Chemical constituents from the endophytic fungus Aspergillus sp. S3 of Hibiscus tiliaceus.

A new sterol, aspersterol E (1), a newly discovered alkaloid, asperginine A (2), and five known compounds (3-7) were obtained from the endophytic fungus Aspergillus sp. S3 of Hibiscus tiliaceus Linn. The compounds were extracted from their fermentation products using silica gel, ODS C18, and semi-preparative HPLC. The structure of each compound was determined through spectroscopic analysis. All the obtained compounds (1-7) were evaluated for their cytotoxic activity against the mouse pre-gastric cancer cell line MFC by using the MTT assay. The IC50 values of compounds 1, 2, 3, and 5 were found to be 153.43 µM, 61.25 µM, 73.19 µM, and 181.69 µM respectively.

How to update esophageal masses imaging using literature review (MRI and CT features).

MRI offers new opportunities for detailed visualization of the different layers of the esophageal wall, as well as early detection and accurate characterization of esophageal lesions. Staging of esophageal tumors including extramural extent of disease, and status of the adjacent organ can also be performed by MRI with higher accuracy compared to other imaging modalities including CT and esophageal endoscopy. Although MDCT appears to be the primary imaging modality that is indicated for preoperative staging of esophageal cancer to assess tumor resectability, MDCT is considered less accurate in T staging. This review aims to update radiologists about emerging imaging techniques and the imaging features of various esophageal masses, emphasizing the imaging features that differentiate between esophageal masses, demonstrating the critical role of MRI in esophageal masses. CRITICAL RELEVANCE STATEMENT: MRI features may help differentiate mucosal high-grade neoplasia from early invasive squamous cell cancer of the esophagus, also esophageal GISTs from leiomyomas, and esophageal malignant melanoma has typical MR features. KEY POINTS: MRI can accurately visualize different layers of the esophagus potentially has a role in T staging. MR may accurately delineate esophageal fistulae, especially small mediastinal fistulae. MRI features of various esophageal masses are helpful in the differentiation.

Nickel foam-loaded Co-MOF@TiO2/MoS2 as electrode materials for dual-function devices for glucose detection and hydrogen evolution.

Dual-functional nanomaterial electrodes have the capability to satisfy the requirements for both sweat analysis and the hydrogen evolution reaction (HER), thereby enabling the integration of electrochemical sensing and hydrogen production. In this study, ZIF-67 cubes are synthesized on nickel foam (NF), while TiO2 is obtained through an annealing process. Subsequently, the ZIF-67@TiO2/MoS2 nanocomposite is fabricated on nickel foam via a hydrothermal method. This composite material exhibits exceptional photocatalytic properties and is also suitable for the detection of glucose in sweat. The glucose detection range spans from 10 nM to 10 mM with a sensitivity of 7.24 µA mM-1 cm-2 for a signal-to-noise ratio of 3 and a detection limit of 0.43 µM. Moreover, when utilized as a hydrogen evolution electrode, this material demonstrates a current density of 10 mA cm-2 at an overpotential of 118 mV, with a Tafel slope of 73 mV/dec. The synthesis process is both straightforward and economical. This research introduces a novel concept for the design of multifunctional chemical sensors.

A cytokine-like factor 1 homolog acts as a macrophage chemoattractant in grass carp.

