Deficiency of ADAR2 ameliorates metabolic-associated fatty liver disease via AMPK signaling pathways in obese mice.

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease caused by hepatic steatosis. Adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine RNA editing. However, the functional role of ADAR2 in NAFLD is unclear. ADAR2+/+/GluR-BR/R mice (wild type, WT) and ADAR2-/-/GluR-BR/R mice (ADAR2 KO) mice are fed with standard chow or high-fat diet (HFD) for 12 weeks. ADAR2 KO mice exhibit protection against HFD-induced glucose intolerance, insulin resistance, and dyslipidemia. Moreover, ADAR2 KO mice display reduced liver lipid droplets in concert with decreased hepatic TG content, improved hepatic insulin signaling, better pyruvate tolerance, and increased glycogen synthesis. Mechanistically, ADAR2 KO effectively mitigates excessive lipid production via AMPK/Sirt1 pathway. ADAR2 KO inhibits hepatic gluconeogenesis via the AMPK/CREB pathway and promotes glycogen synthesis by activating the AMPK/GSK3ß pathway. These results provide evidence that ADAR2 KO protects against NAFLD progression through the activation of AMPK signaling pathways.

Perceptions of social class through Chinese speech cues.

Speech is a complex auditory signal that contains multiple layers of linguistic and non-linguistic structure, it contains both linguistic and social class information. Perceivers are exquisitely sensitive to this layered structure and extract not only linguistic properties, but also indexical characteristics that provide information about individual talkers and groups of talkers. Social class information involves inferring the speaker's social class or forming an impression of their social status based on their speech. Previous research on social class perception in speech has primarily focused on English, with relatively little research on Chinese. This study examines social class perception in Chinese speech. Study 1 employed class judgment and evaluation tasks with a subjective social class scale as the main measure to examine whether listeners could infer class information from Chinese speech and how their own class background influenced their perception. The results of Study 1 showed that subjects could accurately discriminate between speakers' social classes, but there may be a response bias that overestimates lower-class speakers as upper-class speakers. Study 2 focused on whether the speech of different classes of speakers actually differed on a number of indicators. It was found that the speech of higher class speakers was perceived to be more standardised, more pleasant to listen to and less accent-intensive. Overall, listeners can perceive class information from Chinese speech; different classes of Chinese speech do contain different levels of indexical information. In Chinese language societies, individuals can also judge their class information through the speech, which is consistent with the relevant research results in English.

A review of chemotherapeutic drugs-induced arrhythmia and potential intervention with traditional Chinese medicines.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias.

Xanthine oxidase inhibition study of isolated secondary metabolites from Dolichandrone spathacea (Bignoniaceae): In vitro and in silico approach.

Xanthine oxidase (XO) has been widely recognized as a pivotal enzyme in developing hyperuricemia, primarily contributing to the excessive production of uric acid during purine metabolism in the liver. One of the standard treatment approaches involves reducing uric acid levels by inhibiting XO activity. In this study, the leaf extract of Dolichandrone spathacea, traditionally used in folk medicine, was found to inhibit XO activity in the ethyl acetate and butanol fractions at a concentration of 100 µg/mL, their values were 78.57 ± 3.85 % (IC50 = 55.93 ± 5.73 µg/ml) and 69.43 ± 8.68 % (IC50 = 70.17 ± 7.98 µg/ml), respectively. The potential XO inhibitory components were isolated by bioactivity assays and the HR-ESI-MS and NMR spectra system. The main constituents of leaf extracts of Dolichandrone spathacea, six compounds, namely trans-4-methoxycinnamic acid (3), trans-3,4-dimethoxycinnamic acid (4), p-coumaric acid (5), martynoside (6), 6-O-(p-methoxy-E-cinnamoyl)-ajugol (7), and scolymoside (17), were identified as potent XO inhibitors with IC50 values ranging from 19.34 ± 1.63 µM to 64.50 ± 0.94 µM. The enzyme kinetics indicated that compounds 3-5, 7, and 17 displayed competitive inhibition like allopurinol, while compound 6 displayed a mixed-type inhibition. Computational studies corroborated these experimental results, highlighting the interactions between potential metabolites and XO enzyme. The hydrogen bonds played crucial roles in the binding interaction, especially, scolymoside (17) forms a hydrogen bond with Mos3004, exhibited the lowest binding energy (-18.3286 kcal/mol) corresponding to the lowest IC50 (19.34 ± 1.63 µM). Furthermore, nine compounds were isolated for the first time from this plant. In conclusion, Dolichandrone spathacea and its constituents possess the potential to modulate the xanthine oxidase enzyme involved in metabolism.

