Multiomics analysis reveals the potential of LPCAT1-PC axis as a therapeutic target for human intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a highly prevalent musculoskeletal disorder that is associated with considerable morbidity. However, there is currently no drug available that has a definitive therapeutic effect on IDD. In this study, we aimed to identify the molecular features and potential therapeutic targets of IDD through a comprehensive multiomics profiling approach. By integrating transcriptomics, proteomics, and ultrastructural analyses, we discovered dysfunctions in various organelles, including mitochondria, the endoplasmic reticulum, the Golgi apparatus, and lysosomes. Metabolomics analysis revealed a reduction in total phosphatidylcholine (PC) content in IDD. Through integration of multiple omics techniques with disease phenotypes, a pivotal pathway regulated by the lysophosphatidylcholine acyltransferase 1 (LPCAT1)-PC axis was identified. LPCAT1 exhibited low expression levels and exhibited a positive correlation with PC content in IDD. Suppression of LPCAT1 resulted in inhibition of PC synthesis in nucleus pulposus cells, leading to a notable increase in nucleus pulposus cell senescence and damage to cellular organelles. Consequently, PC exhibits potential as a therapeutic agent, as it facilitates the repair of the biomembrane system and alleviates senescence in nucleus pulposus cells via reversal of downregulation of the LPCAT1-PC axis.

Palmitic acid induces lipid droplet accumulation and senescence in nucleus pulposus cells via ER-stress pathway.

Intervertebral disc degeneration (IDD) is a highly prevalent musculoskeletal disorder affecting millions of adults worldwide, but a poor understanding of its pathogenesis has limited the effectiveness of therapy. In the current study, we integrated untargeted LC/MS metabolomics and magnetic resonance spectroscopy data to investigate metabolic profile alterations during IDD. Combined with validation via a large-cohort analysis, we found excessive lipid droplet accumulation in the nucleus pulposus cells of advanced-stage IDD samples. We also found abnormal palmitic acid (PA) accumulation in IDD nucleus pulposus cells, and PA exposure resulted in lipid droplet accumulation and cell senescence in an endoplasmic reticulum stress-dependent manner. Complementary transcriptome and proteome profiles enabled us to identify solute carrier transporter (SLC) 43A3 involvement in the regulation of the intracellular PA level. SLC43A3 was expressed at low levels and negatively correlated with intracellular lipid content in IDD nucleus pulposus cells. Overexpression of SLC43A3 significantly alleviated PA-induced endoplasmic reticulum stress, lipid droplet accumulation and cell senescence by inhibiting PA uptake. This work provides novel integration analysis-based insight into the metabolic profile alterations in IDD and further reveals new therapeutic targets for IDD treatment.

Preparation and properties of lignin-based composite membranes.

Composite membranes were prepared from lignin alkali (LA), polyvinyl alcohol (PVA), and cellulose nanofibrils (CNF) using a simple, low-cost, and environmentally friendly method. The deodorization performances and structures of these membranes were also characterized. The sample referred to as L3C3P5 prepared with a solution containing 35.7 wt% LA, 53.6 wt% PVA, and 10.7 wt% CNF showed the best deodorization properties, and the H2S adsorption time reached 36 min. The adsorption performance was further improved by adding nano-CuO to the membrane, and the H2S adsorption time of the doped membrane L3C3P5C4 reached 60 min. While the H2S adsorption performance improved, structural analysis revealed that the addition of nano-CuO reduced the crystallinity in the membrane, caused the membrane to crack, and led to a decrease in the mechanical properties. The surface oxygens in the L3C3P5C4 membrane were primarily C-O bonds and lattice oxygens in CuO. After the H2S adsorption reaction, the lattice oxygen disappeared, and CuS products appeared.

Development and validation of CT-based radiomics nomogram for the classification of benign parotid gland tumors.