Cytokine-like factor 1 (CYTL1) is a small cytokine and has diverse biological functions in mammals. However, whether CYTL1 exists in lower vertebrates is not clear. In this study, we identified cytl homologs in fish and characterized the immune functions in a teleost species, grass carp (Ctenopharyngodon idella). Fish CYTL1 homologs share conserved molecular features with their mammalian counterparts, including 6 cysteine residues in the mature peptide, genomic organization and synteny. Gene expression analysis revealed that cytl1 was constitutively expressed in tissues of grass carp, with the highest expression detected in the heart. Upon infection with Aeromonas hydrophila (A. hydrophila), cytl1 was downregulated in the hindgut, head kidney, skin, and spleen. In the primary head kidney leukocytes (HKLs), stimulation with inactivated A. hydrophila, LPS, poly(I:C), IL-22, IFN-a or IFN-γrel resulted in downregulation of cytl1 expression. Recombinant grass carp CYTL1 protein produced in the HEK293-F cells was potent to induce il-10 expression, but had little effect on the expression of il-1ß and il-6. In vivo experiments revealed that CYTL1 was effective to recruit macrophages to the muscle injected with cytl expression plasmids. Taken together, our results indicate that CYTL1 is a potent chemokine for recruitment of macrophages in fish.

AHNAK2 Promotes the Progression of Pancreatic Ductal Adenocarcinoma by Maintaining the Stability of c-MET.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant and rapidly progresses. The overall response rate of PDAC to current treatment methods is still unsatisfactory. Thus, identifying novel targets and clarifying the underlying mechanisms associated with PDAC progression may potentially offer additional treatment strategies. AHNAK2 is aberrantly expressed in a variety of tumors and exerts pro-tumorigenic effects. However, the biological role of AHNAK2 in PDAC remains poorly understood. Methods: The expression of AHNAK2 in PDAC and paired non-tumor tissues was detected by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). Lentivirus knockdown was performed to investigate the impact of AHNAK2 on the biological function of pancreatic cancer cells. The subcutaneous cell-derived xenograft (CDX) model and the KPC spontaneous mouse model with AHNAK2 silencing were used to observe the effects of AHNAK2 on tumor growth and prognosis. The expression of c-MET at protein level in response to HGF treatment was assessed using western blot. Results: Our results demonstrated that AHNAK2 was highly expressed in PDAC clinical samples and associated with poor prognosis. Knockdown of AHNAK2 significantly inhibited the proliferation, migration, and invasion of pancreatic cancer cells. AHNAK2 knockdown or knockout resulted in tumor growth suppression and prolonged survival in mice with PDAC. In addition, AHNAK2 and c-MET expression levels showed a significant positive correlation at the post-transcriptional level. Mechanistically, AHNAK2 promoted tumor progression by preventing c-MET degradation and persistently activating the HGF/c-MET signaling pathway. Conclusion: Overall, our study revealed that AHNAK2 plays an important role in PDAC progression by modulating the c-MET signaling pathway, and targeting AHNAK2 may be an effective therapeutic strategy for PDAC.

T-cell lymphopenia is associated with an increased infecting risk in children after cardiopulmonary bypass.

BACKGROUND: children who undergo CPB operations are at an elevated risk of infection due to immunosuppression. This study aims to investigate the association between lymphopenia following CPB and early postoperative infection in children. METHODS: A retrospective analysis including 41 children under 2 years old underwent CPB. Among them, 9 subjects had an early postoperative infection, and 32 subjects were period-matched without infection. Inflammatory cytokines, serum CRP and PCT values were measured in plasma, additionally, circulating total leucocyte and lymphocyte subpopulations were counted. RESULTS: Infected subjects exhibited significantly higher levels of inflammatory cytokines, including IL-6, IL-8, IL-10, IL-1ß and TNF-α, than non-infected subjects after CPB. Additionally, lower absolute number of lymphocyte and their subpopulations CD3+ T cells, CD4+ T-helper cells and CD8+cytotoxic T-cells, were observed in infected subjects. The impairment of T-cells Immune was found to be associated with higher levels of inflammatory cytokines IL-10. The ROC demonstrated that the absolute number of CD3+ T-cells <1934/ul, CD4+ T helper cells <1203/ul and CD8+cytotoxic T-cells <327/ul were associated with early postoperative infection. CONCLUSION: Higher levels of inflammatory cytokines resulted in T-cells lymphopenia after CPB, which significantly increasing the risk of postoperative infection in infants and young children. IMPACT: Infection complications after cardiopulmonary bypass (CPB) in pediatric CHD patients are serious issues, identifing the infection from after CPB remains a challenging. CPB can release numerous inflammatory cytokines associated with T cells lymphopenia, which increases the risk of postoperative infection after surgery. Monitoring T cells lymphopenia maybe more beneficial to predict early postoperative infection than C-reactive protein and procalcitonin.

