet (HSD) can induce dyslipidemia and elucidate the underlying mechanism of salt-induced dyslipidemia in Dahl salt-sensitive (SS) rats. Metabolomic and biochemical analyses revealed that the consumption of an HSD (8 % NaCl) significantly increased the serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in SS rats. The enzyme-linked immunosorbent assay demonstrated an increase in circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels, accompanied by a decrease in hepatic low-density lipoprotein receptor (LDLR) levels due to HSD consumption. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis revealed that HSD consumption activated sterol regulatory element-binding protein-2 (SREBP2) expression in the liver and kidney, resulting in upregulation of PCSK9 at the transcriptional level in the liver and at the translational level in the kidney, ultimately increasing circulating PCSK9 levels. The combined effects of HSD on the liver and kidney contributed to the development of hypercholesterolemia. Furthermore, an in vitro assay confirmed that high-salt exposure led to an increase in the protein expression of SREBP2 and PCSK9 secretion, thereby reducing low-density lipoprotein (LDL) uptake. This study, for the first time, shows that an HSD induces dyslipidemia through activation of the SREBP2/PCSK9 pathway, providing new insights into the prevention and treatment of dyslipidemia in patients with salt sensitivity.

Phosphorylated heat shock protein 27 improves the bone formation ability of osteoblasts and bone marrow stem cells from patients with adolescent idiopathic scoliosis.

Background: Adolescent idiopathic scoliosis (AIS) is a scoliotic deformity of unknown etiology that occurs during adolescent development. Abnormal bone metabolism is closely related to AIS, but the cause is uncertain. Recent studies have shown that heat shock protein 27 (HSP27) and its phosphorylation (pHSP27) play important roles in bone metabolism. However, whether HSP27 and pHSP27 are involved in abnormal bone metabolism in AIS is unclear. Methods: Osteoblasts (OBs) and bone marrow stem cells (BMSCs) were extracted from the facet joints and bone marrow of AIS patients and controls who underwent posterior spinal fusion surgery. The expression levels of HSP27 and pHSP27, as well as the expression levels of bone formation markers in OBs from AIS patients and controls, were examined by quantitative real-time PCR (qRT-PCR) and Western blotting. The mineralization ability of OBs from AIS patients and controls was analyzed by alizarin red staining after osteogenic differentiation. Heat shock and thiolutin were used to increase the levels of pHSP27 in OBs, and the levels of bone formation markers were also investigated. In addition, the levels of pHSP27 and the bone formation ability of BMSCs from AIS patients and controls were investigated after heat shock treatment. Results: Lower pHSP27 levels and impaired osteogenic differentiation abilities were observed in the OBs of AIS patients than in those of controls. Thiolutin increased HSP27 phosphorylation and increased the mRNA levels of SPP1 and ALPL in OBs from AIS patients. Heat shock treatment increased SPP1 and HSP27 mRNA expression, pHSP27 levels, OCN expression, and mineralization ability of both OBs and BMSCs from AIS patients. Conclusion: Heat shock treatment and thiolutin can increase the levels of pHSP27 and further promote the bone formation of OBs and BMSCs from AIS patients. Therefore, decreased pHSP27 levels may be associated with abnormal bone metabolism in AIS patients.

Dendrobium offificinale polysaccharides prevents glucocorticoids-induced osteoporosis by destabilizing KEAP1-NRF2 interaction.

Glucocorticoid-induced osteoporosis (GIOP) represents the foremost cause of secondary osteoporosis and fragility fractures. Novel therapeutic strategies for GIOP are needed, with improved safety profiles and reduced costs compared to current options. Dendrobium officinale (D. officinale) is a traditional Chinese medicine that has been reported to have beneficial effects on bone metabolism. Here, we sought to investigate the impacts of D. officinale polysaccharides (DOP), the main active constituents of D. officinale, on GIOP in vivo models and dexamethasone (DEX)-treated osteoblast lineage cells. We found that low concentrations of DOP are relatively safe in vitro and in vivo, respectively. Importantly, we found that DOP treatment significantly inhibited DEX-induced osteoporosis in two in vivo models, zebrafish and mice, while boosting osteogenic differentiation of hBMSCs exposed to DEX. Futhermore, our data reveal that DOP elevates nuclear Nrf2 levels under DEX treatment, by suppressing of Nrf2 ubiquitination. Leveraging Keap1b knockout zebrafish and RNAi approach, we demonstrated that DOP disrupts the association of Nrf2/Keap1, resulting in the inhibition of Nrf2 ubiquitination. Taken together, these results illuminate that DOP stimulates osteogenesis in the presence of DEX by destabilizing the Nrf2/Keap1 interaction. These findings suggest that DOP may serve as a novel drug against osteoporosis caused by glucocorticoids.

A Hybrid Indoor Altimetry Based on Barometer and UWB.

