Corrigendum: Cardiovascular magnetic resonance findings in Danon disease: a case series of a family.

[This corrects the article DOI: 10.3389/fcvm.2023.1159576.].

T1w/T2w ratio maps identify children with autism spectrum disorder and the relationships between myelin-related changes and symptoms.

BACKGROUND: Modern neuroimaging methods have revealed that autistic symptoms are associated with abnormalities in brain morphology, connectivity, and activity patterns. However, the changes in brain microstructure underlying the neurobiological and behavioral deficits of autism remain largely unknown. METHODS: we characterized the associated abnormalities in intracortical myelination pattern by constructing cortical T1-weighted/T2-weighted ratio maps. Voxel-wise comparisons of cortical myelination were conducted between 150 children with autism spectrum disorder (ASD) and 139 typically developing (TD) children. Group differences in cortical T1-weighted/T2-weighted ratio and gray matter volume were then examined for associations with autistic symptoms. A convolutional neural network (CNN) model was also constructed to examine the utility of these regional abnormalities in cortical myelination for ASD diagnosis. RESULTS: Compared to TD children, the ASD group exhibited widespread reductions in cortical myelination within regions related to default mode, salience, and executive control networks such as the inferior frontal gyrus, bilateral insula, left fusiform gyrus, bilateral hippocampus, right calcarine sulcus, bilateral precentral, and left posterior cingulate gyrus. Moreover, greater myelination deficits in most of these regions were associated with more severe autistic symptoms. In addition, children with ASD exhibited reduced myelination in regions with greater gray matter volume, including left insula, left cerebellum_4_5, left posterior cingulate gyrus, and right calcarine sulcus. Notably, the CNN model based on brain regions with abnormal myelination demonstrated high diagnostic efficacy for ASD. CONCLUSIONS: Our findings suggest that microstructural abnormalities in myelination contribute to autistic symptoms and so are potentially promising therapeutic targets as well as biomarkers for ASD diagnosis.

A transthyretin-like protein acts downstream of miR397 and LACCASE to regulate grain yield in rice.

Increasing grain yield is a major goal of breeders due to the rising global demand for food. We previously reported that the miR397-LACCASE (OsLAC) module regulates brassinosteroid (BR) signaling and grain yield in rice (Oryza sativa). However, the precise roles of laccase enzymes in the BR pathway remain unclear. Here, we report that OsLAC controls grain yield by preventing the turnover of TRANSTHYRETIN-LIKE (OsTTL), a negative regulator of BR signaling. Overexpressing OsTTL decreased BR sensitivity in rice, while loss-of-function of OsTTL led to enhanced BR signaling and increased grain yield. OsLAC directly binds to OsTTL and regulates its phosphorylation-mediated turnover. The phosphorylation site Ser226 of OsTTL is essential for its ubiquitination and degradation. Overexpressing the dephosphorylation-mimic form of OsTTL (OsTTLS226A) resulted in more severe defects than did overexpressing OsTTL. These findings provide insight into the role of an ancient laccase in BR signaling and suggest that the OsLAC-OsTTL module could serve as a target for improving grain yield.

Nomogram Based on High-Resolution Vessel Wall MRI Features to Differentiate Moyamoya Disease From Atherosclerosis-Associated Moyamoya Vasculopathy.

BACKGROUND: The angiographic features of moyamoya disease (MMD) and atherosclerosis-associated moyamoya vasculopathy (AS-MMV) are similar, but the etiology and clinical treatment strategies are different. Differentiating MMD from AS-MMV helps to choose the appropriate treatment. PURPOSE: To investigate the feasibility of a nomogram based on high-resolution vessel wall (HR-VWI) MRI features to differentiate MMD from AS-MMV. STUDY TYPE: Retrospective. SUBJECTS: One hundred and two patients with MMD (N = 52) or AS-MMV (N = 50) in the training cohort (9-72 years; 54 females) and 70 patients with MMD (N = 42) or AS-MMV (N = 28) in the validation cohort (7-69 years; 33 females). FIELD STRENGTH/SEQUENCE: 3-T, three-dimensional time-of-flight MR angiography (3D-TOF-MRA), spin echo high-resolution 3D T1-weighted imaging (3D-T1WI), 3D T2-weighted imaging (3D-T2WI), and contrast-enhanced 3D-T1WI. ASSESSMENT: Image assessment was performed by three neuroradiologists (with 10, 15, and 18 years of experience). Demographic characteristic and image features were evaluated and compared. Independent factors of MMD were screened to construct a nomogram model in the training cohort. The validation cohort was used to validated its generality. STATISTICAL TESTS: Interclass correlation coefficient (ICC), kappa, t-test, χ2 test, receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration curve and concordance index (C-index). A P-value <0.05 was considered statistically significant. RESULTS: Significant differences were observed between MMD and AS-MMV in terms of age, vessel outer diameter, vessel wall thickening pattern, maximum thickness, dot sign, and anterior cerebral artery (ACA) involved. Age, outer diameter, dot sign, and ACA involved were independent factors. The C-index was 0.886 in the training cohort and 0.859 in the validation cohort. The ROC demonstrated high diagnostic efficacy with an AUC of 0.884 in the training cohort and 0.857 in the validation cohort. DATA CONCLUSION: A nomogram model based on age, vessel outer diameter, dot sign and ACA involved may effectively distinguish MMD from AS-MMV with good reliability and accuracy. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Mesenchymal Stem Cells Regulate Microglial Polarization via Inhibition of the HMGB1/TLR4 Signaling Pathway in Diabetic Retinopathy.