The MRI radiomics signature can predict the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma.

OBJECTIVES: To investigate the MRI radiomics signatures in predicting pathologic response among patients with locally advanced esophageal squamous cell carcinoma (ESCC), who received neoadjuvant chemotherapy (NACT). METHODS: Patients who underwent NACT from March 2015 to October 2019 were prospectively included. Each patient underwent esophageal MR scanning within one week before NACT and within 2-3 weeks after completion of NACT, prior to surgery. Radiomics features extracted from T2-TSE-BLADE were randomly split into the training and validation sets at a ratio of 7:3. According to the progressive tumor regression grade (TRG), patients were stratified into two groups: good responders (GR, TRG 0 + 1) and poor responders (non-GR, TRG 2 + 3). We constructed the Pre/Post-NACT model (Pre/Post-model) and the Delta-NACT model (Delta-model). Kruskal-Wallis was used to select features, logistic regression was used to develop the final model. RESULTS: A total of 108 ESCC patients were included, and 3/2/4 out of 107 radiomics features were selected for constructing the Pre/Post/Delta-model, respectively. The selected radiomics features were statistically different between GR and non-GR groups. The highest area under the curve (AUC) was for the Delta-model, which reached 0.851 in the training set and 0.831 in the validation set. Among the three models, Pre-model showed the poorest performance in the training and validation sets (AUC, 0.466 and 0.596), and the Post-model showed better performance than the Pre-model in the training and validation sets (AUC, 0.753 and 0.781). CONCLUSIONS: MRI-based radiomics models can predict the pathological response after NACT in ESCC patients, with the Delta-model exhibiting optimal predictive efficacy. CLINICAL RELEVANCE STATEMENT: MRI radiomics features could be used as a useful tool for predicting the efficacy of neoadjuvant chemotherapy in esophageal carcinoma patients, especially in selecting responders among those patients who may be candidates to benefit from neoadjuvant chemotherapy. KEY POINTS: • The MRI radiomics features based on T2WI-TSE-BLADE could potentially predict the pathologic response to NACT among ESCC patients. • The Delta-model exhibited the best predictive ability for pathologic response, followed by the Post-model, which similarly had better predictive ability, while the Pre-model performed less well in predicting TRG.

Rescue stenting after failure of endovascular thrombectomy for acute vertebrobasilar artery occlusion: data from the PERSIST registry.

BACKGROUND: Among acute vertebrobasilar artery occlusion (VBAO) patients, successful reperfusion is a strong predictor of favorable outcomes. However, failed reperfusion (FR) with endovascular thrombectomy (EVT) in VBAO was observed to occur in 18-50% of cases. We aim to evaluate the safety and efficacy of rescue stenting (RS) for VBAO after failed EVT. METHODS: Patients with VBAO who received EVT were enrolled retrospectively. Propensity score matching was performed as the primary analysis to compare the outcomes between patients with RS and FR. Furthermore, a comparison between using the self-expanding stent (SES) and balloon-mounted stent (BMS) in the RS group was also conducted. The primary and secondary outcomes were defined as a 90-day modified Rankin Scale (mRS) score 0-3, and a 90-day mRS score 0-2, respectively. Safety outcomes included all-cause mortality at 90 days and symptomatic intracranial hemorrhage (sICH). RESULTS: The RS group showed a significantly higher rate of 90-day mRS score 0-3 (46.6% vs 20.7%; adjusted OR (aOR) 5.06, 95% CI 1.88 to 13.59, P=0.001) and a lower rate of 90-day mortality (34.5% vs 55.2%; aOR 0.42, 95% CI 0.23 to 0.90, P=0.026) than the FR group. The rates of 90-day mRS score 0-2 and sICH were not significantly different between the RS group and FR group. There were no differences in all outcomes between SES and BMS groups. CONCLUSIONS: RS appeared to be a safe and effective rescue approach in patients with VBAO who failed EVT, and there was no difference between using SES and BMS.

