An automatic texture feature analysis framework of renal tumor: surgical, pathological, and molecular evaluation based on multi-phase abdominal CT.

OBJECTIVES: To determine whether the texture feature analysis of multi-phase abdominal CT can provide a robust prediction of benign and malignant, histological subtype, pathological stage, nephrectomy risk, pathological grade, and Ki67 index in renal tumor. METHODS: A total of 1051 participants with renal tumor were split into the internal cohort (850 patients from four different hospitals) and the external testing cohort (201 patients from another local hospital). The proposed framework comprised a 3D-kidney and tumor segmentation model by 3D-UNet, a feature extractor for the regions of interest based on radiomics and image dimension reduction, and the six classifiers by XGBoost. A quantitative model interpretation method called SHAP was used to explore the contribution of each feature. RESULTS: The proposed multi-phase abdominal CT model provides robust prediction for benign and malignant, histological subtype, pathological stage, nephrectomy risk, pathological grade, and Ki67 index in the internal validation set, with the AUROC values of 0.88 ± 0.1, 0.90 ± 0.1, 0.91 ± 0.1, 0.89 ± 0.1, 0.84 ± 0.1, and 0.88 ± 0.1, respectively. The external testing set also showed impressive results, with AUROC values of 0.83 ± 0.1, 0.83 ± 0.1, 0.85 ± 0.1, 0.81 ± 0.1, 0.79 ± 0.1, and 0.81 ± 0.1, respectively. The radiomics feature including the first-order statistics, the tumor size-related morphology, and the shape-related tumor features contributed most to the model predictions. CONCLUSIONS: Automatic texture feature analysis of abdominal multi-phase CT provides reliable predictions for multi-tasks, suggesting the potential usage of clinical application. CLINICAL RELEVANCE STATEMENT: The automatic texture feature analysis framework, based on multi-phase abdominal CT, provides robust and reliable predictions for multi-tasks. These valuable insights can serve as a guiding tool for clinical diagnosis and treatment, making medical imaging an essential component in the process. KEY POINTS: • The automatic texture feature analysis framework based on multi-phase abdominal CT can provide more accurate prediction of benign and malignant, histological subtype, pathological stage, nephrectomy risk, pathological grade, and Ki67 index in renal tumor. • The quantitative decomposition of the prediction model was conducted to explore the contribution of the extracted feature. • The study involving 1051 patients from 5 medical centers, along with a heterogeneous external data testing strategy, can be seamlessly transferred to various tasks involving new datasets.

Automatic analysis framework based on 3D-CT multi-scale features for accurate prediction of Ki67 expression levels in substantial renal cell carcinoma.

PURPOSE: To investigate the effectiveness of an automatic analysis framework based on 3D-CT multi-scale features in predicting Ki67 expression levels in substantial renal cell carcinoma (RCC). METHODS: This retrospective study was conducted using multi-center cohorts consisting of 588 participants with pathologically confirmed RCC. The participants were divided into an internal training set (n = 485) and an external testing set (n = 103) from four and one local hospitals, respectively. The proposed automatic analytic framework comprised a 3D kidney and tumor segmentation model constructed by 3D UNet, a 3D-CT multi-scale features extractor based on the renal-tumor feature, and a low or high Ki67 prediction classifier using XGBoost. The framework was validated using a fivefold cross-validation strategy. The Shapley additive explanation (SHAP) method was used to determine the contribution of each feature. RESULTS: In the prediction of low or high Ki67, the combination of renal and tumor features achieved better performance than any single features. Internal validation using a fivefold cross-validation strategy yielded AUROC values of 0.75 ± 0.1, 0.75 ± 0.1, 0.83 ± 0.1, 0.77 ± 0.1, and 0.87 ± 0.1, respectively. The optimal model achieved an AUROC of 0.87 ± 0.1 and 0.82 ± 0.1 for low vs. high Ki67 prediction in the internal validation and external testing sets, respectively. Notably, the tumor first-order-10P was identified as the most influential feature in the model decision. CONCLUSIONS: Our study suggests that the proposed automatic analysis framework based on 3D-CT multi-scale features has great potential for accurately predicting Ki67 expression levels in substantial RCC. CRITICAL RELEVANCE STATEMENT: Automatic analysis framework based on 3D-CT multi-scale features provides reliable predictions for Ki67 expression levels in substantial RCC, indicating the potential usage of clinical applications.

Selenium and Taurine Combination Is Better Than Alone in Protecting Lipopolysaccharide-Induced Mammary Inflammatory Lesions via Activating PI3K/Akt/mTOR Signaling Pathway by Scavenging Intracellular ROS.