Diabetic retinopathy (DR) is recognized as the most prevalent retinal degenerative disorder. Inflammatory response usually precedes microvascular alteration and is the primary factor of diabetic retinopathy. Activated microglia express many pro-inflammatory cytokines that exacerbate retina inflammation and disruption. In the present study, we found that MSCs alleviated blood-retina barrier (BRB) breakdown in diabetic rats, as evidenced by reduced retinal edema, decreased vascular leakage, and increased occludin expression. The MSC-treated retinal microglia exhibited reduced expression of M1-phenotype markers in the diabetic rats, including inducible nitric oxide synthase (iNOS), CD16, and pro-inflammatory cytokines. On the other hand, MSCs increased the expression of M2-phenotype markers, such as arginase-1 (Arg-1), CD206, and anti-inflammatory cytokines. HMGB1/TLR4 signaling pathway is activated in DR and inhibited after MSC treatment. Consistent with in vivo evidence, MSCs drove BV2 microglia toward M2 phenotype in vitro. Overexpression of HMGB1 in microglia reversed the effects of MSC treatment, suggesting HMGB1/TLR4 pathway is necessary for MSCs' regulatory effects on microglia polarization. Collectively, MSCs exert beneficial effects on DR by polarizing microglia from M1 toward M2 phenotype via inhibiting the HMGB1/TLR4 signaling pathway.

IVIM and DCE-MRI in Predicting Phenotypic Subtypes and Nottingham Prognostic Index of Breast Cancer.

OBJECTIVE: To explore the value of intravoxel incoherent motion (IVIM) and dynamic contrast enhanced MRI (DCE-MRI) for predicting phenotypic subtypes and Nottingham prognostic index (NPI) of breast cancer. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Radiology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China, from March 2020 to January 2022. METHODOLOGY: One hundred and forty-one breast cancer patients with preoperative IVIM and DCE imaging were collected. IVIM parameters of D, D*, f, and DCE-MRI parameters of Ktrans, Kep, and Ve were measured. Receiver operating characteristic curves were conducted to assess the diagnostic efficacies. Additionally, 40 patients collected from February 2022 to July 2022 were enrolled as validation cohort. RESULTS: The D value in HER2-enriched (HER2-E) was lower than that in non-HER-E, while D*, Ktrans, and Ve values were higher than that in non-HER-E (p < 0.001, 0.046, < 0.001, and < 0.001, respectively). D + Ktrans + Ve showed an optimal diagnostic efficiency (AUC = 0.868). Meanwhile, D* and f values of triple-negative breast cancer (TNBC) were higher than those of non-TNBC, and Ve value of TNBC was lower than that of non-TNBC (p = 0.013, 0.006, and < 0.001, respectively). D* + f + Ve showed the best prediction performance (AUC = 0.849). Additionally, D and Kep were independent predictors of NPI (p < 0.001, and 0.002, respectively). D + Kep showed a good diagnostic efficiency (AUC = 0.818). CONCLUSION: The combined IVIM and DCE-MRI model showed enhanced diagnostic efficiency in predicting phenotypic subtypes and NPI of breast cancer, and might thus be considered efficient in therapy decision-making for patients. KEY WORDS: Breast neoplasms, Intravoxel incoherent motion, Dynamic contrast enhanced magnetic resonance imaging, Phenotypic subtypes, Nottingham prognostic index.