PURPOSE: Accurate preoperative diagnosis of parotid tumor is essential for the formulation of optimal individualized surgical plans. The study aims to investigate the diagnostic performance of radiomics nomogram based on contrast-enhanced computed tomography (CT) images in the differentiation of the two most common benign parotid gland tumors. METHODS: One hundred and ten patients with parotid gland tumors including 76 with pleomorphic adenoma (PA) and 34 with adenolymphoma (AL) confirmed by histopathology were included in this study. Radiomics features were extracted from contrast-enhanced CT images of venous phase. A radiomics model was established and a radiomics score (Rad-score) was calculated. Clinical factors including clinical data and CT features were assessed to build a clinical factor model. Finally, a nomogram incorporating the Rad-score and independent clinical factors was constructed. Receiver operator characteristics (ROC) curve was generated and the area under the ROC curve (AUC) was calculated to quantify the discriminative performance of each model on both the training and validation cohorts. Decision curve analysis (DCA) was conducted to evaluate the clinical usefulness of each model. RESULTS: The radiomics model showed good discrimination in the training cohort [AUC, 0.89; 95% confidence interval (CI), 0.80-0.98] and validation cohort (AUC, 0.89; 95% CI, 0.77-1.00). The radiomics nomogram showed excellent discrimination in the training cohort (AUC, 0.98; 95% CI, 0.96-1.00) and validation cohort (AUC, 0.95; 95% CI, 0.88-1.00) and displayed better discrimination efficacy compared with the clinical factor model (AUC, 0.93; 95% CI, 0.88-0.99) in the training cohort (p < 0.05). The DCA demonstrated that the combined radiomics nomogram provided superior clinical usefulness than clinical factor model and radiomics model. CONCLUSIONS: The CT-based radiomics nomogram combining Rad-score and clinical factors exhibits excellent predictive capability for differentiating parotid PA from AL, which might hold promise in assisting radiologists and clinicians in the exact differential diagnosis and formulation of appropriate treatment strategy.

Radiographic analysis of dynamic lumbar motion during the five-repetition sit-to-stand test in degenerative lumbar spondylolisthesis.

BACKGROUND: To investigate the mechanisms of low back pain triggered by the five-repetition sit-to-stand test (5R-STS test) in degenerative lumbar spondylolisthesis (DLS) from radiographic perspective, as well as to determine the most useful diagnostic modalities in the evaluation of segmental instability. METHODS: We retrospectively performed a study of 78 patients (23 men and 55 women) with symptomatic DLS at L4/5 in our institution between April 2020 and December 2021. Each patient was assessed by using the 5R-STS test and received a series of radiographs including the upright standing, normal sitting, standing flexion-extension radiographs, and supine sagittal MR images. Enrolled patients were divided into two groups based on the 5R-STS test score: severe group and mild group. Translational and angular motion was determined by comparing normal sitting radiograph (N) with upright standing radiograph (U) (Combined, NU), flexion/extension radiographs (FE) as well as normal sitting radiograph (N) with a supine sagittal MR image (sMR) (Combined, N-sMR). RESULTS: Overall, 78 patients were enrolled, and there were 31(39.7%) patients in group S and 47(60.3%) patients in group M, with an average age of 60.7 ± 8.4 years. The normal sitting radiograph demonstrated the maximum slip percentage (SP) and the highest kyphotic angle both in group S and group M. Compared with group M, group S revealed significantly higher SP in the normal sitting position (24.1 vs 19.6; p = 0.002). The lumbar slip angular in group S with a sitting position was significantly higher than that in group M (-5.2 vs -1.3; p < 0.001). All patients in group S had objective functional impairment (OFI) and 28 patients of them were diagnosed with lumbar instability by using the combination of normal sitting radiograph (N) and supine sagittal MR image (sMR) (Combined, N-sMR). CONCLUSION: DLS patients with positive sign of the 5R-STS test is a distinct subgroup associated with lumbar instability. The modality of the combination of normal sitting radiograph (N) and supine sagittal MR image (sMR) had a significant advantage in terms of the ability to identify segmental instability.

Diagnostic value of 18F-FDG PET/MRI in recurrent pelvis malignancies of female patients: a systematic review and meta-analysis.

The aim of this study was to assess the diagnostic performance of fluorine-18-fluorodeoxyglucose (F-FDG) PET/MRI for suspected recurrence of pelvis malignancies of female patients using a meta-analysis. We performed a systematical literature search for relevant studies in PubMed, Cochrane Library, Google Scholar, and several Chinese databases. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the quality of all included studies. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were calculated per patient and per lesion. Summary receiver operating characteristic curves were also constructed. All procedures involving human participants in this study were performed in conformity with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Finally, seven articles comprising 257 patients and 695 lesions were included in this meta-analysis. On patient-based analysis, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of F-FDG PET/MRI in detecting recurrence of pelvis malignancies were 0.96 [95% confidence interval (CI): 0.93-0.99], 0.95 (95% CI: 0.87-0.99), 9.85 (95% CI: 4.62-21.00), 0.07 (95% CI: 0.04-0.13), and 201.41 (95% CI: 62.89-645.03), respectively. On lesion-based analysis, the corresponding estimates were 0.99 (95% CI: 0.97-1.00), 0.94 (95% CI: 0.89-0.97), 17.11 (95% CI: 4.46-65.60), 0.02 (95% CI: 0.01-0.05), and 1125.24 (95% CI: 211.46-5987.79), respectively. The results of our meta-analysis indicate that F-FDG PET/MRI has excellent diagnostic performance in restaging female patients with suspected recurrence of gynecological pelvic malignancies.