Third-order exceptional line in a nitrogen-vacancy spin system.

Exceptional points (EPs) are singularities in non-Hermitian systems, where k (k ≥ 2) eigenvalues and eigenstates coalesce. High-order EPs exhibit richer topological characteristics and better sensing performance than second-order EPs. Theory predicts even richer non-Hermitian topological phases for high-order EP geometries, such as lines or rings formed entirely by high-order EPs. However, experimental exploration of high-order EP geometries has hitherto proved difficult due to the demand for more degrees of freedom in the Hamiltonian's parameter space or a higher level of symmetries. Here we observe a third-order exceptional line in an atomic-scale system. To this end, we use a nitrogen-vacancy spin in diamond and introduce multiple symmetries in the non-Hermitian Hamiltonian realized with the system. Furthermore, we show that the symmetries play an essential role in the occurrence of high-order EP geometries. Our approach can in future be further applied to explore high-order EP-related topological physics at the atomic scale and, potentially, for applications of high-order EPs in quantum technologies.

Predicting Prognosis and Immunotherapy Response in Multiple Cancers Based on the Association of PANoptosis-Related Genes with Tumor Heterogeneity.

PANoptosis is a newly recognized inflammatory pathway for programmed cell death (PCD). It participates in regulating the internal environment, homeostasis, and disease process in various complex ways and plays a crucial role in tumor development, but its mechanism of action is still unclear. In this study, we comprehensively analyzed the expression of 14 PANoptosis-related genes (PANRGs) in 28 types of tumors. Most PANRGs are upregulated in tumors, including Z-DNA binding protein 1 (ZBP1), nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), caspase (CASP) 1, CASP6, CASP8, PYCARD, FADD, MAP3K7, RNF31, and RBCK1. PANRGs are highly expressed in GBM, LGG, and PAAD, while their levels in ACC are much lower than those in normal tissues. We found that both the CNV and SNV gene sets in BLCA are closely related to survival performance. Subsequently, we conducted clustering and LASSO analysis on each tumor and found that the inhibitory and the stimulating immune checkpoints positively correlate with ZBP1, NLRP3, CASP1, CASP8, and TNFAIP3. The immune infiltration results indicated that KIRC is associated with most infiltrating immune cells. According to the six tumor dryness indicators, PANRGs in LGG show the strongest tumor dryness but have a negative correlation with RNAss. In KIRC, LIHC, and TGCT, most PANRGs play an important role in tumor heterogeneity. Additionally, we analyzed the linear relationship between PANRGs and miRNA and found that MAP3K7 correlates to many miRNAs in most cancers. Finally, we predicted the possible drugs for targeted therapy of the cancers. These data greatly enhance our understanding of the components of cancer and may lead to the discovery of new biomarkers for predicting immunotherapy response and improving the prognosis of cancer patients.

Femtosecond laser lithotripsy: a novel alternative for kidney stone treatment? Evaluating the safety and effectiveness in an ex vivo study.

The Holmium (Ho:YAG) laser is presently the most extensively employed in laser lithotripsy for the management of kidney stones. Despite its adoption as the gold standard for laser lithotripsy, Ho:YAG laser lithotripsy poses three significant challenges, namely thermal effect, insufficient stone fragmentation, and stone displacement, which have garnered increased attention from urologic surgeons. Nowadays, the femtosecond laser is regarded as a potential alternative to the Ho:YAG laser due to its capacity to ablate diverse materials with minimal thermal effect. In our ex vivo investigation, we assessed the dimensions of ablation pits, the efficacy of ablation, the degree of stone fragmentation, the alterations in water temperature surrounding stones, and the degree of tissue damage associated with Femtosecond laser lithotripsy utilizing adjustable power settings (1-50 W). Our findings indicate that the ablation pits generated by the Femtosecond laser exhibited uniform geometries, and the effectiveness of ablation and fragmentation for Femtosecond laser lithotripsy were significantly and positively correlated with laser power. When the laser power remained constant, the Femtosecond laser with higher pulse energy demonstrated superior efficiency in stone ablation, but inferior performance in stone fragmentation. Conversely, the Femtosecond laser with higher pulse frequency exhibited the opposite behavior. Furthermore, the thermal effect increased proportionally with laser power, leading to a tentative recommendation of 10W laser power for future investigations. Our in vitro findings suggest that the Femtosecond laser holds promise as a safe and effective alternative to holmium lasers.

