RNA modification gene WDR4 facilitates tumor progression and immunotherapy resistance in breast cancer.

INTRODUCTION: Growing interest toward RNA modification in cancer has inspired the exploration of datasets related to multiple RNA modifications. However, a comprehensive elucidation of the clinical value of various RNA modifications in breast cancer is still lacking. OBJECTIVES: This study aimed to provide a strategy based on RNA modification-related genes for predicting therapy response and survival outcomes in breast cancer patients. METHODS: Genes related to thirteen RNA modification patterns were integrated for establishing a nine-gene-containing signature-RMscore. Alterations of tumor immune microenvironment and therapy response featured by different RMscore levels were assessed by bulk transcriptome, single-cell transcriptome and genomics analyses. The biological function of key RMscore-related molecules was investigated by cellular experiments in vitro and in vivo, using flow cytometry, immunohistochemistry and immunofluorescence staining. RESULTS: This study has raised an effective therapy strategy for breast cancer patients after a well-rounded investigation of RNA modification-related genes. With a great performance of predicting patient prognosis, high levels of the RMscore proposed in this study represented suppressive immune microenvironment and therapy resistance, including adjuvant chemotherapy and PD-L1 blockade treatment. As the key contributor of the RMscore, inhibition of WDR4 impaired breast cancer progression significantly in vitro and in vivo, as well as participated in regulating cell cycle and mTORC1 signaling pathway via m7G modification. CONCLUSION: Briefly, this study has developed promising and effective tactics to achieve the prediction of survival probabilities and treatment response in breast cancer patients.

Biomineralization for Reducing and Controlling Sand-Dust Storms.

The sand-dust weather and sand-dust storms have become a serious environmental disaster worldwide. It is an important challenge to develop technologies for desert sand solidification in order to prevent and control sand-dust weather. The biomineralization technology for solidifying desert sands has been a novel method for reinforced soils in recent years. The biomineralization solidification sand field tests are completed at the Wuma Highway solidification section in the Tengger Desert. The superiority of the biomineralization for solidifying sands is verified by measuring the water storage capacity of different reinforcement zones including bare sand zone, plant zone, biomineralization solidifying sand zone, and biomineralization combined plant solidifying sand zone. Simultaneously, the molecular dynamics calculation analysis is used to verify the role of biomineralization solidifying sands in preventing sand-dust storms. All results demonstrate that the biomineralization solidification sand method is effective for controlling and preventing sandstorm disasters.

Prediction of short-term progression of COVID-19 pneumonia based on chest CT artificial intelligence: during the Omicron epidemic.

BACKGROUND AND PURPOSE: The persistent progression of pneumonia is a critical determinant of adverse outcomes in patients afflicted with COVID-19. This study aimed to predict personalized COVID-19 pneumonia progression between the duration of two weeks and 1 month after admission by integrating radiological and clinical features. METHODS: A retrospective analysis, approved by the Institutional Review Board, encompassed patients diagnosed with COVID-19 pneumonia between December 2022 and February 2023. The cohort was divided into training and validation groups in a 7:3 ratio. A trained multi-task U-Net network was deployed to segment COVID-19 pneumonia and lung regions in CT images, from which quantitative features were extracted. The eXtreme Gradient Boosting (XGBoost) algorithm was employed to construct a radiological model. A clinical model was constructed by LASSO method and stepwise regression analysis, followed by the subsequent construction of the combined model. Model performance was assessed using ROC and decision curve analysis (DCA), while Shapley's Additive interpretation (SHAP) illustrated the importance of CT features. RESULTS: A total of 214 patients were recruited in our study. Four clinical characteristics and four CT features were identified as pivotal components for constructing the clinical and radiological models. The final four clinical characteristics were incorporated as well as the RS_radiological model to construct the combined prediction model. SHAP analysis revealed that CT score difference exerted the most significant influence on the predictive performance of the radiological model. The training group's radiological, clinical, and combined models exhibited AUC values of 0.89, 0.72, and 0.92, respectively. Correspondingly, in the validation group, these values were observed to be 0.75, 0.72, and 0.81. The DCA curve showed that the combined model exhibited greater clinical utility than the clinical or radiological models. CONCLUSION: Our novel combined model, fusing quantitative CT features with clinical characteristics, demonstrated effective prediction of COVID-19 pneumonia progression from 2 weeks to 1 month after admission. This comprehensive model can potentially serve as a valuable tool for clinicians to develop personalized treatment strategies and improve patient outcomes.

