MRI radiomics-based decision support tool for a personalized classification of cervical disc degeneration: a two-center study

Objectives: To develop and validate an MRI radiomics-based decision support tool for the automated grading of cervical disc degeneration.Methods: The retrospective study included 2,610 cervical disc samples of 435 patients from two hospitals. The cervical magnetic resonance imaging (MRI) analysis of patients confirmed cervical disc degeneration grades using the Pfirrmann grading system. A training set (1,830 samples of 305 patients) and an independent test set (780 samples of 130 patients) were divided for the construction and validation of the machine learning model, respectively. We provided a fine-tuned MedSAM model for automated cervical disc segmentation. Then, we extracted 924 radiomic features from each segmented disc in T1 and T2 MRI modalities. All features were processed and selected using minimum redundancy maximum relevance (mRMR) and multiple machine learning algorithms. Meanwhile, the radiomics models of various machine learning algorithms and MRI images were constructed and compared. Finally, the combined radiomics model was constructed in the training set and validated in the test set. Radiomic feature mapping was provided for auxiliary diagnosis.Results: Of the 2,610 cervical disc samples, 794 (30.4%) were classified as low grade and 1,816 (69.6%) were classified as high grade. The fine-tuned MedSAM model achieved good segmentation performance, with the mean Dice coefficient of 0.93. Higher-order texture features contributed to the dominant force in the diagnostic task (80%). Among various machine learning models, random forest performed better than the other algorithms (p < 0.01), and the T2 MRI radiomics model showed better results than T1 MRI in the diagnostic performance (p < 0.05). The final combined radiomics model had an area under the receiver operating characteristic curve (AUC) of 0.95, an accuracy of 89.51%, a precision of 87.07%, a recall of 98.83%, and an F1 score of 0.93 in the test set, which were all better than those of other models (p < 0.05).Conclusion: The radiomics-based decision support tool using T1 and T2 MRI modalities can be used for cervical disc degeneration grading, facilitating individualized management

Nitrogen Sources Reprogram Carbon and Nitrogen Metabolism to Promote Andrographolide Biosynthesis in <i>Andrographis paniculata</i> (Burm.f.) Nees Seedlings

Carbon (C) and nitrogen (N) metabolisms participate in N source-regulated secondary metabolism in medicinal plants, but the specific mechanisms involved remain to be investigated. By using nitrate (NN), ammonium (AN), urea (UN), and glycine (GN), respectively, as sole N sources, we found that N sources remarkably affected the contents of diterpenoid lactone components along with C and N metabolisms reprograming in Andrographis paniculata, as compared to NN, the other three N sources raised the levels of 14-deoxyandrographolide, andrographolide, dehydroandrographolide (except UN), and neoandrographolide (except AN) with a prominent accumulation of farnesyl pyrophosphate (FPP). These N sources also raised the photosynthetic rate and the levels of fructose and/or sucrose but reduced the activities of phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoenolpyruvate carboxylase (PEPC) and pyruvate dehydrogenase (PDH). Conversely, phosphoenolpyruvate carboxykinase (PEPCK) and malate enzyme (ME) activities were upregulated. Simultaneously, citrate, cis-aconitate and isocitrate levels declined, and N assimilation was inhibited. These results indicated that AN, UN and GN reduced the metabolic flow of carbohydrates from glycolysis into the TCA cycle and downstream N assimilation. Furthermore, they enhanced arginine and GABA metabolism, which increased C replenishment of the TCA cycle, and increased ethylene and salicylic acid (SA) levels. Thus, we proposed that the N sources reprogrammed C and N metabolism, attenuating the competition of N assimilation for C, and promoting the synthesis and accumulation of andrographolide through plant hormone signaling. To obtain a higher production of andrographolide in A. paniculata, AN fertilizer is recommended in its N management

The Correlation between Aquaporin-4 Antibody and the Visual Function of Patients with Demyelinating Optic Neuritis at Onset

ON patients with AQP4-Ab seropositivity tend to be predominantly female and young and have worse visual acuity and more severe damage to their visual fields compared with AQP4-Ab seronegativity

Berberine Protects Human Retinal Pigment Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Damage through Activation of AMPK