MSC-derived small extracellular vesicles mitigate diabetic retinopathy by stabilizing Nrf2 through miR-143-3p-mediated inhibition of neddylation.

Diabetic retinopathy (DR) is a highly hazardous and widespread complication of diabetes mellitus (DM). The accumulated reactive oxygen species (ROS) play a central role in DR development. The aim of this research was to examine the impact and mechanisms of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEV) on regulating ROS and retinal damage in DR. Intravitreal injection of sEV inhibited Cullin3 neddylation, stabilized Nrf2, decreased ROS, reduced retinal inflammation, suppressed Müller gliosis, and mitigated DR. Based on MSC-sEV miRNA sequencing, bioinformatics software, and dual-luciferase reporter assay, miR-143-3p was identified to be the key effector for MSC-sEV's role in regulating neural precursor cell expressed developmentally down-regulated 8 (NEDD8)-mediated neddylation. sEV were able to be internalized by Müller cells. Compared to advanced glycation end-products (AGEs)-induced Müller cells, sEV coculture decreased Cullin3 neddylation, activated Nrf2 signal pathway to combat ROS-induced inflammation. The barrier function of endothelial cells was impaired when endothelial cells were treated with the supernatant of AGEs-induced Müller cells, but was restored when treated with supernatant of AGEs-induced Müller cells cocultured with sEV. The protective effect of sEV was, however, compromised when miR-143-3p was inhibited in sEV. Moreover, the protective efficacy of sEV was diminished when NEDD8 was overexpressed in Müller cells. These findings showed MSC-sEV delivered miR-143-3p to inhibit Cullin3 neddylation, stabilizing Nrf2 to counteract ROS-induced inflammation and reducing vascular leakage. Our findings suggest that MSC-sEV may be a potential nanotherapeutic agent for DR, and that Cullin3 neddylation could be a new target for DR therapy.

Preoperative differentiation of gastric schwannomas and gastrointestinal stromal tumors based on computed tomography: a retrospective multicenter observational study.

Introduction: Gastric schwannoma is a rare benign tumor accounting for only 1-2% of alimentary tract mesenchymal tumors. Owing to their low incidence rate, most cases are misdiagnosed as gastrointestinal stromal tumors (GISTs), especially tumors with a diameter of less than 5 cm. Therefore, this study aimed to develop and validate a diagnostic nomogram based on computed tomography (CT) imaging features for the preoperative prediction of gastric schwannomas and GISTs (diameters = 2-5 cm). Methods: Gastric schwannomas in 47 patients and GISTs in 230 patients were confirmed by surgical pathology. Thirty-four patients with gastric schwannomas and 167 with GISTs admitted between June 2009 and August 2022 at Hospital 1 were retrospectively analyzed as the test and training sets, respectively. Seventy-six patients (13 with gastric schwannomas and 63 with GISTs) were included in the external validation set (June 2017 to September 2022 at Hospital 2). The independent factors for differentiating gastric schwannomas from GISTs were obtained by multivariate logistic regression analysis, and a corresponding nomogram model was established. The accuracy of the nomogram was evaluated using receiver operating characteristic and calibration curves. Results: Logistic regression analysis showed that the growth pattern (odds ratio [OR] 3.626; 95% confidence interval [CI] 1.105-11.900), absence of necrosis (OR 4.752; 95% CI 1.464-15.424), presence of tumor-associated lymph nodes (OR 23.978; 95% CI 6.499-88.466), the difference between CT values during the portal and arterial phases (OR 1.117; 95% CI 1.042-1.198), and the difference between CT values during the delayed and portal phases (OR 1.159; 95% CI 1.080-1.245) were independent factors in differentiating gastric schwannoma from GIST. The resulting individualized prediction nomogram showed good discrimination in the training (area under the curve [AUC], 0.937; 95% CI, 0.900-0.973) and validation (AUC, 0.921; 95% CI, 0.830-1.000) datasets. The calibration curve showed that the probability of gastric schwannomas predicted using the nomogram agreed well with the actual value. Conclusion: The proposed nomogram model based on CT imaging features can be used to differentiate gastric schwannoma from GIST before surgery.

Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins.

BACKGROUND: Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements. METHODS: qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux. RESULTS: The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation. CONCLUSIONS: The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.

Assessment of Myocardial Viability and Risk Stratification in Coronary Chronic Total Occlusion: A Qualitative and Quantitative Stress Cardiac MRI Study.