Predictive value of radiomic features extracted from primary lung adenocarcinoma in forecasting thoracic lymph node metastasis: a systematic review and meta-analysis.

BACKGROUND: The application of radiomics in thoracic lymph node metastasis (LNM) of lung adenocarcinoma is increasing, but diagnostic performance of radiomics from primary tumor to predict LNM has not been systematically reviewed. Therefore, this study sought to provide a general overview regarding the methodological quality and diagnostic performance of using radiomic approaches to predict the likelihood of LNM in lung adenocarcinoma. METHODS: Studies were gathered from literature databases such as PubMed, Embase, the Web of Science Core Collection, and the Cochrane library. The Radiomic Quality Score (RQS) and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) were both used to assess the quality of each study. The pooled sensitivity, specificity, and area under the curve (AUC) of the best radiomics models in the training and validation cohorts were calculated. Subgroup and meta-regression analyses were also conducted. RESULTS: Seventeen studies with 159 to 1202 patients each were enrolled between the years of 2018 to 2022, of which ten studies had sufficient data for the quantitative evaluation. The percentage of RQS was between 11.1% and 44.4% and most of the studies were considered to have a low risk of bias and few applicability concerns in QUADAS-2. Pyradiomics and logistic regression analysis were the most commonly used software and methods for radiomics feature extraction and selection, respectively. In addition, the best prediction models in seventeen studies were mainly based on radiomics features combined with non-radiomics features (semantic features and/or clinical features). The pooled sensitivity, specificity, and AUC of the training cohorts were 0.84 (95% confidence interval (CI) [0.73-0.91]), 0.88 (95% CI [0.81-0.93]), and 0.93(95% CI [0.90-0.95]), respectively. For the validation cohorts, the pooled sensitivity, specificity, and AUC were 0.89 (95% CI [0.82-0.94]), 0.86 (95% CI [0.74-0.93]) and 0.94 (95% CI [0.91-0.96]), respectively. CONCLUSIONS: Radiomic features based on the primary tumor have the potential to predict preoperative LNM of lung adenocarcinoma. However, radiomics workflow needs to be standardized to better promote the applicability of radiomics. TRIAL REGISTRATION: CRD42022375712.

Morphological and regional spontaneous functional aberrations in the brain associated with Crohn's disease: a systematic review and coordinate-based meta-analyses.

Crohn's disease is an acknowledged "brain-gut" disorder with unclear physiopathology. This study aims to identify potential neuroimaging biomarkers of Crohn's disease. Gray matter volume, cortical thickness, amplitude of low-frequency fluctuations, and regional homogeneity were selected as indices of interest and subjected to analyses using both activation likelihood estimation and seed-based d mapping with permutation of subject images. In comparison to healthy controls, Crohn's disease patients in remission exhibited decreased gray matter volume in the medial frontal gyrus and concurrently increased regional homogeneity. Furthermore, gray matter volume reduction in the medial superior frontal gyrus and anterior cingulate/paracingulate gyri, decreased regional homogeneity in the median cingulate/paracingulate gyri, superior frontal gyrus, paracentral lobule, and insula were observed. The gray matter changes of medial frontal gyrus were confirmed through both methods: decreased gray matter volume of medial frontal gyrus and medial superior frontal gyrus were identified by activation likelihood estimation and seed-based d mapping with permutation of subject images, respectively. The meta-regression analyses showed a positive correlation between regional homogeneity alterations and patient age in the supplementary motor area and a negative correlation between gray matter volume changes and patients' anxiety scores in the medial superior frontal gyrus. These anomalies may be associated with clinical manifestations including abdominal pain, psychiatric disorders, and possibly reflective of compensatory mechanisms.

Identifying New Subtypes of Multiple System Atrophy Using Cluster Analysis.