Tumour-associated macrophages and Schwann cells promote perineural invasion via paracrine loop in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently accompanied by perineural invasion (PNI), which is associated with excruciating neuropathic pain and malignant progression. However, the relationship between PNI and tumour stromal cells has not been clarified. METHODS: The dorsal root ganglia or sciatic nerves nerve model was used to observe the paracrine interaction and the activation effect among Schwann cells, tumour-associated macrophages (TAMs), and pancreatic cancer cells in vitro. Next generation sequencing, enzyme-linked immunosorbent assay and chromatin immunoprecipitation were used to explore the specific paracrine signalling between TAMs and Schwann cells. RESULTS: We demonstrated that more macrophages were expressed around nerves that have been infiltrated by pancreatic cancer cells compared with normal nerves in murine and human PNI specimens. In addition, high expression of CD68 or GFAP is associated with an increased incidence of PNI and indicates a poor 5-year survival rate in patients with PDAC. Mechanistically, tumour-associated macrophages (TAMs) activate Schwann cells via the bFGF/PI3K/Akt/c-myc/GFAP pathway. Schwann cells secrete IL-33 to recruit macrophages into the perineural milieu and facilitate the M2 pro-tumourigenic polarisation of macrophages. CONCLUSIONS: Our study demonstrates that the bFGF/IL-33 positive feedback loop between Schwann cells and TAMs is essential in the process of PNI of PDAC. The bFGF/PI3K/Akt/c-myc/GFAP pathway would open potential avenues for targeted therapy of PDAC.

Artificial intelligence-based computer-aided diagnosis system supports diagnosis of lymph node metastasis in esophageal squamous cell carcinoma: A multicenter study.

Background: This study aimed to develop an artificial intelligence-based computer-aided diagnosis system (AI-CAD) emulating the diagnostic logic of radiologists for lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) patients, which contributed to clinical treatment decision-making. Methods: A total of 689 ESCC patients with PET/CT images were enrolled from three hospitals and divided into a training cohort and two external validation cohorts. 452 CT images from three publicly available datasets were also included for pretraining the model. Anatomic information from CT images was first obtained automatically using a U-Net-based multi-organ segmentation model, and metabolic information from PET images was subsequently extracted using a gradient-based approach. AI-CAD was developed in the training cohort and externally validated in two validation cohorts. Results: The AI-CAD achieved an accuracy of 0.744 for predicting pathological LNM in the external cohort and a good agreement with a human expert in two external validation cohorts (kappa = 0.674 and 0.587, p < 0.001). With the aid of AI-CAD, the human expert's diagnostic performance for LNM was significantly improved (accuracy [95% confidence interval]: 0.712 [0.669-0.758] vs. 0.833 [0.797-0.865], specificity [95% confidence interval]: 0.697 [0.636-0.753] vs. 0.891 [0.851-0.928]; p < 0.001) among patients underwent lymphadenectomy in the external validation cohorts. Conclusions: The AI-CAD could aid in preoperative diagnosis of LNM in ESCC patients and thereby support clinical treatment decision-making.

Effect of sample size on prognostic genes analysis in non-small cell lung cancer.