Methyl Canthin-6-one-2-carboxylate Restrains the Migration/Invasion Properties of Fibroblast-like Synoviocytes by Suppressing the Hippo/YAP Signaling Pathway.

Rheumatoid arthritis (RA) is an inflammatory condition that causes severe cartilage degradation and synovial damage in the joints with multiple systemic implications. Previous studies have revealed that fibroblast-like synoviocytes (FLSs) play a pivotal role in the pathogenesis of RA. The appropriate regulation of FLS function is an efficient approach for the treatment of this disease. In the present study, we explored the effects of methyl canthin-6-one-2-carboxylate (Cant), a novel canthin-6-one alkaloid, on the function of FLSs. Our data showed that exposure to Cant significantly suppressed RA-FLS migration and invasion properties in a dose-dependent manner. Meanwhile, pre-treatment with Cant also had an inhibitory effect on the release of several pro-inflammatory cytokines, including IL-6 and IL-1ß, as well as the production of MMP1 and MMP3, which are important mediators of FLS invasion. In further mechanistic studies, we found that Cant had an inhibitory effect on the Hippo/YAP signaling pathway. Treatment with Cant suppressed YAP expression and phosphorylation on serine 127 and serine 397 while enhancing LATS1 and MST1 levels, both being important upstream regulators of YAP. Moreover, YAP-specific siRNA or YAP inhibition significantly inhibited wound healing as well as the migration and invasion rate of FLS cells, an impact similar to Cant treatment. Meanwhile, the over-expression of YAP significantly reversed the Cant-induced decline in RA-FLS cell migration and invasion, indicating that YAP was required in the inhibitory effect of Cant on the migration and invasion of RA-FLS cells. Additionally, supplementation of MMP1, but not MMP3, in culture supernatants significantly reversed the inhibitory effect of Cant on RA-FLS cell invasion. Our data collectively demonstrated that Cant may suppress RA-FLS migration and invasion by inhibiting the production of MMP1 via inhibiting the YAP signaling pathway, suggesting a potential of Cant for the further development of anti-RA drugs.

Development and validation of a nomogram based on biparametric MRI PI-RADS v2.1 and clinical parameters to avoid unnecessary prostate biopsies.

BACKGROUND: Biparametric MRI (bpMRI) is a faster, contrast-free, and less expensive MRI protocol that facilitates the detection of prostate cancer. The aim of this study is to determine whether a biparametric MRI PI-RADS v2.1 score-based model could reduce unnecessary biopsies in patients with suspected prostate cancer (PCa). METHODS: The patients who underwent MRI-guided biopsies and systematic biopsies between January 2020 and January 2022 were retrospectively analyzed. The development cohort used to derive the prediction model consisted of 275 patients. Two validation cohorts included 201 patients and 181 patients from 2 independent institutions. Predictive models based on the bpMRI PI-RADS v2.1 score (bpMRI score) and clinical parameters were used to detect clinically significant prostate cancer (csPCa) and compared by analyzing the area under the curve (AUC) and decision curves. Spearman correlation analysis was utilized to determine the relationship between International Society of Urological Pathology (ISUP) grade and clinical parameters/bpMRI score. RESULTS: Logistic regression models were constructed using data from the development cohort to generate nomograms. By applying the models to the all cohorts, the AUC for csPCa was significantly higher for the bpMRI PI-RADS v2.1 score-based model than for the clinical model in both cohorts (p < 0.001). Considering the test trade-offs, urologists would agree to perform 10 fewer bpMRIs to avoid one unnecessary biopsy, with a risk threshold of 10-20% in practice. Correlation analysis showed a strong correlation between the bpMRI score and ISUP grade. CONCLUSION: A predictive model based on the bpMRI score and clinical parameters significantly improved csPCa risk stratification, and the bpMRI score can be used to determine the aggressiveness of PCa prior to biopsy.