Background: Multiple system atrophy (MSA) is a disease with diverse symptoms and the commonly used classifications, MSA-P and MSA-C, do not cover all the different symptoms seen in MSA patients. Additionally, these classifications do not provide information about how the disease progresses over time or the expected outcome for patients. Objective: To explore clinical subtypes of MSA with a natural disease course through a data-driven approach to assist in the diagnosis and treatment of MSA. Methods: We followed 122 cases of MSA collected from 3 hospitals for 3 years. Demographic characteristics, age of onset, clinical signs, scale assessment scores, and auxiliary examination were collected. Age at onset; time from onset to assisted ambulation; and UMSARS I, II, and IV, COMPASS-31, ICARS, and UPDRS III scores were selected as clustering elements. K-means, partitioning around medoids, and self-organizing maps were used to analyze the clusters. Results: The results of all three clustering methods supported the classification of three MSA subtypes: The aggressive progression subtype (MSA-AP), characterized by mid-to-late onset, rapid progression and severe clinical symptoms; the typical subtype (MSA-T), characterized by mid-to-late onset, moderate progression and moderate severity of clinical symptoms; and the early-onset slow progression subtype (MSA-ESP), characterized by early-to-mid onset, slow progression and mild clinical symptoms. Conclusions: We divided MSA into three subtypes and summarized the characteristics of each subtype. According to the clustering results, MSA patients were divided into three completely different types according to the severity of symptoms, the speed of disease progression, and the age of onset.

circLIFR-007 reduces liver metastasis via promoting hnRNPA1 nuclear export and YAP phosphorylation in breast cancer.

Cancer metastasis is the major cause of death in patients with breast cancer (BC). The liver is a common site of breast cancer metastasis, and the 5-year survival rate of patients with breast cancer liver metastases (BCLMs) is only about 8.5 %. CircRNAs are involved in a variety of cancer-related pathological behaviors, and their unique structure and resistance to RNA degradation enable them to serve as ideal diagnostic biomarkers and therapeutic targets. Therefore, it is important to investigate the role and molecular mechanism of circRNAs in cancer metastasis. CircLIFR-007 was identified as a critical circular RNA in BC metastasis by circRNAs microarray and qRT-PCR experiment. Cell function assays were performed to explore the effect of circLIFR-007 in breast cancer cells. Experiments in vivo validated the function of circLIFR-007. Several molecular assays were performed to investigate the underlying mechanisms. We found that circLIFR-007 acted as a negative controller in breast cancer liver metastasis. CircLIFR-007 upregulates the phosphorylation level of YAP by exporting hnRNPA1 to promote the combination between hnRNPA1 and YAP in the cytoplasm. Overexpression of circLIFR-007 suppressed the expression of liver metastasis-related proteins, SREBF1 and SNAI1, which were regulated by transcription factor YAP. Functionally, circLIFR-007 inhibits the proliferation and metastasis of breast cancer cells both in vivo and in vitro.

PIWI-interacting RNA-YBX1 inhibits proliferation and metastasis by the MAPK signaling pathway via YBX1 in triple-negative breast cancer.

Breast cancer is the second leading cause of death in women worldwide, with triple-negative breast cancer (TNBC) having the worst prognosis. Although there are numerous studies on TNBC, there is no effective treatment for it, and it is still a major problem today. Studies on PIWI-interacting RNAs (piRNAs) are increasing and investigating the mechanism of piRNAs in the proliferation and metastasis of TNBC may lead to new potential treatment targets. Here, we identified a novel piRNA, piR-YBX1, which was downregulated in TNBC compared to matched normal breast tissue. Overexpression of piR-YBX1 significantly inhibited the proliferation, migration, invasion ability of TNBC cells both in vivo and in vitro. Mechanistically, piR-YBX1 could bind directly to mRNA of Y-box binding protein 1 (YBX1) and overexpression of piR-YBX1 downregulated YBX1 in both mRNA and protein levels, while the function of piR-YBX1 could be partly rescued by overexpression of YBX1. In addition, YBX1 could bind to RAF1 which is the key molecule in the MAPK signaling pathway, and overexpression of piR-YBX1 inhibited the p-MEK and p-ERK1/2, which can be reverted by YBX1. In conclusion, our findings discovered that the piR-YBX1/YBX1/MAPK axis suppresses the proliferation and metastasis of TNBC and therefore piR-YBX1 has the potential to be an effective therapeutic agent for breast cancer.