The identification of prognostic genes can help in the clinical management of non-small cell lung cancer (NSCLC). However, there is little overlap in the prognostic genes identified in different NSCLC studies. One reason for this may be the inadequate sample size. Here, the effect of sample size on prognostic genes analysis was investigated based on 515 stage II/III NSCLC cases from two cohorts detected by whole-exome sequencing. Prognostic genes analysis was repeatedly performed 100 times for each sample size level using random resampling methods. In stage II lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) cases from the TCGA Pan-Lung Cancer cohort, the number of statistically significant prognostic genes first increased with sample size in a power law, then fluctuated steadily, and finally decreased slightly. The power law growth curves were also observed in stage III LUAD and LUSC cases from the TCGA Pan-Lung Cancer cohort and stage III Chinese LUAD cases from the OncoSG cohort. The correlation R2 of the fitted power law growth curves were all greater than 0.99. In addition, at the sample size level where the number of prognostic genes peaked, the mean proportion of true prognostic genes in patients with stage II LUAD and LUSC was 28.32% and 23.12%, which could partly explain the little overlap in prognostic genes between reports. In conclusion, the number of prognostic genes takes a power law growth with the sample size in NSCLC, independent of histopathological subtype, race, and stage. These results also show how sample size affects the reliability of prognostic genes and will aid trial design for genomic mutation-based prognostic studies in NSCLC.

Predictive value of fetal echocardiographic parameters in surgical strategy for Tetralogy of Fallot.

OBJECTIVES: This study aimed to evaluate whether fetal echocardiographic parameters were predictive of the postnatal surgical treatment required for fetuses with Tetralogy of Fallot (TOF). METHODS: The fetal echocardiographic and postnatal clinical data of all cases of prenatal TOF at Xinhua Hospital from 2016 to 2020 were reviewed. Patients were categorized based on the operation type, and cardiac parameters were compared between groups. RESULTS: Of the 37 fetuses assessed, the development of the pulmonary valve annulus (PVA) was significantly poorer in the transannular patch group. Patients with a prenatal PVA z-score (Schneider's method) ≥ -2.645, a PVA z-score (Lee's method) ≥ -2.805, a PVA/aortic valve annulus diameter ratio ≥ .697, and a pulmonary annulus index ≥ .823 were more likely to undergo pulmonary valve-sparing surgery. There was a strong correlation between prenatal and postnatal PVA z-scores. The PVA growth potential was greater in the pulmonary valve-sparing surgery group. CONCLUSIONS: PVA-related parameters evaluated by fetal echocardiography can predict the type of surgical intervention required and are valuable in improving prenatal counseling in fetal cases of TOF.

IL-27 suppresses spring viremia of carp virus replication in zebrafish.

Interleukin (IL) 27 is a member of the IL-12 family and is a heterodimeric cytokine composed of IL-27A and Epstein-Barr virus-induced 3 (EBI3). It plays an important role in regulating inflammation and cancer progression. IL-27A not only functions by dimerizing with EBI3 but also acts alone. Here, we report that IL-27A and EBI3 suppress spring viremia of carp virus (SVCV) replication in zebrafish. Expression analysis reveals that il-27a and ebi3 were significantly upregulated in the ZF4 cells by SVCV and poly(I:C), and in the zebrafish caudal fin (ZFIN) cells overexpressed with SVCV genes. Interestingly, il-27a and ebi3 were not modulated by IFNφ1, indicating that they are not IFN stimulated genes (ISGs). Furthermore, overexpression of IL-27A and EBI3 alone inhibited SVCV replication in the EPC cells, but less potent than co-expression of IL-27A and EBI3. Intriguingly, IL-27A could not induce the expression of irf3, ifn, isg15 and mx1. Taken together, our results demonstrate that IL-27A and EBI3 activate innate antiviral response in an IFN independent manner in zebrafish.

Retraction Notice to: Inflammatory-Related P62 Triggers Malignant Transformation of Mesenchymal Stem Cells through the Cascade of CUDR-CTCF-IGFII-RAS Signaling.

[This retracts the article DOI: 10.1016/j.omtn.2018.03.002.].

Two genetic variants in NEXN and ABCC6 genes found in a patient with right coronary artery to right ventricle fistula combined with giant coronary aneurysm and patent ductus arteriosus.