High Expression of CDCA7 in the Prognosis of Glioma and Its Relationship with Ferroptosis and Immunity.

CDCA7 is a copy number amplification gene that promotes tumorigenesis. However, the clinical relevance and potential mechanisms of CDCA7 in glioma are unclear. CDCA7 expression level data were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases, and the enriched genes and related signaling pathways were explored. Data on genes in CDCA7-related signaling pathways and nine marker genes of ferroptosis were retrieved and a protein-protein interaction (PPI) network analysis was performed. The correlation of CDCA7 to ferroptosis and tumor infiltration of 22 kinds of human immune cells and the association between CDCA7 and immune checkpoint molecules were analyzed. CDCA7 was significantly increased in gliomas in comparison to healthy tissues. Gene Ontology (GO) and gene set enrichment analysis (GSEA) revealed the impact of CDCA7 expression on multiple biological processes and signaling pathways. CDCA7 may affect ferroptosis by interacting with genes in the cell cycle pathway and P53 pathway. The increase in CDCA7 was positively correlated with multiple ferroptosis suppressor genes and genes involved in tumor-infiltrating immune cells and immune checkpoint molecules in glioma. CDCA7 can be a new prognostic factor for glioma, which is closely related to ferroptosis, tumor immune cell infiltration, and immune checkpoint.

Non-invasive evaluation of liver steatosis with imaging modalities: New techniques and applications.

In the world, nonalcoholic fatty liver disease (NAFLD) accounts for majority of diffuse hepatic diseases. Notably, substantial liver fat accumulation can trigger and accelerate hepatic fibrosis, thus contributing to disease progression. Moreover, the presence of NAFLD not only puts adverse influences for liver but is also associated with an increased risk of type 2 diabetes and cardiovascular diseases. Therefore, early detection and quantified measurement of hepatic fat content are of great importance. Liver biopsy is currently the most accurate method for the evaluation of hepatic steatosis. However, liver biopsy has several limitations, namely, its invasiveness, sampling error, high cost and moderate intraobserver and interobserver reproducibility. Recently, various quantitative imaging techniques have been developed for the diagnosis and quantified measurement of hepatic fat content, including ultrasound- or magnetic resonance-based methods. These quantitative imaging techniques can provide objective continuous metrics associated with liver fat content and be recorded for comparison when patients receive check-ups to evaluate changes in liver fat content, which is useful for longitudinal follow-up. In this review, we introduce several imaging techniques and describe their diagnostic performance for the diagnosis and quantified measurement of hepatic fat content.

Canthin-6-Ones: Potential Drugs for Chronic Inflammatory Diseases by Targeting Multiple Inflammatory Mediators.

Chronic inflammatory disease (CID) is a category of medical conditions that causes recurrent inflammatory attacks in multiple tissues. The occurrence of CID is related to inappropriate immune responses to normal tissue substances and invading microbes due to many factors, such as defects in the immune system and imbalanced regulation of commensal microbes. Thus, effectively keeping the immune-associated cells and their products in check and inhibiting aberrant activation of the immune system is a key strategy for the management of CID. Canthin-6-ones are a subclass of ß-carboline alkaloids isolated from a wide range of species. Several emerging studies based on in vitro and in vivo experiments reveal that canthin-6-ones may have potential therapeutic effects on many inflammatory diseases. However, no study has yet summarized the anti-inflammatory functions and the underlying mechanisms of this class of compounds. This review provides an overview of these studies, focusing on the disease entities and the inflammatory mediators that have been shown to be affected by canthin-6-ones. In particular, the major signaling pathways affected by canthin-6-ones, such as the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the NF-κB signaling pathway, and their roles in several CIDs are discussed. Moreover, we discuss the limitations in studies of canthin-6-ones and provide possible solutions. In addition, a perspective that may suggest possible future research directions is provided. This work may be helpful for further mechanistic studies and possible therapeutic applications of canthin-6-ones in the treatment of CID.