Could the underlying biological basis of prognostic radiomics and deep learning signatures be explored in patients with lung cancer? A systematic review.

OBJECTIVES: To summarize the underlying biological correlation of prognostic radiomics and deep learning signatures in patients with lung cancer and evaluate the quality of available studies. METHODS: This study examined databases including the PubMed, Embase, Web of Science Core Collection, and Cochrane Library, for studies that elaborated on the underlying biological correlation with prognostic radiomics and deep learning signatures based on CT or PET/CT for predicting the prognosis in patients with lung cancer. Information about the patient and radiogenomic analyses was extracted for the included studies. The Radiomics Quality Score (RQS) and the Prediction Model Risk of Bias Assessment Tool were used to assess the quality of these studies. RESULTS: Twelve studies were included with 7,338 patients from 2014 to 2022. All studies except for one were retrospective. Supervised machine learning was adopted in six studies, and the remaining used unsupervised machine learning methods. Gene sequencing and histopathological data were analyzed by 83.33% and 16.67% of the included studies, respectively. Gene set enrichment analysis and correlation analysis were most used to explore the biological meaning of prognostic signatures. The median RQS for supervised learning articles was 13.5 (range 12-19) and 7.0 (range 5-14) for unsupervised learning articles. The studies included in this report were assessed to have high risk of bias overall. CONCLUSION: The biological basis for the interpretability of data-driven models mainly focused on genomics and histopathological factors, and it may improve the prognosis of lung cancer with more proper biological interpretation in the future.

State-of-the-art review of soil erosion control by MICP and EICP techniques: Problems, applications, and prospects.

In recent years, the application of microbially induced calcite precipitation (MICP) and enzyme-induced carbonate precipitation (EICP) techniques have been extensively studied to mitigate soil erosion, yielding substantial achievements in this regard. This paper presents a comprehensive review of the recent progress in erosion control by MICP and EICP techniques. To further discuss the effectiveness of erosion mitigation in-depth, the estimation methods and characterization of erosion resistance were initially compiled. Moreover, factors affecting the erosion resistance of MICP/EICP-treated soil were expounded, spanning from soil properties to treatment protocols and environmental conditions. The development of optimization and upscaling in erosion mitigation via MICP/EICP was also included in this review. In addition, this review discussed the limitations and correspondingly proposed prospective applications of erosion control via the MICP/EICP approach. The current review presents up-to-date information on the research activities for improving erosion resistance by MICP/EICP, aiming at providing insights for interdisciplinary researchers and guidance for promoting this method to further applications in erosion mitigation.

Transcutaneous electrical acupoint stimulation attenuated neuroinflammation and oxidative stress by activating SIRT1-induced signaling pathway in MCAO/R rat models.