BACKGROUND: Indicators for assessing myocardial viability and risk stratification in patients with coronary chronic total occlusion (CTO) are still in the research stage. PURPOSE: To use stress-MRI to assess myocardial function, blood perfusion, and viability and to explore their relationship with collateral circulation. STUDY TYPE: Prospective. SUBJECTS: Fifty-one patients with CTO in at least one major artery confirmed by X-ray coronary angiography (male: 46; age 55.2 ± 10.8 years). FIELD STRENGTH/SEQUENCE: 3.0T; TurboFlash, balanced steady-state free precession cine, and phase-sensitive inversion recovery sequences. ASSESSMENT: Stress-MRI was used to obtain qualitative and quantitative parameters of segmental myocardium. Myocardial segments supplied by CTO target vessels were grouped according to the degree of collateral circulation assessed by radiographic coronary angiography (no/mild, moderate, or good). Depending on qualitative stress perfusion assessment and late gadolinium enhancement (LGE) extent, segments were also categorized as negative, viable, or trans-infarcted. STATISTICAL TESTS: Independent sample Student's t-test, one-way analysis of variance (ANOVA) test, Mann-Whitney U test, Kruskal-Wallis test, Spearman correlation coefficient (r). P < 0.05 was considered statistically significant. RESULTS: A total of 334 segments were supplied by CTO target vessels. The radial strain (RS), circumferential strain (CS), longitudinal strain (LS) of the negative, viable, and trans-infarcted regions showed a significant and stepwise impairment. Myocardial blood flow at rest was positively correlated with RS, CS, and LS (r = 0.42, 0.43, 0.38, respectively). Among the different collateral circulation, there were no significant differences in RS, CS, LS, and LGE volume (P = 0.788, 0.562, 0.122, 0.170, respectively), and there were also no statistically significant differences in the proportions of negative, viable, and trans-infarcted regions (P = 0.372). DATA CONCLUSION: Myocardial perfusion obtained by stress-MRI combined with strain and LGE may comprehensively evaluate myocardial function and viability, and has potential to facilitate risk stratification of CTO. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

MicroRNA397 promotes rice flowering by regulating the photorespiration pathway.

The precise timing of flowering plays a pivotal role in ensuring successful plant reproduction and seed production. This process is intricately governed by complex genetic networks that integrate internal and external signals. This study delved into the regulatory function of microRNA397 (miR397) and its target gene LACCASE-15 (OsLAC15) in modulating flowering traits in rice (Oryza sativa). Overexpression of miR397 led to earlier heading dates, decreased number of leaves on the main stem, and accelerated differentiation of the spikelet meristem. Conversely, overexpression of OsLAC15 resulted in delayed flowering and prolonged vegetative growth. Through biochemical and physiological assays, we uncovered that miR397-OsLAC15 had a profound impact on carbohydrate accumulation and photosynthetic assimilation, consequently enhancing the photosynthetic intensity in miR397-overexpressing rice plants. Notably, we identified that OsLAC15 is at least partially localized within the peroxisome organelle, where it regulates the photorespiration pathway. Moreover, we observed that a high CO2 concentration could rescue the late flowering phenotype in OsLAC15-overexpressing plants. These findings shed valuable insights into the regulatory mechanisms of miR397-OsLAC15 in rice flowering and provided potential strategies for developing crop varieties with early flowering and high-yield traits through genetic breeding.

MSC-Derived Small Extracellular Vesicles Alleviate Diabetic Retinopathy by Delivering miR-22-3p to Inhibit NLRP3 Inflammasome Activation.

PURPOSE: This study aimed to investigate the effect of mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) on diabetic retinopathy (DR) and its underlying mechanism. METHODS: In vivo, MSC-sEVs were injected intravitreally into diabetic rats to determine the therapeutic efficacy. In vitro, MSC-sEVs with/without miR-22-3p inhibition were cocultured with advanced glycation end-products (AGEs)-induced microglia with/without NLRP3 overexpression to explore the molecular mechanism. RESULTS: In vivo, MSC-sEVs inhibited NLRP3 inflammasome activation, suppressed microglial activation, decreased inflammatory cytokines levels in the retina, and alleviated DR as evidenced by improved histological morphology and blood-retinal barrier function. Based on miRNA sequencing of MSC-sEVs, bioinformatic software, and dual-luciferase reporter assay, miR-22-3p stood out as the critical molecule for the role of MSC-sEVs in regulating NLRP3 inflammasome activation. Diabetic rats had lower level of miR-22-3p in their retina than those of control and sEV-treated rats. Confocal microscopy revealed that sEV could be internalized by microglia both in vivo and in vitro. In vitro, compared with sEV, the anti-inflammation effect of sEVmiR-22-3p(-) on AGEs-induced microglia was compromised, as they gave a lower suppression of NLRP3 inflammasome activation and inflammatory cytokines. In addition, NLRP3 overexpression in microglia damped the anti-inflammatory effect of sEV. CONCLUSION: These results indicated that MSC-sEVs alleviated DR via delivering miR-22-3p to inhibit NLRP3 inflammasome activation. Our findings indicate that MSC-sEVs might be a potential therapeutic method for DR.