Similarities and differences in kinetic characteristics of airways inflammation, formation of inducible bronchial-associated lymphoid tissue and remodeling between young and old murine asthma surrogates induced with house dust mite.

Elderly asthmatics have higher morbidity and mortality compared with those of youngers. It has been shown that there are also some differences in clinic phenomena between young and elderly asthmatics, however, there is lack of the kinetic comparisons of the changes in the development of asthma between two populations. To better understand the specific pathophysiological manifestations in older patients with asthma, we dynamically and parallelly compared pathophysiological changes in the airways and lung tissues between young and old murine asthma surrogates based on sensitization and challenge with house dust mite (HDM). Murine models were established in young (6-8-week-old) and old (16-17-month-old) female wild-type C57BL/6 mice. Our data showed that repetitive HDM exposure induced relatively low type 2 immune responses (airway hyperresponsiveness, eosinophils recruitment, expression of type 2 cytokines, mucus secretion, serum HDM specific immunoglobulin E (IgE) and IgG) in old mice. However, the type 3 immune responses (neutrophils infiltration and IL-17A expression) were enhanced in old HDM exposed mice, which sustained longer and higher than that of young mice. Notably, the relatively weakened allergic inflammation characteristics might be associated with lower numbers of CD20+ B cells and IgE+ cells in the iBALTs in old mice compared with those in young mice. Our data suggest that aging might compromise the ability to induce type 2 immune responses, but enhance type 3 immune responses upon repetitive HDM challenge, which might cause relevant phenomena in old experimental mice and might even be applicable to elderly patients with asthma in the clinic.

Kirigami-Origami-Inspired Lead-Free Piezoelectric Ceramics.

Kirigami- and oirigami-inspired techniques have emerged as effective strategies for material structure design; however, the use of these techniques is usually limited to soft and deformable materials. Piezoelectric ceramics, which are typical functional ceramics, are widely used in electronic and energy devices; however, the processing options for piezoelectric ceramics are limited by their brittleness and feedstock viscosity. Here, a design strategy is proposed for the preparation of lead-free piezoelectric ceramics inspired by kirigami/origami. This strategy involves direct writing printing and control over the external gravity during the calcination process for the preparation of curved and porous piezoelectric ceramics with specific shapes. The sintered BaTiO3 ceramics with curved geometries produced using this strategy exhibit a high piezoelectric constant (d33 = 275 pC N-1 ), which is 45% higher than that of conventionally sintered sheet ceramics. The curved structure of the ceramics is well-suited for use in the human body and it was determined that these curved ceramics can detect pulse signals. This strategy can be applied in the large-scale and low-cost production of other piezoelectric ceramics with various curved shapes and provides a new approach for the preparation of complex-shaped ceramics.

Multi-omics to predict acute radiation esophagitis in patients with lung cancer treated with intensity-modulated radiation therapy.