BACKGROUND: Silent information regulator 1 (SIRT1) plays a beneficial role in cerebral ischemic injury. Previous reports have demonstrated that transcutaneous electrical acupoint stimulation (TEAS) exerts a beneficial effect on ischemic stroke; however, whether SIRT1 participates in the underlying mechanism for the neuroprotective effects of TEAS against ischemic brain damage has not been confirmed. METHODS: The rat models of middle cerebral artery occlusion/reperfusion (MCAO/R) were utilized in the current experiment. After MCAO/R surgery, rats in TEAS, EC and EX group received TEAS intervention with or without the injection of EX527, the SIRT1 inhibitor. Neurological deficit scores, infarct volume, hematoxylin eosin (HE) staining and apoptotic cell number were measured. The results of RNA sequencing were analyzed to determine the differential expression changes of genes among sham, MCAO and TEAS groups, in order to investigate the possible pathological processes involved in cerebral ischemia and explore the protective mechanisms of TEAS. Moreover, oxidative stress markers including MDA, SOD, GSH and GSH-Px were measured with assay kits. The levels of the proinflammatory cytokines, such as IL-6, IL-1ß and TNF-α, were detected by ELISA assay, and Iba-1 (the microglia marker protein) positive cells was measured by immunofluorescence (IF). Western blot and IF were utilized to examine the levels of key molecules in SIRT1/FOXO3a and SIRT1/BRCC3/NLRP3 signaling pathways. RESULTS: TEAS significantly decreased brain infarcted size and apoptotic neuronal number, and alleviated neurological deficit scores and morphological injury by activating SIRT1. The results of RNA-seq and bioinformatic analysis revealed that oxidative stress and inflammation were the key pathological mechanisms, and TEAS alleviated oxidative injury and inflammatory reactions following ischemic stroke. Then, further investigation indicated that TEAS notably attenuated neuronal apoptosis, neuroinflammation and oxidative stress damage in the hippocampus of rats with MCAO/R surgery. Moreover, TEAS intervention in the MCAO/R model significantly elevated the expressions of SIRT1, FOXO3a, CAT, BRCC3, NLRP3 in the hippocampus. Furthermore, EX527, as the inhibitor of SIRT1, obviously abolished the anti-oxidative stress and anti-neuroinflammatory roles of TEAS, as well as reversed the TEAS-mediated elevation of SIRT1, FOXO3a, CAT and reduction of BRCC3 and NLRP3 mediated by following MCAO/R surgery. CONCLUSIONS: In summary, these findings clearly suggested that TEAS attenuated brain damage by suppressing apoptosis, oxidative stress and neuroinflammation through modulating SIRT1/FOXO3a and SIRT1/BRCC3/NLRP3 signaling pathways following ischemic stroke, which can be a promising treatment for stroke patients.

AURKAIP1 actuates tumor progression through stabilizing DDX5 in triple negative breast cancer.

Aurora-A kinase interacting protein 1 (AURKAIP1) has been proved to take an intermediary role in cancer by functioning as a negative regulator of Aurora-A kinase. However, it remains unclear whether and how AURKAIP1 itself would directly engage in regulating malignancies. The expression levels of AURKAIP1 were detected in triple negative breast cancer (TNBC) by immunohistochemistry and western blots. The CCK8, colony formation assays and nude mouse model were conducted to determine cell proliferation whereas transwell and wound healing assays were performed to observe cell migration. The interaction of AURKAIP1 and DEAD-box helicase 5 (DDX5) were verified through co-immunoprecipitation and successively western blots. From the results, we found that AURKAIP1 was explicitly upregulated in TNBC, which was positively associated with tumor size, lymph node metastases, pathological stage and unfavorable prognosis. AURKAIP1 silencing markedly inhibited TNBC cell proliferation and migration in vitro and in vivo. AURKAIP1 directly interacted with and stabilized DDX5 protein by preventing ubiquitination and degradation, and DDX5 overexpression successfully reversed proliferation inhibition induced by knockdown of AURKAIP1. Consequently, AURKAIP1 silencing suppressed the activity of Wnt/ß-catenin signaling in a DDX5-dependent manner. Our study may primarily disclose the molecular mechanism by which AURKAIP1/DDX5/ß-catenin axis modulated TNBC progression, indicating that AURKAIP1 might serve as a therapeutic target as well as a TNBC-specific biomarker for prognosis.

Identification of lactate-related subgroups and prognostic model in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that exhibits elevated glycolytic capacity. Lactate, as a byproduct of glycolysis, is considered a major oncometabolite that plays an important role in oncogenesis and remodeling of the tumor microenvironment. However, the potential roles of lactate in TNBC are not yet fully understood. In this study, our goal was to identify prognosis-related lactate genes (PLGs) and construct a lactate-related prognostic model (LRPM) for TNBC. METHODS: First, we applied lactate-related genes to classify TNBC samples using a hierarchical clustering algorithm. Then, we performed the log-rank analysis and the least absolute shrinkage and selection operator analysis to screen PLGs and construct the LRPM. The biological functions of the identified PLGs in TNBC were investigated using CCK8 assay and clone formation assay. Finally, we constructed a nomogram based on the lactate-risk score and tumor clinical stage. We used the operating characteristic curve and decision curve analysis to evaluate the predictive capability of the nomogram. RESULTS: Our results showed that the TNBC samples could be classified into two subgroups with different survival probabilities. Three genes (NDUFAF3, CARS2 and FH), which can suppress TNBC cell proliferation, were identified as PLGs. Moreover, the LRPM and nomogram exhibited excellent predictive performance for TNBC patient prognosis. CONCLUSION: We have developed a novel LRPM that enables risk stratification and identification of poor molecular subtypes in TNBC patients, showing great potential in clinical practice.