Evaluation of surgical revascularization procedure outcomes for adult Moyamoya disease: a computed tomography perfusion-based study.

BACKGROUND: The effectiveness of surgical interventions, whether direct or indirect, for Moyamoya disease (MMD) remains controversial. This study aims to investigate CT perfusion (CTP) as an objective method to evaluate the outcomes of different surgical modalities for adult MMD. METHODS: The clinical and imaging data of 41 patients who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass and 43 who received encephaloduroarteriosynangiosis (EDAS) were retrospectively analyzed. Intra- and intergroup differences in the Modified Rankin Scale (mRS) score, the change in clinical symptoms, collateral grade, and CTP parameters pre- and postoperatively were compared. RESULTS: The overall level of the change in clinical symptoms in the STA-MCA group was higher than in the EDAS group (p < 0.05). In the operative area, the relative cerebral blood flow (rCBF) was significantly higher whereas the relative time to peak (rTTP) and the relative mean transit time (rMTT) were significantly lower in the STA-MCA and EDAS groups postoperatively than preoperatively (all p < 0.05). In the ipsilateral frontal lobe and basal ganglia, the postoperative rCBF was significantly higher, and the rTTP was significantly lower than the preoperative in the STA-MCA group (all p < 0.05). The postoperative rCBF improvement was higher in each brain area for STA-MCA than in the EDAS group (all p < 0.05). CONCLUSION: Highlighting the utility of CTP, this study demonstrates its effectiveness in assessing postoperative cerebral hemodynamic changes in adult MMD patients. STA-MCA yielded a larger postoperative perfusion area and greater improvement compared to EDAS, suggesting CTP's potential to elucidate symptom variation between two surgical revascularization procedures. CRITICAL RELEVANCE STATEMENT: We analyzed computed tomography perfusion parameters in pre- and postoperative adult Moyamoya disease patients undergoing superficial temporal artery-middle cerebral artery bypass and encephaloduroarteriosynangiosis. Our findings suggest computed tomography perfusion's potential in objectively elucidating symptom variations between these surgical revascularization approaches for MMD. KEY POINTS: • Postoperative perfusion improvement is only confined to the operative area after EDAS. • Besides the operative area, postoperative perfusion in the ipsilateral frontal lobe and basal ganglia was also improved after STA-MCA. • The degree of perfusion improvement in each brain area in the STA-MCA group was generally greater than that in the EDAS group.

New insight into circRNAs: characterization, strategies, and biomedical applications.

Circular RNAs (circRNAs) are a class of covalently closed, endogenous ncRNAs. Most circRNAs are derived from exonic or intronic sequences by precursor RNA back-splicing. Advanced high-throughput RNA sequencing and experimental technologies have enabled the extensive identification and characterization of circRNAs, such as novel types of biogenesis, tissue-specific and cell-specific expression patterns, epigenetic regulation, translation potential, localization and metabolism. Increasing evidence has revealed that circRNAs participate in diverse cellular processes, and their dysregulation is involved in the pathogenesis of various diseases, particularly cancer. In this review, we systematically discuss the characterization of circRNAs, databases, challenges for circRNA discovery, new insight into strategies used in circRNA studies and biomedical applications. Although recent studies have advanced the understanding of circRNAs, advanced knowledge and approaches for circRNA annotation, functional characterization and biomedical applications are continuously needed to provide new insights into circRNAs. The emergence of circRNA-based protein translation strategy will be a promising direction in the field of biomedicine.

Value of 18F-FDG-PET/CT radiomics combined with clinical variables in the differential diagnosis of malignant and benign vertebral compression fractures.