PURPOSE: The study aimed to predict acute radiation esophagitis (ARE) with grade ≥ 2 for patients with locally advanced lung cancer (LALC) treated with intensity-modulated radiation therapy (IMRT) using multi-omics features, including radiomics and dosiomics. METHODS: 161 patients with stage IIIA-IIIB LALC who received chemoradiotherapy (CRT) or radiotherapy by IMRT with a prescribed dose from 45 to 70 Gy from 2015 to 2019 were enrolled retrospectively. All the toxicity gradings were given following the Common Terminology Criteria for Adverse Events V4.0. Multi-omics features, including radiomics, dosiomics (including dose-volume histogram dosimetric parameters), were extracted based on the planning CT image and three-dimensional dose distribution. All data were randomly divided into training cohorts (N = 107) and testing cohorts (N = 54). In the training cohorts, features with reliably high outcome relevance and low redundancy were selected under random patient subsampling. Four classification models (using clinical factors (CF) only, using radiomics features (RFs) only, dosiomics features (DFs) only, and the hybrid features (HFs) containing clinical factors, radiomics and dosiomics) were constructed employing the Ridge classifier using two-thirds of randomly selected patients as the training cohort. The remaining patient was treated as the testing cohort. A series of models were built with 30 times training-testing splits. Their performances were assessed using the area under the ROC curve (AUC) and accuracy. RESULTS: Among all patients, 51 developed ARE grade ≥ 2, with an incidence of 31.7%. Next, 8990 radiomics and 213 dosiomics features were extracted, and 3, 6, 12, and 13 features remained after feature selection in the CF, DF, RF and DF models, respectively. The RF and HF models achieved similar classification performance, with the training and testing AUCs of 0.796 ± 0.023 (95% confidence interval (CI [0.79, 0.80])/0.744 ± 0.044 (95% CI [0.73, 0.76]) and 0.801 ± 0.022 (95% CI [0.79, 0.81]) (p = 0.74), respectively. The model performances using CF and DF features were poorer, with training and testing AUCs of 0.573 ± 0.026 (95% CI [0.56, 0.58])/ 0.509 ± 0.072 (95% CI [0.48, 0.53]) and 0.679 ± 0.027 (95% CI [0.67, 0.69])/0.604 ± 0.041 (95% CI [0.53, 0.63]) compared with the above two models (p < 0.001), respectively. CONCLUSIONS: In LALC patients treated with CRT IMRT, the ARE grade ≥ 2 can be predicted using the pretreatment radiotherapy image features. To predict ARE, the multi-omics features had similar predictability with radiomics features; however, the dosiomics features and clinical factors had a limited classification performance.

Decreased DIO3OS Expression Predicts Poor Prognosis in Hepatocellular Carcinoma and is Associated with Immune Infiltration.

Hepatocellular carcinoma has become one of the most shared cancers in the whole world because of its high morbidity, poor survival rate, and low recovery rate. LncRNA DIO3 opposite strand upstream RNA (DIO3OS) has been reported to be obviously important in several human cancers, while its biological function in hepatocellular carcinoma (HCC) remains unclear. Here, DIO3OS gene expression data and clinical information of HCC patients were extracted from the Cancer Genome Atlas (TCGA) database and the university of California Santa Cruz (UCSC) Xena database. In our study, the Wilcoxon rank sum test was used to compare DIO3OS expression between healthy individuals and HCC patients. It was found that patients with HCC had significantly lower DIO3OS expression than healthy individuals. Furthermore, Kaplan-Meier curves and Cox regression analysis showed that high DIO3OS expression tended to predict better prognosis and higher survival rate in HCC patients. In addition, the gene set enrichment analysis (GSEA) assay was used to annotate the biological function of DIO3OS. It was found that DIO3OS was significantly correlated with immune invasion in HCC. This was also aided by the subsequent ESTIMATE assay. Our study provides a novel biomarker and therapeutic strategy for patients with hepatocellular carcinoma.

Targeting the STAT5A/IDO1 axis overcomes radioresistance and reverses the immunosuppressive tumor microenvironment in NSCLC.

As a metabolic mediator of antitumor immunity, indoleamine­2,3­dioxygenase 1 (IDO1) is upregulated in various types of cancer; however, the regulatory mechanism and clinical significance of IDO1 in non­small cell lung cancer (NSCLC) radiotherapy (RT) remain unclear. The present study investigated the role of IDO1 in the NSCLC microenvironment. MTT assay, immunofluorescence, apoptosis analysis, cell cycle analysis, and C57BL/6 and BALB/c nude mouse tumor models were utilized to evaluate the roles of the STAT5A/IDO1/kynurenine axis in radioresistance and in the immune microenvironment of NSCLC. Protein expression levels were evaluated by western blotting, immunofluorescence and immunohistochemistry. Flow cytometry was performed to assess the status of CD8+ T lymphocytes, regulatory T cells (Tregs) and immune­related inflammatory factors in C57BL/6 mice. Notably, IDO1 and STAT5A were positively associated with the immune microenvironment. RT treatment significantly promoted the expression levels of IDO1. IDO1 knockdown markedly enhanced the radiosensitivity of lung tumor cells and the anti­apoptotic properties of T lymphocytes. It was demonstrated that STAT5A knockdown suppressed T­cell apoptosis by inhibiting IDO1 enzyme function. Finally, in vivo experiments showed that STAT5A knockdown combined with RT was associated with greater numbers of CD8+ T cells and fewer Tregs. Results from the present study indicated that targeting the STAT5A/IDO1 axis may reshape the immune microenvironment and promote the efficacy of RT in NSCLC treatment. The present study may provide a theoretical foundation for more efficient use of immunotherapy regimens in NSCLC treatment.