Accurate altimetry is essential for location-based services in commercial and industrial applications. However, current altimetry methods only provide low-accuracy measurements, particularly in multistorey buildings with irregular structures, such as hollow areas found in various industrial and commercial sites. This paper innovatively proposes a tightly coupled indoor altimetry system that utilizes floor identification to improve height measurement accuracy. The system includes two optimized algorithms that improve floor identification accuracy through activity detection and address the problem of difficult convergence of z-axis coordinates due to indoor coplanarity by applying constraints to iterative least squares (ILS). Two experiments were conducted in a teaching building and a laboratory, including an irregular environment with a hollow area. The results show that our proposed method for identifying floors based on activity detection outperforms other methods. In dynamic experiments, our method effectively eliminates repeated transformations during the up- and downstairs process, and in static experiments, it minimizes the impact of barometric drift. Furthermore, our proposed altimetry method based on constrained ILS achieves significantly improved positioning accuracy compared to ILS, 1D-CNN, and WC. Specifically, in the teaching building, our method achieves improvements of 0.84 m, 0.288 m, and 0.248 m, respectively, while in the laboratory, the improvements are 2.607 m, 0.696 m, and 0.625 m.

Promotion effect of FGF23 on osteopenia in congenital scoliosis through FGFr3/TNAP/OPN pathway.

BACKGROUND: Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. METHODS: We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. RESULTS: DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. CONCLUSIONS: Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.

Mechanically robust conjugated microporous polymer membranes prepared using polyvinylpyrrolidone (PVP) electrospun nanofibers as a template for efficient PM capture.

Air pollution has become a challenging environmental problem worldwide due to rapid industrial development and excessive emissions of vehicle exhaust. Herein, we report a preparation of conjugated microporous polymer membranes (CMPM) with a hierarchical porous structure by electrospun polyvinylpyrrolidone (PVP) nanofibers as a template for effective removal of PM from airborne and vehicle exhaust. CMP membranes have hierarchical holes, where the macropores are from electrospun nanofiber membranes and the mesopores are from polymer synthesis. Taking advantage of its inherent physicochemical and thermal stability and hierarchical hole characteristics, the CMPM-based filter can work continuously for up to 36 h and still maintains a high removal efficiency (>99.56%), and also has a high filtration efficiency in the treatment of vehicle exhausts, with 95.18% for PM0.3, 98% for PM0.5 and >99% for PM2.5-10.0. The superior mechanical properties of CMPM allow the filter to be cleaned and reused. After three cycles, the filtration effectiveness of CMPM is still 94.83% for respirable particulate matter. Under high humidity (RH ≥ 95%) conditions, the CMPM-based filter showed higher than 95.37% filtration of PM0.3-10, and the oil adsorption rate could be maintained at 284% at high speed, proving the great potential of CMPM to clean air in complex situations.

Cervical Staphylococcus aureus Infection after Receiving the Third Dose of COVID-19 Vaccination: A Case Report.

INTRODUCTION: Vaccination is one of the most effective ways to control the COVID-19 pandemic. However, as the number of people vaccinated against COVID-19 continues to increase, there are more reports on the safety of vaccines. So far, there have been no reported cases of spinal infection associated with COVID-19 vaccination. Recently, we admitted a patient who developed cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine when the symptoms of cold did not completely disappear. CASE PRESENTATION: The patient was a 70-year-old man who received the third injection of COVID-19 vaccine when the cold symptoms were not completely gone. On the day after the injection, the patient developed severe neck and shoulder pain, accompanied by numbness and fatigue in the limbs. MRI examination of the cervical spine on day 6 after vaccination showed no obvious signs of infection. The patient had progressive weakness in the extremities. On the ninth day after vaccination, the patient developed paralysis of both lower limbs and significant sensory loss. Cervical abscess and cervical spinal cord injury were considered for cervical CT and MRI examination on the 15th day after vaccination. We used an anterior approach to remove as much of the lesion as possible. Staphylococcus aureus was detected and antibiotic treatment was continued after surgery. The patient's pain symptoms were significantly relieved, which prevented the abscess from further pressing the spinal cord and provided possible conditions for the recovery of neurological function in the later stage. CONCLUSION: This case is the first reported cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine with low immunity. This case raises awareness of this rare but potentially life-threatening adverse reaction, and reminds people to hold off when their immune system is weakened.

Abnormal TNS3 gene methylation in patients with congenital scoliosis.

BACKGROUND: Congenital scoliosis (CS) is a congenital deformity of the spine resulting from abnormal and asymmetrical development of vertebral bodies during pregnancy. However, the etiology and mechanism of CS remain unclear. Epigenetics is the study of heritable variations in gene expression outside of changes in nucleotide sequence. Among these, DNA methylation was described first and is the most characteristic and most stable epigenetic mechanism. Therefore, in this study, we aim to explore the association between genome methylation and CS which are not been studied before. METHODS: Two pairs of monozygotic twins were included, with each pair involving one individual with and one without CS. Agilent SureSelect XT Human Methyl-Sequencing was used for genome methylation sequencing. MethylTarget was used to detect methylation levels in target regions. Immunohistochemistry was performed to visualize expression of associated genes in candidate regions. RESULTS: A total of 75 differentially methylated regions were identified, including 24 with an increased methylation level and 51 with a decreased methylation level in the CS group. Nine of the differentially methylated regions were selected (TNS3, SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, and GRHL2). The results showed that the methylation level of the promoter region of TNS3 was 0.72 ± 0.08 in the CS group and 0.43 ± 0.06 in the control group (p = 0.00070 < 0.01). There was no significant difference in the degree of methylation of SEMAC3, GPR124, MEST, DLK1, SNTG1, PPIB, DEF8, or GRHL2 between the two groups. Immunohistochemistry showed significantly decreased TNS3 expression in the cartilage of the articular process in CS (CS: 0.011 ± 0.002; control: 0.018 ± 0.006, P = 0.003 < 0.01). CONCLUSION: Compared with the control group, high-level methylation of the TNS3 promoter region and low TNS3 expression in the cartilage layer of the articular process characterize CS. Thus, DNA methylation and TNS3 may play important roles in the pathogenesis of CS.