Mastitis is mainly induced by gram-negative bacterial infections, causing devastating economic losses to the global cattle industry. Both selenium (Se) and taurine (Tau) exhibit multiple biological effects, including reducing inflammation. However, no studies have reported the protective effect of the combined use of Se and Tau against mastitis, and the underlying mechanisms remain unclear. In this study, lipopolysaccharide (LPS), the vital virulence factor of gram-negative bacteria, was used to construct the in vivo and vitro mastitis models. The results of in vivo model showed that Se and Tau combination was more effective than either substance alone in reducing tissue hyperemia, edema, and neutrophil infiltration in the mammary acinar cavity, improving the blood-milk barrier in LPS-induced mice mastitis, and decreasing the expression of proinflammatory factors and the activity of MPO. Moreover, Se and Tau combination significantly increased the levels of LPS-induced reduction in PI3K/Akt/mTOR, but the expressions of TLRs and NLRP3 were not significantly changed in the mammary tissue. In the in vitro experiments, the effects of Se and Tau combination or alone on inflammatory factors, inflammatory mediators, MPO activity, and blood-milk barrier were consistent with those in vivo. The Se and Tau combination has also been found to increase the survival rate of BMECs compared with each substance alone via promoting cellular proliferation and inhibiting apoptosis. Also, it has been confirmed that this combination could restore the LPS-induced inhibition in the PI3K/Akt/mTOR signaling pathway. Inhibition of mTOR by Rapamycin counteracted the combined protection of SeMet and Tau against LPS-induced inflammatory damage, the inhibition of PI3K by LY294002 blocked the activation of mTOR, and the accumulation of ROS by the ROS agonist blocked the activation of PI3K. In conclusion, these findings suggested that Se and Tau combination was better than either substance alone in protecting LPS-induced mammary inflammatory lesions by upregulating the PI3K/Akt/mTOR signaling pathway.

Long-Time Instead of Short-Time Exposure in Vitro and Administration in Vivo of Ochratoxin A Is Consistent in Immunosuppression.

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium, contaminating in a wide variety of foods and feeds. Mycotoxins, including OTA, could cause immunosuppression in almost all previous studies in vivo. However, the vast majority of results in vitro showed that mycotoxins caused immunostimulation. Why the results of studies in vitro are contrary to studies in vivo is unknown. Our study aims to explore the underlying reason and mechanism of the paradoxical effect. In this study, porcine alveolar macrophage cell line 3D4/21 was chosen as an in vitro model and treated with 1.0 µg/mL OTA for different times. Some indexes, such as expression of inflammatory cytokines, migration, phagocytosis, macrophage polarization, autophagy-related proteins, and Akt1 phosphorylation, were detected. The results showed that pro-inflammatory cytokine expression, migration, and phagocytosis were increased, with macrophage polarization to the M1 phenotype at 24 h of OTA exposure. Surprisedly, anti-inflammatory cytokine expression was increased, cell phagocytosis and migration were decreased, and macrophage polarization was switched from M1 to M2 at 72 h of OTA exposure. Furthermore, we found that long-time exposure of OTA also suppressed autophagy, and the autophagy activator blocked the OTA-induced immunosuppression. Phosphorylation of Akt1 plays a positive role in autophagy inhibition. In conclusion, long-time instead of short-time exposure of OTA in vitro induced immunosuppression. The immunosuppression mechanism of OTA in vitro involved inhibition of autophagy through upregulating p-Akt1. Our results provide new insight into research on the mechanism of mycotoxin-induced immunosuppression in vitro.

Glutamine Deficiency Promotes PCV2 Infection through Induction of Autophagy via Activation of ROS-Mediated JAK2/STAT3 Signaling Pathway.

Porcine circovirus type 2 (PCV2) is an important pathogen in swine herds. We previously reported that glutamine (Gln) deficiency promoted PCV2 infection in vitro. Here, we established a Gln deficiency model in vivo and further investigated the detailed molecular mechanisms. In vivo and in vitro, Gln deficiency promoted PCV2 infection, which was evident through increased viral yields and PCV2 Cap protein synthesis. It also induced autophagy, as demonstrated by the increases in LC3-II conversion, SQSTM1 degradation, and GFP-LC3 dot accumulation. Autophagy inhibition abolished the effects of Gln deficiency on PCV2 infection. Inhibition of ROS generation alleviated the Gln deficiency-activated JAK2/STAT3 signaling pathway, thereby inhibiting autophagy induction. In vitro, the inhibition of STAT3 by an inhibitor or RNA interference blocked autophagy, thus reversing the effects of Gln deficiency on PCV2 infection. These results indicate that Gln deficiency activates autophagy by upregulating ROS-medicated JAK2/STAT3 signaling and thereby promoting PCV2 infection.

Activation of AMPK-dependent SIRT-1 by astragalus polysaccharide protects against ochratoxin A-induced immune stress in vitro and in vivo.

Recent studies have highlighted the immune stress caused by ochratoxin A (OTA), but little attention was paid to its alleviation. In the present study, the protective effects of astragalus polysaccharide (APS) against OTA-induced immune stress in vitro and in vivo and its mechanism/(s) involved were investigated. The in vitro results showed that APS (20 µg/ml) induced a significant decrease in cytotoxicity, apoptosis and pro-inflammatory cytokine expressions elevated by OTA (1.5 µg/ml) in porcine alveolar macrophages (PAMs). In vivo, APS (200 mg/kg b.w.) significantly alleviated OTA-induced (75 µg/kg b.w.) spleen damages and decreased the expressions of OTA-promoted apoptosis-related protein and pro-inflammatory cytokine. Further study indicated that APS caused significant enhancement of AMPK/SIRT-1 and inhibition of NFκB in PAMs and mice. The down-regulation of SIRT-1 by EX527 in vivo or EX527 and SIRT-1 knockdown in vitro abolished the inhibitory effects of APS on OTA-induced cytotoxicity, apoptosis, spleen damages and pro-inflammatory cytokine expressions. Taken together, these findings indicate that APS could attenuate the immune stress induced by OTA in vitro and in vivo via activation of the AMPK/SIRT-1 signaling pathway.