Specific Pandemic-Related Worries Predict Higher Attention-Related Errors and Negative Affect Independent of Trait Anxiety in UK-Based Students.

Background: The COVID-19 pandemic has resulted in many individuals experiencing increased symptoms of anxiety. We predict that this increase may be underpinned by pandemic-related worry (PRW), characterised by repetitive negative thinking about pandemic-specific outcomes; and that this relationship is mediated through reduced attentional capacity required to regulate negative affect. Methods: We developed a novel scale to measure the contents of PRW in an initial sample of 255 participants, and explored its relationship with cognitive functioning and negative affect in a sample of 382 UK-based university students, whilst controlling for recalled pre-pandemic trait anxiety. Results: A five-factor model of PRW was identified, with factors reflecting worry about decline in quality of life (QoL) and probability of infection correlating with attention and memory-related errors. Importantly, attention-related errors partially mediated the positive relationship between PRW and negative affect, even when controlling for pre-pandemic trait anxiety. Conclusion: PRW's relationship with negative affect was partially mediated through attentional function, consistent with models of anxiety and attentional control. In UK-based students PRW may be predominantly focused on the decline in QoL; therefore, interventions targeting worry about the decline in QoL caused by COVID-19 are especially important in this population in the wake of the pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s10608-022-10336-7.

Lung Subregion Partitioning by Incremental Dose Intervals Improves Omics-Based Prediction for Acute Radiation Pneumonitis in Non-Small-Cell Lung Cancer Patients.

Purpose: To evaluate the effectiveness of features obtained from our proposed incremental-dose-interval-based lung subregion segmentation (IDLSS) for predicting grade ≥ 2 acute radiation pneumonitis (ARP) in lung cancer patients upon intensity-modulated radiotherapy (IMRT). (1) Materials and Methods: A total of 126 non-small-cell lung cancer patients treated with IMRT were retrospectively analyzed. Five lung subregions (SRs) were generated by the intersection of the whole lung (WL) and five sub-regions receiving incremental dose intervals. A total of 4610 radiomics features (RF) from pre-treatment planning computed tomographic (CT) and 213 dosiomics features (DF) were extracted. Six feature groups, including WL-RF, WL-DF, SR-RF, SR-DF, and the combined feature sets of WL-RDF and SR-RDF, were generated. Features were selected by using a variance threshold, followed by a Student t-test. Pearson's correlation test was applied to remove redundant features. Subsequently, Ridge regression was adopted to develop six models for ARP using the six feature groups. Thirty iterations of resampling were implemented to assess overall model performance by using the area under the Receiver-Operating-Characteristic curve (AUC), accuracy, precision, recall, and F1-score. (2) Results: The SR-RDF model achieved the best classification performance and provided significantly better predictability than the WL-RDF model in training cohort (Average AUC: 0.98 ± 0.01 vs. 0.90 ± 0.02, p < 0.001) and testing cohort (Average AUC: 0.88 ± 0.05 vs. 0.80 ± 0.04, p < 0.001). Similarly, predictability of the SR-DF model was significantly stronger than that of the WL-DF model in training cohort (Average AUC: 0.88 ± 0.03 vs. 0.70 ± 0.030, p < 0.001) and in testing cohort (Average AUC: 0.74 ± 0.08 vs. 0.65 ± 0.06, p < 0.001). By contrast, the SR-RF model significantly outperformed the WL-RF model only in the training set (Average AUC: 0.93 ± 0.02 vs. 0.85 ± 0.03, p < 0.001), but not in the testing set (Average AUC: 0.79 ± 0.05 vs. 0.77 ± 0.07, p = 0.13). (3) Conclusions: Our results demonstrated that the IDLSS method improved model performance for classifying ARP with grade ≥ 2 when using dosiomics or combined radiomics-dosiomics features.