Objective: Coronary artery fistula, defined as communication between a coronary artery and a great vessel or a cardiac chamber, is a relatively rare anomaly with an estimated incidence of 0.002% in the general population. It could be combined with a giant coronary artery aneurysm, with an incidence of 5.9% of the total incidence rate of CAF in the general population. The pathogenesis of these two combined anomalies is not clear, and we aimed to detect whether genetic abnormalities underlie the pathogenesis of these rarely combined anomalies. Materials and methods: A 6-year-old patient with a diagnosis of the right coronary artery to right ventricle fistula combined with a giant right coronary artery aneurysm and patent ductus arteriosus underwent a surgical repair at our center. The diagnosis was confirmed by echocardiography, CT, and surgery. DNA was extracted from the peripheral venous blood samples of the patient and his mother after informed consent was obtained. Hematoxylin and Eosin (HE) and Alizarin red staining were performed on the excised coronary artery aneurysm. Exome sequencing and in silico analyses were performed to detect detrimental genetic variants. Results: No obvious abnormalities were found in the excised coronary artery aneurysm. A heterozygous truncated variant (NM_144573: c.G298T; p.G100X) in the NEXN gene and a missense variant (NM_001171: c.G1312A; p.V438M) in the ABCC6 gene were carried by the patient but not by his mother. Conclusion: The NEXN-truncated variant, NEXN-G100X, is associated with the development of coronary arteries and congenital coronary artery anomalies.

Successful adrenaline treatment of perioperative severe bronchospasm combined with a silent lung: two case reports.

Background: Silent lung is a rare and potentially fatal disease. It is a critical sign of strong bronchospasm or extensive mucus plug blockage, which can result in the obvious weakening of breathing sounds or even disappearance of breathing sounds. Silent lung has an acute onset and rapid progress, which seriously threatens the life of patients. It needs early diagnosis, timely and effective treatment to reverse the persistent severe bronchospasm of patients. If not handled in time, silent lung can cause rapid onset of severe hypoxemia, hypoxic brain injury, and even cardiac arrest. Few studies have been reported on the causes and specific treatments for silent lungs. Case Description: We report 2 rare cases of silent lung in this article and summarize the pathogenesis, inducing factors, clinical manifestations of perioperative silent lung. We also review the literature and discuss our solutions and propose other possible solutions for the treatment of silent lung emergencies in clinical settings in order to provide reference for clinical practice of anesthesiologists. Of the patients, 1 displayed a sudden decrease in ventilation volume, an increase in airway resistance, and was changed to pure oxygen. The manual ventilation failed, and there was no fluctuation of the thorax and no respiratory sound during auscultation. Cardiopulmonary resuscitation (CPR) was initiated when cardiac arrest was imminent after hypoxia. The other patient had high airway resistance after anesthesia-induced endotracheal intubation, could not be ventilated, and the carbon dioxide (CO2) waveform at the end of breathing disappeared. Conclusions: Both patients had severe bronchospasm; that is, silent lung. The 2 patients improved after hand-controlled ventilation and the administration of adrenaline and methylprednisolone, and ultimately recovered ventilation.

Tumor Tropic Delivery of Hyaluronic Acid-Poly (D,L-lactide-co-glycolide) Polymeric Micelles Using Mesenchymal Stem Cells for Glioma Therapy.

Tumor penetration and the accumulation of nanomedicines are crucial challenges in solid tumor therapy. By taking advantage of the MSC tumor-tropic property, we developed a mesenchymal stem cell (MSC)-based drug delivery system in which paclitaxel (PTX)-encapsulating hyaluronic acid-poly (D,L-lactide-co-glycolide) polymeric micelles (PTX/HA-PLGA micelles) were loaded for glioma therapy. The results indicated that CD44 overexpressed on the surface of both MSCs and tumor cells not only improved PTX/HA-PLGA micelle loading in MSCs, but also promoted the drug transfer between MSCs and adjacent cancer cells. It was hypothesized that CD44-mediated transcytosis played a crucial role and allowed deep glioma penetration depending on sequential intra-intercellular delivery via endocytosis-exocytosis. MSC-micelles were able to infiltrate from normal brain parenchyma towards contralateral tumors and led to the eradication of glioma. The survival of orthotopic glioma-bearing rats was significantly extended. In conclusion, the MSC-based delivery of HA-PLGA micelles is a potential strategy for tumor-targeting drug delivery.