Novel Implication of the Basement Membrane for Breast Cancer Outcome and Immune Infiltration.

Therapeutic failure in breast cancer patients is largely attributed to postoperative advancement and therapy resistance. Nevertheless, an efficacious prognostic signature for recognizing this population is lacking. The basement membrane (BM) has been proven to be strongly involved in cancer progression and metastasis, and has the potential to be a powerful predictor in breast cancer. In this study, substantial bulk RNA transcriptomics, single cell RNA transcriptomics and clinical information were collected from TCGA-BRCA, METABRIC and GSE96058, and Kaplan-Meier survival curves, single cell analysis and in vitro experiments were conducted to validate the signature. From the results, a prognostic index, namely, the BMscore, was established with six pivotal BM genes, specifically LOXL1, FBLN1, FBLN5, SDC1, ADAMTS8 and PXDNL. Verification by independent cohorts showed that breast cancer patients with high BMscore had a distinctly worse outcome. By integrating the BMscore and clinical factors, we constructed a prognostic nomogram that displayed good predictive capability. Furthermore, we evaluated the implication of the BMscore in breast cancer immune infiltration. More importantly, a strongly positive correlation between the BMscore and EMT activity was revealed with immunohistochemistry and in vitro experiments. Taken together, we provided a novel BMscore gene signature for breast cancer patients to predict clinical prognosis and metastasis accurately, which may help with individualized clinical decision-making.

Transcutaneous Electrical Nerve Stimulation (TENS) Alleviates Brain Ischemic Injury by Regulating Neuronal Oxidative Stress, Pyroptosis, and Mitophagy.

Background: As a noninvasive treatment, transcutaneous electrical nerve stimulation (TENS) has been utilized to treat various diseases in clinic. However, whether TENS can be an effective intervention in the acute stage of ischemic stroke still remains unclear. In the present study, we aimed to explore whether TENS could alleviate brain infarct volume, reduce oxidative stress and neuronal pyroptosis, and activate mitophagy following ischemic stroke. Methods: TENS was performed at 24 h after middle cerebral artery occlusion/reperfusion (MCAO/R) in rats for 3 consecutive days. Neurological scores, the volume of infarction, and the activity of SOD, MDA, GSH, and GSH-px were measured. Moreover, western blot was performed to detect the related protein expression, including Bcl-2, Bax, TXNIP, GSDMD, caspase-1, NLRP3, BRCC3, HIF-1α, BNIP3, LC3, and P62. Real-time PCR was performed to detect NLRP3 expression. Immunofluorescence was performed to detect the levels of LC3. Results: There was no significant difference of neurological deficit scores between the MCAO group and the TENS group at 2 h after MCAO/R operation (P > 0.05), while the neurological deficit scores of TENS group significantly decreased in comparison with MCAO group at 72 h following MACO/R injury (P < 0.05). Similarly, TENS treatment significantly reduced the brain infarct volume compared with the MCAO group (P < 0.05). Moreover, TENS decreased the expression of Bax, TXNIP, GSDMD, caspase-1, BRCC3, NLRP3, and P62 and the activity of MDA as well as increasing the level of Bcl-2, HIF-1α, BNIP3, and LC3 and the activity of SOD, GSH, and GSH-px (P < 0.05). Conclusions: In conclusion, our results indicated that TENS alleviated brain damage following ischemic stroke via inhibiting neuronal oxidative stress and pyroptosis and activating mitophagy, possibly via the regulation of TXNIP, BRCC3/NLRP3, and HIF-1α/BNIP3 pathways.