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly with less effective treatment, especially for dry AMD (90% of AMD). Although the etiology of this disease is not well elucidated, increasing evidences indicate that excessive reactive oxygen species (ROS) impairing the physiological functions of retinal pigment epithelium (RPE) cells may be one of the main causes. Therefore, it could be a great strategy to find some drugs that can effectively protect RPE cells from oxidative damage which is desired to treat and slow the process of AMD. In the present study, a well-known traditional Chinese medicine berberine (BBR) was found to suppress hydrogen peroxide (H2O2)-induced oxidative damage in D407 cells, a human RPE cell line. Pre-treatment of D407 cells with BBR significantly suppressed H2O2-induced cell apoptosis by restoring abnormal changes in nuclear morphology, preventing the decline of mitochondrial membrane potential, reducing lactate dehydrogenase release and inhibiting caspase 3/7 activities induced by H2O2. Western blot analysis showed that BBR was able to stimulate the phosphorylation/activation of AMPK in a time- and dose-dependent manner in D407 cells, while treatment of cells with AMPK pathway inhibitor Compound C, or knockdown of the AMPK by specific siRNA blocked the effect of BBR. Similar results were obtained in primary cultured human RPE cells. Taken together, these results demonstrated that BBR was able to protect RPE cells against oxidative stress via the activation of AMPK pathway. Our findings also indicate the potential application of BBR in AMD treatment

Metabolomics reveals the reasons for the occurrence of Pendulous-comb related to egg production performance

ABSTRACT: The chicken comb is an essential secondary sexual characteristic to measure sexual maturity and is closely related to reproductive performance. Pendulous comb (PC) and upright comb (UC) are 2 common comb phenotypes in hens, which have been highly associated with egg production performance. However, the reasons for the formation of PC remain undetermined. In this study, we first characterized the PC and UC chicken at start (at 175 d age), peak (at 217 d age), and postlaying (at 300 d age) and found that PC and UC could transform for each other. Furthermore, we suggested that PC chicken demonstrated better egg production performance than UC chicken, especially characterizing comb type in the start-laying period. Moreover, we performed histological evaluation of PC and UC tissue, which suggested that the low density of collagen fibers and acid mucopolysaccharides might lead to the formation of PC. To further explore the possible reasons for PC formation, we performed an untargeted metabolomic analysis of serum between PC and UC chicken in the start, peak, and postlaying periods. The enrichment analysis of period-unique differentially expressed metabolites (DEMs) between PC and UC showed that the different metabolic pathways and nutritional levels might contribute to the formation of PC in the different laying periods. Our research provided critical insights into the phenotypic diversity of chicken comb, establishing a foundation for early selection of chicken egg production performance

Insufficient phosphorylation of STAT5 in Tregs inhibits the expression of BLIMP-1 but not IRF4, reduction the proportion of Tregs in pediatric aplastic anemia

Deficiency in regulatory T cells (Tregs) is an important mechanism underlying the pathogenesis of pediatric aplastic anemia, but its specific mechanism is unclear. In our study, we aimed to investigate whether IL-2/STAT5 can regulate the proliferation of Tregs in aplastic anemia (AA) by regulating their expression of B lymphocyte-induced mature protein-1 (BLIMP-1) or interferon regulatory factor 4 (IRF4). Through clinical research and animal experiments, we found that poor activation of the IL-2/STAT5 signaling pathway may leads to low expression of BLIMP-1 in Tregs of children with AA, which leads to defects in the differentiation and proliferation of Tregs in AA. In AA model mice, treatment with IL-2c reversed the decrease in Treg proportions and reduction in Blimp-1 expression in Tregs by increasing the phosphorylation of Stat5 in Tregs. In AA, deficiency of IRF4 expression in Tregs is closely related to the deficiency of Tregs, but is not regulated by the IL-2/STAT5 pathway

Mir155 regulates osteogenesis and bone mass phenotype via targeting S1pr1 gene

MicroRNA-155 (miR155) is overexpressed in various inflammatory diseases and cancer, in which bone resorption and osteolysis are frequently observed. However, the role of miR155 on osteogenesis and bone mass phenotype is still unknown. Here, we report a low bone mass phenotype in the long bone of Mir155-Tg mice compared with wild-type mice. In contrast, Mir155-KO mice showed a high bone mass phenotype and protective effect against inflammation-induced bone loss. Mir155-KO mice showed robust bone regeneration in the ectopic and orthotopic model, but Mir155-Tg mice showed compromised bone regeneration compared with the wild-type mice. Similarly, the osteogenic differentiation potential of bone marrow stromal stem cells (BMSCs) from Mir155-KO mice was robust and Mir155-Tg was compromised compared with that of wild-type mice. Moreover, Mir155 knockdown in BMSCs from wild-type mice showed higher osteogenic differentiation potential, supporting the results from Mir155-KO mice. TargetScan analysis predicted sphingosine 1-phosphate receptor-1 (S1pr1) as a target gene of Mir155, which was further confirmed by luciferase assay and Mir155 knockdown. S1pr1 overexpression in BMSCs robustly promoted osteogenic differentiation without affecting cell viability and proliferation. Furthermore, osteoclastogenic differentiation of Mir155-Tg bone marrow-derived macrophages was inhibited compared with that of wild-type mice. Thus, Mir155 showed a catabolic effect on osteogenesis and bone mass phenotype via interaction with the S1pr1 gene, suggesting inhibition of Mir155 as a potential strategy for bone regeneration and bone defect healing