Atorvastatin Induces Mitochondria-Dependent Ferroptosis via the Modulation of Nrf2-xCT/GPx4 Axis.

As one of the cornerstones of clinical cardiovascular disease treatment, statins have an extensive range of applications. However, statins commonly used have side reactions, especially muscle-related symptoms (SAMS), such as muscle weakness, pain, cramps, and severe condition of rhabdomyolysis. This undesirable muscular effect is one of the chief reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. Moreover, the underlying mechanism of muscle cell damage is still unclear. Here, we discovered that ferroptosis, a programmed iron-dependent cell death, serves as a mechanism in statin-induced myopathy. Among four candidates including atorvastatin, lovastatin, rosuvastatin, and pravastatin, only atorvastatin could lead to ferroptosis in human cardiomyocytes (HCM) and murine skeletal muscle cells (C2C12), instead of human umbilical vein endothelial cell (HUVEC). Atorvastatin inhibits HCM and C2C12 cell viability in a dose-dependent manner, accompanying with significant augmentation in intracellular iron ions, reactive oxygen species (ROS), and lipid peroxidation. A noteworthy investigation found that those alterations particularly occurred in mitochondria and resulted in mitochondrial dysfunction. Biomarkers of myocardial injury increase significantly during atorvastatin intervention. However, all of the aforementioned enhancement could be restrained by ferroptosis inhibitors. Mechanistically, GSH depletion and the decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPx4), and xCT cystine-glutamate antiporter (the main component is SLC7A11) are involved in atorvastatin-induced muscular cell ferroptosis and damage. The downregulation of GPx4 in mitochondria-mediated ferroptosis signaling may be the core of it. In conclusion, our findings explore an innovative underlying pathophysiological mechanism of atorvastatin-induced myopathy and highlight that targeting ferroptosis serves as a protective strategy for clinical application.

DCE-MRI radiomics nomogram can predict response to neoadjuvant chemotherapy in esophageal cancer.

OBJECTIVES: To assess volumetric DCE-MRI radiomics nomogram in predicting response to neoadjuvant chemotherapy (nCT) in EC patients. METHODS: This retrospective analysis of a prospective study enrolled EC patients with stage cT1N + M0 or cT2-4aN0-3M0 who received DCE-MRI within 7 days before chemotherapy, followed by surgery. Response assessment was graded from 1 to 5 according to the tumor regression grade (TRG). Patients were stratified into responders (TRG1 + 2) and non-responders (TRG3 + 4 + 5). 72 radiomics features and vascular permeability parameters were extracted from DCE-MRI. The discriminating performance was assessed with ROC. Decision curve analysis (DCA) was used for comparing three different models. RESULTS: This cohort included 82 patients, and 72 tumor radiomics features and vascular permeability parameters acquired from DCE-MRI. mRMR and LASSO were performed to choose the optimized subset of radiomics features, and 3 features were selected to create the radiomics signature that were significantly associated with response (P < 0.001). AUC of combining radiomics signature and DCE-MRI performance in the training (n = 41) and validation (n = 41) cohort was 0.84 (95% CI 0.57-1) and 0.86 (95% CI 0.74-0.97), respectively. This combined model showed the best discrimination between responders and non-responders, and showed the highest positive and positive predictive value in both training set and test set. CONCLUSIONS: The radiomics features are useful for nCT response prediction in EC patients.