The Role of Iron Metabolism, Lipid Metabolism, and Redox Homeostasis in Alzheimer's Disease: from the Perspective of Ferroptosis.

In the development of Alzheimer's disease (AD), cell death is common. Novel cell death form-ferroptosis is discovered in recent years. Ferroptosis is an iron-regulated programmed cell death mechanism and has been identified in AD clinical samples. Typical characteristics of ferroptosis involve the specific changes in cell morphology, iron-dependent aggregation of reactive oxygen species (ROS) and lipid peroxides, loss of glutathione (GSH), inactivation of glutathione peroxidase 4 (GPX4), and a unique group of regulatory genes. Increasing evidence demonstrates that ferroptosis may be associated with neurological dysfunction in AD. However, the underlying mechanisms have not been fully elucidated. This article reviews the potential role of ferroptosis in AD, the involvement of ferroptosis in the pathological progression of AD through the mechanisms of iron metabolism, lipid metabolism, and redox homeostasis, as well as a range of potential therapies targeting ferroptosis for AD. Intervention strategies based on ferroptosis are promising for Alzheimer's disease treatment at present, but further researches are still needed.

The Single-Cell Landscape of Intratumoral Heterogeneity and The Immunosuppressive Microenvironment in Liver and Brain Metastases of Breast Cancer.

Distant metastasis remains the major cause of morbidity for breast cancer. Individuals with liver or brain metastasis have an extremely poor prognosis and low response rates to anti-PD-1/L1 immune checkpoint therapy compared to those with metastasis at other sites. Therefore, it is urgent to investigate the underlying mechanism of anti-PD-1/L1 resistance and develop more effective immunotherapy strategies for these patients. Using single-cell RNA sequencing, a high-resolution map of the entire tumor ecosystem based on 44 473 cells from breast cancer liver and brain metastases is depicted. Identified by canonical markers and confirmed by multiplex immunofluorescent staining, the metastatic ecosystem features remarkable reprogramming of immunosuppressive cells such as FOXP3+ regulatory T cells, LAMP3+ tolerogenic dendritic cells, CCL18+ M2-like macrophages, RGS5+ cancer-associated fibroblasts, and LGALS1+ microglial cells. In addition, PD-1 and PD-L1/2 are barely expressed in CD8+ T cells and cancer/immune/stromal cells, respectively. Interactions of the immune checkpoint molecules LAG3-LGALS3 and TIGIT-NECTIN2 between CD8+ T cells and cancer/immune/stromal cells are found to play dominant roles in the immune escape. In summary, this study dissects the intratumoral heterogeneity and immunosuppressive microenvironment in liver and brain metastases of breast cancer for the first time, providing insights into the most appropriate immunotherapy strategies for these patients.

Can quantitative peritumoral CT radiomics features predict the prognosis of patients with non-small cell lung cancer? A systematic review.

OBJECTIVES: To provide an overarching evaluation of the value of peritumoral CT radiomics features for predicting the prognosis of non-small cell lung cancer and to assess the quality of the available studies. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched for studies predicting the prognosis in patients with non-small cell lung cancer (NSCLC) using CT-based peritumoral radiomics features. Information about the patient, CT-scanner, and radiomics analyses were all extracted for the included studies. Study quality was assessed using the Radiomics Quality Score (RQS) and the Prediction Model Risk of Bias Assessment Tool (PROBAST). RESULTS: Thirteen studies were included with 2942 patients from 2017 to 2022. Only one study was prospective, and the others were all retrospectively designed. Manual segmentation and multicenter studies were performed by 69% and 46% of the included studies, respectively. 3D-Slicer and MATLAB software were most commonly used for the segmentation of lesions and extraction of features. The peritumoral region was most frequently defined as dilated from the tumor boundary of 15 mm, 20 mm, or 30 mm. The median RQS of the studies was 13 (range 4-19), while all of included studies were assessed as having a high risk of bias (ROB) overall. CONCLUSIONS: Peritumoral radiomics features based on CT images showed promise in predicting the prognosis of NSCLC, although well-designed studies and further biological validation are still needed. KEY POINTS: • Peritumoral radiomics features based on CT images are promising and encouraging for predicting the prognosis of non-small cell lung cancer. • The peritumoral region was often dilated from the tumor boundary of 15 mm or 20 mm because these were considered safe margins. • The median Radiomics Quality Score of the included studies was 13 (range 4-19), and all of studies were considered to have a high risk of bias overall.