BACKGROUND: Vertebral compression fractures (VCFs) are common clinical problems that arise from various reasons. The differential diagnosis of benign and malignant VCFs is challenging. This study was designed to develop and validate a radiomics model to predict benign and malignant VCFs with 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). RESULTS: Twenty-six features (9 PET features and 17 CT features) and eight clinical variables (age, SUVmax, SUVpeak, SULmax, SULpeak, osteolytic destruction, fracture line, and appendices/posterior vertebrae involvement) were ultimately selected. The area under the curve (AUCs) of the radiomics and clinical-radiomics models were significantly different from that of the clinical model in both the training group (0.986, 0.987 vs. 0.884, p < 0.05) and test group (0.962, 0.948 vs. 0.858, p < 0.05), while there was no significant difference between the radiomics model and clinical-radiomics model (p > 0.05). The accuracies of the radiomics and clinical-radiomics models were 94.0% and 95.0% in the training group and 93.2% and 93.2% in the test group, respectively. The three models all showed good calibration (Hosmer-Lemeshow test, p > 0.05). According to the decision curve analysis (DCA), the radiomics model and clinical-radiomics model exhibited higher overall net benefit than the clinical model. CONCLUSIONS: The PET/CT-based radiomics and clinical-radiomics models showed good performance in distinguishing between malignant and benign VCFs. The radiomics method may be valuable for treatment decision-making.

Circular RNA hsa_circ_001350 contributes to osteosarcoma progression by regulating microRNA-578/CCR4-NOT transcription complex and subunit 7/Wnt signaling.

Accumulating evidence has revealed that circular RNAs (circRNAs) play important roles in cancer by sponging microRNAs (miRNAs). A previous study has shown that hsa_circ_001350 expression is increased in glioma tissue samples and cells and that hsa_circ_001350 directly sponges miR-1236. Here, we investigated the role of hsa_circ_001350 in osteosarcoma (OS). Bioinformatics analysis was performed to examine the potential interactions among hsa_circ_001350, miR-578, and the CCR4-NOT transcription complex and subunit 7 (CNOT7). Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to analyze gene expression and protein levels, respectively. Hsa_circ_001350 expression was upregulated in OS tissues and cell lines. The deletion of hsa_circ_001350 inhibited the proliferation, migration, and invasion of OS cells. The downregulation of hsa_circ_001350 suppressed CNOT7 expression by sponging miR-578 as confirmed by rescue experiments and luciferase reporter assays. Specifically, the depletion of hsa_circ_001350 inhibited the protein expression of ß-catenin, cyclin D1, and c-myc in OS cells, and CNOT7 overexpression reversed this effect. We conclude that hsa_circ_001350 contributes to OS progression by regulating miR-578/CNOT7/Wnt signaling. Thus, hsa_circ_001350, miR-578, and CNOT7 may be potential targets for the treatment of OS.

Rhein protects retinal Müller cells from high glucose-induced injury via activating the AMPK/Sirt1/PGC-1α pathway.

Oxidative stress, inflammation and apoptosis are important pathogenic factors of diabetic retinopathy (DR). In the current study, we aimed to evaluate the potential role of Rhein, a natural anthraquinone compound found in rhubarb, in high glucose (HG)-induced Müller cells (MIO-M1). Cell Counting Kit­8 assay, TUNEL assay, Western blot analysis, Reverse transcription quantitative polymerase chain reaction (RT-qPCR), and ELISA were conducted to assess the effects of Rhein on Müller cells. Additionally, the EX-527, an Sirt1 inhibitor, was used to study whether the effects of Rhein, on HG-induced Müller cells were mediated by activation of the Sirt1 signaling pathway. Our data showed that Rhein improved cell viability of HG-induced Müller cells. Rhein reduced the ROS and MDA production and increased the activities of SOD and CAT in Müller cells in response to HG stimulation. Rhein decreased the production of VEGF, IL-1ß, IL-6 and TNF-α. Moreover, Rhein attenuated HG-induced apoptosis, evidenced by increase in Bcl-2 level and decreases in the Bax, caspase-3 expression. It was also found that EX-527 counteracted Rhein-mediated anti-inflammatory, antioxidant and anti-apoptosis effects on Müller cells. The protein levels of p-AMPK and PGC-1α were also upregulated by Rhein. In conclusion, these findings support that Rhein may ameliorate HG-induced inflammation, oxidative stress, apoptosis and protect against mitochondrial dysfunction by the activation of the AMPK/Sirt1/PGC-1α signaling pathway.