Elucidation of the Application of Blood Test Biomarkers to Predict Immune-Related Adverse Events in Atezolizumab-Treated NSCLC Patients Using Machine Learning Methods.

Background: Development of severe immune-related adverse events (irAEs) is a major predicament to stop treatment with immune checkpoint inhibitors, even though tumor progression is suppressed. However, no effective early phase biomarker has been established to predict irAE until now. Method: This study retrospectively used the data of four international, multi-center clinical trials to investigate the application of blood test biomarkers to predict irAEs in atezolizumab-treated advanced non-small cell lung cancer (NSCLC) patients. Seven machine learning methods were exploited to dissect the importance score of 21 blood test biomarkers after 1,000 simulations by the training cohort consisting of 80%, 70%, and 60% of the combined cohort with 1,320 eligible patients. Results: XGBoost and LASSO exhibited the best performance in this study with relatively higher consistency between the training and test cohorts. The best area under the curve (AUC) was obtained by a 10-biomarker panel using the XGBoost method for the 8:2 training:test cohort ratio (training cohort AUC = 0.692, test cohort AUC = 0.681). This panel could be further narrowed down to a three-biomarker panel consisting of C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), and thyroid-stimulating hormone (TSH) with a small median AUC difference using the XGBoost method [for the 8:2 training:test cohort ratio, training cohort AUC difference = -0.035 (p < 0.0001), and test cohort AUC difference = 0.001 (p=0.965)]. Conclusion: Blood test biomarkers currently do not have sufficient predictive power to predict irAE development in atezolizumab-treated advanced NSCLC patients. Nevertheless, biomarkers related to adaptive immunity and liver or thyroid dysfunction warrant further investigation.

A Two-Step Fusion Method of Wi-Fi FTM for Indoor Positioning.

The Wi-Fi fine time measurement (FTM) protocol specified in the IEEE 802.11-2016 standard provides a new two-way ranging approach to enhance positioning capability. Similar to other wireless signals, the accuracy of the real-time range measurement of FTM is influenced by various errors. In this work, the characteristics of the ranging errors is analyzed and an abstract ranging model is introduced. From the perspective of making full use of the range measurements from FTM, this paper designs two positioning steps and proposes a fusion method to refine the performance of indoor positioning. The first step is named single-point positioning, locating the position with the real-time range measurements based on the geometric principle. The second step is named the improved matching positioning, which constructs a distance database by utilizing the existing scene information and uses the modified matching algorithm to obtain the position. In view of the different positioning accuracies and error distributions from the results of the aforementioned two steps, a fusion method using the indirect adjustment principle is proposed to adjust the positioning results, and the advantages of the matching scene information and the range measurements are served simultaneously. Finally, a number of tests are conducted to assess the performance of the proposed method. The experimental results demonstrate that the precision and stability of indoor positioning are improved by the proposed fusion method.

Holey Ti3C2 nanosheets based membranes for efficient separation and removal of microplastics from water.

The accumulation of non-degradable microplastics (MPs) originated from the mass production and huge consumption of plastics of modern industry in the water environment has resulted in severe pollution problems globally. Herein, we report for the first time the preparation of holey Ti3C2Tx (h-Ti3C2Tx) membranes obtained by etching Co3O4 nanoparticles embedded on Ti3C2Tx nanosheets followed by simple vacuum filtration using polymeric membranes as supporting matrix for efficient removal of MPs from wastewater. The h-Ti3C2Tx nanosheets exhibit a planar porous structure which present nano-holes with an average hole-size of 25 nm in diameter, which facilitated the construction of membranes with better water flux for the separation of MPs. Using fluorescent PS (FP) microspheres of different diameters as microplastic models, the obtained h-Ti3C2Tx membranes exhibited extremely high MPs removal performance (up to 99.3% under our conditions). Moreover, a large water flux of 196.7 L h-1 m-2 k Pa-1 can be obtained, which can compete or be larger than that of most of the membranes composed of untreated two-dimension nanomaterials. Due to the physicochemical stability, tremendous large water reflux, and the high MPs removal efficiency of h-Ti3C2Tx membranes, there may be a great potential for practical applications in the separation and removal of various contaminants such as MPs or suspended solids from water.