The long-term course of subsolid nodules and predictors of interval growth on chest CT: a systematic review and meta-analysis.

OBJECTIVES: To calculate the pooled incidence of interval growth after long-term follow-up and identify predictors of interval growth in subsolid nodules (SSNs) on chest CT. METHODS: A search of MEDLINE (PubMed), Cochrane Library, Web of Science Core Collection, and Embase was performed on November 08, 2021, for relevant studies. Patient information, CT scanner, and SSN follow-up information were extracted from each included study. A random-effects model was applied along with subgroup and meta-regression analyses. Study quality was assessed by the Newcastle-Ottawa scale, and publication bias was assessed by Egger's test. RESULTS: Of the 6802 retrieved articles, 16 articles were included and analyzed, providing a total of 2898 available SSNs. The pooled incidence of growth in the 2898 SSNs was 22% (95% confidence interval [CI], 15-29%). The pooled incidence of growth in the subgroup analysis of pure ground-glass nodules was 26% (95% CI: 12-39%). The incidence of SSN growth after 2 or more years of stability was only 5% (95% CI: 3-7%). An initially large SSN size was found to be the most frequent risk factor affecting the incidence of SSN growth and the time of growth. CONCLUSIONS: The pooled incidence of SSN growth was as high as 22%, with a 26% incidence reported for pure ground-glass nodules. Although the incidence of growth was only 5% after 2 or more years of stability, long-term follow-up is needed in certain cases. Moreover, the initial size of the SSN was the most frequent risk factor for growth. KEY POINTS: • Based on a meta-analysis of 2898 available subsolid nodules in the literature, the pooled incidence of growth was 22% for all subsolid nodules and 26% for pure ground-glass nodules. • After 2 or more years of stability on follow-up CT, the pooled incidence of subsolid nodule growth was only 5%. • Given the incidence of subsolid nodule growth, management of these lesions with long-term follow-up is preferred.

Transcutaneous electrical acupoint stimulation alleviates cerebral ischemic injury through the TLR4/MyD88/NF-κ B pathway.

This study was to explore whether transcutaneous electrical acupoint stimulation (TEAS) treatment could mediate inflammation, apoptosis, and pyroptosis of neuronal cells and microglia activation through the TLR4/MyD88/NF-κB pathway in the early stage of ischemic stroke. TEAS treatment at Baihui (GV20) and Hegu (LI4) acupoints of the affected limb was administered at 24, 48, and 72 h following middle cerebral artery occlusion/reperfusion (MCAO/R), with lasting for 30 min each time. Neurological impairment scores were assessed 2 h and 72 h after ischemia/reperfusion (I/R). TTC staining was used to evaluate the volume of brain infarction. The histopathologic changes of hippocampus were detected by H&E staining. WB analysis was performed to assess the levels of TLR4, MyD88, p-NF-κB p65/NF-κB p65, and inflammation, apoptosis, pyroptosis-related proteins. TLR4 expression was measured using immunohistochemistry. The expression of inflammation-related proteins was also measured using ELISA. Immunofluorescence was used to detect the expression level of Iba1. Our findings demonstrated that TEAS intervention after I/R improved neurological function, reduced the volume of brain infarction, and mitigated pathological damage. Moreover, TEAS reduced the levels of TLR4, MyD88, p-NF-κB p65/NF-κB p65, TNF-α, IL-6, Bax, NLRP3, cleaved caspase-1/pro caspase-1, IL-1ß, IL-18, GSDMD, and Iba1 while enhancing Bcl-2 expression. Moreover, the protective effects of TEAS could be counteracted by lipopolysaccharide (LPS, a TLR4 agonist). In conclusion, TEAS can reduce cerebral damage and suppress inflammation, cell death, and microglia activation after ischemic stroke via inhibiting the TLR4/MyD88/NF-κB pathway.